CHAPTER ONE

Rehabilitation: From Bedside To Community Following Spinal Cord Injury (SCI)

Janice J Eng, PhD, BSc (PT/OT) William C Miller, PhD, OT

Table of Contents

1.1 Background ......................................................................................................................1-1 1.2 Epidmiology .....................................................................................................................1-2 1.2.1 Traumatic SCI .................................................................................................................1-2 1.2.2 Non-traumatic SCI ..........................................................................................................1-3 1.3 Recovery...........................................................................................................................1-3 1.3.1 Neuroplasticity ................................................................................................................1-4 1.3.2 Measures of Recovery ....................................................................................................1-4 1.4 Rehabilitation ...................................................................................................................1-6 1.5 Community Re-integration..............................................................................................1-7 References................................................................................................................................1-9

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Eng JJ, Miller WC (2006). Rehabilitation: From Bedside To Community Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 1.1-1.11. www.icord.org/scire

Rehabilitation: From Bedside To Community Following Spinal Cord Injury (SCI)

1.1 Background The spinal cord extends from the foramen magnum (opening at the base of the skull) to the conus medullaris (most distal bulbous part of the cord) at the level of the first and second lumbar vertebrae. It consists of 31 segments associated with 31 pairs of spinal nerves (8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 1 coccygeal). The ascending sensory nerves within the spinal cord receive and transmit sensory information to the brain. The descending motor nerves transmit information from the higher brain structures to various parts of the body to initiate motor functions such as movement and to regulate autonomic functions such as respiration and blood pressure. The spinal cord is also critical for transmitting and integrating information within the spinal cord. Figure 1.1
C2-3 C3-5 C5 C6 C7 C8 T1 Sternomastoid Diaphragm Elbow Flexors Wrist Extensors Elbow Extensors Long Fingers Flexors Small Finger Abductors

Cervical

Thoracic

T1-11 T7-L1

Intercostals Abdominals Muscle

Conus medullaris Lumbar Cauda Equina

Sacral

T11-L2 L2 L3 L4 L5 S1 S2-3 S2-4

Ejaculation Hip Flexors Knee Extensors Ankle Dorsiflexors Long Toe Extensor Ankle Plantarflexors Bowel / Bladder Penile Erection

Coccygeal

Spinal cord injury (SCI) which results in disruption of the nervous transmission can have considerable physical and emotion consequences to an individuals life. Paralysis, altered sensation, or weakness in the parts of the body innervated by areas below the injured region almost always occur. In addition to a loss of sensation, muscle functioning and movement, individuals with SCI also experience many other changes which may affect bowel and bladder, presence of pain, sexual functioning, gastrointestinal function, swallowing ability, blood pressure, temperature regulation and breathing ability. Numerous secondary complications

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may arise from SCI including deep vein thrombosis, heterotopic ossification, pressure ulcers and spasticity. The recovery can be long from the acute hospital admission to the return of full participation in the individuals community. Even those individuals who make significant gains in rehabilitation may experience difficulty when returning to pre-injury activities. Thus, SCI has a severe effect on quality of life. It also has an enormous cost on the health care system. Dryden et al. (2005) examined the health care costs following a SCI in Canada. The acute and rehabilitation care represented 68.2% of the total health care costs incurred over the first 6 years for an individual following an injury to the spinal cord. The direct costs of a spinal cord injury were estimated at $146,000 Canadian in the first year for a person with a complete traumatic injury and $42,000 for an incomplete injury. Annual costs in the subsequent 5 years post-injury were reported to be $5400 Canadian per person with a complete injury and $2800 for an incomplete injury (Dryden et al. 2005). Compared to age and gender-matched controls, individuals with SCI discharged from hospital are more likely to be re-hospitalized, have physician contact and use more hours of home care services (Dryden et al. 2004). The need for evidence-based SCI rehabilitation programs has never been greater given the enormous cost of SCI rehabilitation, the growing demands on the Canadian health care system and the devastating impact that an SCI has on the quality of lives of individuals. 1.2 Epidemiology Injuries to the spinal cord have been classified as either traumatic in cause (e.g., motor vehicle accidents, falls, violent incidences, diving) or non-traumatic (e.g., tumors, spinal stenosis, vascular). Traumatic SCI accounts for the larger proportion of SCI injuries, however, the exact proportion compared to non-traumatic SCI is difficult to ascertain because reporting of nontraumatic SCI has been inconsistent. The percent of traumatic SCI to overall SCI injury has been reported to range from 75% in Germany (Exner & Meinecke 1997), 61% in the United States (McKinley et al. 1999a) and 48% in the Netherlands (Schonherr et al. 1996). 1.2.1 Traumatic SCI Much of the following epidemiology data on traumatic spinal cord injury in Canada has been extracted from the 2006 Canadian Institute of Health Information Report on Traumatic SCI (CIHI 2006a) using 2003-2004 data from the Canadian National Trauma Registry (NTR). Over 950 traumatic spinal cord injuries occurred in 2003-2004 (CIHI 2006a). Reports of the annual incidence vary in part due to differing methods of identifying and tracking injuries, and due to regional differences. The annual incidence has been estimated at 52.5 per million population in Alberta (Dryden et al. 2003) and 46.2 to 37.1 per million population over the 1994 to 1999 period in Ontario (Pickett et al. 2003). The global incidence of SCI estimated primarily from developed countries ranges between 10.4 to 83 per million population per year when including only patients who survived before hospital admission (Wyndaele & Wyndaele 2006). In Canada, males comprise over three-quarters of these traumatic injuries with the majority occurring in those under 35 years of age. Motor vehicle accidents are the leading cause of SCI injury (43%), while falls are the second leading cause (36%) (NTR 1999). The number of spinal cord injuries resulting from falls are increasing due to the growing older adult segment of the population. This has contributed to the increase in age of a person with traumatic SCI (from average age 46 in 1994 to average 49 in 1998). In fact, we are now seeing a bimodal distribution of SCI in the population with one mode centralizing at approximately 30 years of age and another mode centralizing at 60 years of age. Interestingly, falls are the primary cause of

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spinal cord injury admissions in seniors (64%), while motor vehicle accidents are the leading cause in young adults (NRT 1999). Fractures of the vertebral column, in addition to spinal cord injury represent 71% of all SCI hospital admissions (NTR 1999). Of the SCI admissions, 44% result in paraplegia and 56% tetraplegia (NTR 1999). Traumatic SCI can be complex as motor vehicle accidents or other violent incidents often result in more than injury to the spinal cord. In particular, patients with the dual diagnosis of traumatic brain injury and spinal cord injury present a challenge to the rehabilitation professional as they are often agitated and have poor concentration. The percentage of SCI injuries which are accompanied by a traumatic brain injury are substantial, for example, Lida et al. (1999) reported that 35% of SCI had a traumatic brain injury. There appears to be a trend towards more severe injuries in Canada. In the 1970s, the Canadian Paraplegic Association (CPA) reported that about 25% of injuries resulted in tetraplegia and 75% paraplegia. Of the new injuries reported to CPA during 1999, 47% resulted in tetraplegia and 53% resulted in paraplegia. This increase in tetraplegic injuries concurs with a slight significant increase from 53.5% tetraplegia in the 1970s to 56.5% in 2000 at the facilities with the Model Spinal Cord Systems in the US (Jackson et al. 2004). A survey of the epidemiology literature (Wyndaele and Wyndaele 2006) suggests increasing proportions of tetraplegia with a global proportion of approximately two-thirds tetraplegia. There have been some suggestions that there are increasing numbers of incomplete lesions in some regions (Calancie et al. 2005). However, these finding are not consistent. The Model Spinal Cord Systems in the US (Jackson et al. 2004) reported an increase in complete injuries in the 1990s which has since dropped back to pre-1990 levels with just less than half of the injuries being complete. The Australian Spinal Cord Injury Registry reported increasing rates in elderly males, fall-related injury and incomplete tetraplegia and complete paraplegia over an eleven year period (OConnor 2006). 1.2.2 Non-traumatic SCI There are many different causes of non-traumatic SCI, the more common conditions include spinal stenosis (narrowing of the spinal canal), tumor compression and vascular ischemia. Individuals with a non-traumatic SCI do not necessarily enter major trauma or rehabilitation centres and thus are not easily tracked in SCI registries or databases. Non-traumatic SCI has different demographics than traumatic SCI as spinal stenosis and spinal tumors are more common in adults over 50 years of age. In addition, specific diseases such as multiple sclerosis, paediatric spina bifida or poliomyelitis can also contribute to non-traumatic spinal cord injury and each has demographics specific to the condition. Overall, compared to traumatic SCI, individuals with non-traumatic SCI tend to be older with less severe injuries, more likely to be female, married, retired, and have an incomplete paraplegic injury (McKinley et al. 1999, 2002a, 2002b). Differences in demographics, clinical presentation and rehabilitation outcomes have important implications for management of nontraumatic SCI. 1.3 Recovery The majority of individuals experience some neurological recovery (changes in motor or sensory status) following a SCI, in addition to functional recovery. Given that all patients receive some

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treatment (e.g., pharmacological, self-care and mobility training), it is difficult to separate the contributions of spontaneous recovery with those from active rehabilitation in humans. 1.3.1 Neuroplasticity Spontaneous neuronal plasticity occurs through various mechanisms and has been demonstrated primarily in animal models. Recovery mechanisms following complete injuries may include recovery of nerve roots beside the lesion level, changes in the gray matter of the spinal cord at the lesion level, reorganization of existing spinal circuits and peripheral changes (Bradbury & McMahon 2006; Kern et al. 2005; Ding et al. 2005; Hagg & Oudega 2006; Ramer et al. 2005). The evidence for spontaneous axonal regeneration is limited as a small proportion of fibres regenerate and over a modest distance (Bradbury & McMahon 2006). However, cortical re-organization can occur, for example, Lotze et al. (2006) showed that cortical representation of elbow movements following a complete thoracic injury in humans was moved toward cortical areas which represented the injured thoracic regions. There is evidence that a pattern-generating spinal circuitry (also known as a central pattern generator) is retained following a complete injury which can produce stepping-like movements and activation patterns with epidural lumbar cord stimulation (Kern et al. 2005) or treadmill stimulation (Dietz et al. 2002). However, the functional consequences of these observations are yet to be determined. Incomplete injuries may have a greater extent of axonal sprouting and axonal growth (Ding et al. 2005; Hagg & Oudega 2006). In incomplete spinal cord injury in rats, transected hindlimb corticospinal tract axons sprouted into the cervical gray matter to contact short and long propriospinal neurons (Bareyre et al. 2004). Following cervical lesions of the rat dorsal corticospinal motor pathway which contains more than 95% of all corticospinal axons, there was spontaneous sprouting from the ventral corticospinal tract onto medial motoneuron pools (Weidner et al. 2001). This sprouting was paralleled by functional recovery. Ramer et al. (2005) suggested that if axonal regeneration occurs or if synaptic spaces become occupied with different axons, functional recovery will require retraining to optimize these new circuits. The neuroplastic changes which underlie spontaneous recovery may be enhanced by physical interventions (e.g., exercise, electrical stimulation) and pharmacological agents (Ramer et al. 2005). 1.3.2 Measures of Recovery Changes in the American Spinal Injury Association (ASIA) International Classification of Spinal Cord Injury, neurological level of injury and completeness of injury are often used to indicate human neurological recovery. ASIA International Standards for Neurological Classification of Spinal Cord Injury consists of 1) 5 category ASIA Impairment Scale (A-E), 2) motor score and 3) sensory score (ASIA 2002). Twenty-eight dermatomes are assessed bilaterally using pinprick and light touch sensation for the sensory score (maximum of 112 for pinprick and 112 for light touch sensation). Ten key muscles are assessed bilaterally with manual muscle testing for the motor score (maximum of 50 for lower limbs and 50 for upper limbs). The results are used in combination with evaluation of anal sensory and motor function as a basis for the determination of the ASIA Impairment Scale and the 5 categories are summarized below (ASIA 2002).

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Table 1.1 Descriptions of Categories from ASIA Impairment Scale

ASIA A: Complete injury where no sensory or motor function is preserved in sacral segments S4-S5. ASIA B: Incomplete injury where sensory, but not motor, function is preserved below the neurologic level and extends through sacral segments S4-S5. ASIA C: Incomplete injury where motor function is preserved below the neurologic level, and most key muscles below the neurologic level have muscle grade less than 3 (active full-range movement against gravity). ASIA D: Incomplete injury where motor function is preserved below the neurologic level, and most key muscles below the neurologic level have muscle grade greater than or equal to 3. ASIA E: Normal sensory and motor functions.

Neurological level of injury is the most caudal level at which both motor and sensory levels are intact and has been shown to change in some individuals over recovery. Completeness of injury are based on the ASIA standards where the absence of sensory and motor functions in the lowest sacral segments indicates a complete injury and preservation of sensory or motor function below the level of injury, including the lowest sacral segments indicates an incomplete injury. Sacral-sparing is an important indicator of motor recovery and provides evidence of the physiologic continuity of spinal cord long tract fibers with the sacral fibers at the end of the cord. The requirement of sacral sparing to identify an incomplete injury provides a more rigorous definition and less patients will convert from incomplete to complete injury over time when using this definition. Stauffer (1976) proposed that individuals with tetraplegia would recover one neurological level, although this has been revised in recent years to qualify that recovery of one neurologic level in subjects with tetraplegia depends on severity, initial level of the injury and the strength of muscles below the level of injury (Dittuno et al. 2005). Dittuno et al. (1992) reported that 70 to 80% of motor-complete tetraplegia subjects with some motor strength at the injury level would recover to the next neurologic level within 3 to 6 months. Although those with complete lesions are generally limited to improvements of one or two levels, subjects with incomplete lesions may exhibit recovery at multiple levels below the injury site (Dittuno et al. 2005). Triceps elbow extension (C7) is a significant determinant for functional independence in self-care for community-living individuals with tetraplegia (Welch et al. 1986). For those with complete paraplegia, Waters et al. (1992) reported that 73% of 108 patients (T2L2) did not change in neurological level at one year post-injury compared to the rehabilitation admission assessment. 18% recovered to the next neurological level, while 7% had 2 levels of recovery. For incomplete paraplegia, 78% of 45 cases (T1-L3) had no changes in neurological level between the first and 12th month but there was substantial improvement in motor function particularly within the first 3 months (Waters et al. 1994). 70% of this sample were able to ambulate within 1 or 2 years post-injury (27% without any devices). Patients with initial grade 2 hip flexor and knee extensor motor strength achieved community ambulation. In terms of function, individuals with a T2-T9 injury have some trunk control and may be able to stand using braces and an assistive device such as a walker. Although injuries below T11 have increased potential for ambulation with bracing, successful community ambulation often involves individuals with an injury at the L3 level or below. Marino et al. (1999) assessed data from 21 Model System SCI systems with 3585 individuals with SCI over the first year of recovery. They found that 10 to 15% of those with initial complete ASIA A injuries converted to incomplete injuries. For ASIA B injuries, 1/3 converted to ASIA C 1-5

and 1/3 to ASIA D or E. For ASIA C injuries, over 2/3 converted to ASIA D. However, the accurate prediction of ASIA conversion can be fraught with problems. Burns et al. (2003) found that individuals with cognitive factors (e.g., traumatic brain injury, alcohol intoxication, analgesic administration, psychological disorders) and communication barriers (e.g., language barriers, ventilatory dependency) had a higher percent of ASIA conversion over the first year likely due to an inaccurate initial assessment. 1.4 Rehabilitation Rehabilitation has been defined by the World Health Organization as a progressive, dynamic, goal-oriented and often time-limited process, which enables an individual with an impairment to identify and reach his/her optimal mental, physical, cognitive and social functional level. Enhancing quality of life is regarded as an inherent goal of rehabilitation services and programs given their focus on interventions to minimize the impact of pain and physical and cognitive impairment, and on enhancing participation in work and everyday activities. SCI rehabilitation involves a multitude of services and health professionals and is initiated in the acute phase and continues with extensive and specialized inpatient services during the sub-acute phase. Inpatient rehabilitation is an important stepping stone towards regaining and learning new skills for independent living. Here patients engage in an intensive full day program with services which may include nursing, physical therapy, occupational therapy, respiratory management, medical management, recreation and leisure, psychology, vocational counseling, driver training, nutritional services, speech pathology, social worker, sexual health counseling, assistive device prescription and pharmaceutical services. Rehabilitation continues with planning for discharge back to the community and finally, re-integration into former or new roles and activities within the community. Family and peers have important roles throughout the rehabilitation process. In Canada, the median length of inpatient rehabilitation stay for traumatic SCI is 59 days with longer stays for those with complete injuries or tetraplegic injuries ranging from 49 days for those with incomplete paraplegia to 101 days to those with complete tetraplegia (CIHI 2006a). SCI has the longest inpatient rehab length of stay over all other rehabilitation patient groups except for burns (CIHI 2006b). Functional recovery is often measured by the Functional Independence Measure (FIM), an 18 item scale that is intended to measure caregiver burden and includes tasks related to cognition, mobility, bowel and bladder management and self-care. During inpatient rehabilitation, patients with complete tetraplegia have the lowest FIM admission score and make less change compared to those with incomplete or paraplegic injuries (CIHI 2006a). Persons with the dual diagnosis of spinal cord injury and traumatic brain injury achieve smaller functional gains in rehabilitation (Macciocchi et al. 2004). Compared to traumatic SCI, the non-traumatic SCI rehabilitation length of stay is shorter, with a lower FIM change and fewer medical complications including deep venous thrombosis, orthostatic hypotension, pressure ulcers, wound infections, spasticity, autonomic dysrelfexia were less likely (McKinley et al. 2002a, 2002b). The shorter length of stay may be a result of the less severe injury. However, the earlier discharge in metastatic tumors may reflect the terminal nature of the disease and patients and family may wish for the remaining time to be spent at home.

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1.5 Community Re-integration There is a fundamental belief among consumers with SCI that there needs to be a paradigm shift in the approach to rehabilitation from an institutionally based physical restoration model to a community-based independent living model (Rick Hansen SCI Network 2005). Going home is a frequent goal established by patients newly admitted to hospital and 79% of individuals with traumatic SCI injuries return home. Only 62% of individuals with complete tetraplegia return home with 15% discharged back to acute care and 18% to long term care (CIHI 2006a). In a study of high lesion SCI (C1-C4), it was found that 40% of these clients were discharged to extended care units post rehabilitation, while the majority of these respiratory dependent patients returned to the community (Anzai et al. 2006). Life expectancy is less than normal, particularly for people with tetraplegia and who are ventilator-dependent (NSCISC 2004). The life expectancy of a 40 year old paraplegic who has survived at least 1 year post-injury is 10 years less than a person without a SCI (NSCISC 2004). Although the mortality rate during the first 2 years after SCI has been reduced over the past 30 years, Strauss et al. (2006) noted that there has not been a substantial change in life expectancy following the second year post-injury. In contrast, there has been an increase in life expectancy over the last 2 decades in the general population. Given that the majority of traumatic SCI occur in young adults, return to work or school is of high importance, but often necessitates a change in vocation. Less than 18% of those employed at the time of injury were able to return to the same job (CPA 1997). Within 3-6 months post inpatient rehabilitation, 14% of people with SCI are employed, while 64% were employed prior to injury. Approximately 9% are students (roughly double the pre-injury status). The majority are unemployed (26%) or on disability status (35%) at 3-6 months follow-up (CIHI 2006a). Canadians living with SCI tend to have a higher level of education than the general Canadian population (CPA 1997). In a survey of Canadians who had been injured at least 5 years, 62% were unemployed while 38% are employed (CPA 1997). Education is key to employment higher education or increasing education following injury result in more success with employment. Of those who find employment, 44% do so within 2 years of injury while 77% find employment within 5 years. Accessible infrastructure and disability support are two major areas which people with SCI feel would improve quality of life (RHMIMF 2004). When considering priorities for research, individuals living with SCI rank finding a cure for SCI similarly to developing advances in rehabilitation/therapy (RHMIMF 2004). Regaining arm and hand function has been cited as one of the most important priorities to tetraplegics, while regaining sexual function has been cited as the highest priority for paraplegics (Anderson 2004). Improving bladder and bowel function was important to both injury groups (Anderson 2004). Although the majority of participants indicated that exercise was important to functional recovery, more than half did not have access to exercise (Anderson 2004). Anderson (2004) emphasized the need for researchers to be aware of the needs of SCI consumers in their quest for discovery. The continuum of health care in the community includes mechanisms for people to access information resources about living with a SCI. However, it appears that people with SCI do not approach traditional health care sources for their information (e.g., physician, hospital). For people living with SCI, the internet was by far the number one source for information about SCI (48%), while support groups and media ranked higher than hospitals, books, rehab centres, physicians and peers (RHMIMF 2004). It appears that the internet can be an ideal medium for promoting health-related education. To facilitate accessibility of information, the SCIRE 1-7

information is available on CD, print version, as well as through web-access (www.icord.org/scire). In a recent survey, the majority (70%) of individuals with SCI rated the quality of life of people with SCI as good or very good while 23% rated it as poor or very poor (RHMIMF 2004). It is encouraging that 65% of individuals with SCI felt that the quality of life of people with SCI has improved over the past 5 years (RHMIMF 2004). As enhancing quality of life is an inherent goal of rehabilitation, there is a continual challenge to close the gap between treatment activities and functional competence in the individuals actual environment.

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References American Spinal Injury Association. Reference Manual for International standards for neurological and functional classification of spinal cord injury patients (revised 2002). Chicago: American Spinal Injury Association, 2002. Anderson KD. Targeting recovery: priorities of the spinal cord-injured population. J Neurotrauma. 2004;21:1371-1383. Bareyre FM, Kerschensteiner M, Raineteau O, Mettenleiter TC, Weinmann O, Schwab ME. The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. Nat Neurosci. 2004;7:269-277. Burns AS, Lee BS, Ditunno JF Jr, Tessler A. Patient selection for clinical trials: the reliability of the early spinal cord injury examination. J Neurotrauma. 2003;20:477-482. Calancie B, Molano MR, Broton JG. Epidemiology and demography of acute spinal cord injury in a large urban setting. J Spinal Cord Med. 2005;28:92-96. Canadian Institute for Health Information (2006a). Life after traumatic spinal cord injury: From inpatient rehabilitation back to the community. Analysis in Brief. Canadian Institute for Health Information (2006b). Inpatient rehabilitation in Canada 2004-2005. Canadian Paraplegic Association (CPA) (1997). Spinal Cord Injury Workforce Participation National Survey. Curt A, Keck ME, Dietz V. Functional outcome following spinal cord injury: significance of motorevoked potentials and ASIA scores. Arch Phys Med Rehabil. 1998;79:81-86. Ding Y, Kastin AJ, Pan W. Neural plasticity after spinal cord injury. Curr Pharm Des. 2005;11:1441-1450. Dietz V, Muller R, Colombo G. Locomotor activity in spinal man: significance of afferent input from joint and load receptors. Brain. 2002;125:2626-2634. Ditunno JF Jr, Stover SL, Freed MM, Ahn JH. Motor recovery of the upper extremities in traumatic quadriplegia: a multicenter study. Arch Phys Med Rehabil. 1992;73:431-436. Ditunno JF Jr, Burns AS, Marino RJ. Neurological and functional capacity outcome measures: essential to spinal cord injury clinical trials. J Rehabil Res Dev. 2005;42:35-41. Ditunno JF Jr, Cohen ME, Hauck WW, Jackson AB, Sipski ML. Recovery of upper-extremity strength in complete and incomplete tetraplegia: a multicenter study. Arch Phys Med Rehabil. 2000;81:389-393. Dryden DM, Saunders LD, Rowe BH, May LA, Yiannakoulia NY, Svenson LW, Shchopflocher DP, Voaklander DC. The epidemiology of traumatic spinal cord injury in Alberta, Canada, Can J Neurol Sci. 2003;30:113-121. Dryden DM, Saunders LD, Rowe BH, May LA, Yiannakoulias N, Svenson LW, Schopflocher DP, Voaklander DC. Utilization of health services following spinal cord injury: a 6-year follow-up study. Spinal Cord. 2004;42:513-525. Dryden DM, Saunders LD, Jacobs P, Schopflocher DP, Rowe BH, May LA, Yiannakoulias N, Svenson LW, Voaklander DC. Direct health care costs after traumatic spinal cord injury. J Trauma. 2005;59:443-449. Exner G, Meinecke FW. Trends in the treatment of patients with spinal cord lesions seen within a period of 20 years in German centers. Spinal Cord. 1997;35:415-419. Hagg T, Oudega M. Degenerative and spontaneous regenerative processes after spinal cord injury. J Neurotrauma. 2006;23:264-280. Jackson AB, Dijkers M, Devivo MJ, Poczatek RB. A demographic profile of new traumatic spinal cord injuries: change and stability over 30 years. Arch Phys Med Rehabil. 2004; 85:1740-1748. Kern H, McKay WB, Dimitrijevic MM, Dimitrijevic MR. Motor control in the human spinal cord and the repair of cord function. Curr Pharm Des. 2005;11:1429-1439.

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Lotze M, Laubis-Herrmann U, Topka H. Combination of TMS and fMRI reveals a specific pattern of reorganization in M1 in patients after complete spinal cord injury. Restor Neurol Neurosci. 2006;24:97-107. Macciocchi SN, Bowman B, Coker J, Apple D, Leslie D. Effect of co-morbid traumatic brain injury on functional outcome of persons with spinal cord injuries. Am J Phys Med Rehabil. 2004;83:22-26. Marino RJ, Ditunno JF Jr, Donovan WH, Maynard F Jr. Neurologic recovery after traumatic spinal cord injury: data from the Model Spinal Cord Injury Systems. Arch Phys Med Rehabil. 1999;80:1391-1396. McKinley WO, Seel RT, Hardman JT. Nontraumatic spinal cord injury: incidence, epidemiology, and functional outcome. Arch Phys Med Rehabil. 1999a;80:619-623. McKinley WO, Huang ME, Brunsvold KT. Neoplastic versus traumatic spinal cord injury: an outcome comparison after inpatient rehabilitation. Arch Phys Med Rehabil. 1999b;80:12531257. McKinley WO, Seel RT, Gadi RK, Tewksbury MA. Nontraumatic vs. traumatic spinal cord injury: a rehabilitation outcome comparison. Am J Phys Med Rehabil. 2001;80:693-699. McKinley WO, Tewksbury MA, Godbout CJ. Comparison of medical complications following nontraumatic and traumatic spinal cord injury. J Spinal Cord Med. 2002a;25:88-93. Mckinley WO, Tewksbury MA, Mujteba NM. Spinal stenosis vs traumatic spinal cord injury: a rehabilitation outcome comparison. J Spinal Cord Med. 2002b;25:28-32. National Spinal Cord Injury Statistical Center (NSCISC 2004). Annual Statistical Report for the Model Spinal Cord Injury Care Systems. National Trauma Registry - 2003 dataset, Canadian Institute for Health Information, 2003. National Trauma Registry - 1999 dataset, Canadian Institute for Health Information, 1999. New PW. Non-traumatic spinal cord injury: what is the ideal setting for rehabilitation? Aust Health Rev. 2006;30:353-361. O'Connor PJ. Trends in spinal cord injury. Accid Anal Prev. 2006;38:71-77. Ontario Traumatic Registry Analytic Bulletin Major Head and Spinal Cord Injury Hospitalizations in Ontario 2001/2002. Pickett W, Simpson K, Walker J, Brison RJ. Traumatic spinal cord injury in Ontario, Canada. J Trauma. 2003;55:1070-1076. Pickett GE, Campos-Benitez M, Keller JL, Duggal N. Epidemiology of traumatic spinal cord injury in Canada. Spine. 2006;31:799-805. Rick Hansen SCI Network (2004). Inventory of Services: An overview of SCI services across Canada. Rick Hansen Man-in-Motion Foundation (RHMIMF) (2004). Ipsos Reid SCI Community Survey. Rick Hansen SCI Network (2005). Cross-Canada Checkup. Interim Report of the National Consultations on SCI services in Canada a qualitative overview. Schonherr MC, Groothoff JW, Mulder GA, Eisma WH. Rehabilitation of patients with spinal cord lesions in The Netherlands: an epidemiological study. Spinal Cord. 1996;34:679-683. Sommer JL, Witkiewicz PM. The therapeutic challenges of dual diagnosis: TBI/SCI. Brain Inj. 2004;18:1297-1308. Stauffer ES. Diagnosis and prognosis of acute cervical spinal cord injury. Clin Orthop Relat Res. 1975;112:9-15. Strauss DJ, Devivo MJ, Paculdo DR, Shavelle RM. Trends in life expectancy after spinal cord injury. Arch Phys Med Rehabil. 2006;87:1079-1085. Waters RL, Adkins RH, Yakura JS, Sie I. Motor and sensory recovery following incomplete paraplegia. Arch Phys Med Rehabil. 1994;75:67-72. Waters RL, Yakura JS, Adkins RH, Sie I. Recovery following complete paraplegia. Arch Phys Med Rehabil. 1992;73:784-789.

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Welch RD, Lobley SJ, O'Sullivan SB, Freed MM. Functional independence in quadriplegia: critical levels. Arch Phys Med Rehabil. 1986;67:235-40. Wyndaele M, Wyndaele JJ. Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal Cord. 2006 44:523-9.

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CHAPTER TWO
Methods of Systematic Reviews

Table of Contents
2.1 Introduction ......................................................................................................................2-1 2.2 Article Assessment..........................................................................................................2-2 2.2.1 Literature Search Strategy ..............................................................................................2-2 2.2.2 Quality Assessment Tool and Data Extraction................................................................2-2 2.3 Determining Levels of Evidence and Formulating Conclusions .................................2-3 Appendix 1. Specific Search Terms .....................................................................................2-5 Appendix 2. The PEDro Scale...............................................................................................2-8 Appendix 3. Downs and Black tool (Downs and Black 1998) ..........................................2-10 References...............................................................................................................................2-11
19H

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Methods of the Systematic Reviews. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. 2006: Vancouver, p 2.1-2.11. www.icord.org/scire

Methods of the Systematic Reviews

2.1 Introduction Providing a framework for evidence-base practice was championed in the early 1990s, although it was practiced and discussed in medical circles long before this. In 1992, the Evidence-Based Practice Working Group (EBPWG) described a new framework of using research to guide and augment the practice of medicine (Evidence-based Medicine Working Group 1992). Dr. David Sackett, a pioneer in the field and also a member of the original working group described evidence-based practice as: Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research. (Sackett et al. 1996) Although the original definitions were framed for the practice of medicine, the practice has spread to all fields of health care with the more generic term evidence-based practice. Evidence-based practice does not ignore clinical experience and patient preferences, but weights these against a background of the highest quality scientific evidence that is available. The importance of clinical judgement was emphasized by Dr. Sackett in his original editorial: Because it [evidence-based medicine] requires a bottom up approach that integrates the best external evidence with individual clinical expertise and patients' choice, it cannot result in slavish, cookbook approaches to individual patient care. External clinical evidence can inform, but can never replace, individual clinical expertise, and it is this expertise that decides whether the external evidence applies to the individual patient at all and, if so, how it should be integrated into a clinical decision. Sackett et al. (1996) Acquiring and interpreting the evidence from the research literature can be daunting. Not only is there a wealth of ever changing information from multiple sources, but it is often difficult for a front-line clinician not intimately familiar with the research methods to interpret the results of a study. In addition, the interpretation is further complicated by the presence of multiple studies on an intervention, often with what appears to be conflicting messages. The Spinal Cord Injury Rehabilitation Evidence (SCIRE) is dedicated to providing up-to-date, accurate information about the effect of rehabilitation health-care for people with SCI. The SCIRE used a systematic and transparent procedure to assess and synthesize the evidence of the effects of rehabilitation healthcare interventions in SCI and is designed for health professionals inform them of best practice. Consumers with SCI and their families may also find the synthesis useful to better understand their health care. In addition, such a research synthesis will enable relevant decision-making in public policy and practice settings applicable to SCI rehabilitation. Lastly, transparent and unbiased evidence-based reviews will guide the research community and funding organizations to strategically focus their time and resources on the gaps in knowledge and identify research priorities.

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2.2 Article Assessment 2.2.1 Literature Search Strategy A systematic review was undertaken using multiple databases (MEDLINE/PubMed, CINAHL, EMBASE, PsycINFO) to identify and synthesize all relevant literature published from 19802005. An initial broad search was performed with five types of SCI therapies searched: drug therapy, radiotherapy, diet therapy, rehabilitation therapy and therapy. To further refine the search, the search was limited to human subjects and articles published in English. Based on the above search criteria, the total number of references from all databases was 8007. Two investigators reviewed both the title of the citation and the abstract (of all 8007 references) to determine its suitability for inclusion. Articles suitability was based on the above inclusion criteria as well as the following exclusion criteria: less than half the reported population had a spinal cord injury; no measurable outcome associated with treatment; animal studies. Unless there were no other supporting literature, studies with less than 3 subjects were excluded. Meta-analyses, systematic reviews and review articles were identified at this point and studies cited with these works that were not identified in the original literature search, were also sought, through hand searching. The review was restricted to published works. MeSH headings were used with the keywords. Key words were paired with spinal cord injury, tetraplegia, quadriplegia or paraplegia Specific SCI rehabilitation topics (e.g., pressure ulcers) were identified by a multi-disciplinary team of expert scientists, clinicians, consumers with SCI and policy-makers. These specific topics were searched with additional keywords generated from expert scientists and clinicians in SCI rehabilitation familiar with the topic and more titles and abstracts were reviewed. The reference lists of previous review articles, key articles, systematic reviews and clinical practice guidelines were hand searched. It is known that hand searching may provide higher rates of return than electronic searching within a particular subject area (Hopewell et al. 2002). The number of titles and abstracts reviewed is approximately 8400. Additional keywords used for each specific topic are outlined in Appendix 1. 2.2.2 Quality Assessment Tool and Data Extraction Methodological quality of individual RCTs was assessed using the Physiotherapy Evidence Database (PEDro) tool (http://www.pedro.fhs.usyd.edu.au/scale_item.html). PEDro was developed for the purpose of accessing bibliographic details and abstracts of randomizedcontrolled trials (RCT), quasi-randomized studies and systematic reviews in physiotherapy. PEDro has been used to assess both pharmacological and non-pharmacological studies with good agreement between raters at an individual item level and in total PEDro scores (Foley et al. 2006). Maher et al. (2003) found the reliability of PEDro scale item ratings varied from "fair" to "substantial," while the reliability of the total PEDro score was "fair" to "good. Studies included in this review using a non-experimental or uncontrolled design (non-randomized comparative trials, cohort studies or retrospective studies) could not be assigned a PEDro score and were given a not applicable (n/a) designation. The PEDro is an 11-item scale, in which the first item relates to external validity and the other ten items assess the internal validity of a clinical trial. One point was given for each satisfied

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criterion (except for the first item, which was given a YES or NO), yielding a maximum score of ten. The higher the score, the better the quality of the study and the following cut-points were used where 9-10: excellent; 6-8: good; 4-5: fair; <4: poor. A point for a particular criterion was awarded only if the article explicitly reported that the criterion was met. The scoring system is detailed in Appendix 2. Two independent raters reviewed each article. Scoring discrepancies were resolved through discussion. All other studies with an intervention were assessed with the Downs and Black Tool (Downs and Black 1998) for methodological quality. This tool consists of 27 questions in the following subsections: Reporting, External Validity, Internal Validity bias and Internal Validity confounding (selection bias). The original tool range from 0 to 32. However, we modified the last question form a scale of 0 to 5 to a scale of 0 to 1 where 1 was scored if a power calculation or sample size calculation was present while 0 was scored if there was no power calculation, sample size calculation or explanation whether the number of subjects was appropriate. Thus, our modified version ranged from 0 to 28, with a higher score indicating higher methodological quality. The Downs and Black tool is attached in Appendix 3. Data were extracted to form tables. Sample subject characteristics (Population), nature of the treatment (Intervention), measurements (Outcome Measures) and key results are presented in the tables. In cases, where a single study overlapped into multiple chapters (e.g., treadmill training has effects on the cardiorespiratory, lower extremity and bone health), the results focus on the outcomes relevant to that chapter. 2.3 Determining Levels of Evidence and Formulating Conclusions Table 2.1 Five levels of evidence
Level Level 1 Research Design Randomized controlled trial (RCT) RCT Prospective controlled trial Cohort Level 3 Case control Pre-post Level 4 Post-test Case Series Observational Level 5 Clinical Consensus Case Report Description Randomized controlled trial, PEDro score 6. Includes within subjects comparison with randomized conditions and crossover designs Randomized controlled trial, PEDro score < 6. Prospective controlled trial (not randomized) Prospective longitudinal study using at least 2 similar groups with one exposed to a particular condition. A retrospective study comparing conditions, including historical controls A prospective trial with a baseline measure, intervention, and a post-test using a single group of subjects. A prospective post-test with two or more groups intervention, then post-test (no pre-test or baseline measurement) using a single group of subjects. A retrospective study usually collecting variables from a chart review. Study using cross-sectional analysis to interpret relations. Expert opinion without explicit critical appraisal, or based on physiology, biomechanics or "first principles" Pre-post or case series involving one subject

Level 2

The levels of evidence used to summarize the findings are based on the levels of evidence developed by Sackett et al. (2000). The levels proposed by Sackett et al. (2000) were modified to collapse the subcategories within a level (e.g., level 1a, 1b, 1c) into a single level. This was performed to reduce the 10 categories from Sackett et al. (2000) to a less complex system from level 1 to level 5. We provided additional descriptions specific to the types of research designs encountered in SCI rehabilitation to facilitate the decision-making process. Sackett et al. (2000)

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distinguishes high and low quality randomized controlled trials (RCTs) into level 1b and level 2b, respectively. To provide a more reliable decision-making process, we required that a level 1 RCT had a PEDro score of greater than or equal to 6 (good to excellent quality), while a level 2 RCT had a PEDro score of 5 or less. The appropriateness of the control group was assessed per study. In some studies, an able-bodied group may not have been an adequate control for the particular intervention used, but simply provided normative values for comparison. In those studies, the study was considered not controlled and the level of evidence reduced (e.g., level 4 pre-post). RCTs received priority when formulating conclusions. Conclusions were not difficult to form when the results of multiple studies were in agreement. However, interpretation became difficult when the study results conflicted. In cases where studies differed in terms of quality, the results of the study (or studies) with the higher quality score were more heavily weighted to arrive at the final conclusions. Sometimes, interpretation was difficult, for example, the authors needed to make a judgment when the results of a single study of higher quality conflicted with those of several studies of inferior quality. In these cases we attempted to provide a rationale for our decision and to make the process as transparent as possible. As emphasized by Sackett et al. (1996), the evidence from systematic research should be integrated with clinical expertise and patients' choice to form best practice.

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Appendix 1. Specific Search Terms Specific SCI rehabilitation topics were identified by a multi-disciplinary team of expert scientists, clinicians, consumers with SCI and policy-makers. These specific topics were searched with additional keywords generated from expert scientists and clinicians in SCI rehabilitation familiar with the topic and more titles and abstracts are reviewed. MeSH headings were used with the keywords. Key words were paired with spinal cord injury, tetraplegia, quadriplegia or paraplegia. The reference lists of previous review articles, systematic reviews and clinical practice guidelines were hand searched. It is known that hand searching may provide higher rates of return than electronic searching within a particular subject area (Hopewell et al. 2002). Chapter 3: Rehabilitation Practice: ("rehabilitation"[Subheading] OR "Rehabilitation"[MeSH]) AND "Spinal Cord Injuries"[MeSH] AND "Treatment Outcome"[MeSH] Chapter 4: Community Reintegration: accessibility, attendant care, attitudes, community + leisure + recreation, community involvement, community Involvement, community living, community participation, community reintegration, community reintegration, daily functioning, domestic life, employment, empowerment, environment + functioning, environment + reintegration, environment + social, environment + social + home, environmental policy, family involvement, HRQOL, intervention trial, control group, treatment group; income support, independent living, interpersonal relations, leisure intervention, control group, treatment, clinical trials, leisure + use of time, life happiness, life satisfaction, living independent, occupations, personal assistance, personal satisfaction, productivity, psychosocial rehabilitation, QOL intervention, trial, control group, treatment group, recreation therapy, school education, self care, social environment, social interactions, social network, social policy, social roles, social support, socializing, use of technology, volunteer Chapter 5: Upper Limb: upper limb, FES and upper limb, exercise programs, upper limb injuries, splinting, specific researchers [Popovic] Chapter 6: Lower Limb: 4-AP, 4-AP + ambulation, assisted walking device, walking, assisted rehabilitation device, biofeedback, body weight support, body weight supported treadmill training (BWSTT), brace, bracing, Clonidine, Cyproheptadine, EMG + feedback, epidural stimulation / epidural lumbar stimulation, FES + muscle, flexibility, gait, gait + bracing, gait + orthotics, gait devices, GM-1 ganglioside, knee-ankle-foot, leg + bracing, leg + FES, locomotion, locomotor training, lower extremity spasticity, orthotics, orthotics + lower limb, parawalker, robotics, salbutamol, scott-craig knee ankle foot orthosis, spasticity management, stepping, stretching, treadmill, trendelenburg gait, Vannini-rizzoli stabilizing orthosis, virtual reality, walking, weakness Chapter 7: Cardiovascular Exercise: cardiac output, cardiovascular disease, cardiovascular fitness, coronary heart disease, endothelium, epoetin alfa, FES + blood pressure, fludrocortisone, glucose intolerance, glucose sensitivity, hydralazine, lipid, lipid + metabolism, neuromuscular + blood, nifedipine, orthostatic hypotension, oxygen consumption, phenazopyridine, physiotherapy + blood, stroke volume, thromboembolism, ventilation, ventilatory threshold, VO2 Chapter 8: Respiratory: abdominal binder, acapello, assisted cough, asthma incidence, prevalence, atelectasis, autogenic drainage, barotraumas, BiPAP, breathing exercises, bronchial lavage, bronchitis, bronchoscopy, cardiopulmonary function, chest physiotherapy, COPD incidence, prevalence, CPAP, diaphragmatic pacemaker, dysphagia, exsufflation, 2-5

flutter, flutter device, flutter valve, forced expiratory technique, Garshick, glossopharyngeal breathing, incentive spirometry, insufflation, intermittent positive pressure breathing, intrapulmonary percussive ventilation, IPPB stretch, manual percussion, manual vibration, mechanical vibration, paripep , PEP / PEEP, percussion, phrenic pacemaker, pneumonia incidence, prevalence, positive pressure breathing, postural drainage, progressive ventilatory free breathing, pulmonary capacity, pulmonary complications incidence, prevalence, pulmonary embolism, pulmonary health, pulmonary secretions, respiratory complications incidence, prevalence, secretion removal, sleep apnea, smoking incidence, prevalence, spirometry, synchronous intermittent mandatory ventilation, TheraPep, tidal volume, tracheostomy, ventilator weaning, ventilatory capacity, ventilatory failure incidence, prevalence Chapter 9 Bone Health alendronate, Amino-bisphosphonates, bone + fracture, bone health, cyclic etidonate, exercise therapy, FES, heterotopic ossification, incidence + fracture, osteoporosis, pamidronate, skeletal + fracture, vibration Chapter 10 Depression: alcohol abuse, drug abuse, depression, anxiety, gender differences, sexuality, [specific researches: Krause, Noreau], aging, sexual health, male and female, spinal cord, vocational issues, sexual issues, psychosocial Chapter 11 Sexual Health: autonomic dysreflexia, birth control, birthing, bladder + sex, bladder management + body image, bladder management + mitrofanoff, bladder management + sexual life, bladder management + suprapubic, body image, bowel + sex, Cesarean section, contraception, dysparunia, dyspareunia + infertility, ejaculation, ejaculatory disorder, electroejaculation, erection, female fertility, hypogonadism, ICSI, infertility + pregnancy, intercavernosal injection, intraurethral palette, intraurethro palette, urethra palette, IVF, labour, labour + delivery, marital, marital status + sexuality, menopause, menstruation, penile injection, post-partum, pregnancy, premature labour, semen quality, seminal emissions, sex, sex + depression, sex/sexual + foley catheter, sex/sexual + intermittent catheter, sexual adjustment, sexual changes, sexual function + medications, sexual functioning + foley catheter, sexual position, sexual relationships, sexual self-esteem, sexual self-views, sexuality, sexuality + depression, sperm/semen quality, sperm/semen retrieval, vacuum device, vaginal lubrication, Viagra, vibrator, vibrostimulation Chapter 12 Bowel Management: bowel management, cisapride, colonic, colostomy, constipation, dietary fibre, hemorrhoids, incontinence, irregular, laxative, neurogenic bowel, suppositories Chapter 13 Bladder: Bladder, Neurogenic"[MeSH] AND "Spinal Cord Injuries"[MeSH] Chapter 14 Pain: pain treatment, pharmacology, pain, surgical intervention, pain management Secondary complications Chapter 15 Venous Thromboembolism: Deep venous thrombosis, thrombosis, emboli, DVT, thromboembolism, heparin, vena cava filtration Chapter 16 Orthostatic hypotension: orthostatic hypotension, dysreflexia, autonomic, hyperreflexia, midodrine, postural hypotension, orthostatic intolerance, orthostatic tolerance, orthostatic stress, blood flow, blood flow + exercise, blood pressure, blood vessel health

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Chatper 17 Autonomic dysreflexia: AD, autonomic, dyreflexia, hyperreflexia, midodrine, fludrocortisone, beta-blockers, Viagra, nifedipine, phenazopyridine Chapter 18 Heterotopic Ossification: heterotopic ossification, excision surgery, etidronate Chapter 19 Nutrition: diabetes, energy requirements, energy needs, caloric intake, weight gain, obesity, overweight, prevention, body composition, cardiovasular disease risk, nutrient, supplementation, supplements, dietary, nutrition intervention, folate, vitamin B6, vitamin B12, omega 3 fatty acids, essential fatty acids, pressure ulcers, vitamin supplementation, mineral supplementation, vitamin C, vitamin A, zinc, iron, protein, diabetes risk, hydration/optimal hydration, cranberry juice, neurogenic bowel, dietary fibre, soluble fibre, insoluble fibre, fibre supplements, peristalsis, osteoporosis, osteopenia, bone mineral density, calcium, vitamin D, magnesium, renal stone/kidney stone and calcium intake/supplementation, urinary tract, hypercalcemia Chapter 20 Pressure Sores: pressure sores, ulcers Chapter 21 Spasticity: botox, baclofen, spasticity

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Appendix 2. The PEDro Scale (www.pedro.fhs.usyd.edu.au/scale_item.html) 1. Subjects were randomly allocated to groups. (in a crossover study, subjects were randomly allocated an order in which treatments were received). A point for random allocation was awarded if random allocation of patients was stated in its methods. The precise method of randomization need not be specified. Procedures such as coin-tossing and dice-rolling were considered random. Quasi-randomization allocation procedures such as allocation by bed availability did not satisfy this criterion. 2. Allocation was concealed. A point was awarded for concealed allocation if this was explicitly stated in the methods section or if there was reference that allocation was by sealed opaque envelopes or that allocation involved contacting the holder of the allocation schedule who was "off-site." 3. The groups were similar at baseline regarding the most important prognostic indicators. A trial was awarded a point for baseline comparability if at least one key outcome measure at baseline was reported for the study and control groups. This criterion was satisfied even if only baseline data of study completed-only subjects were presented. 4. There was blinding of all subjects. The person in question (subject, therapist or assessor) was considered blinded if he/she did not know which group the subject had been allocated to. In addition, subjects and therapists were only considered to be "blind" if it could be expected that they would have been unable to distinguish between the treatments applied to different groups. In drug therapy trials, the administrator of the drug was considered the therapist and was considered blinded if he/she did not prepare the drug and was unaware of the drug being administered. 5. There was blinding of all therapists who administered the therapy. (criteria 4.) 6. There was blinding of all assessors who measured at least one key outcome (criteria 4). 7. Adequacy of follow-up. For the purposes of this review, follow-up was considered adequate if all of the subjects that had been originally randomized could be accounted for at the end of the study. The interpretation of this criterion differs from that described by PEDro, where adequacy is defined as the measurement of the main outcome in more than 85% of subjects. 8. Intention to treat. All subjects for whom outcome measures were available received the treatment or control condition as allocated or, where this was not the case, data for at least one key outcome was analyzed by "intention to treat". For purpose of the present evidencebased review, a trial was awarded a point for intention-to-treat if the trial explicitly stated that an intention-to-treat analysis was performed. 9. The results of between-group statistical comparisons are reported for at least one key outcome. Scoring of this criterion was design dependent. As such, between groups comparison may have involved comparison of two or more treatments, or comparison of treatment with a control condition. The analysis was considered a between-group analysis if either a simple comparison of outcomes measured after the treatment was administered was made, or a comparison of the change in one group with the change in another was made. The comparison may be in the form of hypothesis testing (e.g. p-value) or in the form of an estimate (e.g. the mean, median difference, difference in proportion, number needed to treat, relative risk or hazard ratio) and its confidence interval. A trial was awarded a point for this criterion if between group comparison on at least one outcome measure was made and its analysis of comparison was provided. 10. The study provides both point measures and measures of variability for at least one key outcome. A point measure was referred as to the measure of the size of the treatment effect. The treatment effect was described as being either a difference in group outcomes, or as the outcome in (each of) all groups. Measures of variability included standard deviations, standard errors, confidence intervals, interquartile ranges (or other quartile 2-8

ranges), and ranges. Point measures and/or measures of variability that were provided graphically (for example, SDs may be given as error bars in a Figure) were awarded a point as long as it was clear what was being graphed (e.g. whether error bars represent SDs or SEs). For those outcomes that were categorical, this criterion was considered to have been met if the number of subjects in each category was given for each group.

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Appendix 3. Downs and Black tool (Downs and Black 1998) Reporting 1) Is the hypothesis/aim/objective of the study clearly described? 2) Are the main outcomes to be measured clearly described in the Introduction or Methods section? 3) Are the characteristics of the patients included in the study clearly described ? I4) Are the interventions of interest clearly described? 5) Are the distributions of principal confounders in each group of subjects to be compared clearly described? 6) Are the main findings of the study clearly described? 7) Does the study provide estimates of the random variability in the data for the main outcomes? 8) Have all important adverse events that may be a consequence of the intervention been reported? 9) Have the characteristics of patients lost to follow-up been described? 10) Have actual probability values been reported (e.g. 0.035 rather than <0.05) for the main outcomes except where the probability value is less than 0.001? External validity 11) Were the subjects asked to participate in the study representative of the entire population from which they were recruited? 12) Were those subjects who were prepared to participate representative of the entire population from which they were recruited? 13) Were the staff, places, and facilities where the patients were treated, representative of the treatment the majority of patients receive? Internal validity - bias 14) Was an attempt made to blind study subjects to the intervention they have received? 15) Was an attempt made to blind those measuring the main outcomes of the intervention? 16) If any of the results of the study were based on data dredging, was this made clear? 17) In trials and cohort studies, do the analyses adjust for different lengths of follow-up of patients, or in case-control studies, is the time period between the intervention and outcome the same for cases and controls ? 18) Were the statistical tests used to assess the main outcomes appropriate? 19) Was compliance with the intervention/s reliable? 20) Were the main outcome measures used accurate (valid and reliable)? Internal validity confounding (selection bias) 21) Were the patients in different intervention groups (trials and cohort studies) or were the cases and controls (case-control studies) recruited from the same population? 22) Were study subjects in different intervention groups (trials and cohort studies) or were the cases and controls (case-control studies) recruited over the same period of time? 23) Were study subjects randomised to intervention groups? 24) Was the randomised intervention assignment concealed from both patients and health care staff until recruitment was complete and irrevocable? 25) Was there adequate adjustment for confounding in the analyses from which the main findings were drawn? 26) Were losses of patients to follow-up taken into account? 27) Did the study have sufficient power to detect a clinically important effect where the probability value for a difference being due to chance is less than 5%? 2-10

References
Downs SH and Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health (1998); 52:377-384. Evidence-Based Medicine Working Group (1992): A new approach to teaching the practice of medicine. JAMA: The Journal of the American Medical Association 268: 2420-2425. Fitzpatrick R, Davey C, Buxton MJ, Jones DR. Evaluation of patient-based outcome measures for use in clinical trials. Health Technology Assessment 1998;2:1 74. Foley NC, Bhogal SK, Teasell RW, Bureau Y, Speechley MR. Estimates of quality and reliability with the physiotherapy evidence-based database scale to assess the methodology of randomized controlled trials of pharmacological and nonpharmacological interventions. Phys Ther. 2006;86:817-24. Hopewell S, Clarke M, Lefebvre C, Scherer R. Handsearching versus electronic searching to identify reports of randomized trials. The Cochrane Database of Methodology Reviews 2002, Issue 4. Art. No. MR000001. Maher CG, Sherrington C, Herbert RD, Moseley AM, Elkins M. Reliability of the PEDro scale for rating quality of randomized controlled trials. Phys Ther. 2003;83:713-21. PEDro: http://www.pedro.fhs.usyd.edu.au/scale_item.html Sackett DL, Straus SE, Richardson WS, Rosenberg W, Haynes RB. Evidence-based medicine: how to practice and teach EBM. Toronto, Ontario: Churchill Livingstone, 2000. Sackett DL. Rules of evidence and clinical recommendations on the use of antithrombotic agents. Chest 1989;95:2S-3S. Sackett DL, Rosenberg WM, et al. Evidence based medicine: what it is and what it isn't. BMJ 1996;312:71-72. 52.

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CHAPTER THREE
Rehabilitation Practice And Associated Outcomes Following Spinal Cord Injury
Dalton L. Wolfe, PhD Jane TC Hsieh, MSc

Key Points Those with higher level and more severe injuries have longer rehabilitation LoS (Length of Stay. Rehabilitation LoS in the US has become progressively shorter up to the mid1990s. Most individuals make significant functional gains during inpatient rehabilitation. A significant proportion of people improve 1 AIS (ASIA Impairment Scale) grade in the first few months post-injury particularly those initially assessed AIS B and C. Increased therapeutic intensity may not necessarily lead to functional benefits, but data is scarce. Younger individuals with paraplegia are more likely to have shorter rehabilitation LoS than older individuals. Younger individuals are more likely to make greater functional gains during rehabilitation than older individuals. Younger individuals with tetraplegia (or in a mixed traumatic, non-traumatic sample) are more likely to make gains in neurological status during rehabilitation than older individuals. Individuals with non-traumatic SCI have reduced LoS and less functional improvement with rehabilitation as compared to those with traumatic SCI although controlled comparisons are limited to data from the US Model Systems. Neither gender nor race effects have been demonstrated for discharge destination, rehabilitation LoS and neurological or functional status in US Model Systems data. More specialized, interdisciplinary acute SCI care is associated with faster transfers to rehabilitation and may result in fewer medical secondary complications, more efficient functional gains and reductions in overall mortality. Earlier admission to specialized, interdisciplinary SCI care is associated with reduced length of total hospital stay and greater and faster rehabilitation gains with fewer medical secondary complications. Prospective studies with stronger designs are needed to strengthen the evidence and provide more direction as to the optimal model of care. Routine, comprehensive, specialist follow-up services may result in improved health.

Table of Contents
3.1 Introduction ......................................................................................................................3-1 3.2 Common Abbreviations Used In SCI Rehabilitation.....................................................3-1 3.3 Description of SCI Rehabilitation Outcomes ................................................................3-2 3.3.1 Describing SCI Rehabilitation Outcomes ........................................................................3-2 3.3.1.1 Health Delivery Indicators ............................................................................................3-3 3.3.1.1.1 Rehabilitation Length of Stay ....................................................................................3-3 3.3.1.2 Neurological and Functional Status .............................................................................3-6 3.4 Factors for Optimal Outcomes .......................................................................................3-9 3.4.1 Effect of Intensity on Rehabilitation Outcomes ...............................................................3-9 3.4.2 Effect of Age on Rehabilitation Outcomes ....................................................................3-10 3.4.3 Differences in Traumatic vs Non-Traumatic SCI Rehabilitation Outcomes...................3-14 3.4.4 Effect of Gender and Race on Rehabilitation Outcomes ..............................................3-18 3.5 Specialized vs General SCI Units (Acute Care)...........................................................3-21 3.6 Early vs Delayed Admission to Specialized SCI Units ...............................................3-24 3.7 Outpatient and Follow-up Care.....................................................................................3-30 3.8 Summary.........................................................................................................................3-31 Appendix Studies Describing Rehabilitation Outcomes.................................................3-34 References..............................................................................................................................3-41

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Wolfe DL, Hsieh, JTC (2006). Rehabilitation Practices and Associated Outcomes Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 3.1-3.44. www.icord.org/scire

Rehabilitation Practice And Associated Outcomes Following Spinal Cord Injury

3.1 Introduction The SCI rehabilitation practices of today were influenced greatly by the pioneering efforts of Sir Ludwig Guttman who was instrumental in the creation of specialized spinal units to care for injured soldiers returning to England during and after WWII (Guttmann 1967). Eventual adoption of this more specialized and integrated approach followed in many additional jurisdictions (Bors 1967; Bedbrook 1979), bolstered by reports of reduced mortality and enhanced long-term survival which was attributed in part to more effective management of secondary conditions associated with SCI (e.g., UTIs, pressure sores, respiratory conditions) (Richardson & Meyer Jr. 1981; Le & Price 1982;. Geisler et al.1983). At present, the ideal scenario for modern SCI care is purported to be treatment in specialized, integrated centres with an interdisciplinary team of health care professional providing care as early as possible following injury and throughout the rehabilitation process with appropriate discharge to the community characterized by ongoing outpatient care and follow-up (Donovan et al. 1984; Tator et al. 1995). This is best facilitated under one roof or within an organized system which is distinguished by seamless transitions as patients proceed from acute care through rehabilitation to outpatient care. While it is generally accepted that this ideal more specialized, integrated approach should result in better outcomes, there is very little robust evidence that supports this directly. This is understandable, given the relatively low incidence of SCI, limitations in designing trials with adequate controls and the inherent difficulty in ascribing potential outcomes to such a multi-faceted process as rehabilitation. For these reasons, we have adopted a more lenient approach within the present chapter with respect to the reviewed articles as compared to most other chapters. Many of the articles presented in the current chapter do not investigate a specific intervention although they do describe rehabilitation outcomes and the various factors that are associated with producing optimal outcomes. Accordingly, when no specific intervention is assessed experimentally, a PEDro or Downs and Black (Downs & Black 1998) score is not provided. These articles were separated into five categories: Description of Rehabilitation Outcomes, Factors for Optimal Outcomes, Specialized vs. General SCI Units, Early vs. Delayed Admission to Specialized Units and Outpatient and Follow-up Care. In addition, in some studies the distinction between acute vs. rehabilitative care is somewhat blurred as studies may have been conducted in centers or systems where these services are more integrated. The present chapter is focused on issues associated with rehabilitation care and we have attempted to clearly identify when acute care practice may have been merged within the reporting of rehabilitation research results. 3.2 Common Abbreviations Used In SCI Rehabilitation AIS ASIA Impairment Scale ASIA American Spinal Injury Association (and associated International Guidelines for Neurological Classification) BI Barthel Index 3-1

FIM Functional Independence Measure LoS Length of Stay MBI Modified Barthel Index OT Occupational Therapy SLT Speech & Language Therapy PT Physical Therapy (Physiotherapy) UTI Urinary Tract Infection 3.3 Description of SCI Rehabilitation Outcomes Much research has been directed at describing outcomes following SCI rehabilitation and examining various factors that might be associated with good (or poor) outcomes. Ethical and practical considerations limit the application of randomized controlled designs or other experimental designs in investigating methods for enhancing patient outcomes. Typically, investigators employ case series, case control or pre-post trial designs and often utilize correlational or predictive analyses (e.g., univariate or multivariate regression) of large single or multi-centre patient databases to determine specific associations or factors that are associated with optimal rehabilitation outcomes. Often these studies are quite large in scope as investigators explore relationships among a variety of socio-demographic and injury-related variables as they endeavour to determine optimal rehabilitation practice. Given the inherent breadth of findings present in individual studies in this area in which large databases are mined for relationships among large arrays of variables, it is difficult to follow the same pattern of brevity and topic focus found in most chapters of the present review. In the present section we have taken a slightly different approach. First, a comprehensive table can be found in Section 3.9 Appendix 3.1 that lists specific studies in more detail and which outlines various findings directed at describing outcomes associated with comprehensive inpatient SCI rehabilitation. This is intended as an overall resource for those interested in the specific findings relating to outcomes associated with rehabilitation practice. In the text are more focused tables summarizing specific data culled from the more comprehensive table, thereby permitting an assessment of similar types of rehabilitation outcomes. This is intended for those interested in more specific information about particular issues pertaining to rehabilitation outcomes. The subsequent section then describes more focused investigations that examine the effect of the various factors in producing optimal outcomes. These include studies that assess the effect of the intensity of rehabilitation, age, gender and race on rehabilitation outcomes. 3.3.1 Describing SCI Rehabilitation Outcomes There are many types of outcomes that have been associated with SCI rehabilitation. In the present review, we will focus on the most commonly employed measures and have outlined these along with a few typical examples of outcome measurement tools in Table 3.1. In particular, these include measures that examine the effectiveness of health delivery as well as measures that assess functional, neurological and general health status of patients. As noted earlier, each of these measurement types will form the basis of separate summary tables following the overall more comprehensive table. It should be noted that other measures of obvious importance to SCI rehabilitation care providers and people with SCI such as measures of health-related quality of life and those that assess different facets of community integration (e.g., employment status, Reintegration to Normal Living Index) have not been included in the present chapter as they are considered in the chapter entitled Community Reintegration Issues 3-2

Post Spinal Cord Injury. In addition, studies examining health status have not been addressed in the present chapter as these typically report the incidence of specific secondary conditions (most notably, pressure sores and UTIs) and these will be described more fully in the specific chapters devoted to these issues. Table 3.1 Outcome Measure Types and Examples Relevant to SCI Rehabilitation
Outcome Measure Type Health Delivery Indicators Functional Status Neurological Status Health Status Specific Outcome Measures LoS, Hospital Charges, Discharge Destination FIM, MBI AIS, ASIA motor scores, Frankel Index Incidence of secondary complications

It should also be noted that specific outcome measurement tools can combine 2 of these outcome measure types such as in measures of efficiency. Most commonly, change scores for functional (e.g., FIM) or neurological (e.g., ASIA motor scores) measures are divided by LoS to get an average change for that particular measure, thereby providing an indication of the efficiency of the rehabilitation process in effecting change. Measures of this nature will be profiled in the sub-section for which the numerator is related. For example, ASIA motor score efficiency would be addressed under findings associated with neurological status. However, before these specific summary tables are presented, see Section 3.9 Appendix 3.1 for a more comprehensive table summarizing studies describing various SCI rehabilitation outcomes. 3.3.1.1 Health Delivery Indicators 3.3.1.1.1 Rehabilitation Length of Stay Several authors have made comparisons of rehabilitation length of stay (LoS) between countries or across other jurisdictions (Burke et al. 1985; Muslumanoglu et al. 1997; Pagliacci et al. 2003; Chan & Chan 2005). Additionally, others have noted the trend for progressively shorter LoS over the past several decades, especially in the US (De Vivo et al. 1991; Morrison & Stanwyck 1999; Eastwood et al. 1999). Stover noted that reductions in the 1970s and early 1980s were likely due to increased efficiency of rehabilitation teams (Stover 1995). More recent reductions in the US have been attributed to restrictions imposed by payers (Morrison & Stanwyck 1999). Table 3.2 summarizes various reports in the literature for LoS organized by jurisdiction and also by the time period for which the data was collected. Data were only included in this table if the underlying sample was deemed representative of an overall heterogeneous population of individuals with SCI (i.e., unselected sample of a single or multicentre study). Some data grouped for evaluating specific hypotheses has been included and this has been appropriately indicated. In addition, data from studies for which it was not clear that the purpose of admission was for comprehensive inpatient rehabilitation (and may have involved acute care) were not included. Table 3.2 Rehabilitation Length of Stay (by Country and Sample Period)
Study Tooth et al. 2003 Jurisdiction Australia (single centre) Population (N, Trauma &/or Nontrauma) 167, Trauma Sample Period 1993-1998 Length of Stay Result 83.0 (Median)

3-3

Study Scivoletto et al. 2005 Scivoletto et al. 2003 Pagliacci et al. 2005 Sumida et al. 2001

Jurisdiction Italy (single centre) Italy (single centre) Italy (multi-centre) Japan (multi-centre)

Population (N, Trauma &/or Nontrauma) 150, Trauma & Nontrauma 150, Trauma & Nontrauma 684, Trauma 123, Trauma

Sample Period 1997-2001 1997-2001 1997-1999

Length of Stay Result 112.469.3 98.768.13 135.5 185.6130.4 (N=60) 267.8171.6 (N=63)2 1 Early vs 2delayed admission 60.838.7 54.334.9 60.137.1 57.635.5 70.144.0 80.946.9 77.342.0 74.041.1 95.8 (N=66) 54.2 (N=61) 68.1 (1986 data only) 84.9 (N=185)1 87.7 (N=153)2 1 Specialist vs 2more general care 84.9 (N=185)1 2 87.7 (N=153) 1 2 Specialist vs more general care
1

1994-1997 1997 1996 1995 1994 1993 1992 1991 1990 1995 1991 1972-1986

Eastwood et al. 1999

USA (multi-centre)

3,904, Trauma

Morrison & Stanwyck 1999 Yarkony et al. 1990 Heinemann et al. 1989

USA (single centre) USA (single centre) USA (single centre)

127, Trauma 1382, Trauma 338, unknown

1981-1985

Yarkony et al. 1987

USA (single centre)

711, Trauma

1973-1980

Rehabilitation LoS is also known to vary according to neurological status and data from studies reporting LoS organized by level of injury (i.e., paraplegia vs. tetraplegia) or completeness are shown in Table 3.3. Again this is organized by jurisdiction (country) and the time period over which the sample was analyzed. Table 3.3 Rehabilitation Length of Stay (by Neurological Status
Study Jurisdiction Population (N, Trauma &/or Nontrauma) Sample Period Length of Stay Result (Mean in days) (SD if available) Incomplete paraplegia 43.0 (All Medians) Complete paraplegia 96.5 Incomplete tetraplegia 64.5 Complete tetraplegia 206.0

Tooth et al. 2003

Australia (single centre)

167, Trauma

1993-1998

3-4

Study

Jurisdiction

Population (N, Trauma &/or Nontrauma)

Sample Period

Length of Stay Result (Mean in days) (SD if available) AIS D paraplegia 79.4220.07 (N=3) AIS ABC low paraplegia 52.001.41 (N=2) AIS ABC high paraplegia 55.843.0 (N=2) AIS D tetraplegia 143.7569.25 (N=4) AIS ABC low tetraplegia 215.956.1 (N=7) AIS ABC high tetraplegia 146.575.4 (N=6) Paraplegia - 46.7 Tetraplegia 61.9 Paraplegia - 82.2 Tetraplegia 110.9 Paraplegia 54.3 (1986 data only) Tetraplegia 82.8 Paraplegia 68.71, 70.72 Tetraplegia 98.0, 103.4 1 Specialist (N=185) vs 2more general (N=153) care. Incomplete paraplegia 1 2 46.3 , 50.6 Complete paraplegia 62.2, 62.9 Incomplete tetraplegia 59.7, 71.3 Complete tetraplegia 90.4, 83.8 1 2 ( Early (N=284) vs later (N=377) admitted patients) Paraplegia ~105 Tetraplegia ~165 Incomplete paraplegia 78.2 Complete paraplegia 83.4 Incomplete tetraplegia 107.6 Complete tetraplegia 135.3

Chan & Chan 2005

China (Hong Kong) (single centre)

33, Trauma

2002

Morrison & Stanwyck 1999

USA (single centre)

127, Trauma

1995 1991

Yarkony et al. 1990

USA (single centre)

1382, Trauma

1972-1986

Heinemann et al. 1989

USA (single centre)

338, unknown

1981-1985

DeVivo et al. 1990

USA (single centre)

661, Trauma

1973-1985

Woolsey et al. 1985

USA (single centre)

100, Trauma

Unknown (pre 1985)

Yarkony et al. 1987

USA (single centre)

711, Trauma

1973-1980

Discussion As seen in Tables 3.2 and 3.3, rehabilitation LoS varies widely from country to country. While no investigators have systematically analyzed country-by-country variation it is apparent that the US has typically shorter rehabilitation LoS times than other countries reporting data. Most data has originated in the US, bolstered by the development of the US model systems database, with reports from other countries for the most part limited to a handful of descriptions of single-centre experience.

3-5

Within the US, it is clear that the trend for progressively shorter rehabilitation LoS has continued to at least the mid 1990s. In 2 separate investigations, Morrison and Stanwyck (1999) and Eastwood et al. (1990) described reduced LoS from the period between the early 1990s to the mid 1990s. Eastwood et al. (1990) examined the large US Model systems database of individuals with traumatic SCI (N=3,904) and reported annual mean LoS values from 1990 to1997. For these years, the highest value was 80.9 days in 1992 and the lowest was 54.3 days in 1996. Mean LoS values for 1990-1992 seemed fairly stable at higher values, with 1994-1997 values lower and 1993 at an intermediate value. Morrison and Stanwyck (1999) performed a direct comparison of 1991 vs 1995 mean LoS values in the largest SCI rehabilitation in the US in order to assess the effect of shorter rehabilitation LoS on functional outcomes. These authors confirmed an even more striking difference between these 2 years given an average LoS of 95.8 days in 1991 as compared to 54.2 days in 1995 (p<0.001). Other reports have described reductions over earlier periods, most notably multi-centre investigations associated with the US Model Systems databases (De Vivo et al. 1991). It is uncertain if these trends have continued or if the same patterns have been seen in other countries. Also apparent from Table 10.5 is the relationship of longer LoS associated with higher level of injury and greater severity of injury. Similar patterns were seen in all studies describing rehabilitation LoS for individuals with varying injuries. That is, the greatest mean rehabilitation LoS values were seen for those with complete tetraplegia (especially high level) whereas the shortest mean values occurred for those with incomplete paraplegia (DeVivo et al. 1990; Tooth et al. 2003; Chan & Chan 2005). Conclusions There is Level 3 evidence (with US data only) that rehabilitation LoS has become progressively shorter up to the mid-1990s. No other jurisdiction has published data that supports this contention. There is Level 3 evidence that those with higher level and more severe injuries have longer rehabilitation LoS.

Those with higher level and more severe injuries have longer rehabilitation LoS. (Length of Stay) Rehabilitation LoS in the US has become progressively shorter up to the mid-1990s.

3.3.1.2 Neurological and Functional StatusError! Bookmark not defined. Several studies have identified patterns of neurological and/or functional improvement over the first few months post-injury. The majority of these studies examine neurological and/or functional status and associated changes between rehabilitation admission and discharge. In addition, the Consortium for Spinal Cord Medicine (1999) has published a review of expected neurological and functional outcomes following SCI. This Clinical Practice Guideline refers to the work of Bracken et al. (1993, 1997), Geisler et al. (1991) and Waters et al. (1994a, 1994b) in noting that over half of the expected recovery occurs in the first 2 months following injury and recovery may continue but slows noticeably after 3-6 months. This change in neurological status may represent the natural course of recovery, however, it is uncertain as to the extent that rehabilitation practices play in enhancing this recovery. 3-6

In addition, the reader is directed to the Consortium for Spinal Cord Medicine (1999) Clinical Practice Guideline for a comprehensive consensus review itemizing expected functional achievements for individuals at every level of SCI. Table 3.4 summarizes various reports in the literature for neurological and/or functional status organized by jurisdiction and also by the time period for which the data was collected. As above, data were only included in this table if the underlying sample was deemed representative of an overall heterogeneous population of individuals with SCI (i.e., unselected sample of a single or multi-centre study). Table 3.4 Neurological and/or Functional Status (by Country and Sample Period)
Study Jurisdiction and Sample Period Population (N, Trauma &/or Nontrauma) Outcome Measure Australia (single centre) 1993-1998 Neurological and/or Functional Change with Rehabilitation

Tooth et al. 2003

167, Trauma

FIM

from 68.7 (admission) to 102.2 (discharge) due almost entirely to gains in motor FIM scores. Total FIM scores were lowest for those with complete tetraplegia and highest for those with incomplete paraplegia. Those with complete tetraplegia had the least change in FIM scores. 31% of people improved, 66% remained unchanged, and 3% deteriorated. 23% initially complete became incomplete and 40% of those initially incomplete improved. All groups showed in FIM motor scores from admission to discharge but these were only significant for tetraplegia ASIA D. All patient groups (i.e., levels and severity of injury) had similar FIM motor scores at discharge as noted by American Consortium for Spinal Cord Medicine (1999). was associated with ASIA B and C, shorter LoS, earlier admission and no complications (especially pressure sores). in ASIA motor scores and light touch scores for those with incomplete injuries but not complete injuries. FIM showed f for those with incomplete injuries and those with complete paraplegia but not complete tetraplegia.

Burke et al. 1985 Australia (single centre) 262, Trauma Frankel

China (Hong Kong) (single centre) 2002

Chan & Chan 2005

33, Trauma

FIM

Pagliacci et al. 2003

Italy (multi-centre) 1997-1999

684, Trauma

AIS

Mslman-olu et al. 1997 Turkey (single centre) 1992-1995 52, Trauma & Nontrauma ASIA FIM

3-7

Study

Jurisdiction and Sample Period

Population (N, Trauma &/or Nontrauma)

Outcome Measure

Neurological and/or Functional Change with Rehabilitation

DeVivo et al. 1991

USA (multi-centre) 1973-1990

13,763, Trauma

AIS FIM

Proportion showing were 10.3% (A), 45.2% (B), 55.9% (C), 7.3% (D) vs no change 89% (A), 50.3% (B), 41.5% (C), 90.5% (D) vs declined 4.5% (B), 2.6% (C), 2.0% (D) From 1973-1990 the proportion of incomplete patients increased from 40% to 55.2%. Average FIM gain was 37 (incomplete paraplegia, 36 (complete paraplegia), 34 (incomplete tetraplegia and 15 (complete tetraplegia). in total scores & self-care and mobility subscores. greater for incomplete vs complete and for those with paraplegia vs tetraplegia.

Yarkony et al. 1987

USA (single centre) 1973-1980

711, Trauma MBI

Discussion The AIS represents an internationally recognized system for the classification of individuals with SCI, and as such, has been employed to characterize overall improvement in the neurological status of people with SCI (ASIA 2002). The AIS is an ordinal 5 grade scale classifying individuals from A to E with A designating those with complete SCI and E designating individuals with normal sensory and motor function. Most notably, Pagliacci et al. (2003) and DeVivo et al. (1991) employed large multi-centre databases and found that individuals with incomplete injuries (especially AIS B or C) were more likely to improve at least 1 grade over the course of rehabilitation. In particular, DeVivo et al. (1991) reported that 45.2% and 55.9% of those initially admitted as AIS B and C respectively improved at least 1 AIS grade as compared to only 10.3% and 7.3% of individuals initially classified as AIS A or D respectively. Similarly, many individuals also make significant functional gains during comprehensive inpatient rehabilitation. Most often functional status has been assessed at admission and discharge from rehabilitation using the FIM (Vivo et al. 1991; Muslumanoglu et al. 1997; Tooth et al. 2003; De Chan & Chan 2005) or MBI (Yarkony et al. 1987). Typically, functional gains are greater with rehabilitation for those with incomplete injuries as compared to complete injuries and for those with paraplegia as compared to those with tetraplegia (De Vivo et al. 1991; Muslumanoglu et al. 1997;Tooth et al. 2003; Chan & Chan 2005). In particular, DeVivo et al. (1991) reported similar average FIM gains for those with incomplete and complete paraplegia and incomplete tetraplegia (i.e., 37, 36 and 34 respectively) but much reduced gains for those with complete tetraplegia (i.e., 15). For the most part increases seen in the FIM have been attributed to motor FIM changes with little change in cognitive FIM scores at least partly due to an apparent ceiling effect (Chan & Chan 2005). Conclusions There is Level 4 evidence that a significant proportion of people (~50%) initially assessed as AIS B and C will improve by at least 1 AIS grade in the first few months post-injury 3-8

concomitant with inpatient rehabilitation. Fewer individuals (~10%) initially assessed as AIS A and D will improve by 1 AIS grade. There is Level 4 evidence that individuals make significant functional gains during inpatient rehabilitation, more so for those with complete and incomplete paraplegia and incomplete tetraplegia. Most individuals make significant functional gains during inpatient rehabilitation. A significant proportion of people improve 1 AIS (ASIA Impairment Scale) grade in the first few months post-injury particularly those initially assessed AIS B and C.

3.4 Factors for Optimal Outcomes 3.4.1 Effect of Intensity on Rehabilitation Outcomes Although it is commonly assumed that the therapies delivered during inpatient rehabilitation are effective, there is generally little direct evidence that demonstrates a clear relationship between typical therapeutic practice and enhanced functional outcomes (Heinemann et al. 1995). Moreover, there is no evidence that establishes a recommended intensity or amount of therapy that should be delivered to produce a desired result. In SCI rehabilitation, there exists a paucity of studies that examine this issue. Table 3.5 Individual Studies - Intensity of Rehabilitation
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Heinemann et al. 1995; USA Downs & Black score=18 Case Series Initial N=264; Final N=246

Population: SCI and ABI, SCI subjects had a mean of 38.9 years old and were 79% male. Treatment: Variation in therapy intensity (OT, PT, SLT, Psych). Also examined effect of various other factors including LoS, Interruptions, Onset days, Admission scores and age. Outcome Measures: FIM (motor, cognitive, total), FIM Efficiency (motor or cognitive) all collected at Discharge.

(SCI findings only) 1. When analysed together, none of the individual therapy intensities were predictive of improved outcomes. When analysed individually, very little was significant in the prediction with only greater LoS associated with greater achievement of potential motor gains (p<.05) and interrupted rehab associated with less achievement of potential motor gains (p<.05). 2. Patients with > intervals between onset and admission had less motor function at discharge, achieved less of their potential motor gains and made less efficient motor gains (all p<.05). 3. Therapy intensity was predicted to a small degree by the various functional, demographic and medical variables (psychology intensity had highest explained variance with 26.3% ; SLT 17.2%, All therapies combined 16.6%, OT 7.3%, PT 6.5%). 4. People with lower cognitive and motor function at admission receive more

3-9

Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

intense therapy (psychology and all p<.001, speech & OT - p<.01, PT p<.05);

Discussion Heinemann et al. (1995) employed a case series design to examine the effect of increased therapeutic intensity on functional rehabilitation outcomes as indicated by motor, cognitive and total FIM scores as well as FIM efficiencies. These investigators performed a comprehensive chart review of patients with SCI (N=106) and traumatic brain injury (N=140) to determine the number of 15-minute therapy units delivered in the provision of PT, OT, SLT and Psychology services. They then performed multiple regression analyses to determine if the amount of therapy was associated with positive outcomes. For the most part, there was little evidence that increased therapeutic intensity had any effect on improving outcomes for the SCI sub-sample although the paucity of well-controlled studies in this area limits the strength of the conclusions that can be drawn. Conclusions There is Level 4 evidence based on a single case series that increased therapeutic intensity may not be associated with any functional benefit as measured by the FIM.

Increased therapeutic intensity may not necessarily lead to functional benefits, but data is scarce.

3.4.2 Effect of Age on Rehabilitation Outcomes Historically, traumatic SCI has been viewed as a young, male concern although there have been recent shifts in the demographics of SCI such that an increasing proportion of recently injured individuals are older (both male and female). In fact, recent epidemiological evidence from Ontario, Canada found that the highest rates of SCI-related hospital admission following trauma in this jurisdiction was for those over 70 years of age although the frequency of specific etiologies (e.g., falls vs motor vehicle crashes) varied with age (Pickett et al. 2003). In the US the average age at injury has increased steadily over the last 30 years with the US Model Systems National SCI Statistical Center (2006) reporting an average age of injury of 38.0 years for the period from 2000-2006 as compared to 28.7 years for the period from 1973-1979. In addition, many centers in various jurisdictions around the world also provide rehabilitation services to individuals with spinal cord damage as the result of a variety of non-traumatic etiologies and often these people are much older than those injured due to trauma (McKinley et al. 2001; McKinley et al. 2002; Scivoletto et al. 2003; New 2005). Given these trends for increasing age in those undergoing rehabilitation it is important to understand the effects of age on rehabilitation outcomes. Several investigators have employed retrospective assessments of single or multi-centre patient databases to examine this issue (Cifu et al. 1999a; Cifu et al. 1999b; Seel et al. 2001; Scivoletto et al. 2003; Kennedy et al. 2003). 3 - 10

Table 3.6 Individual Studies The Effect of Age on Rehabilitation Outcomes

Author Year; Country Research Design Total Sample Size Methods Population: Traumatic and non-traumatic SCI, 147 males, 45 females, Mean age=40.716.5 years, (152 aged 16-54, 40 aged 55-85), incomplete tetraplegia (23%), complete tetraplegia (21%), complete paraplegia (34%) and incomplete paraplegia (22%), Mean time post-injury to admission=28.8 days. Treatment: No treatment per se, but various outcomes associated with inpatient rehabilitation focusing on goal attainment in younger vs. older patients. Outcome Measures: Needs Assessment Checklist (NAC) collected within 2 weeks of mobilization and within 6 weeks of discharge. 1. Outcome Improvements were noted in percentage to be achieved" scores for all 9 areas of need (p<0.0001). No significant differences were seen between age groups. Those with complete lesions showed greater improvement in bowel management than those with incomplete lesions (p<0.005) and those with tetraplegia showed greater improvement in the area of skin care than those with paraplegia group (p<0.005) Otherwise no other differences. Mobility needs of older subjects were significantly higher compared to the younger subjects (p<0.005) initially, but lower for the community score (p=0.01). Higher scores (i.e., more unmet need) assessed close to discharge were noted for older vs younger for the areas of skin management (p<0.01), bladder management (p<0.01), bowel management (p<0.05) and mobility (p<0.01). Although LoS was longer for younger patients (111.363.88 vs 8969.9, p<0.008) which was related to a higher incidence of incomplete lesions and etiology, a matched-block subanalysis (N=130) showed differences were not significant. Neurological recovery was more frequent with younger group (p=0.006) and for those at ASIA C. Matched group sub-analysis showed more ASIA grade (p=0.027) and motor score improvements in younger group. Gains for independence of daily living measures (BI and RMI) were significantly greater for younger group (p<0.001). Younger age group had more people reach independent walking levels on WISCI than in older group (p<0.004). Similar findings for related subscales in BI and RMI. Younger age group had more people reach autonomous bladder (p=0.005) and bowel control (p=0.014) than in older group. Similar findings for bladder subscales in BI.

2.

Kennedy et al. 2003;UK Case Control (Inadequate control) Initial N=200; Final N=192

3.

Scivoletto et al. 2003; Italy Case Control Initial N=284; Final N=284

Population: Traumatic (105) and nontraumatic (179) SCI, 184 males, 100 females, Mean age=50.419.3 (12-86) years, cervical (81), thoracic (148), lumbosacral (55), ASIA A-D, Mean time post-lesion to admission was 56.943.9 days. Treatment: No treatment per se, but various outcomes associated with inpatient rehabilitation focusing on younger (<50) vs older (>50) patients. Mean LoS was 98.768.1 days. Outcome Measures: LoS, ASIA Impairment Scale, ASIA Motor Index, Barthel Index (BI), Rivermead Mobility Index (RMI), Walking Index for SCI (WISCI), Discharge Destination. All collected at admission and discharge.

1.

2.

3.

4.

5.

3 - 11

Author Year; Country Research Design Total Sample Size

Methods Population: Traumatic SCI from US Model Systems database, 83% male, Mean age=31.7212.68 (18-92) years, paraplegia, ASIA A-D. Treatment: No treatment per se, but various outcomes associated with inpatient acute and rehabilitation care focusing on age effects by comparing results between 11 age categories. Mean acute LoS was 13.216.92 days. Mean rehabilitation LoS was 56.7634.28 days. Outcome Measures: LoS, Charges, ASIA motor index score, Functional Independence Measure (FIM), change scores and efficiencies for FIM and ASIA motor index. All collected at admission to acute care and admission to rehabilitation care and discharge. 1. 2.

Outcome FIM improvement was less for people 60 than those younger. There were no significant differences in ASIA motor index scores, change scores or efficiency scores across different ages. No systematic significant differences were noted for acute care LoS or hospital charges. Rehabilitation LoS was longer and associated hospital charges greater for older individuals (trend beginning for those > 54 and peaking in the 6064 age group). Younger age groups were more likely injured as a result of vehicular crashes or violence while older groups were more likely injured as a result of falls or other events including being struck by falling objects, pedestrian accidents and medical/surgical complications. The younger the age group, the greater the FIM motor score improvement and greater FIM motor efficiency. The younger and middle age groups had significantly greater ASIA motor index score increases and efficiency than the older age group. No systematic significant differences related to age were noted for acute care or rehabilitation Length of Stay or hospital charges. The older the age group, the more likely individuals would be discharged to an institutional setting.

3. 4.

Cifu et al.1999; USA Case Control (Inadequate control) Initial N=2,169; Final N=2,169

5.

Cifu et al. 1999; USA Case Control Initial N=375; Final N=375

Population: Traumatic SCI from US Model Systems database, male and female, 3 equal (N=125) age groups (18-34, 35-64, >64) matched for neurological level and completeness, tetraplegia, ASIA A-D, 85% admitted within 21 days post-injury. Treatment: No treatment per se, but various outcomes associated with inpatient acute and rehabilitation care focusing on age effects by comparing results between 3 age categories. Outcome Measures: LoS, Charges, ASIA motor index score, Functional Independence Measure (FIM), change scores and efficiencies for FIM and ASIA motor index, Discharge destination. All collected at admission to acute care and admission to rehabilitation care and discharge. Population: Traumatic SCI from US Model Systems database, male, female, 3 equal (N=60) age groups (18-39, 40-59, >59) matched for neurological level and ASIA classification, paraplegia, ASIA A-D, 84% admitted within 21 days post-injury. Treatment: No treatment per se, but various outcomes associated with inpatient acute and rehabilitation care focusing on age effects by comparing results between 3 age categories. Outcome Measures: LoS, Charges, ASIA motor index score, Functional Independence Measure (FIM), change scores and efficiencies for FIM. All collected at admission to acute care and

1.

2.

3.

4.

1.

Seel et al. 2001; USA Case Control Initial N=180; Final N=180

2.

3. 4.

FIM improvement was greater for the younger and middle group that for the older group (p<0.001). FIM efficiency was greater for the young group as compared to the 2 older groups (p<0.001). There were no significant differences in ASIA motor index scores at any of the time points across the different ages. No systematic significant differences were noted between the 3 age groups for acute care LoS or hospital charges. Rehabilitation LoS was significantly shorter for younger than middle or older groups. There was no difference

3 - 12

Author Year; Country Research Design Total Sample Size

Methods admission to rehabilitation care and discharge. 5.

Outcome in associated hospital charges for the 3 groups. All age groups were equally likely to be discharged to a private residence (92%).

Discussion Similar approaches involving case control study designs have been employed by various investigators to examine the effect of age on rehabilitation outcomes. However, in the present review, studies employing some form of matching across different age groups were assessed as representing a higher level of evidence (i.e., Level 3) (Cifu et al. 1999b; Seel et al. 2001; Scivoletto et al. 2003) as compared to those deemed as having an inadequate method of controlling for potential confounds (i.e., Level 4) (Cifu et al. 1999a; Kennedy et al. 2003). Several of these studies have demonstrated differences between age groups for a variety of rehabilitation outcomes although there were also some contradictory findings within these studies, albeit some of this may have been due to variation between the sampling frames and methods employed in each study. For example, Seel et al. (2001) and Cifu et al. (1999a) reported reduced rehabilitation LoS for those with paraplegia due to trauma whereas no differences were seen in investigations of those with tetraplegia due to trauma (Cifu et al. 1999b) and also with the mixed sample of people with both traumatic and non-traumatic SCI (Scivoletto et al. 2003). Conversely, all studies examining functional change showed that younger individuals demonstrated greater functional improvements as indicated by increases with the FIM (i.e., motor FIM scores, change scores, efficiencies) (Cifu et al. 1999a; Cifu et al. 1999b; Seel et al. 2001) or BI (Scivoletto et al. 2003). These similar results were obtained from studies involving those with paraplegia (Cifu et al. 1999a; Seel et al. 2001), tetraplegia (Cifu et al. 1999b) and a mixed sample comprised of those with both traumatic and non-traumatic SCI (Scivoletto et al. 2003). On the other hand, Kennedy et al. (2003) employed the Needs Assessment Checklist (NAC) developed internally at Stoke-Mandeville, UK and demonstrated that there were few systematic age-related differences associated with goal attainment in a mixed traumatic, nontraumatic sample. The NAC is a client-focused outcome measure that assesses the degree to which specific behavioural outcomes particularly relevant to the client are achieved. In addition to functional outcomes, effective rehabilitation has also been associated with increases in neurological status as indicated by AIS or ASIA motor scores. Of the studies reviewed and possessing measures of neurological status, both studies limited to those with paraplegia showed no age effects (Cifu et al. 1999a; Seel et al. 2001;). Conversely, similar studies of those with tetraplegia or a mixed traumatic and non-traumatic SCI sample demonstrated that younger individuals were more likely to make significant neurological gains during inpatient rehabilitation (Cifu et al. 1999b; Scivoletto et al. 2003). Conclusions There is Level 3 evidence that significantly shorter rehabilitation LoS is associated with younger vs older individuals with paraplegia. The same may not be true for those with tetraplegia or for mixed cohorts involving traumatic and non-traumatic SCI.

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There is Level 3 evidence that younger as compared to older individuals are more likely to obtain greater functional benefits during rehabilitation. There is Level 3 evidence that significant increases in neurological status during rehabilitation are more likely with younger than older individuals with tetraplegia or for mixed cohorts involving traumatic and non-traumatic SCI. The same may not be true for those with paraplegia. Younger individuals with paraplegia are more likely to have shorter rehabilitation LoS than older individuals. Younger individuals are more likely to make greater functional gains during rehabilitation than older individuals. Younger individuals with tetraplegia (or in a mixed traumatic, non-traumatic sample) are more likely to make gains in neurological status during rehabilitation than older individuals.

3.4.3 Differences in Traumatic vs Non-Traumatic SCI Rehabilitation Outcomes Those individuals sustaining damage to the spinal cord due to non-traumatic causes are often treated in specialized inpatient SCI rehabilitation centres more commonly associated with those with SCI due to traumatic etiologies. Various reports have estimated that one-quarter to one half of all cases seen in specialized SCI rehabilitation centers are associated with non-traumatic etiologies (Muslumanoglu et al. 1997; McKinley et al. 1999b; van der Putten et al. 2001). Despite these significant numbers, relatively little systematic research is directed at nontraumatic SCI (van der Putten et al. 2001; McKinley et al. 2002). Common causes of nontraumatic SCI includes space occupying lesions such as tumours or prolapsed intervertebral discs, spondylosis such as that seen with degenerative spinal changes resulting in compression of the spinal cord, vascular ischemia as in arteriovenous malformations or spinal infarction, inflammation (e.g., idiopathic transverse myelitis, tropical spastic paraparesis, sarcoid) and those associated with congenital or familial etiologies ( Adams & Salam-Adams 1991; McKinley et al. 1999b; McKinley et al. 2001). Although estimates of the incidence of non-traumatic SCI have been provided (e.g., 8 per 100,000) (Kurtzke 1975), it is difficult to ensure accuracy given the heterogeneous nature of non-traumatic SCI and the variety of facilities and programs where these patients may receive care. Studies comparing those with damage to the spinal cord due to non-traumatic vs. traumatic etiologies have demonstrated a variety of systematic differences between these 2 patient groups. In general, those with non-traumatic SCI are more likely to be older, female, have paraplegia and have an incomplete injury than those with traumatic SCI (McKinley et al. 1996; McKinley et al. 2001; McKinley et al. 2002; New 2005). In the present section, we review the studies characterizing rehabilitation outcomes between those with SCI due to non-traumatic vs traumatic causes. Table 3.7 Individual Studies Non-Traumatic SCI and Rehabilitation Outcomes
Author Year; Country Research Design Total Sample Size McKinley et al. 2001; USA Case Control Methods Population: Non-traumatic SCI (n=87) from a single centre vs traumatic SCI (n=87) from the US Model Systems 1. Outcome As compared to those with trauma (after matching), those with nontraumatic SCI had

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Author Year; Country Research Design Total Sample Size Initial N=174; Final N=174

Methods database; Matched on level and completeness of lesion and age; 2/3rds 3059 years, 1/3rd 60+ years; 93% were admitted within 21 days of injury; 68% were paraplegic; AIS C 36%, AIS D 41%. Treatment: No treatment per se, outcomes associated with non-traumatic vs traumatic rehabilitation. Outcome Measures: LoS, charges, motor FIM (score, change and efficiency). Collected at admission to and discharge from rehabilitation. Population: Non-traumatic SCI secondary to stenosis (n=81) vs traumatic SCI (n=102) within a single centre; Matching from N=381 sample on paraplegia vs tetraplegia and completeness. Treatment: No treatment per se, but various outcomes associated with nontraumatic (stenosis) vs traumatic SCI rehabilitation. Outcome Measures: LoS, charges, Discharge rates to home, FIM (score, change and efficiency). Collected at admission to and discharge from rehabilitation. 2. 3. 4. 5. 6.

Outcome rehabilitation LoS (22.46 vs 41.49days) (p=0.000) overall charges (p=0.003) and daily charges (p=0.019) no difference on motor FIM at admission and motor FIM efficiency with rehabilitation motor FIM at discharge and motor FIM change no difference in discharge destination.

1.

McKinley et al. 2002; USA Case Control Initial N=381; Final N=183

2.

As compared to those with trauma (before matching), those with stenosis were significantly (p<0.01) older (64.1 vs 44.4). more likely female (38.8 vs 21.2%) more likely to have paraplegia (69.4% vs 45.5%) more likely to be incomplete injury (AIS C or D) (100% vs 49.3%) As compared to those with trauma (after matching), those with stenosis had significantly (p<0.05) LoS (22.1 vs 32.2 days) charges admission FIM and FIM motor scores total and motor FIM change and FIM efficiency no difference in discharge FIM totals No difference in discharge destination. As compared to those with trauma (before matching), those with neoplastic cord compression were older (57.8 vs 30.45). more likely to have paraplegia (88.2% vs 52.5%) more likely to be incomplete (88.2% vs 56.7% As compared to those with trauma (after matching), those with neoplastic cord compression had LoS (25.17 vs 57.46 days) had motor FIM change had motor FIM scores at discharge no different FIM efficiency no different for discharge destination

McKinley et al. 1999; USA Case Control Initial N = 4,035; Final N=58

Population: Non-traumatic SCI secondary to neoplastic cord compression admitted over 5 years (within a single centre (n=29) vs traumatic SCI (n=29) from the US Model Systems database matched by age, level of injury and AIS; Age = 57.8 years; AIS AD; C4-L2. Treatment: No treatment per se, but various outcomes associated with rehabilitation care of non-traumatic (neoplastic cord compression) vs traumatic SCI. Outcome Measures: LoS, Discharge destination, FIM (total score, change and efficiency). Collected at admission to and discharge from rehabilitation.

1.

2.

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Author Year; Country Research Design Total Sample Size

Methods Population: Non-traumatic SCI; median age=69 years (29-86); AIS B-D tetraplegia 32.9%, AIS A paraplegia=8.6%, AIS B-D= 58/6%; 78.6% had relatively fast onset (<7 days) and were admitted to rehabilitation=30.9 days, 21.4% had gradual onset and were admitted=11.0 months. Treatment: No treatment per se, outcomes associated with non-traumatic SCI rehabilitation. Outcome Measures: Demographics, clinical characteristics, LoS, Discharge setting, level of lesion and AIS, FIM, mobility, bowel and bladder function. Collected at admission to and discharge from rehabilitation. Population: Non-traumatic SCI; mean age=55 years (16-88); 54% male; cervical 49%, upper thoracic 21%, lower thoracic and lumbar 22%; Time from onset to rehabilitation=4.8 years (0.1-32 years). Treatment: No treatment per se, but optimal outcomes were regressed against various factors associated with nontraumatic rehabilitation. Outcome Measures: Demographics, clinical characteristics, level of lesion and AIS, FIM motor score and change score. Collected at admission to and discharge from rehabilitation. Population: Non-traumatic SCI secondary to neoplastic cord compression admitted over 5 years within a single centre; Mean age=64 years; 18 men, 14 women. Treatment: No treatment per se, but outcomes associated with rehabilitation care. Outcome Measures: Medical complications, AIS, LoS, bladder function, FIM, Discharge destination. All collected at admission to and discharge from rehabilitation. Level of ambulation and dressing ability assessed at 3-15 months post-discharge. 1. 2.

Outcome LoS =55.8 days (7-413 days). FIM motor scores during rehabilitation from 40.8 to 67.1, cognitive FIM showed no change due to initial ceiling effect. 17.7% overall and 26.9% over the age of 70 were discharged to a nursing home. Those subjects male, younger, more mobile, more independent bowel and bladder function and less severe AIS grades were more likely to be discharged home. Major non-traumatic classifications were tumour (32.9%), degenerative (25.7%), vascular (14.3%) and other (27.1%). LoS = 31.5 days (9-184 days). FIM motor score was associated with lower score on admission and reduced time between onset-admission (overall predictive model). Age (i.e., younger), etiology (i.e., hereditary pathology) and lesion level (i.e., cervical) were individually associated with improved functional outcomes but did not improve prediction of overall model.

3. 4.

New et al. 2005; Australia Case Series Initial N=70; Final N=62

5.

1. 2.

Van der Putten et al. 2001; England, UK Case Series Initial N=100; Final N=100

3.

1. 2.

3. 4.

McKinley et al. 1996; USA Case Series Initial N=32; Final N=20

5.

LoS = 27 days (7-54 days). People showed significant in 9 FIM categories (0<0.005) associated with mobility and self-care during rehabilitation. 11 individuals improved from AIS C to D at discharge. 27/32 were discharged home, 4 transferred for medical reasons (and died within 2 months) and 1 died before discharge. Of 20 people with assessed at 3-15 month follow-up, 16 had maintained mobility and dressing function as compared to discharge. However, 12/20 had eventually died at a mean of 101 days post-discharge.

Discussion Studies examining non-traumatic SCI typically make use of retrospective case series designs describing rehabilitation outcomes directly (McKinley et al. 1996; van der Putten et al. 2001; New 2005) or involve case control designs employing matching techniques to make comparisons with traumatic SCI while controlling for such things as age and level and 3 - 16

completeness of injury (McKinley et al. 1999; McKinley et al. 2001; McKinley et al. 2002). As noted above, those with non-traumatic SCI were more likely to be older, female, have paraplegia and have an incomplete injury than those with traumatic SCI (McKinley et al. 1996; McKinley et al. 2001; McKinley et al. 2002; New 2005). When direct comparisons of traumatic and non-traumatic SCI of various etiologies have been conducted using matching procedures, it is clear that shorter rehabilitation LoS was seen for those with non-traumatic SCI (McKinley et al. 2001). In addition, this shorter LoS was associated with reduced hospital charges for both an overall and a per diem basis (McKinley et al. 2001). These findings were replicated with similar studies examining subsets of those with non-traumatic SCI including those with stenosis (McKinley et al. 2002) and those with neoplastic cord compression (McKinley et al. 1999). However, these findings have only been established with data from the US Model Systems. For example, others have reported longer rehabilitation LoS (van der Putten et al. 2001; New 2005) although these reports were conducted in other jurisdictions (i.e., Australia, UK respectively) and employed case series designs such that direct comparisons with traumatic SCI were not possible. None of the studies employing matching procedures noted differences in discharge destinations for those with non-traumatic SCI as compared to those with traumatic SCI (McKinley et al. 1999; McKinley et al. 2001; McKinley et al. 2002). although New et al. (2005) did note that within nontraumatic subjects, those individuals male, younger, more mobile, more independent with bowel and bladder function and having less severe AIS grades were more likely to be discharged home. In addition, the relatively poor prognosis and low survival rate of those with neoplastic cord compression has specific implications for discharge disposition (McKinley et al. 1996) although no specific differences were noted in a matched comparison (McKinley et al. 1999). All studies reviewed employed the FIM to assess the functional status of individuals and generally demonstrated improved function with rehabilitation. Typically, motor FIM scores were employed or in the event total FIM scores were used it was acknowledged that changes were due primarily to the motor FIM subscale given a ceiling effect associated with the cognitive FIM subscale (McKinley et al. 1999; New 2005). For the most part, improvements seen in FIM during rehabilitation for non-traumatic SCI were lesser as those compared to traumatic SCI as reflected by lower FIM change scores (McKinley et al. 1999; McKinley et al. 2001; McKinley et al. 2002). When examining a mixed population of non-traumatic SCI, there were no differences between trauma and non-trauma groups with respect to admission FIM but there was a reduced FIM at discharge for the non-traumatic group accounting for the lower FIM change score (McKinley et al. 2001). This lower FIM change did not result in a lower FIM efficiency given the reduced LoS for the non-traumatic group. When examining only those with stenosis vs those with traumatic SCI, those with non-traumatic SCI had higher FIM scores on admission, similar scores on discharge, resulting in reduced change scores and lower efficiency (McKinley et al. 2002). On the other hand, those with neoplastic cord compression demonstrated similar FIM scores on admission, reduced scores on discharge, resulting in reduced change scores but no difference in efficiency (McKinley et al. 1999). Van der Putten (2001) assessed a variety of factors using multiple linear regression techniques in order to predict those most associated with increases in FIM motor scores during rehabilitation. They included 100 consecutively admitted patients with non-traumatic SCI with rehabilitation periods of > 1 week. The primary factors associated with improved motor FIM scores accounting for 54% of the variance were having a lower score on admission and reduced time between symptom onset-admission. Age, specific diagnostic subgroup (i.e., spaceoccupying, vascular, spondylosis, inflammation or hereditary), or lesion level did not improve the prediction significantly.

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Conclusions There is Level 4 evidence that those with non-traumatic SCI are more likely to be older, female, have paraplegia and have an incomplete injury as compared to those with traumatic SCI. There is Level 3 evidence that those with non-traumatic SCI have generally reduced rehabilitation LoS, reduced hospital charges but similar discharge destinations as compared to those with traumatic SCI. There is Level 3 evidence that those with non-traumatic SCI have generally reduced motor FIM improvement during rehabilitation as compared to those with traumatic SCI.

Individuals with non-traumatic SCI have reduced LoS and less functional improvement with rehabilitation as compared to those with traumatic SCI although controlled comparisons are limited to data from the US Model Systems.

3.4.4 Effect of Gender and Race on Rehabilitation Outcomes Potentially, there are many additional factors that may affect rehabilitation outcomes following inpatient SCI rehabilitation. Two of these factors include gender and race, although neither has been examined comprehensively. With respect to gender effects, studies investigating rehabilitation outcomes associated with women have focused on long-term psychosocial outcomes associated with issues such as marriage or motherhood or issues associated with community and vocational reintegration (Westgren & Levi 1994; DeVivo et al. 1995; Shackelford et al. 1998; Krause et al. 1998). Studies of the effects of race on rehabilitation outcomes have been limited to evaluations of the differences between whites and African Americans using US Model Systems data (Meade et al. 2004a; Putzke et al. 2002), although as with studies of gender, investigations of the effects of race have focused more on vocational issues and satisfaction with life (James et al. 1993; Krause et al. 1998; Krause 1998; Meade et al. 2004b). Table 3.8 Individual Studies The Effect of Gender and Race on Rehabilitation Outcomes
Author Year; Country Research Design Total Sample Size Methods Population: Traumatic SCI from US Model Systems database; matched white vs African American subjects matched by level of function, ASIA Impairment Scale, age and primary care sponsor; 84.2% male; age=34.215.3 years; tetraplegia, paraplegia; ASIA A-D. Treatment: No treatment per se, but various outcomes associated with inpatient acute and rehabilitation care focusing on race effects by comparing outcomes of African Americans and whites. Outcome Measures: ASIA motor index scores, FIM motor score, Medical complications, discharge disposition, 1. 2. 3. Outcome No significant differences between whites vs African Americans for ASIA and FIM motor index scores. No significant differences for discharge disposition (P=0.622). African Americans were more likely to be injured as a result of violence and whites were more likely to be injured in MVCs. African Americans were significantly more likely to receive laparotomies (p<0.001) and be catheter free in comparison to caucasians. Whites were more likely to receive spine surgeries (p<0.001) and have

Meade et al., 2004; USA Case Control Initial N=628; Final N=628

4.

5.

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Author Year; Country Research Design Total Sample Size

Methods medical procedures and medical management. Collected at admission to acute care and admission to and discharge from rehabilitation.

Outcome more suprapubic cystomies in comparison to African Americans. No significant differences between racial groups in the occurrence of medical complications during either acute care or rehabilitation.

6.

Greenwald et al., 2001; USA Case Control Initial N=1074; Final N=1074

Population: Traumatic SCI from US Model Systems database; matched male vs female by level of function, AIS and age; 50% were 18-34 years, 42% were 36-64 years and 8% were >64 years old; tetraplegia, paraplegia; ASIA A-D; 86% were admitted to Model systems within 21 days post-injury. Treatment: No treatment per se, outcomes associated with inpatient acute and rehabilitation care focusing on gender effects. Outcome Measures: Length of Stay, Charges, ASIA motor index total score, FIM motor score, FIM motor change scores, FIM motor efficiency scores, and medical complications. Collected at admission to acute care and admission to and discharge from rehabilitation.

5.

No significant differences were seen for acute care or rehabilitation Length of Stay or charges between males and females. 6. No significant differences were seen in discharge destinations between males and females. 7. No significant differences were seen in admission, discharge, or change scores for both functional (i.e., FIM) and neurological (i.e., ASIA) assessments between males and females. 8. Gender differences in the development of complications during rehabilitation, notably, pressure sores (p<0.001) and DVTs (p=0.003) were more likely in men. 9. Younger patients had better functional outcomes than older patients with significantly higher FIM motor scores at discharge. 10. Older patients had significantly greater ASIA motor scores on admission and discharge than middle-aged patients, who had significantly greater scores than younger patients. Study 1 1. Significant differences between race were not found relating to any of the outcome measures including FIM, Length of Stay (acute or rehabilitation care), Discharge destination and charges (p>0.05). 2. The 2 groups were significantly different (p<0.001) on numerous other demographic and injury-related factors including age, education, gender, race, marital and occupational status, lesion level, and injury duration. Study 2 No significant differences were seen with SWLS, SF-12 and CHART (p=0.25). None of the medical outcome variables differed significantly (p>0.05) with race, including days rehospitalized and number of rehospitalizations in the previous year, impairment level, and total medical

Putzke et al. 2002; USA Case Control Study 1: Initial N=2438; Final N=374 Study 2: Initial N=3301; Final N=316

Population: Traumatic SCI admitted within 1 day of injury to integrated (acute and rehabilitation) US Model Systems Center (Study 1: eligible N=2438) or having 1 year or later follow-up data in the US Model Systems database (Study 2: eligible N=3301), matched white and African American by various injury and demographic factors, tetraplegia, paraplegia, complete, incomplete, Study 1: Age=34.815.9 (white) & 35.315.6 (African American) years, Gender 90% male (both groups), Study 2: Age=37.712.2 (white) & 37.812.0 (African American) years, Gender 93% male (both groups). Treatment: No treatment per se, but race effects on various outcomes associated with integrated acute and rehabilitation care (study 1) or long-term (study 2) studied by comparing results between whites and African Americans. Outcome Measures: Study 1: FIM motor

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Author Year; Country Research Design Total Sample Size

Methods and efficiency scores, Length of Stay, Discharge destination, medical complications, Charges. Study 2: FIM motor and efficiency scores, CHART, Satisfaction with Life Scale (SWLS), SF-12 (measured the individuals perception of his/her health status), medical complications and number of hospitalizations. All collected at admission, discharge or at annual follow-up (Study 2 only).

Outcome complications. Despite non-significant results with multivariate analyses, univariate analyses were also conducted and were generally non-significant except that whites reported less handicap on the CHART mobility subscale (p=0.03). As with Study 1, both groups differed significantly on numerous demographic and injury-related factors (p<0.001).

Discussion Greenwald et al. (2001) employed a mixed, block design, matching male and female subjects so as to control for covariant effects of injury characteristics (level and AIS) and age at injury. They retrospectively analyzed 1,074 subjects over a 10-year period from 1988-1998 by using US Model Systems data culled from 20 different SCI centers from a variety of geographic regions. In general, there were no significant differences between males and females for rehabilitation outcomes including discharge disposition, LoS, FIM motor scores (including change scores and efficiencies) or ASIA motor scores. There were also no reported gender-related differences for the incidence of most medical complications encountered during rehabilitation stay including pneumonia, autonomic dysreflexia, pulmonary embolism, cardiac arrest, kidney calculi or gastrointestinal hemorrhage. However, men did have significantly higher rates for DVT and pressure sores although the authors reported that these differences were not robust and did not result in increased stays, charges or lower functional outcomes. Similar case control designs employing matched groups of whites vs. African Americans from the US Model Systems database have also been employed to examine race effects on rehabilitation outcomes. Putzke et al. (2002) matched race groups according to age, education, gender, occupational status, impairment level, etiology, primary sponsor of care and geographic region whereas Meade et al. (2004) matched according to level of injury, AIS, age and primary sponsor of care. By controlling for all these variables, these authors were able to establish that race acts more as a proxy variable than a predictor of outcomes (Putzke et al. 2002). For example, differences did exist in a wide variety of demographic, rehabilitation outcomes and specific medical conditions provided to African Americans vs. whites when considering but these were generally accounted for by socio-demographic and etiological differences associated with these groups (Putzke et al. 2002; Meade et al. 2004). For example, African Americans were significantly more likely to be injured as the result of violence and have 11th grade education or less while whites were more likely injured as a result of motor vehicle crashes and had high school education or more (Putzke et al. 2002; Meade et al. 2004). For the most part, there were no differences between the two groups with respect to rehabilitation outcomes when the variables noted above were accounted for in the matching process. Conclusions There is Level 3 evidence that there is no difference with respect to gender on discharge destination, rehabilitation LoS and neurological or functional outcomes associated with rehabilitation. 3 - 20

There is Level 3 evidence that there is no difference with respect to race (white vs African-American) on rehabilitation LoS and neurological or functional outcomes associated with rehabilitation that are not otherwise explained by socio-demographic or etiological differences.

Neither gender nor race effects have been demonstrated for discharge destination, rehabilitation LoS and neurological or functional status in US Model Systems data.

3.5 Specialized vs General SCI Units (Acute Care) Donovan et al. (1984) contend that best practice for SCI care consists of a situation in which every individual sustaining a SCI is admitted to an integrated, comprehensive system where expertise, facilities and equipment are focused on optimal patient care and cost effectiveness. At the other extreme is the situation condemned by Bedbrook and Sedgley (1980), of piecemeal care for those with SCI characterized by the occasional patient being treated by the occasional doctor. In practice, care provided by most SCI centers likely falls somewhere in between these extremes of specialized vs. general care. The present section outlines the studies that are focused on examining the hypothesis that care provided through specialized SCI centers is more efficient and effective than that delivered at general centers. The reader should note that while the majority of these studies were conducted from rehabilitation centers the experimental manipulation of interest concerns the degree to ehich specialist care is delivered during acute care period. Table 3.9 Individual Studies Specialized vs General SCI Units
Author Year; Country Research Design Total Sample Size Methods Population: 338 SCI admitted to Rehabilitation, paraplegia, tetraplegia, complete, incomplete. Treatment: N=185 initially treated in a specialized short-term acute care unit; Control: N=153 initially treated in general hospitals. Outcome Measures: Modified Barthel index (MBI), MRSCICS Patient Functional Level Scheme, Length of Rehabilitation Stay (LoS), Efficiency of Rehabilitation Gains (MBI / natural logarithm of LoS) 1. Outcome Those receiving specialized care made functional gains with significantly greater efficiency and were transferred to rehabilitation significantly faster (p<.001). A significantly greater number of people were transferred from general centers with spine instability than from specialized SCI centers (p=.02). There was no difference between specialized and general acute care with respect to functional status at rehabilitation admission or discharge nor on rehabilitation LoS. Those admitted from the specialized SCI unit had significantly improved joint motions (i.e., reduced contractures). More had normal range of motion (p<0.05) and fewer abnormalities. Those admitted from the specialized SCI unit were admitted significantly earlier for rehabilitation as compared

Heinemann et al. 1989; USA Case Control Initial N=338; Final N=338

2.

3.

Yarkony et al. 1985; USA Case Control Initial N=181; Final N=181

Population: Traumatic SCI admitted to a specialized rehabilitation unit; Males (n=149) and females (n=32); Avg age 28 years; Tetraplegia (54%), paraplegia (46%); incomplete (58%), complete (42%). Treatment: Comparison of those treated acutely in a specialized interdisciplinary spinal unit (n=90) vs a general hospital unit (n=91).

1.

2.

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Author Year; Country Research Design Total Sample Size

Methods Outcome Measures: Joint motion, time to rehabilitation admission, all collected at admission to rehabilitation. 3.

Outcome to those admitted from the general hospital unit (p<0.01). Those admitted earlier to rehabilitation had reduced numbers of contractures (p<0.01). Those with tetraplegia had an increased incidence of contractures (p<0.01). Subjects who were cared for in the integrated, specialized unit (Australia) encountered the fewest complications. (no statistical analysis was performed) People sustained progressively more complications with longer periods of delayed admission (US Model Systems). Individuals admitted at these longer delays were cared for initially in general hospital units.

Donovan et al. 1984; USA / Australia Case Control Initial N=1,672; Final N=1,672

Population: Traumatic SCI, admitted to a specialized, integrated rehabilitation unit in Australia (n=66) vs those admitted to the US Model Systems (n=1606); tetraplegia, paraplegia; incomplete, complete. Treatment: Those treated in an integrated, specialized interdisciplinary spinal unit (Australia) admitted <48 hours post-injury vs those admitted to the US Model Systems at 1-15, 16-30, 31-45 or 46-60 days post-injury (reflecting progressively less specialized care). Outcome Measures: Incidence of 7 complications collected at 1-15, 16-30, 3145 or 46-60 days post-injury. Population: traumatic SCI; 201/220 consecutive admissions to a newly established specialized interdisciplinary acute SCI unit vs 351 admissions to one of two general hospital trauma units; tetraplegia, paraplegia; incomplete, complete; Male/female ~ 4/1; Median age 27 years (SCI Specialist unit), 32.0 years (general hospital). Treatment: Comparison of those treated in a SCI specialist spinal unit (1973-1981) vs a general hospital trauma unit (1947-1973). Outcome Measures: LoS, Mortality rate, Cord Injury Neurological Recovery Index. All collected at 6 months (complete) or 12 months (incomplete).

1.

2.

1.

Tator et al. 1995; Canada Case Control Initial N=552; Final N=552

2.

3.

Subjects who were admitted to the specialized SCI unit had significantly shorter acute care LoS than those admitted to the general units (p<0.001). Within the specialized unit subsample, an increased delay from accident to admission resulted in longer LoS (p=0.032). Subjects who were admitted to the specialized SCI unit had significantly reduced mortality than those admitted to the general units (p=0.022). This was especially evident in those with complete SCI. Subjects who were admitted to the specialized SCI unit had significantly greater neurologic recovery (p<0.001).

Discussion The majority of the studies examining the effect of specialist vs. general SCI care settings focused on this issue during the acute period of care only, with the primary outcome measures being taken at admission to rehabilitation and no follow-up after this point. Of the four studies reviewed, only one investigated the results associated with a specialized, integrated unit comprised of both acute and rehabilitation services (Donovan et al. 1984). In this study, rates of six of seven different medical secondary complications typically encountered by individuals with SCI were lowest for the cohort admitted initially (i.e., typically within 48 hours post-injury) to the specialist SCI centre. This cohort was analyzed retrospectively with complication rates determined at various times throughout rehabilitation (i.e., 1-15, 16-30, 31-45, 46-60 days) and compared with those being admitted to specialist SCI centers from more general care settings at similar time periods. Most striking was the absence of decubitis ulcers during any time period 3 - 22

for those under more specialized care vs. a progressively greater incidence for those with greater time spent in general care. No statistical analysis was conducted for this study. In the remaining 3 studies all comparisons were limited to specialized vs. general acute care and were retrospective in nature. Two of these studies compared subjects as they were being admitted for comprehensive rehabilitation (Yarkony et al. 1985; Heinemann et al. 1989). In both studies, patients were transferred significantly faster to comprehensive inpatient rehabilitation from more specialized acute care settings than from general hospital settings. In the remaining study by Tator et al. (1995), the same issue was investigated by examining outcomes associated with a seven year experience of a newly developed specialist SCI unit as compared to historical data culled from pre-existing trauma units reflecting more general settings (Tator et al. 1995). In this study, subjects were also transferred to rehabilitation faster from the specialist SCI unit resulting in a reduced length of stay (LoS) in acute care. In general, all of these studies demonstrated improved medical outcomes associated with more specialized care. In addition to the reduced complication rates noted above by Donovan et al. (1984), others have noted that more specialized acute care resulted in less spine instability (Heinemann et al. 1989) and significantly improved joint motion with reduced incidence of contractures (Yarkony et al. 1985) upon admission to a comprehensive rehabilitation program. In addition, reduced mortality and improved neurological recovery (as demonstrated by higher scores on the Cord Injury Neurological Recovery Index) were seen in the newly developed specialist SCI unit as compared to the data from pre-existing general trauma units (Tator et al. 1995). It should be noted that a gradual reduction of mortality was seen over the entire study period and that reductions attributed to the specialist unit might also be due to many general gradual improvements in medical care, especially as a historical control was used as the primary basis for comparison. Only one study has examined the functional benefits realized during rehabilitation associated with SCI-specific acute care vs. that delivered in more general settings. Heinemann et al. (1989) used the Modified Barthel Index to show that those individuals receiving more specialist care made functional gains during subsequent rehabilitation with significantly greater efficiency (i.e., functional change/LoS) than those referred from general settings. No statistically significant differences were seen between the specialist vs. general groups for either admission or discharge functional levels nor were significant differences seen with LoS. There was, however, a significant reduction in the time from injury to rehabilitation admission for those receiving care in the specialist SCI unit. This implies an overall reduced length of total hospitalization for this group, although this data was not reported. Functional benefits associated with early admission and reduced LoS will be reviewed in the next section. A primary limitation of all studies reported here was the use of retrospective data collection methods and in the case of Tator et al. (1995), the use of historical controls. Another important limitation of some of these studies is the failure to control for (or at least adequately describe) the time to admission to initial care following injury, especially with respect to control subjects (e.g., Donovan et al. 1984; Yarkony et al. 1985; Heinemann et al. 1989). This is an important confounding variable as early admission to a specialized system of care is likely associated with better outcomes as demonstrated in the following section. Therefore, the present conclusions are limited to a Grade 3 level of evidence and some findings have been reduced to Grade 4 if not corroborated and involving inadequate controls. While more carefully controlled prospective studies would be difficult to implement, they would be required to strengthen the evidence in this area.

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Conclusions - Benefits of Specialized vs General SCI Units Based on several retrospective, case-control studies there is Type 3 evidence that individuals cared for in interdisciplinary, specialist SCI acute care units soon after injury (most being admitted within 48 hours) begin their rehabilitation program earlier. There is Level 3 evidence that individuals cared for in interdisciplinary, specialist acute care SCI units have fewer complications upon entering and during their rehabilitation programs. There is Level 4 evidence that individuals initially cared for in interdisciplinary, specialist acute care SCI units make more efficient functional gains during rehabilitation (i.e., more or faster improvement). There is Level 4 evidence that individuals cared for in interdisciplinary, specialist SCI units have reduced mortality.

More specialized, interdisciplinary acute SCI care is associated with faster transfers to rehabilitation and may result in fewer medical secondary complications, more efficient functional gains and reductions in overall mortality.

3.6 Early vs Delayed Admission to Specialized SCI Units As noted by others and in the previous section, earlier as opposed to delayed admission to interdisciplinary, specialized SCI units has been associated with a variety of beneficial outcomes (DeVivo et al., 1990). The question of whether earlier admission to an organized system leads to enhanced outcomes is inexorably linked to the question of specialist vs general care for individuals with SCI. In all studies in this and the preceding section the authors framed their studies as addressing either the question of delay or the question of interdisciplinary, specialist care yet similar designs were employed for each (i.e., retrospective case control). For those subjects experiencing a delay to admission to a specialized SCI unit, it was either presumed or established that preceding acute care was conducted at a general hospital unit. The author simply chose to characterize this as either a delay or more general care. For the present review we have maintained this distinction as originally intended by each author, especially, as in some cases, there is little or no verification of the general nature of the pre-admission care or the time of first admission, respectively. However, the reader is advised that the specific findings and conclusions reached in both sections are most likely associated with a delay to an interdisciplinary, specialized acute or rehabilitation SCI unit with prior care delivered at a general hospital facility. In addition, much variation exists in the literature that addresses the question of delayed admission. There is no uniform or accepted definition of what constitutes a delay and this varies depending on the context of the study, most notably whether it is conducted from an acute vs rehabilitation perspective. For the present review, all studies which examine this question by comparing 2 or more groups within the first week post-injury have been examined separately

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from those with an initial time period greater than 1 week post-injury. These have been termed 1) Acute and 2) Post-acute studies, respectively. Table 3.10 Individual Studies Early vs Delayed Admission (Acute Studies)
Author Year; Country Research Design Total Sample Size Methods Population: 661 people with SCI admitted to a US Model Care System Centre with specialized SCI rehabilitation services. Subjects included those with tetraplegia and paraplegia and also those with incomplete vs complete injuries but frequencies were not provided. Average ages for early vs delayed admission groups were 29.5 and 32.0 years old respectively. Treatment: No tx per se, comparison of those admitted earlier (< 24 hours post injury) vs later (> 24 hours) to a specialized integrated spinal unit (i.e., combined acute care and rehabilitation). Subjects were sub-grouped into i) paraplegia, incomplete, ii) paraplegia, complete, iii) tetraplegia, incomplete, iv) tetraplegia, complete. Outcome Measures: Length of Stay (LoS), Hospital charges, Incidence of medical complications, Neurologic recovery, Mortality all collected at Discharge. 1. Outcome Those with complete paraplegia (p=0.0169) & incomplete tetraplegia (p=0.0001) admitted earlier (<24 hours) had significantly shorter total hospitalization LoS. A similar trend for those with incomplete paraplegia (p=0.0568), no difference for those with complete tetraplegia (p=0.928). Mean hospital charges were less for subjects with complete (p=0.0099) and incomplete (p=0.0134) tetraplegia who were admitted earlier. Similar trend for those with incomplete paraplegia (p=0.0607), no difference for complete paraplegia (p=0.4777). In general, no overall differences were seen in the development of medical complications between the early vs late admission groups. A few differences for incidence specific complications. Trend for increased neurologic recovery with early admission in that 10/315 (3.2%) vs 4/401 (1.0%) in early vs late groups had complete recovery (p=0.08). Author warns of bias in this finding. Mortality comparisons not possible within sample for early vs late admission groups. Comparison with historical data suggests enhanced survival rates with early admission. Subjects who were admitted earlier (<24 hours) had significantly fewer contractures than those admitted later (>24 hours 60 days) (p=0.05). Other factors associated with an increased incidence of contractures included tetraplegia vs paraplegia (p<0.01), presence of a pressure ulcer (p=0.05), co-existence of head injury (p<0.05).

2.

DeVivo et al. 1990; USA Case Control Initial N=661; Final N=661

3.

4.

5.

Daylan et al. 1998; USA Case Control Initial N=482; Final N=482

Population: 482 men and women with traumatic SCI admitted to a US Model Systems SCI Centre with specialized SCI acute care and rehabilitation services. Subjects included those with tetraplegia (256) & paraplegia (226) and ASIA A, B, C (362) & D (120). Treatment: No tx per se, comparison of those admitted 1. (< 24 hours post injury) vs 2. (> 24 hours 60 days post-injury) to a specialized spinal acute care and rehabilitation unit. Outcome Measures: Incidence of contractures during initial post-traumatic hospitalization.

1.

2.

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Table 3.11 Individual Studies Early vs Delayed Admission (Post-Acute Studies)

Author Year; Country Research Design Total Sample Size Methods Population: SCI, tetraplegia, paraplegia, complete, incomplete, traumatic. Treatment: No tx per se, comparison of those admitted to a specialized Spinal Rehabilitation unit at one of 3 time periods following injury (<30 days, 31-60 days, > 60 days). Outcome Measures: LoS, ASIA motor scores and impairment grade, Barthel Index (BI), Rivermead Motor Index (RMI), Walking Index for SCI (WISCI), Efficiency measures for all were calculated by dividing by LoS. 1. Outcome Those admitted earliest (<30 days) had significantly performance on activities of daily living (i.e., Barthel Index scores) at discharge than those with longer delays (>60 days) (p=.006). They also demonstrated significantly greater changes (p=.003) and greater efficiency (p<.001) for the Barthel Index. Those admitted the earliest (<30 days) had significantly better mobility (i.e., RMI) at discharge than those with longer delays (>60 days) (p=.03). They also demonstrated significantly greater changes (p=.001) and greater efficiency (p=.04) for the RMI. There were no significant differences between the early vs later admissions with respect to walking (WISCI) or ASIA motor scores (p=.63 or p=.81). Those admitted earliest had the shortest LoS; these differences were not significant (p=.15). Those admitted with a delay (> 7 days) following referral had significantly longer LoS (p<.001). This was for people with both complete (N=59) and incomplete (N=29) injuries but not for those without spinal cord damage (N=24). More severe injuries (as determined by Injury Severity Scores) were more likely to have longer LoS (Spearmans = 0.593, p<0.0001). Those who were admitted with a delay between injury and referral (>3 days) did not differ on LoS with those who did not experience a delay (p=0.44). The primary reasons for delays between referral and admission for those with complete injuries were I) achieving medical stability and ii) absence of beds. For those with incomplete injuries the same primary reasons were identified but in reverse order. Those admitted earlier had significantly shorter total hospitalization LoS (p<.01). Those admitted earlier with tetraplegia had fewer medical complications and less frequent spinal surgery vs those admitted later (no group analysis performed). Those admitted earlier with paraplegia had no difference in

Scivoletto et al. 2005; Italy Case Control Initial N=150; Final N=150

2.

3.

4.

Population: SCI, tetraplegia, paraplegia, traumatic. Treatment: No tx per se, comparison of those admitted to a specialized integrated spinal unit (i.e., combined acute and rehabilitation) with or without a delay between injury and referral (>3 days) and between referral and admission (>7 days). Outcome Measures: LoS. Amin et al. 2005; England Case Control Initial N=432; Final N=432

1.

2.

3.

4.

Oakes et al. 1990; USA Case Control Initial N=197; Final N=197

Population: 197 people with traumatic SCI admitted within 1 year of injury to a Level 1 trauma Centre with specialized SCI rehabilitation services. Male / female (158 / 39); Tetraplegia / paraplegia (102 / 95); Average ages for groups were 27.2 32 years old. Treatment: No tx per se, comparison of those admitted earlier (< median) vs later

1. 2.

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Author Year; Country Research Design Total Sample Size

Methods (> median) to a specialized integrated spinal unit (i.e., combined acute care and rehabilitation). Subjects were grouped by tetra vs para and by early vs late admission by median admission values of 11 (Tetra) vs 21 (Para) days. Outcome Measures: LoS, incidence of medical complications, incidence of surgical intervention. Population: 123 people with SCI admitted to a Japanese Hospital System with specialized SCI rehabilitation services following acute care. Subjects included those with tetraplegia and paraplegia (frequencies not provided) with ASIA A (51), B (8), C (35) and D (29). Treatment: No tx per se, comparison of those admitted earlier (< 2 weeks post injury) vs later (> 2 weeks) to a specialized spinal rehabilitation unit. Subjects were sub-grouped into i) tetraplegia, ii) paraplegia, iii) central cord. Outcome Measures: LoS, FIM, FIM motor score, FIM gain, FIM efficiency all collected at Discharge.

Outcome medical complications and more frequent spinal surgery. Similar reductions in total hospitalization LoS with earlier admissions for both those with tetraplegia (p<.01) and paraplegia (p<.05) in a re-analysis of the sample with groupings based on admissions < 24 hours vs > 24 hours post-injury. Subjects who were admitted earlier (<2 weeks) had significantly shorter LoS than those admitted later (p<0.0005). FIM gain (p<0.0001) and FIM efficiency (p<0.0001) were significantly greater for subjects admitted earlier vs later. Note: the early admission subjects had lower initial motor and total FIM scores than did the delayed admission group (p<0.05). Correlations between ASIA motor and FIM scores in various subgroups and at admission and discharge yielded a variety of associations ranging from very weak to strong correlations (r=0.03-0.92) with the majority of these correlations significant (p<.05). Subjects with paraplegia who were admitted earlier (<1 week and < 2 months) had significantly shorter LoS than those admitted later (p<0.05). Subjects with tetraplegia who were admitted earlier (<1 week) had significantly shorter LoS than those admitted later (>2 months) (p<0.05). The incidence of most secondary conditions did not differ between early vs later admissions for those with paraplegia or tetraplegia. However, those with paraplegia or tetraplegia did have lower incidence of pressure sores with earlier admission (<1 week) (p<0.001).

3.

1.

2.

Sumida et al. 2001; Japan Case Control Initial N=139; Final N =123

3.

Aung & El Masry 1997; UK (Wales) Case Control Initial N=219; Final N=219

Population: 173 men (mean age 35.5) and 46 women (mean age 44.2) with traumatic SCI admitted to a Spinal Injuries Centre with specialized SCI acute care and rehabilitation services. Subjects included those with tetraplegia (116) and paraplegia (103). Treatment: No tx per se, comparison of those admitted 1. (< 1 week post injury) vs 2. (< 2 month) vs 3. (> 2 months) to a specialized spinal acute care and rehabilitation unit. Outcome Measures: LoS, incidence of secondary complications all collected at discharge (i.e, during initial post-traumatic hospitalization).

1.

2.

3.

Discussion The present section describes a series of studies in which investigators examined the effect of delayed admission to a specialist SCI unit. However, there is not a common definition of what constitutes a delayed admission. Therefore, to assist the reader in summarizing these delays, the details of the various time frames under examination are outlined along with their respective results in Table 3.12.

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Table 3.12 Studies Examining Delayed Admission to SCI Unit

Study DeVivo et al. 1990 Experimental Groups (time post-injury) or or <= 24 hours* > 24 hours <= 24 hours* > 24 hours <= 30 days* 30-59 days > 60 days <= 3 days > 3 days <= 7 days from referral* > 7 days from referral <= 11 days (for tetra)* > 11 days <= 21 days (for para)* > 21 days <= 2 weeks* > 2 weeks <= 1 week* < 2 months LoS Functional Status Neurological Status LoS Secondary complications + + + Outcome Measure LoS Secondary complications Neurological Status Secondary complications (contractures) LoS Functional Status Neurological Status LoS LoS LoS Secondary complications Result + ~ + ~ + + + + (tetra only)

Daylan et al. 1998

Scivoletto et al. 2005

Amin et al. 2005

Oakes et al. 1990

Sumida et al. 2001

Aung & El Masry 1997

(*= Condition with most positive result, + = Positive results, ~ = Trend, - = No effect)

Two acute studies were reviewed which each employed retrospective, 2 group (case control) designs with a definition of 24 hours as to what constituted an early vs a delayed admission (DeVivo et al. 1990; Dalyan et al. 1998). Each study examined a fairly large cohort admitted to a multidisciplinary, specialized SCI unit (i.e., US model system center) within 24 hours post-injury vs those admitted after 24 hours. Neither study reported the actual injury to admission times for the delayed admission group and both failed to provide information about the referral sources (e.g., specialist vs. general nature). DeVivo et al. (1990) noted that total hospital LoS (i.e., acute and rehabilitation) was reduced for all patient groups except for those with complete tetraplegia when admission was not delayed. Mean hospital charges were also reduced for early admission subjects except those with complete paraplegia and there were some reductions in the incidence of specific medical complications with early admission for some patient groups, most notably a trend for a reduction in pressure sores for all but those with incomplete paraplegia. In addition these authors also reported a trend for increased neurologic recovery and reduced mortality with earlier admission, although they also noted methodological concerns associated with the actual measures employed. Dalyan et al. (1998), in a study focusing on the development of contractures, noted an increased incidence of contractures for those admitted within 24 hours to a specialized unit. Of the studies examining time periods longer than one week (i.e., post-acute), five studies have been reviewed (Oakes et al. 1990; Aung & el Masry 1997; Sumida et al., 2001; Amin et al. 2005; Scivoletto et al. 2005). The initial admission delays examined ranged from 1 week (Aung & el Masry, 1997) to 1 month (Scivoletto et al. 2005). All studies employed retrospective case 3 - 28

control designs and all examined LoS for the entire period of initial hospitalization as a primary outcome measure. In all cases, those admitted earlier had reduced LoS, regardless of the considerable variation between studies in the definition of what constituted a delay in admission. It should be noted that this difference was statistically significant for all studies but one; for which it was reported as a trend (p=0.15). This study examined the longest delay of 1 month (Scivoletto et al. 2005). Functional benefits were also demonstrated for individuals admitted earlier. Scivoletto et al. (2005) reported that those admitted earlier than 1 month had significantly greater gains and greater efficiency associated with the Barthel Index as well as greater mobility gains and efficiency as measured by the Rivermead Mobility Index but there was no difference with respect to walking as measured by the Walking Index for SCI (WISCI). Similarly, Sumida et al. (2001) reported increased Functional Independence Measure (FIM) gains and efficiencies for those admitted earlier than 2 weeks post-injury as compared to those admitted later. Interestingly, these investigators also showed that for a majority of the various patient groups tested (i.e., paraplegia and tetraplegia, early and late), significant associations were seen between a measure of function (i.e., FIM) and a measure of impairment (i.e., ASIA motor scores). However, Scivoletto et al. (2005) found no effect of early vs. late admission on ASIA motor scores. Other investigators examined the role of early vs late admission on the incidence of secondary medical complications. Oakes et al. (1990) reported that earlier admissions were associated with a reduced incidence of secondary medical complications in those with tetraplegia and Aung and el Masry (1997) noted a reduction in the number of pressure sores for all subjects with earlier admission. Despite the apparent benefits of earlier admission to a multidisciplinary, specialized integrated SCI unit, there are significant issues which serve to constrain the strength of evidence in this area. First and foremost is the retrospective nature of all studies conducted to date. It is difficult to ascertain how comparable the early vs later groups truly are with respect to potential confounding variables. In particular, there is a paucity of information on the pre-admission level of care and medical status, especially for the delayed admission groups. In addition, it is difficult to discern the potential role that medical status or the presence of secondary medical complications may have played in admission delays. The retrospective nature of the studies outlined in this and the previous section makes it difficult to determine if individuals prone to complications and with poorer medical status would have naturally comprised a greater proportion of the delayed admission groups. Therefore, as noted earlier, more carefully controlled prospective studies would be required to strengthen the evidence in this area. Conclusions - Benefits of Early vs Later Admission Based on several retrospective, case-control studies there is Type 3 evidence that individuals admitted earlier to interdisciplinary, integrated specialist SCI units have a shorter total hospitalization length of stay than those admitted later. There is Level 3 evidence that individuals admitted earlier to interdisciplinary, integrated specialist SCI units make greater functional gains in a shorter period of time (i.e., greater efficiency) than those admitted later. There is Level 3 evidence that individuals admitted earlier to interdisciplinary, integrated specialist SCI units have fewer secondary medical complications (especially pressure sores) than those admitted later.

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Because of the variability between studies as to what constitutes early admission to interdisciplinary, specialist integrated SCI units it is not possible to determine a specific period for optimal admission. At least one study has demonstrated benefits with an early admission described as anything within 30 days post-injury. The majority of studies defined early admissions as 1-2 weeks post-injury, while studies focused on acute care describe early admission as within 24 hours post-injury. Earlier admission to specialized, interdisciplinary SCI care is associated with reduced length of total hospital stay and greater and faster rehabilitation gains with fewer medical secondary complications. Prospective studies with stronger designs are needed to strengthen the evidence and provide more direction as to the optimal model of care. 3.7 Outpatient and Follow-up Care Various authors have noted the importance of providing continued, regular, specialized followup care following discharge from rehabilitation (Ernst et al. 1998; Cox et al. 2001; Dryden et al., 2004). In a recent review, Bloemen-Vrencken et al. (2005) described various follow-up programmes for persons with SCI. These authors noted that the vast majority of the papers in this area offered little more than a description of the program with 5 of these being identified as either experimental or quasi-experimental in nature. Of these, 3 studies were focused on evaluations of telemedicine or nursing education for the prevention of pressure sores or UTIs (Barber et al. 1999; Phillips et al. 1999; Phillips et al., 2001), whereas the remaining two had broader goals of general heath and well-being (Dinsdale et al. 1981; Dunn et al. 2000). Those articles evaluating programs addressing specific goals (i.e., pressure sores or UTIs) will be reviewed in the chapters related to these specific issues. The present section focuses on those studies with more generic aims. Cox et al. (2001) performed a needs assessment of 54 community-dwelling individuals with SCI using structured telephone interviews and reported a perceived high need for a specialist, multidisciplinary SCI outreach service. Some of the issues identified as the greatest areas of need included dealing with physical changes, transportation, work issues, ongoing education and pain management. The primary barriers to needs being met were overwhelmingly related to limitations of local expert knowledge but also included inadequate funding, complicated processes or service fragmentation and no knowing where to go for help. Preferred service delivery options in order of preference included telephone advice, home visits, SCI outpatient clinics, community-based service and regional hospital clinics (Cox et al. 2001). Similar suggestions have been provided by clinicians, especially as they observe the consequences of inadequate care received by some individuals upon discharge from inpatient rehabilitation programmes (Vaidyanathan et al. 2004). Despite these reports, little direct evidence has been established for the effectiveness of different methods of providing follow-up care. Table 3.13 Individual Studies Outpatient and Follow-up Care
Author Year; Country Score Research Design Total Sample Size Dunn et al. 2000; USA Downs & Black score=12 Methods Outcome

Population: People with SCI receiving SCI-specialist follow-up care (N=235) vs

1.

Those receiving regular follow-up scored higher on all 3 subscales of

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Prospective Controlled Trial (inadequate control) Initial N=371; Final N=371

those not (N=136); Age = 56.6 vs 47.9; Gender = 99% Male vs 66% Male; paraplegic, tetraplegic; complete, incomplete; Time since injury = 19.4 vs 18.2 years. Treatment: Follow-up care (routine checkups in SCI Outpatient Clinic) vs no Followup care (presumably problem-based primary care). Outcome Measures: Secondary Condition Surveillance Instrument (SCSI), Check Your Health (CYH) Questionnaire. One time survey of both groups.

2.

CYH, Health (p=0.0068), Independence (p=0.005) and Absence of Depression (p<0.0001). Those receiving regular follow-up reported similar secondary conditions as those without routine follow-up but with reduced frequency and rated it as less severe.

Discussion Dunn et al. (2000) performed an exploratory study of the value of receiving regular, comprehensive outpatient health care follow-up as compared to those who were deemed to have no access to these services. Although this investigation was limited by a poor description of the specific services offered to both the experimental and control groups, there were significant differences in the perceived health, independence, and absence of depression in those seen regularly in outpatient clinics. In addition, this group had significantly less frequent occurrences of specific secondary conditions and also rated the severity of these conditions as less than those having no access to these clinics (Dunn et al. 2000). Although this trial was prospective in nature and attempted a quasi-experimental controlled methodology, the potential confounds (i.e., gender, completeness, race, age, veteran status) varied greatly between the experimental and control groups. In addition, it was uncertain if selection bias may also have been an issue, as the authors did not specify what percentage of individuals within their own service provision cohort refused or did not receive regular outpatient care. These limitations resulted in this study being assessed as having a Level 4 level of evidence. Conclusions There is Level 4 evidence that provision of routine, comprehensive, specialist follow-up services may result in perceived improvements of health, independence and less feelings of depression. Routine, comprehensive, specialist follow-up services may result in improved health

3.8 Summary There is Level 3 evidence (with US data only) that rehabilitation LoS has become progressively shorter up to the mid-1990s. No other jurisdiction has published data that supports this contention. There is Level 3 evidence that those with higher level and more severe injuries have longer rehabilitation LoS. There is Level 4 evidence that a significant proportion of people (~50%) initially assessed as AIS B and C will improve by at least 1 AIS grade in the first few months post-injury

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concomitant with inpatient rehabilitation. Fewer individuals (~10%) initially assessed as AIS A and D will improve by 1 AIS grade. There is Level 4 evidence that individuals make significant functional gains during inpatient rehabilitation, more so for those with complete and incomplete paraplegia and incomplete tetraplegia. There is Level 4 evidence based on a single case series that increased therapeutic intensity may not be associated with any functional benefit as measured by the FIM. There is Level 3 evidence that significantly shorter rehabilitation LoS is associated with younger vs older individuals with paraplegia. The same may not be true for those with tetraplegia or for mixed cohorts involving traumatic and non-traumatic SCI. There is Level 3 evidence that younger as compared to older individuals are more likely to obtain greater functional benefits during rehabilitation. There is Level 3 evidence that significant increases in neurological status during rehabilitation are more likely with younger than older individuals with tetraplegia or for mixed cohorts involving traumatic and non-traumatic SCI. The same may not be true for those with paraplegia. There is Level 4 evidence that those with non-traumatic SCI are more likely to be older, female, have paraplegia and have an incomplete injury as compared to those with traumatic SCI. There is Level 3 evidence that those with non-traumatic SCI have generally reduced rehabilitation LoS, reduced hospital charges but similar discharge destinations as compared to those with traumatic SCI. There is Level 3 evidence that those with non-traumatic SCI have generally reduced motor FIM improvement during rehabilitation as compared to those with traumatic SCI. There is Level 3 evidence that there is no difference with respect to gender on discharge destination, rehabilitation LoS and neurological or functional outcomes associated with rehabilitation. There is Level 3 evidence that there is no difference with respect to race (white vs African-American) on rehabilitation LoS and neurological or functional outcomes associated with rehabilitation that are not otherwise explained by socio-demographic or etiological differences. Based on several retrospective, case-control studies there is Type 3 evidence that individuals cared for in interdisciplinary, specialist SCI acute care units soon after injury (most being admitted within 48 hours) begin their rehabilitation program earlier. There is Level 3 evidence that individuals cared for in interdisciplinary, specialist acute care SCI units have fewer complications upon entering and during their rehabilitation programs.

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There is Level 4 evidence that individuals initially cared for in interdisciplinary, specialist acute care SCI units make more efficient functional gains during rehabilitation (i.e., more or faster improvement). There is Level 4 evidence that individuals cared for in interdisciplinary, specialist SCI units have reduced mortality. Based on several retrospective, case-control studies there is Type 3 evidence that individuals admitted earlier to interdisciplinary, integrated specialist SCI units have a shorter total hospitalization length of stay than those admitted later. There is Level 3 evidence that individuals admitted earlier to interdisciplinary, integrated specialist SCI units make greater functional gains in a shorter period of time (i.e., greater efficiency) than those admitted later. There is Level 3 evidence that individuals admitted earlier to interdisciplinary, integrated specialist SCI units have fewer secondary medical complications (especially pressure sores) than those admitted later. Because of the variability between studies as to what constitutes early admission to interdisciplinary, specialist integrated SCI units it is not possible to determine a specific period for optimal admission. At least one study has demonstrated benefits with an early admission described as anything within 30 days post-injury. The majority of studies defined early admissions as 1-2 weeks post-injury, while studies focused on acute care describe early admission as within 24 hours post-injury. There is Level 4 evidence that provision of routine, comprehensive, specialist follow-up services may result in perceived improvements of health, independence and less feelings of depression

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Appendix Studies Describing Rehabilitation Outcomes Table 3.14 Individual Studies Describing SCI Rehabilitation Outcomes
Author Year; Country Research Design Total Sample Size Methods Population: Traumatic SCI, 82% male, Mean age=28.3 years, tetraplegia (55%), paraplegia (45%), incomplete, complete, Mean time post-injury to admission=28.8 days. Treatment: No treatment per se, but outcomes associated with inpatient rehabilitation. LoS 69.6 + 39.2 days. Outcome Measures: LoS, Modified Barthel Index (MBI) collected at admission and discharge. 1. Outcome Tetraplegics had significantly longer stays in rehabilitation than the paraplegic group (121 vs 81 days, p<0.001). Those who were diagnosed with incomplete lesions also had significantly shorter stays than those diagnosed with complete injuries regardless of level of injury (p=0.001). Incomplete (107.6 days) vs complete (135.3) tetraplegia and incomplete (78.2 days) vs complete (83.4) paraplegia. Overall, patients showed significant increases in total MBI and self-care and mobility MBI subscores (p<0.001). Improvements and discharge scores were greater for incomplete vs complete (p<0.001) and for those with paraplegia vs tetraplegia (p<0.001). Significant improvements were noted in the MBI self care subscores, MBI mobility subscores and MBI total scores from admission to discharge (p<0.001 for all). At least 70% of patients were independent on each of the individuals tasks comprising the MBI at discharge. 89% of patients were discharged home. Continent spontaneous voiding was achieved by 84% at discharge as compared to 23% at admission. Regulation of bowel management was achieved by 99% at discharge as compared to 54% at admission. Medical complications requiring management occurred in 66.7% of patients during rehabilitation. Most gains in motor and sensory scores were found in first year. An average of 35 motor points (18% during acute care, 53% during rehabilitation, 8% during the remainder of the year) and 46 sensory points (46% during acute care, 46% during rehabilitation, 8% during the remainder of the year) were recovered. Younger individuals (<18) had more improvement in motor scores but not sensory scores than older people (p=0.002). People with Brown Sequard and

Yarkony et al. 1987; USA Case series Initial N=711 Final N=711

2.

Roth et al. 1990; USA Case series Initial N=81 Final N=81

Population: Traumatic central cord syndrome, 67 males, 14 females, Age=45.520.0 years Tetraplegia, Frankel C and D, Mean time post-injury to admission=29.818.0 days. Treatment: No treatment per se, but outcomes associated with inpatient rehabilitation. LoS 69.6 + 39.2 days. Outcome Measures: Modified Barthel Index (MBI) collected at admission and discharge.

1.

2. 3. 4. 5.

Pollard & Apple 2003; USA Case Series Initial N=412 Final N=95

Population: Patient Database (N=412), traumatic, incomplete tetraplegia admitted within 90 days post-injury (N=95). Treatment: No treatment per se, but various outcomes associated with inpatient acute care and rehabilitation. Main factors examined were effect of intravenous steroids, early definitive surgery (<24 hours after injury) and early decompression surgery. Mean acute care LoS was 1516 days and mean rehabilitation LoS was 4730 days. Outcome Measures: Change in sensory score, final sensory score, change in motor

1.

2.

3.

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Author Year; Country Research Design Total Sample Size

Methods score, final motor score. All collected at admission and discharge (also for some at time of injury and 1, 2, 3 years post-injury or the latest anniversary). 4.

Outcome Central Cord injuries had more improvement in motor scores but not sensory scores than those with anterior cord (p=0.019). There was no effect of methylprednisolone (MP) administration, early anterior decompression, decompression of stenosis without fracture, gender or race. Those with MP administration did have greater improvements in sensory scores (p=0.027) although there was no difference in the final sensory score for those with and without MP. Overall, significant increases were seen from admission to discharge with total MBI (p<0.001), self care subscore (p<0.001) and mobility subscore (p<0.001). Discharge functional status was dependent on the admission functional status (p<0.001) and the rehab LoS (p<0.05) but not on acute care LoS, level of paraplegia or presence of surgical stabilization. No statistically significant differences were noted between those with high vs low paraplegia on 14 of the 15 components of the MBI other than low paraplegic patients were more likely to walk 50 yards (p<0.001). All patient groups (i.e., levels and severity of injury) had similar FIM motor scores at discharge as noted by American Consortium for Spinal Cord Medicine. All groups showed increases in FIM motor scores from admission to discharge but these were only significant for tetraplegia ASIA D (p<0.05) given small group sizes. Little change in cognitive FIM was seen between admission and discharge due to ceiling effects. FIM motor scores generally continued to increase at 1 and 3 months postinjury although small N sizes and missed follow-ups precluded statistical significance. LoS was generally longer for tetraplegia (low level was significant, p<0.0005) although there were low Ns for each group (varied from 52.0-215.9 days).

Yarkony et al. 1990; USA Case series Initial N=184 Final N=184

Population: Traumatic Complete Thoracic SCI, 81% male, Mean age=27.211.4 years, Mean time post-injury to admission=46 days. Treatment: No treatment per se, but outcomes presented associated with inpatient rehabilitation. Length of stay 84 days. Outcome Measures: Modified Barthel Index (MBI) collected at admission and discharge.

1.

2.

3.

Population: Traumatic SCI, 30 males, 3 females, Age=48.415.6 years, 24 tetraplegia and 9 paraplegia. Treatment: No treatment per se, but various outcomes associated with inpatient rehabilitation. Outcome Measures: FIM, LoS. All collected at admission, discharge, and 1 and 3 months post-discharge. Chan & Chan 2005; Hong Kong, China Case Series Initial N=33 Final N=33

1.

2.

3. 4.

5.

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Author Year; Country Research Design Total Sample Size

Methods Population: Gender: 51 males, 17 females, Age=43 years. Treatment: No treatment per se, but LoS is modeled (predicted) by various measures associated with inpatient rehabilitation. Outcome Measures: LoS and various predictor variables (age, gender, ADLs, subjective well-being and cognitive-social skills). Predictor variables collected at admission to inpatient rehabilitation. Population: Traumatic (42) and nontraumatic (10) SCI, 32 males, 20 females, Age=36.4 17.7 (5-75) years, complete (6) and incomplete (18) tetraplegia and complete (9) and incomplete (19) paraplegia. Treatment: No treatment per se, but various outcomes associated with inpatient rehabilitation of 93.9 44.95 (14-258) days. Outcome Measures: Motor scores, light touch scores and FIM. All collected at admission, discharge, and 1 year postdischarge (N=10 only). 1.

Outcome Performance on ADLs was the only direct predictor of LoS, while subjective well-being and gender affect LoS indirectly through other predictors (subjective well-being via ADLs). LoS increases as ADL performance deteriorates. Clients with good subjective well-being scores will tend to perform better on ADLs, resulting in shorter LoS. Neurological assessments (Motor scores and light touch scores) showed increases from admission to discharge for those with incomplete injuries (p<0.001) but not complete injuries. FIM showed increases from admission to discharge for those with incomplete injuries (p<0.05) and those with complete paraplegia (p<0.05) but not complete tetraplegia. FIM scores (p<0.05), but not motor scores or light touch scores showed significant increases from discharge to 1 year post-discharge in a subsample of 10 with paraplegia. In general, the group with shorter LoS did not differ dramatically from the group with longer LoS. Subjects also spent less time in PT and OT from 1991 to 1995 (p<0.001). There were higher discharge scores for bowel management, stairs, manual locomotion, rolling supine to prone and rolling side to side for those with longer LoS in paraplegics. No significant differences were seen in tetraplegic patients. (Many results showing no differences not presented). Post discharge performance skills in those with tetraplegia showed that those with shorter LoS had higher function in the following areas: bathing (p=0.39), bed transfer (p=0.27), and toilet transfer (p=0.047). For those with paraplegia, the shorter LoS group was higher in the following areas: grooming (p<0.011), upper body dressing (p=0.003), car transfer (p=0.018) and manual locomotion (p=0.031). The proportion of subjects who reported UTIs, pressure sores and pain was higher in the shorter LoS group. Rehabilitation Length of Stay decreased over study period from 56.5

Chung et al. 2003; Taiwan Case Series Initial N=68 Final N=68

2.

1.

Mslmanolu et al. 1997; Turkey Pre-Post Initial N=52 Final N=10

2.

3.

Morrison & Stanwyck, 1999; USA Case Control N = 127

Population: 127 males and females with acute traumatic SCI with motor complete paraplegia or tetraplegia (C5-L2) admitted for acute rehabilitation. Ages range from 11-60 years (mean 28.81). Treatment: No treatment per se, but effect of Length of Stay on functional and medical status was examined by comparing those admitted in 1991 vs those in 1995. (LoS was significantly reduced in 1995, p<0.001). Outcome Measures: FIM (Individual scores for 11 items), Functional motor skills (5 skills, custom), Locomotor skill (5 skills, custom), incidence of medical complications (pressure sores, UTIs, pain), employment status all collected at discharge and 2 month post-discharge.

1.

2.

3.

4.

Yarkony et al. 1990; USA

Population: Traumatic SCI, 83% male, incomplete tetraplegia (30%), complete

1.

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Author Year; Country Research Design Total Sample Size Case Series N=1,382

Methods tetraplegia (27%), complete paraplegia (27%) and incomplete paraplegia (16%). Treatment: No treatment per se, but various outcomes associated with inpatient rehabilitation. Outcome Measures: LoS, Discharge destination.

Outcome days in 1974 to 68.1 days in 1986 (82.8 for tetraplegia and 54.3 for paraplegia). Days hospitalized prior to rehabilitation admission decreased over the years of the study from 56.5 days in 1974 to 33.4 days in 1986. 93% were discharged to a private residence 5% to nursing homes. Of 4,934 admitted within 24 hours post-injury, the proportion showing increases in ASIA were 10.3% (A), 45.2% (B), 55.9& (C), 7.3% (D) vs no change 89% (A), 50.3% (B), 41.5% (C), 90.5% (D) vs declined 4.5% (B), 2.6% (C), 2.0% (D). Some people continued to improve neurologically for up to 18 months after discharge, thereafter only rarely. From 1973-1990 the proportion of incomplete patients discharged increased from 40% to 55.2% whereas the proportion of complete patients decreased accordingly. Of 751 patients, average FIM gain was 37 (incomplete paraplegia, 36 (complete paraplegia), 34 (incomplete tetraplegia and 15 (complete tetraplegia). Total hospital LoS declined from 19741989. For tetraplegia it went from 149.6 to 92.4 days and for paraplegia from 122.3 to 74.9 days. 94.1% patients were discharged to a private residence, 4.0% to nursing homes, 1.5% to other hospitals. Of 1,306 followed 10 years, 98.0% resided in private residences. 51.2% of those with grade 9-11 completed high school within 5 years after injury and 11.6% of those with high school education completed a higher academic degree within 5 years. The proportion of people employed increased from 12.6% 2 years after injury to 38.3% 12 years after injury. In the second year post-discharge, 35.7% of people were rehospitalized and this declined to 25% at 12 years. Overall survival rate was 76.9%. During the first 12 years after injury, cumulative survival rate increased to 88% of what it would be in the absence of injury. Highest causes of death were pneumonia, pulmonary embolism and septicemia (due to pressure sores, respiratory infections or UTIs).

2.

3. Population: US Model Systems database, Traumatic SCI, Gender: 82.3% males, Age=30.514.9 years, Tetraplegia, Paraplegia, ASIA A-E. Treatment: No treatment per se, but various outcomes associated with inpatient acute care, rehabilitation and follow-up. Outcome Measures: ASIA, FIM, Total hospital LoS, Discharge destination, Education, Employment, Marital status, Readmission, Mortality. Collected at admission, discharge and in some cases annually thereafter. 1.

2.

3.

4. DeVivo et al. 1991; USA Case Series Initial N=13,763 Final N=13,763

5.

6.

7. 8. 9.

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Author Year; Country Research Design Total Sample Size

Methods Population: Multi-centre Italian prospective survey, Traumatic SCI, Gender: 80.1 % males, Age: mean=38.5, median=33.7 (1194) years, Tetraplegia, Paraplegia, ASIA AE. Treatment: No treatment per se, but various outcomes associated with inpatient acute care and rehabilitation. 7 participating centers provided integrated acute and rehabilitation care while 30 centres provided only rehabilitation care. Outcome Measures: ASIA (neurological status), various complication incidence, LoS, Bladder management method, Bowel status, Feeling of dependency, Discharge destination. Collected at admission and discharge. 1.

Outcome Neurological improvement was associated with ASIA B and C, shorter LoS, greater chance of seeing neurological improvement with earlier admission (3-30 days vs > 30 days, p<0.001). Presence of complications (especially pressure sores) on admission or during stay reduced likelihood of attaining neurological improvement. Multivariate analysis also showed incompleteness was independently predictive of improvement. Average rehabilitation LoS was 135.5 days (median 122 days). Longer LoS was associated with younger age, longer time from injury to admission, previous place of management, surgical management, tetraplegia, completeness, presence of complications at admission or during stay and marginally, admission to an integrated (vs Rehab only) centre. 81.9% of people were discharged to home (private residence). Increased likelihood of being discharged home were seen with paraplegia, bladder and bowel autonomy, absence of pressure sore on discharge, longer Length of Stay and marginally, younger age. Bladder autonomy was attained in 65% of patients. Reduced likelihood of achieving bladder autonomy was seen with tetraplegia, completeness, at least 1 complication, longer time from injury to admission, longer LoS. Reduced likelihood of feelings of dependency was associated with paraplegia, neurological improvement, discharge home, bladder and bowel autonomy, no pressure sores and incompleteness. Multivariate analysis also showed a shorter time between injury and admission was independently predictive of lower feelings of dependency. Mean acute care LoS was 45.635.9 days and median rehabilitation LoS was 83 days (3-317 days) (Mean = 99.6 days). Rehabilitation LoS was significantly longer for those with complete tetraplegia as compared to those with incomplete tetraplegia or incomplete/complete paraplegia (p<0.001).

2.

Pagliaccu et al. 2003; Italy Case Series Initial N=684 Final N=684

3.

4.

5.

Tooth et al. 2003; Australia Case SeriesInitial N=587 Final N=167

Population: Traumatic SCI, 77.8% males, Age=34.917.1 (13-90) years, incomplete tetraplegia (47.9%), complete tetraplegia (13.2%), incomplete paraplegia (16.2%) and complete paraplegia (22.8%). Treatment: No treatment per se, but various outcomes associated with admission to an integrated unit for acute and rehabilitation care. Sub-analysis focused on effects of level of impairment as

1.

2.

3 - 38

Author Year; Country Research Design Total Sample Size

Methods measured by neurological status and by the Australian National Sub-acute and Nonacute Patient Classification System (ANSNAP) on Length of Stay. Outcome Measures: LoS, FIM (motor, cognitive and total), Discharge destination. All collected at admission and discharge. 3.

Outcome Mean total FIM increased from 68.7 (admission) to 102.2 (discharge) due almost entirely to gains in motor FIM scores. Total FIM scores were lowest for those with complete tetraplegia and highest for those with incomplete paraplegia with significant differences found between the various neurological categories. Those with complete tetraplegia had the least change in FIM scores. 75.4% were discharged to a community dwelling and 10.8% to a transitional rehabilitation program. Those with greater impairment were less likely to be discharged to a community setting (i.e., 92.6% with incomplete paraplegia vs 72.7% with complete tetraplegia). AN-SNAP-predicted LoS was generally much shorter than actual LoS. 31% of people improved neurologically as indicated by Frankel, 66% remained unchanged, and 3% deteriorated. 23% initially complete became incomplete and 40% of those initially incomplete improved. Of those discharged normally, Total hospital LoS ranged from 113 (D, E paraplegia) to 282 (A, B tetraplegia) days with completeness having a greater impact on stay than level. 69.1% of people were discharged catheter-free with 14.9% (26.4% of females and 12.0% of males) discharged with an indwelling catheter. 77.9% were discharged with sterile urine. 77% could dress themselves independently at discharge (95% with complete paraplegia and 27% with complete tetraplegia). 79% could transfer independently at discharge. 40% with complete tetraplegia could drive with hand controls at discharge.

4.

5. Population: 209 males, 53 females, Frankel A-E, tetraplegia and paraplegia. Treatment: No treatment per se, but various outcomes associated with admission to an integrated unit for acute and rehabilitation care. Outcome Measures: Frankel scale, Mortality, Urinary tract management and pathogen status, physical independence (Walking, Dressing, Transfers, Driving, Finances), Total hospital LoS. All collected at admission and discharge. 1.

2.

Burke et al. 1985; Australia Case Series Initial N=352 Final N=262

3.

4.

5. 6. Population: 100 traumatic SCI in VA SCI Service, all males, tetraplegia (62) and paraplegia (38), incomplete (27) and complete (73), time post-injury: < 1 month (59), < 2 months (28), > 2 months (13). Treatment: No treatment per se, but various outcomes associated with inpatient rehabilitation. LoS = 3.3 (paraplegia) and 5.5 months (tetraplegia). Outcome Measures: Attainment of

Woolsey, 1985; USA Downs & Black score:n/a Case Series Initial N=100 Final N=96

No statistical analysis. 1. The higher the injury, the more likely an individual did not meet goals of selfcare and mobility. 2. 83/100 were discharged to their homes, 13 to nursing homes.

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Author Year; Country Research Design Total Sample Size

Methods functional goals by discharge or in some cases later follow-up. Population: Traumatic SCI from US Model Systems database, age categories from <21 to >51, 80.9% males, tetraplegia and paraplegia, incomplete and complete. Treatment: No treatment per se, but various outcomes associated with inpatient rehabilitation to predict LoS, rehospitalization, residence, days out of residence (QoL) and pressure sores. Outcome Measures: Rehabilitation LoS, rehospitalization, residence, days out of residence (QoL), pressure sore incidence and many predictor variables. Collected at admission, discharge and 1 year postinjury. 1.

Outcome

2.

Eastwood et al. 1999; USA Case Series Initial N=5,180 Final N=3,904

3.

4.

5.

Rehabilitation LoS was reduced from 74.1 days in 1990 to 60.8 days in 1997 (p<0.001). Acute care LoS was 21 days in 1990 and 20 days in 1991. Many variables significantly predicted increases in LoS at p<0.001 level of significance (in descending order): low admission FIM, earlier discharge year, complete tetraplegia, indwelling catheter, intermittent catheterization, condom catheter. Other variables included being African-American, having a high-school education or less, being married, being <21 years old and being retired or engaged in other nonpaid activities. Individuals initially discharged to a skilled nursing facility were more likely to return home by 1 year if they were young, had higher admission and discharge FIM scores, greater FIM change, if they were able to leave the institution more frequently and more likely to use IC vs indwelling catheter. Individuals were more likely to be rehospitalized if they had lower discharge FIM scores, complete paraplegia, having an indwelling catheter or using intermittent catheterization and with a shorter rehabilitation Length of Stay. Predictors of having pressure sores at year 1 were having complete paraplegia, not having incomplete tetraplegia, lower FIM scores and older age.

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CHAPTER FOUR
Community Reintegration Following Spinal Cord Injury
William C Miller, PhD, OT Susan J Forwell, PhD, OT(C), FCAOT Luc Noreau, PhD Lyn Jongbloed, PhD, OT Emily S Procter, BSc Caroline Abramson, MA

Key Points Attitudes towards disability may be positively influenced by having contact with an individual with SCI. For women with SCI, a supportive social network may positively influence their ability to participate in an occupation. The main barriers to community reintegration are barriers in the natural environment, transport, home services, health care and government policies. Assistive equipment, such as modified vans and environmental control units, may contribute to better reintegration. Consumer-directed personal assistance services and independent living programs may facilitate community reintegration; however, services are not always available. Successful community reintegration may promote productivity and physical and mental well-being. Employment specialists may aid in the process of job placement and work reintegration. There is a dearth of high quality research in this field therefore conclusions are based on observational research methodology. At discharge from a rehabilitation unit there is improvement in self care and mobility that is preserved for 1 year. Persons with tetraplegia who completed a driving training program were more likely to drive if younger in age, were able to perform transfers independently, had a lower level of SCI, drove prior to SCI and were employed and involved in sports. Employment following SCI was positively correlated to being male, and having more years since injury, younger age, the ability to drive a car, a higher education and a professional job prior to the SC. Having tetraplegia has a negative impact on gaining and maintaining employment. Employed persons with SCI had greater satisfaction with employment and finances while those unemployed had lower activity levels and higher economic dissatisfaction. Persons with disabilities experience discrimination and are less likely to obtain an interview or be hired. Facilitators for leisure involvement are social support, being healthy and being employed or attending school. Barriers are lack of physical ability, health concerns, cost, and lack of opportunity or interest. Participation in leisure occupations have a positive impact on adjustment to SCI, physical independence, mobility, hours in activities of daily living and social integration. Use of the GAMEWHEELS system showed physiological and motivational benefits for engaging in wheelchair exercise.

FES is a motivator to engage in exercise and standing, augments ability to do more things and enhances the sense of well-being. Drawbacks included lack of time to use the system and reluctance to wear all day. Average level of QOL after SCI is slightly lower than in people without disability but a substantial number of people with SCI report good or excellent QOL. Severity of injury and other diagnostic factors do not significantly impact QOL. There influence may become significant through restrictions in community integration/social participation. A limited amount of variation in QOL has been explained by quantitative research methods. Qualitative reports suggest that factors affecting QOL after SCI do not seem to differ from those impacting QOL in people without disability. They are related to life issues such as achieving meaningful social roles, having control over ones life and maintaining adequate access to the environment. Overall, there is a paucity of information from clinical trials on the most appropriate interventions favouring subjective QOL on people with SCI and their significant others. QOL can be indirectly enhanced through use of an exercise program designed to reduce pain and stress. Providing group therapy to spouses of individuals with SCI can decrease their symptoms of depression, anxiety, psychological distress with a potential impact on QOL.

Table of Contents
4.1 Introduction ......................................................................................................................4-1 4.2 Environment .....................................................................................................................4-2 4.2.1 Social Environment .........................................................................................................4-3 4.2.2 Other Environmental Factors ..........................................................................................4-4 4.2.2.1 Physical Environment ..................................................................................................4-5 4.2.2.2 Institutional Environment..............................................................................................4-7 4.2.3 Summary Environment ..............................................................................................4-10 4.3 Occupation .....................................................................................................................4-11 4.3.1 Daily Living Activities ....................................................................................................4-11 4.3.2 Work..............................................................................................................................4-13 4.3.3 Leisure and Recreation.................................................................................................4-17 4.4 Quality of Life .................................................................................................................4-20 4.4.1 QOL Definitions and Models .........................................................................................4-21 4.4.2 Exploring QOL after SCI from a Scientific Perspective .................................................4-22 4.4.3 Quantitative Measurement Approach of QOL Determinants.........................................4-22 4.4.4 Qualitative Research Methods to Understand QOL and its Determinants....................4-25 4.4.5 Trials Examining QOL as an Outcome .........................................................................4-25 4.4.6 Summary QOL ...........................................................................................................4-28 4.5 Summary Community Reintegration.........................................................................4-28 References..............................................................................................................................4-31

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Miller WC, Forwell SJ, Noreau L, Jongbloed L, Procter ES, Abramson C. (2006). Community Reintegration Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 4.1-4.37. www.icord.org/scire

Community Reintegration Following Spinal Cord Injury

4.1 Introduction There are more than 286,000 North Americans currently living with a spinal cord injury (SCI) and incidence rates suggest that approximately 1000 Canadians and 11,000 Americans survive a traumatic SCI each year (Canadian Paraplegics Association [CPA] 2000; National Spinal Cord Injury Database 2005). The majority of injuries occur in males (75%) and over 60% occur in individuals under the age of 50 (median age 35 years) (Dryden et al. 2003). Over the past 20 years, the life expectancies of individuals have improved vastly due to advances in medicine with life expectancy reaching to within 10% of the general population. As a result the number of individuals living with SCI is steadily increasing (CPA 2000). The journey from acute care through inpatient rehabilitation and back to community living following a spinal cord injury is one that is filled with challenges. Individuals with SCI face numerous secondary medical conditions including spacticity, pain, pressure ulcers, bladder infections, depression and anxiety, all of which can make daily tasks of living demanding and, at times, impossible. Beyond impairments the severity of disability for SCI survivors spans the dependence independence continuum. The usual simple self-care activities of dressing, bathing or getting around, for example, can be monumental. For instance, even individuals who are capable of dressing independently often dont because of the time (up to an hour) and effort required (Weingarden & Martin 1989). Walking with or without a walking aid(s) or use of a wheelchair for mobility can result in an increased energy cost that ranges from 9-74% depending on the floor surface (Waters & Lundsford 1985; Glasser et al. 1995) and the condition of the wheelchair (Sawatzky et al. 2005) compared typical bipedal walking. Returning home after rehabilitation is the most common goal of individuals with SCI. On average 75% of those who survive their trauma return to a private residence including over 60% with complete tetraplegia (CIHI 2006). Interestingly even the majority of individuals with high cervical lesions who are respiratory dependent can return to the community to live out the majority of their lives (Anzai et al. 2006). The direct cost of SCI to the Canadian healthcare system is estimated to be $750 million each year (Rick Hansen Foundation 2006) with an average $530,000 resulting from new injury for hospitalization alone (SmartRisk 1998). The overall economic burden of healthcare for idividuals with SCI in Canada is between $1.25 million and $25 million each during their lifetime depending on injury severity (Rick Hansen Foundation 2006). Sixty-two percent of individuals with SCI are employed prior to injury and only 10-14% return to work post injury (CIHI 2006). The lost contributions from these potentially employable individuals to the economy and tax base is substantial in addition to the loss of productivity by family caregivers who stop or reduce employment to take on this role. The environment surrounding the delivery of rehabilitation services has changed substantially over the decade. Cost containment strategies have emphasized efficiency and effectiveness resulting in reduced hospital length of stay (Rhoads et al. 1992; Holcomb 2000). As a result of

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the shorter hospitalization prior to discharge, people with spinal cord injuries have more complex needs, are more dependent and use more equipment than they did 10-15 years ago. An advantage associated with reduced length of stay is that the home environment usually promotes recovery. But the transition to the community needs to occur with appropriate supports to facilitate successful integration. The complex requirements of those with SCI and the fact that their disabilities are permanent, suggest there are wider gaps in supports which have profound impact for these people and their family members. Transition is a difficult process, made even more challenging by lack of/gaps in support. Successful transition from hospital to the community is influenced by a combination of factors at the individual, social/family, environmental and provincial policy levels (White & Holloway 1990; Pollack et al. 1992; Clandinin & Connelly 1994). The term community reintegration is used to refer to returning to the mainstream of family and community life, engaging in normal roles and responsibilities, actively contributing to ones social groups and of society as a whole (Dijkers 1998). Thus successful reintegration means resumption of those occupations that are important to each individual, such as taking care of oneself and participating in productive occupations of work and leisure. The environment, whether social, institutional, cultural or physical, can either create barriers or facilitate access to the community at large. Without exception successful reintegration can lead to improved quality of life (Anderson 2004). This chapter summarizes the results of selected studies to provide an overview of community reintegration post SCI. The chapter incorporates research about the person engaging in occupations and in context to the environment. The issues related to participation are described as self care, work and leisure while the environmental issues are primarily related to social aspects of study in SCI. This chapter closes with a review of evidence related to quality of life, an area of research that brings together the impact of participation and the environment relative to community reintegration. 4.2 Environment Rehabilitation assists persons with spinal cord injuries to regain independence and during this time, the primary focus is on the individual. Following discharge into the community, the emphasis shifts to people engaging, or attempting to engage, in activities that are important to them and this is strongly influenced by the environment. Broadly defined as the cultural, institutional, physical and social aspects that surround the individual (Law et al. 1997), the environment is the dynamic and inseparable situational context that shapes what a person chooses to do, how successful and how satisfied they are in doing it. The environment can support people or constrain them in their performance of activities and thus has a powerful impact on community re-integration. A review of studies on the impact of the environment on the community integration of those with spinal cord injuries indicates that the term environment is infrequently used. This is likely because the environment is a broad construct which includes the social environment as well as health and social policies. Many of the studies below focus on one aspect of the environment. In this chapter, studies related to the environment are divided into two areas: the social environment, and other environmental factors. The social environment includes the individuals network of friends and family members as well as societal attitudes about disability and spinal cord injury. Other environmental factors include adapted vans for transportation, environmental control units, government policies that influence the availability and accessibility of

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transportation and the availability of personal assistance in the home. The studies are summarized in Table 4.1 below. 4.2.1 Social Environment The social environment can be defined as social and cultural institutions and processes that influence the life of an individual. Family members and friends form the persons social network and provide him/her with social support and encouragement. People who experience a spinal cord injury have to deal with changes in their social network as well as changes in how they are perceived by society. Table 4.1 Social Environment
Author Year; Country Score Research Design Total Sample Size Methods Population: 45 non-disabled students (27 treatment, 18 control) and 18 disabled patients, mean age 27.4 years, 13 C2-C6 (quadriplegic), 5 T7-T12 (paraplegic); DOI 2wk - >1yr. Treatment: Information and social meetings between female students and individuals with SCI. The comparison group had information alone. After the activity the students had posttest measurements, and patients had a verbal posttest Outcome Measures: Attitude Toward Disabled Person (ATDP) scale, Student Comfort Level Scale (SCLS), Patient Comfort Level Scale (PCLS), Student Satisfaction Measurement Form (SSMF), Patient Satisfaction Measurement Form (PSMF), Patient Post-Measurement (PPM) form. Population: all female, age range 2561yrs, traumatic or non-traumatic, 4 cervical (tetraplegia) and 9 thoracic (paraplegia), DOI 2-11yrs. Treatment: Two interviews obtaining etiology info and current situation regarding social network and their ability to participate in occupation. Outcome Measures: perceptions of change in social network and participation. Outcome 1. There was a significant difference between the groups on their pre- and post-scores for the Attitude Toward Disabled Persons scale (F=7.36, p=.001) (treatment group (t=5.6, p<.001), comparison group (t=2.5, p<.05)). 2. Significant positive correlation between prior degree of contact and changes in ATDP scores of the treatment group (r=.49, p<.01). 3. 60%-100% of the patients found that the contact experience affected boredom, morale, social skills and a sense of attractiveness to the opposite sex from moderately to very much so. 4. 67% of the women students returned to see the patients whom they were originally introduced (~weekly). 1. The women described an emotional need for social support and practical social support in order to participate in occupation. 2. The women reported having developed new habits through close cooperation with members in the social network. 3. They felt that they had become more responsible for the development of their relations. Some relations improved, others deteriorated and several new ones were made with other persons with disabilities.

Haney & Rabin 1984; USA Downs & Black score=13 Post-test Initial N=45; Final N=18

Isaksson et al. 2005; Sweden Downs & Black score=8 Observational N=13

Discussion The social environment includes societal attitudes and values as well as networks of relationships. The studies above suggest that the social environment may be a powerful factor in community integration of people with SCI. The complex interactions between the social environment and those with spinal cord injuries are difficult to study. Popular culture tends to present people with disabilities as tragic victims and

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attitudes towards those with SCI may be biased by these stereotypes, by the lack of social recognition of people with SCI and other disabilities and by a lack of exposure to individuals with disabilities. Simply reading or watching a television program about a person with SCI may not be sufficient to change attitudes. In their experiment, Haney & Rabin (1984) demonstrate that individuals attitudes can be positively influenced by exposure to people with SCI. Developing a relationship with a person with SCI will likely reduce stigma by enabling people to recognize that those with SCI are similar to them and contribute to the opportunity for individuals with SCI to reintegrate into the community. Introducing people with spinal cord injuries to young people who have never been exposed to someone with a severe disability may also be a good strategy to influence societys invisible barrier, thereby promoting community re-integration. Isaksson et al. (2005) describe how practical and emotional support assisted women with SCI to participate in occupation. Although not evidenced in the literature, it seems plausible that individuals who have experienced a SCI may need support following the injury as they deal with changed relationships. Strategies that encourage them to be assertive in developing new relationships may be warranted. Conclusion There is Level 4 evidence from a single post-test study that having contact with a person who has an SCI has a significant impact on attitudes towards disability. There is Level 5 evidence based on a qualitative study that SCI results in a changed social network - some relationships are lost but others improve. Attitudes towards disability may be positively influenced by having contact with an individual with SCI. For women with SCI, a supportive social network may positively influence their ability to participate in an occupation.

4.2.2 Other Environmental Factors In this chapter, studies on other environmental factors focus on equipment and services that assist people with SCI to function in the community. These include adapted vans and environmental control units (physical environment, see Table 4.2) as well as follow-up services after discharge, independent living services, personal assistance services and support to reenter competitive employment (institutional environment, see Table 4.3). Government policies have a large impact on availability of equipment and services and on definitions of eligibility. Policies are purposeful sets of actions aimed to address identified social problems in a particular way. Policy may address structures (e.g. resources), processes (e.g. access, roles) and outcomes (e.g. justice, equity) (Boyce 2002).

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4.2.2.1 Physical Environment Table 4.2 Physical Environment

Author Year; Country Score Research Design Total Sample Size Methods Population: 2762 subjects (78%M, 22%F), DOI: 30% 1yr, 20% 5yrs, 15% 10yrs, 13% 15yrs, 13% 20yrs, 10% 25yrs. Treatment: Initial information from National Spinal Cord Injury database. Also inperson or telephone interviews. Outcome Measures: Craig Hospital Inventory of Environmental Factors - Short Form (CHIEF-SF), Craig Handicap Assessment and Reporting Technique (CHART-SF), FIM instrument, Satisfaction with Life Scale (SWLS). Outcome 1. The top five environmental barriers reported by the CHIEF scores were barriers in the natural environment, transportation, help at home, health care and government policy. 2. Significant predictors of higher CHIEF total scores (i.e. more perceived environmental barriers): mid age range at time of injury, female, minority ethnicity, more recent injury, more severe injury, higher degree of activity limitations (p<0.05 for all). 3. Significant predictors of low CHART total scores (i.e. low participation): older age at time of injury, minority ethnicity, less education, being unmarried at injury, higher level of injury, injury by falling or violence and low FIM scores. 4. Significant predictors of low life satisfaction: more recent injury, high scores of physical/structural, services/assistance and attitudes/support (CHIEF) and low scores on mobility, occupation and social integration (CHART). Equipment Utilization 1. No significant changes over time in use of power wheelchairs, house hold lifts, adaptive bathroom equipment or vans. Participation 2. Hours/day out of bed and # of days out of the house remained constant. 3. Hours spent reading and listening to radio were significantly higher in phase 1 compared to phase 2 (p=0.02). 4. Participation was correlated to age older individuals spent fewer hours out of bed and out of the house compared to younger individuals and participated in fewer leisure activities at home (phase 3) (p<0.01). Self Esteem and QOL 5. 94% of participants stated they were glad to be alive. Access to Equipment 6. Having a van with a lift caused increased time spent out of bed (p<0.02) and correlated to increased hours spent out of the house (p<0.01) in phases 2 and 3.

Whiteneck et al. 2004; USA Downs & Black=12 Observational N=2762

Population: from initial sample, n=58 completed all three phases of testing mean age 43yrs, 40 C1-C4, 11 C3, 6 C2, 1 C1, mean DOI 18.5yrs. Treatment: In-person interviews and chart review. Outcome Measures: High Quadriplegia Questionnaire (HQQ), Level of Free Time Activities Scale, and Rosenberg Self Esteem Scale (RSE). Bushnik 2002; USA Downs & Black score=11 Observational N=168

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Author Year; Country Score Research Design Total Sample Size

Methods Population: mean age 24.2yrs, 89.7% males, injuries C6 and above, tetraplegia. Treatment: Structured interview. Outcome Measures: Environmental Control Unit (ECU) use.

Outcome 1. 93% of the subjects perceived the ECU as increasing their independence. 2. Operation of the telephone was indicated as the most important function (61%), followed by TV (21%). 3. Of the subjects who worked or went to school, only two used their ECUs for those purposes. 4. Subjects felt comfortable for longer periods without attendant care when the ECU was available. 5. Some of the subjects felt that they had received inadequate training (30%) and that their attendants lacked understanding of the ECU (36%).

McDonald et al. 1989; USA Downs & Black score=5 Observational N=29

Discussion People with SCI have reduced physical abilities and consequently require specific equipment to function in their environment. The studies above illustrate the following associations: a) various demographic characteristics and perceived environmental barriers, b) having a van with a lift and increased time out of bed and out of the house, and c) the increased control of telephones and televisions with the use of environmental control units; however, the study designs limit the conclusions that can be drawn from these associations. It should be noted that obtaining equipment such as environmental control units and vans requires considerable personal financial means and/or public support. The support team should investigate an individuals eligibility for various sources of income, services and equipment. Conclusion There is very limited (Level 5) evidence that people with SCI consider the following factors as the main barriers to community integrations: barriers in the natural environment, transport, help at home, health care and government policy. There is very limited (level 5) evidence from two observational studies that assistive equipment may promote increased activity and participation in and outside of the home. The main barriers to community reintegration are barriers in the natural environment, transport, home services, health care and government policies. Assistive equipment, such as modified vans and environmental control units, may contribute to better reintegration.

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4.2.2.2 Institutional Environment Table 4.3 Institutional Environment

Author Year; Country Score Research Design Total Sample Size Methods Population: sex, age, injury location and etiology-matched groups. Treatment: Randomization into a community based or hospital based SCI rehabilitation program. (Hospital = physiatrist and physician, assessments at 6wks and 6-12mo post-injury; Community = physician, with rehabilitation nurse to lead assessment/follow-up). Outcome Measures: Comparison of physical and psychosocial variables at one year post-discharge from the Rehab Centre. Outcome Physical Well Being 1. Bladder function: Community based n=12 (residual urine 100cc's n=4 sterile urine n=4 requires catheter n=1) Hospital based n=11 (residual urine 100cc's n=5; sterile urine n=4; requires catheter n=3) 2. Bowel function: more use of enemas by the hospital based program. 3. Hospital Readmissions: n=7 community; n=13 hospital. 4. ADLs: similar between groups. Psychological Functioning 1. Professional emotional support: n=5 community; n=2 hospital. 2. Major emotional crisis: n=3 community; n=1 hospital. 3. Good adjustment: n=8 community; n=6 hospital. Social Vocational Functioning 1. Both groups have similar integration, spare more extensive use of health agency and vocational support by the community group. 1. Participants with TBI were significantly more productive than participants with SCI (74.5% of TBI vs. 28.9% of SCI). 2. 70% of SCI participants reported receiving weekly assistance compared to less than 15% of TBI participants. 3. Productivity status was correlated to the subjective experience of community integration (r=-.4013, p<.0001). 1. Changed personal relationships owing to lack of access to primary care services or durable medical equipment. And greater need to rely on others due to this. 2. Depression, frustration, stress, and devaluation were frequently reported, but 4x as much by women (p=0.012). 3. A general deterioration in health was the most frequent complaint regarding physical health. 1. An initial MANOVA showed significant differences (Wilk's Lamda=.32; p<.01) in outcomes between the 2 groups. 2. In terms of overall health, those in the self managed care group had significantly higher scores on Rand-36 (i.e. perceived better health). 3. Fewer persons in the self managed

Dinsdale et al. 1981; Canada PEDro=1 RCT N=23

Harker et al. 2002; Canada Downs & Black score=13 Observational N=487

Neri & Kroll 2003; USA Downs & Black score=12 Observational N=30

Population: 440 SCI, mean age 39.7yrs, 46.5% paraplegia, 53.6% tetraplegia, 89.7% incomplete, 10.4% % complete, mean DOI 27.4yrs. (Demographics for TBI patients not reported here, n=47.) Treatment: mailed surveys (SCI patients), in-person interviews (TBI patients). Outcome Measures: Independent living outcomes (DeJong & Hughes 1982), Reintegration to Normal Living Index, environmental support. Population: mean age 44yrs, 16 women and 14 men, cerebral palsy, multiple sclerosis and SCI (10 in each category). Treatment: semi-structured, in-depth telephone interviews. Outcome Measures: perceptions of barriers, access, participation, experience.

Prince et al. 1995; USA Downs & Black score=12 Observational N=71

Population: Agency-Provided Model (n=29, mean age=35.3 yrs, tetraplegia C1C4, complete, mean 7.9yrs post-injury), Self-Managed Model ( n=42, mean age 37.1 yrs, tetraplegia C1-C4, complete, mean 11.5yrs post-injury). Treatment: Telphone interview. Outcome Measures: Personal Assistance

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Author Year; Country Score Research Design Total Sample Size

Methods Satisfaction Index (PASI), Personal Independence Profile (PIP), Craig Handicap Reporting Technique (CHART), Rand-36, Life Satisfaction Index-Acute (LSI-A). Population: n=24 (intervention), mean age: 38.6yrs, 14% ASIA D, 35% paraplegia ASIA A,B,C, 51% tetraplegia ASIA A,B,C; n=56 (control) mean age 34.4yrs. Treatment: Questionnaires. Outcome Measures: The Independent Living Services Evaluation Questionnaire, Craig Handicap Reporting Technique (CHART), Satisfaction With Life Scale (SWLS), Personal Independence Profile (PIP), Institutional and CIL Surveys.

Outcome group reported hospitalization during the past 6 mos (19% vs. 31%). 4. The self-managed care group perceived having more control over their day-to-day lives and personal care (from mean PIP scores, p<0.01). Independent Living Services (ILS) Received and Reported Needs 1. Both groups reported a similar number of unmet and met needs. 2. Participants of the program used support services more frequently and were more satisfied compared to program non-participants and (p<0.01). 3. Program participants were more likely to report assistance from government benefits, vocational services and legal advocacy while non participants were more likely to report assistance from insurance sponsors and from personal attendants. 4. The most commonly reported unmet needs while using ILS were legal rights, recreation, and obtaining government benefits. Program Intervention 1. Participants and non-participants levels of control, QOL and societal participation along the five domains of CHART were not significantly different. 2. PIP - personal independence was significantly lower for those who received housing services or had unmet needs compared to those without housing or unmet needs (p<0.005). Those without needs for legal services had higher PIP, QOL and CHART scores (p<0.01). 3. Overall there was no benefit noted for the ILS follow-up program. 1. PAS were more likely to be "extremely" or "very" satisfied than the WL grp (non-consumer directed) on the 6 individual PASI items. 2. 85% of PAS and 59.4% of WL were extremely or very satisfied with the cost of PA. 3. 88.3% of PAS and 46.9% of WL were extremely or very satisfied with the amount of control they had over the choice of PA. 4. 93.3% of PAS and 59.4% of WL were satisfied with the amount of authority they had to direct their PAs. 5. 53.3% of PAS and 31.3% of WL were extremely or very satisfied with the availability of assistance in an emergency.

Forchheimer & Tate 2004; USA Downs & Black score=10 Case Series N=81

Population: n=92 (n=60 consumerdirected PA, n=32 on waiting list), mean age: 41.7yrs (PAS group), 43.7yrs (WL group), 51 males and 41 females. Treatment: Mail or telephone survey. Outcome Measures: Personal Assistance Satisfaction Index (PASI). Beatty et al. 1998; USA Downs & Black score=8 Observational N=92

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Author Year; Country Score Research Design Total Sample Size

Methods Population: 2 males, 1 female, age range 38-53yrs, traumatic SCI, C5-C7 tetraplegics, DOI range 11-34 yrs. Treatment: Employment specialists lead job development and restructuring ventures, involving the SCI individual and identified potential businesses. Outcome Measures: the effect of supported employment and assistive technology on job placement. Population: Individuals with cerebral palsy, multiple sclerosis, or SCI. Treatment: Survey. Outcome Measures: rates of access to assistive equipment and medical rehabilitation services, health plan type.

Outcome 1. Two individuals required only low technological accommodations (e.g. learning a computerized cash and book database system, electronic letter opener) to support their return to work. 2. One individual required more intense support, as well as more conscious workplace cooperation, prior to independent work. An employment specialist stayed on the job site full-time for ~3mos. 1. 56.5% and 39.6% indicated that they needed assistive equipment in the last 12 and 3 months, respectively. 2. Of those who indicated a need in each area, 28.4% and 52.2% did not receive assistive equipment and rehabilitation services, respectively, each time they were needed. 1. A positive relationship was found between the adequacy of personal assistance and the ability of individuals disabled primarily by stroke, SCI, or traumatic brain injury (TBI) to maintain good physical & mental health. Inadequate PA led to extended hospital stays, threats to safety, poor nutrition, & poor personal hygiene. 2. Reliance on family alone for assistance was considered inadequate and common adverse effects were burnout, family role changes & economic strain. 3. Persons with the best health combined assistance by relatives & unrelated persons.

Inge et al. 1998; USA Downs & Black score=8 Observational N=3

Bingham & Beatty 2003; USA Downs & Black score=7 Observational N=500

Nosek 1993; USA Downs & Black score=4 Observational N=41

Population: 7 physicians, 8 PTs, 7 OTs, 9 social workers, and 10 nurses in 5 rehab hospitals. Treatment: Standardized, open-ended, taped interviews by trained interviewers who were also users of PA services. Outcome Measures: views and experience of/with PA services.

Discussion The above studies illustrate aspects of the institutional environment faced by those with SCI independent living services, consumer and non-consumer directed personal assistance services, financial aid services and job placement. The health care system is of primary importance during the acute care and rehabilitation phases of treatment of people with SCI. Once these people have been discharged and are in the community, other factors and resources assume considerable importance. People want assistance with self-care at home, they desire the ability to move around freely in their communities, and they want to work. As noted previously, it can be a considerable financial burden to access personal assistance services and government or insurance support is not always obvious or available.

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Conclusion There is moderate (Level 2) evidence from one RCT study that a community based system for post discharge monitoring in no more effective in terms of community integration than a hospital based system. There is very limited (Level 5) evidence from one observational study that productivity was correlated to the individuals subjective experience of community reintegration. There is very limited (Level 5) evidence from two observational studies that a positive relationship exists between the adequacy of personal assistance and the physical and mental health of those with SCI. There is very limited (Level 5) evidence from two observational studies that people who receive consumer directed personal assistance services are more satisfied with services than those who receive services that are not consumer directed. There is limited (Level 4) evidence from one case series that an independent living follow-up program is more beneficial than no program. There is very limited (Level 5) evidence from one observational study that supported employment assists job placement of some people with SCI. There is very limited (Level 5) evidence from one observational study that individuals with disabilities did not receive adequate equipment or services on more than half of the occasions in which they were requested. Consumer-directed personal assistance services and independent living programs may facilitate community reintegration; however, services are not always available. Successful community reintegration may promote productivity and physical and mental wellbeing. Employment specialists may aid in the process of job placement and work reintegration. There is a dearth of high quality research in this field therefore conclusions are based on observational research methodology.

4.2.3 Summary Environment There are limitations to examining the impact of the environment on community reintegration of persons with spinal cord injuries. The environment is not easily manipulated as an independent variable. Consequently, many of the studies are not experimental in design. They describe the impact of social policies or access to health care on a sample and may use regression analysis to assess which factors are the most significant influences on an outcome. Overall, the evidence provided in most of the above studies is insufficient to warrant firm conclusions in this field of study.

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4.3 Occupation Occupation, meaning the way and means by which people occupy themselves in meaningful activities, may refer to time limited activities such as preparing meals, enormous undertakings such as years of training to compete in the Olympics, or monumental milestones such as taking the first steps after a SCI or returning to work after months of retraining. Because occupation refers to a broad range of activities that occupy daily lives it is useful to have a system to organize such activities into occupational groupings. Occupations may be categorized by the routines or sequences, the physical environment(s) in which they are completed, the social network involved (or not, as the case may be) or the nature of the activities. For the purposes of community integration for persons with SCI, which involves the transition to daily occupations in ones relevant community, the nature or type of activity as typically described in the literature is used in this chapter. As such, the following occupational groupings are described: activities of daily living, work, and leisure. The literature that examines interventions that enhance the experience of activities of daily living tasks, work and leisure is in its infancy and is limited to evidence level 4 and 5 studies. It is these preliminary studies that are summarized here. 4.3.1 Daily Living Activities Daily living activities refers to tasks completed to take care of oneself and the surroundings and includes eating, dressing, bathing, grooming, dental hygiene, meal preparation and maintaining the home. Also grouped in this category is function related to mobility and includes standing, transfers, walking and driving. Often it is these very basic occupations that are interrupted with SCI, though following rehabilitation, there is improved performance in self care and mobility skills (Lysack et al. 2001). In the community, the use of standing frames showed several benefits and few drawbacks (Dunn et al. 1998) and a driver-training program was successful for persons with tetraplegia who had driven prior to SCI, had a lower level of SCI, were able to perform bed, tub and toilet transfers and dressed their lower extremity (Kiyono et al. 2001). In society, ability for adults to perform personal self care functions is a basic and assumed independent skill set. The impact of traumatic SCI can dramatically alter that independence and change subjective evaluation of oneself and future possibilities. Lysack and colleagues (2001) show that with rehabilitation most function, though modified, can be restored. Table 4.4 Daily Living Activities
Author Year; Country Score Research Design Total Sample Size Methods Population: 21 complete, 34 incomplete, mean age at admit: 38.8 yrs, at discharge: 37.7 yrs, at f/u: 43.2 yrs. Intervention: 3 structured questionnaires administered by an OT assistant at admission, at discharge, and at 1 year post injury. Outcome Measures: Functional Independence measure (FIM), self-care questionnaires (focused on eating, bathing, dressing, and grooming). 1. Outcome Self Care Importance: at admission 76% eating independence was of "upmost importance", 84% at discharge & 92% at 12 mo f/u. Bathing independently, dressing, & grooming followed a similar trend. Self Care Expectations- at admission 70% of pts expected to eat "all by themselves without any help at all", 15% had goal of independence & 15% thought they would need some personal assistance. Actual Self Care Performance subjects underestimated their skills at admission for eating, bathing, dressing (p<0.001) & grooming (p<0.003), but showed improvements in mean FIM

Lysack et al. 2001; USA Downs & Black score=17 Observational Cross-sectional Design N=55

2.

3.

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome motor scores from 22.2 to 47.6 (p<0.0005). Subjects tended to rank skills that they did well with more importance that other life tasks. This was apparent for all skills, but was significant only for grooming & dressing (p<0.02 and p<0.05, respectively).

4.

Discussion The data suggests that over 90% of persons with SCI are eating and feeding themselves independently (Lysack et al. 2001). This prospective study (n=55) that included three data collection points (admission to a rehabilitation unit, discharge and 1-year follow-up) showed that at discharge (n=45) significant gains were demonstrated in the performance of the daily activities specifically related to personal self care and mobility and that this function was preserved at the 1-year follow-up (n=25). Regrettably, there are no intervention trials for other daily living tasks such as bathing, maintaining the home, or meal preparation. Conclusion There is level 5 evidence (1 cross sectional study) that suggests that at discharge from a rehabilitation unit there is improvement in self care and mobility that is preserved for 1 year. At discharge from a rehabilitation unit there is improvement in self care and mobility that is preserved for 1 year.

Driving is one of the key elements of community reintegration. It provides access to the larger community and is highly valued. The consequences of SCI can complicate the level of independence related to driving. Table 4.5 Driver Training
Author Year; Country Score Research Design Total Sample Size Methods Population: mean age 34.5 yrs; all complete injuries. Intervention: Subjects completed the Driver training program at Nagano Rehabiliation Centre. Driving ability was subdivided into three categories independant, assisted, or unable. Outcome Measures: car driving status, vocational and sport questions. 1. 2. 3. 4. Outcome As SCI level and age increased, the ability to drive decreased. 20/33 subjects that were able to drive after training had driven before their SCI. Toilet transfer was most correlated with driving ability. 27/31 (87%) of subjects who could transfer from the toilet independently were able to drive independently (p<0.0001).

Kiyono et al. 2001; Japan Downs & Black score=13 Observational N=62

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Discussion Kiyono et al. (2001) showed that of the 62 patients with tetraplegia involved in a driver-training program 33 were able to drive following the training. Ability to drive was positively related to independence in activities of daily living (p<.001), specifically toilet, bed and tub transfers as well as lower extremity dressing. It was also related to lower level of SCI, a younger age, driving a car prior to SCI, being employed and active participation in sports. Conclusion There is level 5 evidence (1 observational study) suggesting that following a driving training program, persons with tetraplegia who drove tended to be of younger age, have a lower level of SCI, drove prior to injury, were able to perform independent transfers, employed and involved in sports.

Persons with tetraplegia most likely to drive following a driver training program were younger in age, were able to perform transfers independently, had a lower level of SCI, drove prior to SCI and were employed and involved in sports.

4.3.2 Work Being employed or having productive and meaningful responsibility is an important and critical aspect for adults in society, despite disability. It is, however, acknowledged that for persons with SCI certain work is better suited for individuals with injuries at different lesions and is related to several factors. The literature related to employment for persons with SCI primarily focuses on factors contributing to obtaining, returning to, and staying employed as well as adjustment after SCI. There is general consensus in level 5 evidence cross-sectional studies that a number of factors are associated with or predictive of post-injury employment. Table 4.6 provides a summary of these factors as well as the positive or negative direction of the impact. Table 4.6 Factors Contributing to Employment Among Individuals with SCI
Factors identified to have a relationship with employment among SCI Demographic Characteristics Male gender Impact ( + positive; - negative) + + + + (more yrs) + (more yrs) Study (N) 234 259 277 195 259 301 195 231 418 192 114 170 5925 154 Study reference Tomassen et al. 2000 Krause 2003 Ville & Ravaud 1996 Anderson & Vogel 2002 Krause 2003 Krause 1996 Anderson & Vogel 2002 Krause & Anson 1996 Noreau et al. 1999 Young & Murphy 2002 Castle 1994 Tate et al. 1993 Meade et al. 2004 Crewe & Krause 1990

Level of injury (cervical or tetraplegia)

Years since injury

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Factors identified to have a relationship with employment among SCI

Impact ( + positive; - negative)

Study (N)

Study reference Tate et al. 1993 Krause & Anson 1996 Tomassen et al. 2000 Krause & Anson 1996 Tate et al. 1993 Noreau et al. 1999 Ville & Ravaud 1996 Tomassen et al. 2000 Krause 2003 Krause & Anson 1996 MacKenzie et al. 1986 Goldberg & Freed 1982 Ville & Ravaud 1996 Noreau et al. 1999 Castle 1994 Tomassen et al. 2000 Krause 2003 Goldberg & Freed 1982 MacKenzie et al. 1986 Tate et al. 1993 Meade et al. 2004 Krause 2003 Tomassen et al. 2000 Krause 2003 Ville & Ravaud 1996 Young & Murphy 2002 Anderson & Vogel 2002 Tomassen et al. 2000 Anderson & Vogel 2002 Anderson & Vogel 2002 Noreau et al. 1999 Castle 1994 Anderson & Vogel 2002 Krause & Anson. 1996 Krause 1996 Anderson & Vogel 2002 MacKenzie et al. 1986 Krause & Anson 1997 Goldberg & Freed 1982 Goldberg & Freed 1982 Krause & Anson. 1996 Yavuzer & Ergin 2002 McNeal et al. 1999

Age Age at time of injury

Higher education pre-injury

Education & training post injury Higher number of children Higher income Private insurance Racial & ethnic minorities Ability to return to pre-injury job1 Pre-injury work of light to moderate physical intensity Professional job-type pre-injury1 Independent living Independence in daily activities Ability to drive independently Health issues (UTIs, spasticity, pressure sores etc.) Lower activity level Use of illicit drugs Presence of social network Quality of Life with SCI Motivation to work Includes vocation and/or education goals In-accessibility of the workplace Job accommodations

+ (more yrs) 170 + (less yrs) 301 + (ages 36-45yrs) 234 + (younger) 301 + (younger) 170 + (younger) 418 + (before 15 yr) 277 + 234 + 259 + 301 + 266 + 24 + 277 + 418 + 114 + 234 + 259 + 24 + 301 + 170 5925 Pre-injury job factors + 259 234 + + + + + + + + + + + + + 259 277 192 Personal issues 195 234 195 195 418 114 195 231 256 195 Psycho-social factors 301 362 24 Discharge planning from hospital/rehab 24 Workplace issues 231 70 96 School participation and performance among adolescents 53 53 53

+ +

Curriculum changes/ modifications Human assistance In-accessibility of school

+ + -

Dudgeon et al. 1997 Dudgeon et al. 1997 Dudgeon et al. 1997

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Factors identified to have a relationship with employment among SCI Lack of transportation

Impact ( + positive; - negative)

Study (N)

Study reference Dudgeon et al. 1997 Dudgeon et al. 1997 Dudgeon et al. 1997

- (extra-curricular 53 participation) - (extra-curricular Health concerns 53 participation) Adaptive writing techniques + 53 1 Also associated with a much shorter interval between injury and return to work.

Discussion Several factors emerged in repeated studies to have significant impact on the employment of persons with SCI. In 4 studies, the factor of being male was shown to have a significant impact, of which 3 studies suggested it was positive (across studies total n = 770) and one study (n = 195) indicated it had a negative impact. There are 4 studies that suggest years since injury had an impact on employment with 3 of these showing that more years had a positive impact (total n = 6249 across studies) and one study (n = 301) indicated that fewer years post-injury was positively related. In 8 studies, having tetraplegia (total n = 1880) was found to have a negative impact, while higher education prior to the SCI (total n = 1893 across studies) had a positive impact on employment. Employment is also positively related to the factors of younger age (3 studies, total n = 705), professional pre-injury job (3 studies, total n = 728) and ability to drive a car (3 studies, total n = 727). Conclusion There are several level 5 evidence studies that show the following factors have a positive impact on employment: male, more years since injury, younger age, car driving ability, higher education and professional job prior to the SCI. Many studies also show that having tetraplegia has a negative impact on gaining and maintaining employment. Being male, more years since injury, younger age, the ability to drive a car and having a higher education and a professional job prior to the SCI positively impact employment. Having tetraplegia has a negative impact on gaining and maintaining employment.

In terms of adjustment to SCI, being employed significantly facilitates the coping and adjustment to disability. Table 4.7 Employment
Author Year; Country Score Research Design Total Sample Size Methods Population: n=559 highly qualified disabled applications, n=557 highly qualified AB applications, n=556 modestly qualified disabled applicants n=556, modestly qualified AB applicants. Intervention: Fictional resumes of varying qualities were randomly assigned to be sent to one of four companies in Outcome Effect of Qualifications 1. Across all company sizes, disabled persons had less chance of obtaining an interview irrespective of their qualifications (p<0.01). 2. Highly qualified disabled applicants had fewer favorable

Ravaud et al. 1992; France PEDro=2 RCT N=2228

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Author Year; Country Score Research Design Total Sample Size

Methods France. Outcome Measures: level of response to application (negative or positive), effect of qualification, effect of company size.

Outcome

Krause 1992; USA Downs & Black score=11 Observational N=135

responses (2.60%) compared to highly qualified AB applicants (4.54%). 3. Modestly qualified disabled applicants had fewer favorable responses (1.24%) compared to modestly qualified AB applicants (3.95%). Effect of Company Size 4. The larger the company (>500), the greater the chance of discrimination against highly qualified disabled applicants (p<0.01). 5. For modestly qualified applicants, discrimination was more visible in smaller companies (200-499 employees; p<0.001) compared to larger ones (>500 employees; p<0.06). Population: age at beginning of study: 1. During 15 yrs there was an increase 45.6 yrs, mean DOI: 24.4 yrs, 82% men, in married individuals (1974=31.9%, 68% had tetraplegia, 32% had paraplegia. 1985=48.9%) and a decrease in the Sample size n=154 (in 1985) and n=135 number of single people (in 1992 at follow-up). (1974=60.7%, 1989=37.8%). Intervention: Completion of a 2. More participants were working in questionnaire. This was the 15-year 1989 (50%) than in 1974 (44%). follow-up from phase one of an earlier 3. There were significant increases in study. years of education (p<0.001), sitting Outcome Measures: Life Situation tolerance (p<0.05), satisfaction with Questionnaire (LSQ). employment (p<0.05) and satisfaction with finances (p<0.05). 4. There were significant correlations between the two times for interpersonal (r=+.31) and activity (+.45) items. Population: age at time 2 40.57.3yrs, mean DOI 205.3yrs. Intervention: Survey at time 1 and time 2 (11 year follow-up). Outcome Measures: Life Situation Questionnaire (LSQ). 1. Those who made positive transitions (POS) into work were significantly younger (p<0.05) and had a shorter DOI (p<0.01). POS and employed individuals had significantly higher education than those chronically unemployed (p<0.001). Unemployed and POS groups had a significantly higher proportion of quadriplegics (p<0.05) and chronically unemployed individuals had lower activity scores compared to the employed groups (p<0.001). POS group had significantly lower interpersonal dissatisfaction compared to the other grps (p<0.05).

2.

Krause 1996; USA Downs & Black score=15 Observational N=142

3.

4.

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Discussion A longitudinal study showed, that over a 15-year period post-SCI (n=135), significant gains were realized in work, satisfaction, a reduction in the need for medical services, and improved sitting tolerance (Krause 1992). The greatest gains were related to employment where significant improvements were demonstrated in satisfaction with employment and finances and more individuals were employed (Krause 1992). In another longitudinal study, Krause (1996) showed that after 11 years (n=142) persons with SCI who were unemployed had significantly lower activity levels (F(3, 130)=5.0, p<.01) and high levels of economic dissatisfaction (F(3,118)=3.8, p<.05) than those with SCI who were employed. In addition, having a disability was a significant discriminating factor for gaining employment. In a study completed in France, Ravaud and colleagues (1992) reported that persons with disabilities were significantly less likely to obtain an interview or be hired than their able-bodied counterparts (p<.01). Larger companies were more likely to discriminate against highly qualified individuals, while modest qualifications were less discriminated against in medium and large companies though remained a source of discrimination in small companies. Conclusion There are level 5 evidence studies (2 longitudinal) that show that those persons with SCI that were employed 15 years post-SCI had greater satisfaction with employment and finances while those who were unemployed 11 years post-SCI had lower activity levels and greater economic dissatisfaction. There is level 5 evidence (one cross-sectional study) that persons with disabilities in France experience discrimination related to employment, as they are less likely to obtain an interview or be hired. Employed persons with SCI had greater satisfaction with employment and finances while those unemployed had lower activity levels and higher economic dissatisfaction. Persons with disabilities experience discrimination and are less likely to obtain an interview or be hired. 4.3.3 Leisure and Recreation In the face of catastrophic events such as a SCI, adjustment generally involves engaging in the necessary or important tasks to sustain life. Typically these activities consume available time with leisure and recreational occupations relegated to ones memory. This, however, is unfortunate as the enjoyment and satisfaction of participating in leisure occupations have positive effects on other aspects of life and should not be disregarded. The studies in leisure and recreation among persons with SCI primarily use cross-sectional research designs. Collectively this research investigates the influence of engaging in leisure and its impact on adjustment to SCI, community integration, and employment. Table 4.8 provides a summary of these studies and the factors related to leisure and recreational engagement of persons with SCI.

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Table 4.8 Factors Relating to Leisure Among Individuals with SCI

Factors identified to have a relationship with leisure among SCI Involvement in leisure activities Impact ( + positive; - negative) + adjustment to SCI + physical independence + mobility 1 + occupation + social integration Characteristics of leisure occupations Leisure Diversity Leisure Intensity Facilitators to leisure participation Social support system Being healthy Being employed or attending school Expectations for leisure participation Adventure activities Crafts Intellectual activities Perceived Barriers to Leisure Participation Health concerns Cost of program Lack of leisure opportunities in the community Intrinsic (Intrapersonal)2 Physical ability3 + subjective well-being + subjective well-being + + - if lack of support + + Study N 178 48 Study reference Loy et al. 2003 Hanson et al. 2001

178 178 178 14 72 178 48

Loy et al. 2003 Loy et al. 2003 Loy et al. 2003 Dattilo et al. 1998 Scelza 2005 Loy et al. 2003 Hanson et al. 2001

- (tetraplegia) -

388

Kennedy & Smith 1990

72 72 14 72 14 72

Scelza 2005 Scelza 2005 Dattilo et al. 1998 Scelza 2005 Dattilo et al. 1998 Scelza 2005

Having a SCI Engaging in sporting activities 45 Tasiemski et al. 2000 Engaging in recreation activities 45 Tasiemski et al. 2000 1 Items include # of hours per week to engage in homemaking, working, school, self improvement, maintenance, recreation and volunteering. 2 Refers to lack of motivation, energy and interest in exercise. 3 Refers to lack or loss of physical balance, mobility and strength.

Discussion Studies suggest that the primary facilitator for leisure involvement is a supportive social network (3 studies, total n = 264). Other facilitators are being healthy and being employed or attending school. The main barrier to leisure participation was lack of physical ability (2 studies, total n= 86) with other barriers noted as health concerns, cost, and lack of opportunity or interest. Participation in leisure occupations were shown to have a positive impact on adjustment to SCI, physical independence, mobility, hours in activities of daily living and social integration. Conclusion Level 5 evidence (several cross-sectional studies) suggests that facilitators for leisure involvement are social support, being healthy and being employed or attending school.

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Facilitators for leisure involvement are social support, being healthy and being employed or attending school. Barriers are lack of physical ability, health concerns, cost, and lack of opportunity or interest. Participation in leisure occupations have a positive impact on adjustment to SCI, physical independence, mobility, hours in activities of daily living and social integration. Limited research has also been reported on the use of 2 technologies to support the engagement in leisure activities. These are a computer video game called GAMEWHEELS and functional electrical stimulation (FES). Each of these is described in turn. Table 4.9 Wheelchair Exercise
Author Year; Country Score Research Design Total Sample Size Methods Population: 10 males, 5 females, age 34.7yrs (male) and 39.6yrs (female), all incomplete injuries at C6-L2. Intervention: Submaximal oxygen consumption test with and without simultaneous use of the GAME system (a video game device). The order in which the trials were administered was randomized. Outcome Measures: HR, ventilation rate (Ve), VO2. 1. Outcome Mean Ve was significantly higher for the GAME group at the 16 and 20 min time points (during exercise); however, there were no significant differences in Ve max values at these time points. Mean VO2 was significantly higher for the GAME group at the 16 and 20 min time points (during exercise). There were significant differences in Ve and VO2 between conditions during transition points (warm-up to exercise).

OConnor et al. 2001; USA Downs & Black score=12 Prospective Controlled Trial N=15

2.

3.

Discussion A study (n = 15) investigated the effects of the GAMEWHEELS system (an interface between a portable roller system and a computer that is controlled by propulsion of a wheelchairs wheels on the roller) on physiological responses during and motivators for engaging in fitness and exercise activities when wheeling a wheelchair. Results suggest that metabolic activity was greater and significantly different (specifically, oxygen consumption (p<.05) and ventilation rate (p<.05) when exercising using the GAMEWHEELS than when not. There was no difference in heart rate between the two conditions. The system also allowed individuals to achieve their target exercise training zone faster and to maintain it for the entire session. 87% (13) reported that the system assisted them to work out on a regular basis. Conclusion Level 2 evidence (1 non-randomized controlled study) showed the physiological and motivational benefits of using the GAMEWHEELS system when engaging in wheelchair exercise. Use of the GAMEWHEELS system showed physiological and motivational benefits for engaging in wheelchair exercise.

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Table 4.10 FES Assisted Exercise

Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

Moynahan et al. 1996; USA Downs & Black score=12 Post-test N=5

Population: N=5, age 17-20yrs, LOI T4T11, all complete, at least 1 year postinjury, all ASIA A. Intervention: FES system implanted into the major muscles used for standing (quadriceps, gluteus maximus, gluteus medius, and posterior fibers of the adductor magnus). Sometimes erector spinae, hamstrings, adductor longus, and tibialis anterior were included. Stimulation patterns were conducted every 1-4 weeks. The protocol was changed in order to finetune the timing, intensity and coordination of muscle activity. Subjects wore either hinged, molded ankle-foot orthosis or molded shoe inserts depending on requirement for ankle stability. All subjects underwent an 8-week FES exercise program designed to increase muscle strength and endurance. Outcome Measures: FES usage, adherence, functional skill level and mobility.

1. 2.

3. 4.

FES was used mainly for exercise purposes (51%-84% of total days used) and less for mobility. Even though all subjects had previous brace training, standing balance training was needed before progressing to functional skills training with FES. Eventually, subjects showed a range of proficiency at manoeuvring and short-distance ambulation. The primary factor that motivated FES standing was enjoyment of being able to stand. Most common reason for non-use was not having time during the day, not wanting to wear the device all day and not wearing it in public.

Discussion Home use of FES training was investigated in a 1 year study with 5 adolescents who had paraplegia. Results showed that the FES was primarily used for exercise and standing, both of which were regarded as motivators for use. Other benefits were ability to do more things and a sense of well-being. Barriers were lack of time to use the system and reluctance to wear the FES all day. Conclusion There is level 4 evidence (one uncontrolled study) that suggests that FES is beneficial as a motivator to engage in exercise and standing. Drawbacks included lack of time to use the system and reluctance to wear all day. FES is a motivator to engage in exercise and standing, augments ability to do more things and enhances the sense of well-being. Drawbacks included lack of time to use the system and reluctance to wear all day. 4.4 Quality of Life Spinal cord injury (SCI) is a devastating life situation that occurs suddenly and unexpectedly. After the initial (acute) phase of care, individuals start a long period of rehabilitation that aims at

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returning them to the community and allowing them to resume, as much as possible, daily activities and social roles so that they may ultimately begin to enjoy life again. It might be seen as irrelevant to discuss quality of life (QOL) shortly after SCI, however, being part of the fundamental nature of life, QOL becomes a significant issue after rehabilitation discharge. Some reports suggest that compared to the general population people with SCI might experience a slightly lower QOL (Westgren & Levi 1998) but a substantial number of these individuals regain a good to excellent QOL after a period of time (Post et al. 1998a). As expressed by Albrecht and Devlieger (1999), it may be seen as a paradox that many people with disabilities report experiencing a good or excellent QOL when to most observers these people seem to live an undesirable daily existence (p. 977). This situation brings out a fundamental issue in the assessment of QOL unlike other QOLrelated constructs that are described below, subjective QOL (life satisfaction, well-being) is such an intimate feeling that any process trying to measure QOL from an external observer indubitably remains imperfect. As it is mostly influenced by ones personal experiences, comparisons with societal values usually brought about by an external point of view, are likely to misjudge ones QOL. Furthermore, making QOL more difficult to understand, it has been observed that individuals sustaining alterations in health status or a life event such as a SCI, may change their internal standards, their values or their conceptualization of QOL (Spranger 1999). These phenomena might partly explain why it is likely that a difference exists between the external vision of QOL and what is really experienced by people with SCI. 4.4.1 QOL Definitions and Models Although the term goodness of life (Baker & Intagliata 1982) seems appropriate to express the overall concept of QOL, its apparent simplicity hides a multidimensional concept that is among the most difficult to define and translate into a functioning and operating reality. Nonetheless, two main conceptualizations of QOL are well-accepted: (1) the subjective approach, whose focal point is the persons emotional or cognitive assessment of the congruence between his/her life expectations and achievements, usually associated with life satisfaction or well-being and (2) the objective approach, based on ones characteristics that can be objectively measured by an external appraiser (Dijkers 2003). The latter includes the concept of Health-Related Quality of Life (HRQOL) that focuses mostly on physical and mental health, social and role achievements, and thus it is more oriented toward functional performance than is subjective QOL (Wood-Dauphinee et al. 2002). Several models explaining the overall concepts of QOL and its determinants have been presented in the field of disability with a particular link to the disablement process (WoodDauphinee & Kuchler 1992; Whiteneck 1994; Post et al. 1999; Dijkers 2003). Post and collegues (Post et al. 1999; Post & Noreau 2005) proposed a conceptual model that integrates 1) the dimensions of The International Classification of Functioning, Disability and Health (ICF) (World Health Organization 2001) seen as observable deviations from normal functioning and 2) a subjective dimension based on ones perception of satisfaction, perceived health and wellbeing. For example, paralysis (Body Function), inability to walk (Activities), level of social support (Environment) and employment restrictions (Participation) can be assessed from an external observer and some of these dimensions will potentially influence QOL. Conversely, perceived health, satisfaction with social participation and general well-being can only be reported by the person him/herself. All these dimensions form the global (superordinate) construct of QOL that include the objective and subjective approach. Dijkers (2003; 2005) proposed a more generic model that integrates different conceptualizations: 1) QOL as subjective well-being, reflecting the congruence between ones expectations, values and

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achievements, 2) QOL as achievements focusing on ones accomplishments, performances and statuses and including the concept of HRQOL (health and functioning), and 3) QOL as a utility that compares achievements/statuses with societal norms and standards. These models can help clinicians to differentiate between QOL as subjective well-being and its objective determinants. Needless to say, depending on the conceptualization of QOL that would be valued for a specific research or clinical purpose, the choice of an appropriate measure is a critical issue. Some concerns exist regarding the use of the term HRQOL for the conceptualization of QOL given its emphasis on health status and functioning (Moons 2004) especially given that a shift in QOL may occur after SCI, and therefore, just because people may have significant health problems does not necessarily mean they have poor QOL (Smith et al. 1999). Health status should be considered an important determinant of QOL instead of being regarded as an integral dimension of QOL itself. Consequently, QOL as an outcome seems to be more appropriately defined in terms of life satisfaction and this review will mainly focus on that concept. 4.4.2 Exploring QOL after SCI from a Scientific Perspective An impressive number of studies have addressed Health-related and subjective QOL after SCI. Several reports have attempted to identify the potential determinants of QOL from different perspectives but it remains difficult to compare this substantial bulk of information due to the methodological discrepancy between the studies and the lack of consistency in the assessment of the construct of QOL (well-being, life satisfaction) with different measures. Moreover, most studies focused on a single or limited number of variables as very few studies have been conducted with a conceptual framework that takes into account the spectrum of factors that influence QOL. As a result, these studies predict only a small percentage of the variance in QOL (Dijkers 2005) and therefore give a limited scope of the QOL determinants. 4.4.3 Quantitative Measurement Approach of QOL Determinants To overcome the problem of reduced statistical power in many studies with small sample sizes, common with SCI studies, researchers recommend the use of meta-analyses which consist of combining the results of several studies that address similar research hypotheses (e.g. impact of SCI on QOL). Because of limited rigor of research design and poor validity of measurements in the reviewed studies, Evans et al. (1994) failed to determine whether or not rehabilitative care improves QOL. Unlike an overwhelming number of recent reports, this meta-analysis supported an association between QOL and the level of injury. In his meta-analysis, Dijkers (1997b) focused on determining the relationships between QOL and each dimension of the International Classification of Impairment Disability and Handicap (the disablement process). Results showed that overall, slightly lower mean QOL scores are observed in individuals with a SCI than in people without disability, but the relationship between the level of injury and QOL (mostly paraplegia vs. tetraplegia) was almost non existent or weak at best. Conversely, consistent relationships (r = .30 - .50) were observed between QOL and some aspects of handicap (social integration, occupation). It remains possible that severity of injury indirectly affects QOL through its influence on societal participation (Post et al. 1998; Dijkers 1999). If the level of societal participation valued by a person is not affected because of favourable conditions (e.g. education, appropriate environmental adaptations, social support), it is likely that subjective well-being will not be affected, regardless the severity of injury. The potential predictors of QOL that have been mentioned in studies are summarized in Table 4.11. They were grouped into global dimensions for the purpose of this review and not

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surprisingly, predictors related to community integration/participation are among those most often cited in the literature, which supports their importance to enhance QOL. However, it is not necessarily all dimensions of participation that strongly influence QOL. Mobility, occupation, and community life (including interpersonal relationships) are seen as the most important predictors. Poor health status and the occurrence of secondary impairments are also known to diminish QOL. Interestingly, there is growing interest regarding the impact of the environment on societal participation and QOL. Perceived social support (particularly from a spouse) has been considered in several studies as a major predictor of QOL but it is unclear if this variable is a mediator that will promote the level of community integration/social participation or a direct contributor to QOL. The physical environment also has the potential to influence QOL. Richards et al. (1999) observed that access to the environment (home and transportation) was positively and linearly associated with satisfaction with life. It contributed to the explanatory model predicting life satisfaction even after all the other independent measures were considered. As previously mentioned, few studies have used a conceptual framework in order to account for the spectrum of factors that influence QOL. Even with a strong conceptualization, difficulties still exist in attempting to capture the complete picture of QOL determinants using quantitative research methods. For example, Whiteneck et al. (2004) studied the relative impact of environmental barriers on life satisfaction compared to injury-related variables, demographics and activity/participation limitations. A limited amount of variance in QOL (10%) was explained by the environmental barriers compared to participation (15%) and demographics (11%). Overall, 26% of the variance was explained by all subsets of predictors, meaning that about 75% of the variance is unknown or unexplained by factors measured in such a study. This lack of prediction is probably attributable to methodological difficulties such as using measures that do not fully translate the concepts into good metrics rather than a misidentification of the potential factors that influence QOL. Despite the large number of studies on QOL after SCI that applied a quantitative approach, our objective knowledge of how well-being after SCI develops and what factors have a positive or negative influence on the course of QOL remains limited (Post & Noreau 2005). Further research is needed using an integrative approach with measures that strongly fit distinct constructs as those defined in the ICF or other models explaining the consequences of health, disease and trauma. Table 4.11 Potential Predictors of Subjective QOL
Issues perceived to influence subjective QOL Meta analyses or relationships with the disablement process Demographics Age, time since injury, ethnicity, education, marital status Post et al. 1998; Dijkers 1999; Holicky & Charlifue 1999; McColl et al. 1999; Kennedy & Rogers 2000; Putzke et al. 2001 Post et al. 1998; Westgren & Levi 1998; Hall et al. 1999; Putzke et al. 2001 References Fuhrer et al. 1992; Evans et al. 1994; Dijkers 1997b; Pierce et al. 1999; Whiteneck et al. 2004

Injury-related factors Health-related factors Mobility, perceived health, rehospitalization, secondary impairments (respiratory problems, pressure sores,

Decker & Schulz 1985; Schulz & Decker 1985; Crisp 1992; Fuhrer et al. 1992; Lin et al. 1997; Post et al. 1998;

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Issues perceived to influence subjective QOL spasticity) Pain

References Kemp & Krause 1999; Pierce et al. 1999 Putzke et al. 2002; Anderson & Vogel 2003; Franceschini et al. 2003 Sisteen et al. 1990; Lundqvist & Sisteen 1991; Stensman 1994; Anke et al. 1995; Krause 1997; Post et al. 1998; Vogel et al. 1998; Westgren & Levi 1998; Ville et al. 2001; Bnony et al. 2002

Psychological factors Loneliness, boredom Perceived control on life Krause & Kjorsvig 1992 Decker & Schulz 1985; Schulz & Decker 1985; Crisp 1992; Fuhrer et al. 1992; Krause 1992; Krause 1997; Mcneil et al. 1998; Tate & Forcheimer 1998; Putzke et al. 2002; Franceschini et al. 2003

Community integration/participation Social functioning/integration Decker & Schulz 1985; Schulz & Decker 1985; Krause & Crewe 1987; Sisteen et al. 1990; Lundqvist & Sisteen 1991; Crisp 1992; Clayton & Chubon 1994; Dijkers 1997b; Post et al. 1998; Dijkers 1999; Pierce et al. 1999; Kemp & Ettelson 2001; Ville et al. 2001; May & Warren 2002; Putzke et al. 2002 Krasue 1997; Bnony et al. 2002; Putzke et al. 2003; Franceschini et al. 2003 Schulz & Decker 1985; Fuhrer et al. 1992; Cayton & Chubon 1994; Nosek et al. 1995; Dijkers 1997a; Hansen et al. 1998 Krause & Crewe 1987; Lundqvist & Sisteen 1991; Crisp 1992; Fuhrer et al. 1992; Krause 1992; Krause & Kjorsvig 1992; Dijkers 1997b; Krause 1997; Lin et al. 1997; Pentland et al. 1998; Westgren & Levi 1998; Dijkers 1999; Kemp & Krause 1999; McColl et al. 1999; Ville et al. 2001; Putzke et al. 2002; Franceschini et al. 2003 Decker & Schulz 1985; Schulz & Decker 1985; Crisp 1992; Fuhrer et al. 1992; Rintala et al. 1992; Warren et al. 1996; Dijkers 1997b; Kemp & Krause 1999 Richards et al. 1999; Deconinck 2003 Cushman & Hassett 1992 Gerhart 1991; Krause 1992; Clayton & Chubon 1994; Vogel et al. 1998; Heck & Makuc 2000; Ville et al. 2001 Dijkers 1999; Putzke & Richards 2001

Interpersonal relationships/social interactions

Community access/participation

Occupation/employment status (including satisfaction with), life opportunities

Environmental issues Perceived social support

Accessibility (home/health care)

Preferred living situation

Level of income

Residence (nursing home)

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Average level of QOL after SCI is slightly lower than in people without disability but a substantial number of people with SCI report good or excellent QOL. Severity of injury and other diagnostic factors do not significantly impact QOL. There influence may become significant through restrictions in community integration and social participation. A limited amount of variation in QOL has been explained by quantitative research methods. 4.4.4 Qualitative Research Methods to Understand QOL and its Determinants Because of the difficulty quantitatively capturing complete information on QOL and its determinants, few reports have used qualitative methods and shed light on the issue of QOL when living with SCI (Bach & McDaniel 1994; Hillebrand et al. 2001; Manns & Chad 2001; Whalley Hammell 2004). These studies confirm that several people with SCI enjoy life and have a good or excellent QOL, even those with a severe injury. Overall, QOL is seen as something dynamic and subjective. It is generated by the individuals personal experiences and changes over the course of life in response to changing priorities and values. The latter is a concept frequently mentioned and corresponds to the response shift theory (Rapkin 2004). Several elements that make life enjoyable do not differ in persons with SCI compared to those without disability. These elements include satisfying interpersonal relationships, financial security, meaningful social roles (including those related to work and productivity) and opportunity to pursue leisure and community services. In general, factors reflecting participation in life situations or reintegration into the community are very influential to QOL. Having control over ones life, assertiveness and balance between dependence and independence have all been reported as major QOL determinants. Access to various resources (physical, emotional, social) is seen as a necessary foundation to QOL and refers to the overall contribution of the environment. There is an interactive process between correlates of QOL that suggests a complex interrelationship between the domains influencing QOL. Moreover, each domain, taken independently, is insufficient to maintain QOL and rather, it is the interaction between personal attributes, meaningful roles and environmental assets that build an optimal QOL. Albrecht and Devlieger (1999) nicely summarize this perspective by stating that it refers to the ability of the self to build and manage a balance between the body, mind and spirit in searching for a state of well-being and to maintain an harmonious relationship with the environment (page 986). Qualitative reports suggest that factors affecting QOL after SCI do not seem to differ from those impacting QOL in people without disability. They are related to life issues such as achieving meaningful social roles, having control over ones life and maintaining adequate access to the environment 4.4.5 Trials Examining QOL as an Outcome Unlike the concept of HRQOL, which has been the object of an infinite number of clinical trials, there is a paucity of experimental studies that examine QOL as subjective well-being or use this concept as a primary outcome. One reason for this is related to the concept of subjective QOL itself, resulting from subjective feelings where the appraisal is built on the accomplishment of

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valued life dimensions. Therefore, subjective QOL cannot be the primary outcome of a clinical intervention and thus, the aim of a study must be to examine the life dimensions valued by the person (e.g., health status, functional independence, occupation, etc.) and to presume an indirect effect of enhanced life dimensions on QOL. The aforementioned findings suggest that dimensions related to community integration (in particular, active participation and full citizenship) are the most likely to enhance QOL after SCI. Thus, interventions to enhance QOL should pay careful attention to these determinants. In Table 4.12 we present 4 studies which use experimental and quasi-experimental designs to examine changes in QOL after an intervention. Three studies focus on people with SCI while another one involves spouses. Table 4.12 Clinical Trials Examining the Effect of Specific Interventions on QOL
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Martin Ginis et al. 2003; Canada PEDro=5 RCT N=34

Phillips et al. 2001; USA PEDro=4 RCT N=111

Population: 34 subjects (23 men, 11 women), complete-incomplete, LOI: 1011 years. Treatment: exercise training ( aerobic and resistive) performed in groups of 3-5 people, twice weekly (24 sessions: avg. 15 wks to complete; range 12-22 weeks). Mediators: pain perception, self-efficacy, stress. Outcome Measures: self-concept, depression, subjective well-being. Population: Total n=111 Treatment n=72, Control n=39; acute phase and 1 yr post-discharge. Treatment: Participants randomly assigned into 3 groups (n=36 video, n=36 telephone, n=39 standard care) for education on various SCI issued. Follow-up (1 yr) to monitor QOL. Outcome Measures: Depression (CES-D), HRQOL-QALY (Quality of Well-Being). Population: 36 SCI spouses: 19 treatment subjects, 17 controls, Age: Support group 32.5yrs, Control spouse 38.5yrs, DOI: Support=21 mo, Control= 36 mo. Intervention: Support groups met 7 times (1 h) over a 2-wk period. Controls did not. Program: discussions on previous sessions home task, topic specific performance, assignment of home task, wind down. Outcome Measures: General Health Questionnaire (GHQ), Hospital anxiety and depression rating scale (HAD) and QOL (WHOQOL-BREF). Population: 25 treatment subjects, 25 control subjects. Treatment: Experimental group had five leisure group sessions (1 hr) included: 1) intro and group interaction, 2) importance of leisure, 3) problems faced in leisure participation, 4) strategies to overcome

1. 2.

Exercisers reported less pain, depression, stress and greater perceived QOL and self-concept. Stress and pain mediated exercise induced-changes in QOL.

1.

2.

The standard care group spent an average of 8.0 days/yr in the hospital vs. 5.2 for the telephone and 3.0 for the video group. At 1 yr post-discharge, QWB scores were slightly higher in the intervention groups (video-telephone) (n = only 42% of the initial sample).

1.

Sheija & Manigandan, 2005; India Downs & Black score=16 Prospective Controlled Trial N=36

2.

All values from QOL were significantly improved after the treatment in the support group compared to the control group (physical, psychological, social relation (p<0.0001). Significant reduction in anxiety and depression in the support group.

Daniel & Manigandan 2005; India Downs & Black score=15 Prospective Controlled Trial N=50

1.

Significant improvement in all domains of the LSS and WHO QOL-BREF in the experimental group (except for social relationships) as compared with the control group (p=0.0001).

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

them, & 5) revision and summary, along with carrying out an activity suggested by the group members] as intervention while the control group had none. Outcome Measures: leisure (Leisure satisfaction scale), QOL (WHOQOL-BREF)

Discussion Even though reality is more complex, some studies support the straightforward hypothesis that an intervention can modify a particular dimension of life, and the latter will directly influence QOL. For example, Martin Ginis et al. (2003) suggest that the effect of an exercise program on QOL is mediated by modifying pain and stress. Sometimes, weaker designs and less sophisticated analyses (prospective controlled trial) can also be used to suggest the indirect impact of an intervention on QOL, as shown by Daniel and Manigandan (2005). These authors attempt to determine if a leisure intervention program would influence subjects attitudes toward leisure, the level of leisure satisfaction and, consequently, QOL. One experiment that we located did not lead to an obvious effect on QOL. In their post-discharge follow-up conducted by telehealth or telephone Philips et al. (2001) found that telehealth lead to a more positive outcome than standard care but this did not translate into better subjective QOL. The aforementioned hypothesis could also be validated with the partners of people with SCI who are impacted by the new life context. A good example is Sheija and Manigandans investigation of a spouse support program (2005). They found significant improvements in all domains of QOL and psychological variables while marginal changes were observed in the control group. Overall, only one study (Martin Ginis et al. 2003) provided strong evidence that a specific intervention on life domains will have an impact on QOL. The conclusions from the other studies would have been stronger if secondary analyses had been conducted to demonstrate an association between the changes in an intermediate outcome (depression, anxiety, psychological distress, etc.) and QOL. At present we can only assume that eliciting changes in an individuals characteristics or life situations would enhance subjective QOL. Conclusion There is Level 1 evidence in 1 RCT study that supports the use of exercise to reduce pain and stress which in turn mediates changes in QOL. There is level 1 evidence from 1 RCTstudy that suggests that telehealth provides better prevention education than telephone or standard care, however, there was little influence on the QOL. There is level 2 evidence from 1 non-RCT study that suggests the positive impact of a 2week leisure educational program (group therapy) on leisure satisfaction and, potentially, QOL. There is level 2 evidence from 1 non-RCT study that suggests the use of group therapy to support spouses of individuals with SCI will decrease the symptoms of depression, anxiety and psychological distress with a potential impact on QOL.

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Overall, there is a paucity of information from clinical trials on the most appropriate interventions favouring subjective QOL in people with SCI and their significant others. QOL can be indirectly enhanced through the use of an exercise program designed to reduce pain and stress. Providing group therapy to spouses of individuals with SCI can decrease their symptoms of depression, anxiety and psychological distress with a potential impact on QOL. 4.4.6 Summary QOL One of the highlights of this section refers to the inherent difficulty in studying the concept of QOL as an outcome. QOL, being such an intimate feeling and influenced by ones personal experiences, is difficult but not impossible to study as the primary outcome of an intervention study. Moreover, the theory of response shift suggests that the essence of QOL (values, personal standards, expectations) might change over time, making this concept changeable over the course of life. Nonetheless, some methodological considerations could facilitate the design of proper QOL studies. Firstly, there is a need to identify and define what construct of QOL will be the focus of the study as well as the underlying conceptualization (e.g. subjective vs. objective, general well-being vs. life satisfaction per domain). The proposed measure must fit the selected construct of QOL and must have sound psychometric properties (validity, reliability, responsiveness). Secondly, studies that aim to identify predictors of QOL must use strong conceptual models that will include all the potentially important facets of life (individual characteristics, environmental dimensions and societal involvement, etc.). Again, appropriate measures are a critical issue. Thirdly, in the case of clinical trials designed to enhance QOL, the interventions should be appropriately selected, such that there is a sensical indirect connection between the intervention and QOL. For example, one could exam the influence of placement in a long term care facility versus the return to community living on QOL. The outcome should, therefore, be identified from the dimensions of a conceptual model, such as the ICF model of health and disability (body functions and structures, activities, participation, contextual factors). Finally, there is a necessity to carry out further statistical analyses (multivariate analyses, group differences, path analyses) to provide evidence of the association between the intermediate or mediating factors and QOL. 4.5 Summary Community Reintegration There is Level 4 evidence from a single post-test study that having contact with a person who has an SCI has a significant impact on attitudes towards disability. There is Level 5 evidence based on a qualitative study that SCI results in a changed social network - some relationships are lost but others improve. There is very limited (Level 5) evidence that people with SCI consider the following factors as the main barriers to community integrations: barriers in the natural environment, transport, help at home, health care and government policy. There is very limited (level 5) evidence from two observational studies that assistive equipment may promote increased activity and participation in and outside of the home.

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There is moderate (Level 2) evidence from one RCT study that a community based system for post discharge monitoring in no more effective in terms of community integration than a hospital based system. There is very limited (Level 5) evidence from one observational study that productivity was correlated to the individuals subjective experience of community reintegration. There is very limited (Level 5) evidence from two observational studies that a positive relationship exists between the adequacy of personal assistance and the physical and mental health of those with SCI. There is very limited (Level 5) evidence from two observational studies that people who receive consumer directed personal assistance services are more satisfied with services than those who receive services that are not consumer directed. There is limited (Level 4) evidence from one case series that an independent living follow-up program is more beneficial than no program. There is very limited (Level 5) evidence from one observational study that supported employment assists job placement of some people with SCI. There is very limited (Level 5) evidence from one observational study that individuals with disabilities (SCI, cerebral palsy, multiple sclerosis) did not receive adequate equipment or services on more than half of the occasions in which they were requested. There is level 5 evidence (1 cross sectional study) that suggests that at discharge from a rehabilitation unit there is improvement in self care and mobility that is preserved for 1 year. There is level 5 evidence (1 observational study) suggesting that following a driving training program, persons with tetraplegia who drove tended to be of younger age, have a lower level of SCI, drove prior to injury, able to perform independent transfers, employed and involved in sports. There are several level 5 evidence studies that show the following factors have a positive impact on employment: male, more years since injury, younger age, car driving ability, higher education and professional job prior to the SCI. Many studies also show that having tetraplegia has a negative impact on gaining and maintaining employment. There are level 5 evidence studies (2 longitudinal) that show that those persons with SCI that were employed 15 years post-SCI had greater satisfaction with employment and finances while those who were unemployed 11 years post-SCI had lower activity levels and greater economic dissatisfaction. There is level 5 evidence (one cross-sectional study) that persons with disabilities in France experience discrimination related to employment, as they are less likely to obtain an interview or be hired regardless of qualification or size of company. Level 5 evidence (several cross-sectional studies) suggests that facilitators for leisure involvement are social support, being healthy and being employed or attending school.

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Level 2 evidence (1 non-randomized controlled study) showed the physiological and motivational benefits of using the GAMEWHEELS system when engaging in wheelchair exercise. There is level 4 evidence (one uncontrolled study) that suggests that FES is beneficial as a motivator to engage in exercise and standing. Drawbacks included lack of time to use the system and reluctance to wear all day. There is Level 1 evidence in 1 RCT study that supports the use of exercise to reduce pain and stress which in turn mediates changes in QOL. There is level 1 evidence from 1 RCTstudy that suggests that telehealth provides better prevention education than telephone or standard care, however, there was little influence on the QOL. There is level 2 evidence from 1 non-RCT study that suggests the positive impact of a 2week leisure educational program (group therapy) on leisure satisfaction and, potentially, QOL. There is level 2 evidence from 1 non-RCT study that suggests the use of group therapy to support spouses of individuals with SCI will decrease the symptoms of depression, anxiety and psychological distress with a potential impact on QOL.

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CHAPTER FIVE
Upper Limb Rehabilitation Following Spinal Cord Injury
Sandra Connolly, BHScOT, OT Reg (Ont.) JoAnne Aubut, BA Robert W Teasell MD FRCPC Tal Jarus, PhD, OTR

Key Points Neuromuscular stimulation-assisted exercise following a spinal cord injury is effective in improving muscle strength, preventing injury and increasing independence in all phases of rehabilitation. Augmented feedback does not improve motor function of the upper extremity in SCI rehabilitation patients. Intrathecal baclofen may be an effective intervention for upper extremity hypertonia of spinal cord origin. Afferent inputs in the form of sensory stimulation associated with repetitive movement and peripheral nerve stimulation may induce beneficial cortical neuroplasticity. Restorative therapy interventions need to be associated with meaningful change in functional motor performance and incorporate technology that is available in the clinic and at home. The use of concomitant auricular and electrical acupuncture therapies when implemented early in acute spinal cord injured persons may contribute to neurologic and functional recoveries in spinal cord injured individuals with ASIA A and B. There is clinical and intuitive support for the use of splinting for the prevention of joint problems and promotion of function for the tetraplegic hand. However, there is very little research evidence to validate its overall effectiveness. Shoulder exercise and stretching protocol reduces post SCI shoulder pain intensity. Acupuncture and Trager therapy may reduce post-SCI upper limb pain. Prevention of upper limb injury and subsequent pain is critical. Reconstructive surgery appears to improve pinch, grip and elbow extension functions that improve both ADL performance and quality of life in tetraplegia. The use of neuroprostheses appears to have a positive impact on pinch and grip strength and ADL functions in C5-C6 complete tetraplegia, however, access to the devices are limited and continue to be expensive in use.

Table of Contents
5.1 Introduction ......................................................................................................................5-1 5.2 Acute Phase of Rehabilitation ........................................................................................5-2 5.2.1 Exercise and Strengthening............................................................................................5-3 5.3 Augmented Feedback on Motor Functions ...................................................................5-6 5.4 Pharmacological Interventions.......................................................................................5-9 5.5 Restorative Strategies ...................................................................................................5-11 5.5.1 Plasticity of Motor Systems ...........................................................................................5-11 5.5.2 Complimentary Alternative Therapies (CAM) ...............................................................5-13 5.5.3 Splinting of the Hand.....................................................................................................5-14 5.6 Sub Acute Phase of Rehabilitation ..............................................................................5-16 5.6.1 Upper Limb Injuries.......................................................................................................5-16 5.6.1.1 Shoulder Injuries ........................................................................................................5-17 5.6.1.2 Elbow/Wrist and Hand Injuries...................................................................................5-18 5.7 Reconstructive Surgery ................................................................................................5-22 5.7.1 Hand .............................................................................................................................5-22 5.7.2 Elbow Extension ...........................................................................................................5-29 5.7.2.1 Elbow Extension (Biceps to Triceps) .........................................................................5-30 5.7.3 Multiple Reconstructions...............................................................................................5-31 5.8 Neuroprostheses ...........................................................................................................5-35 5.8.1 Types of Neuroprostheses............................................................................................5-36 5.8.1.1 Freehand System.......................................................................................................5-36 5.8.1.2 HandMaster-NMS-1 ...................................................................................................5-42 5.8.1.3 Bionic Glove...............................................................................................................5-43 5.8.1.4 ETHZ-ParaCare System ............................................................................................5-44 5.8.2 Other Surface or Percutaneous Neuroprosthesis Systems ..........................................5-45 5.8.2.1 NEC-FES System ......................................................................................................5-45 5.8.2.2 Neuroprosthesis developed by Rebersek and Vodovik (1973)..................................5-45 5.8.2.3 Belgrade Grasping-Reaching System (BGS).............................................................5-46 5.8.3 Reported Benefits of Neuroprosthesis Use...................................................................5-46 5.8.4 Clinical Results of Neuroprosthesis Use.......................................................................5-46 5.8.5 Challenges in Neuroprosthesis Use..............................................................................5-46 5.9 Summary.........................................................................................................................5-48 References..............................................................................................................................5-50
This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Connolly S, Aubut J, Teasell RW, Jarus T (2006). Upper Limb Rehabilitation Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 5.1-5.58. www.icord.org/scire

Upper Limb Rehabilitation Following Spinal Cord Injury

5.1 Introduction Raineteau and Schwab (2001) defined a spinal cord injury as a lesion within the spinal cord that results in the disruption of nerve fibre bundles that convey ascending sensory and descending motor information. A spinal cord injury (SCI) at the cervical level results in tetraplegia, the loss of hand and upper limb function with impairment or loss of motor and/or sensory function. In incomplete spinal cord injuries, some neural transmissions can still pass through the spinal cord but it is often fragmentary or distorted which leads to additional neurological complications such as chronic pain or spasticity. Tetraplegia results in impairment of function in the arms as well as in the trunk, legs and pelvic organs. Individuals with tetraplegia rely on the use of their hands and upper limbs in order to complete basic activities of daily living such as self-feeding, dressing, bathing and toileting. Mobility needs such as transfers from surface to surface, transitional movements such as rolling, bridging and sit to lying down, crutch walking and wheeled mobility are also completed by using their arms (Snoek et al. 2004). The level at which the injury or lesion occurs and the completeness of the lesion (incomplete or complete) indicate the level of independence of the person (Ditunno1999). The Paralyzed Veterans of America (PVA) have published a clinical practice guideline (CPG), Outcomes Following Traumatic Spinal Cord Injury: Clinical Practice Guidelines for Health Care Professionals, that outlines the expected skills and outcomes that a person is expected to acquire and achieve at each significant level of injury (Consortium for Spinal Cord Medicine 1999). As medical care of the spinal cord injured person has improved, life expectancy now approaches the rest of the population. Secondary complications from SCI and aging are ongoing challenges and include pain and upper limb musculoskeletal injuries (Sipski and Richards 2006). Hanson and Franklin (1976) compared sexual function to three other impairments in patients with SCI. 75.7% of the subjects gave the highest priority to upper extremity function. Snoek et al. (2004) surveyed the needs of patients with SCI and found a high impact and high priority for improvement in hand function in tetraplegics comparable to that for bladder and bowel dysfunction. Given the above, the initial care, management, rehabilitation and prevention of injuries in the upper limb of tetraplegics are of great importance in maximizing and maintaining independence. According to Murphy and Chuinard (1998), management and care of the upper limb can be divided into three phases: the acute, the sub acute and the reconstructive phase. The aim of the first two phases is to: prevent complications; to achieve optimal functioning within the limits of the neurological deficit; and to create optimal conditions for the reconstructive phase (Bedbrook 1981; Keith et al. 1991; Curtin 1994; Harvey 1996). In the latter phase, various surgical options and functional electrical stimulation (FES) are available to improve positioning and stabilization of the arm as well as key and palmar grasp function (Waters et al. 1996; Triolo et al. 1996; Johnstone et al. 1988; Snoek et al. 2000; Peckham et al. 2001). In the new clinical practice guidelines by the Consortium for Spinal Cord Medicine (2005) emphasizes prevention of upper limb injuries of tetraplegic individuals in maintaining independence.

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Although, there is no overall consensus regarding the management of the tetraplegic upper limb, Hummel et al. (2005), Snoek et al. (2005) and the Consortium for Spinal Cord Medicine (2005) provide excellent discussions and recommendations. There is agreement that restoration of hand function is an important goal in rehabilitation. It is also worth noting that there are very few upper extremity tests that accurately evaluate upper limb function in this population (van Truijl et al. 2002). Curtin (1994) and Krajnik and Bridle (1992) noted a great inconsistency in evaluation and documentation of the tetraplegic upper limb between therapists. The main focus in rehabilitation of the spinal cord injured person is compensation of functional loss and using those parts of the sensorimotor system, which are still intact (van Truijl et al. 2002). Research findings regarding neuroplasticity and neurological recovery of the spinal cord also include current rehabilitation practices that should focus on strategies to restore function lost after SCI. Several studies have explored increased hand function as a result of reconstructive surgery and/or neuroprothesis. Although these and many other treatment options exist, and have proven to improve the overall functioning and functional independence of the person with tetraplegia, clinical practice has shown that suitable candidates for reconstructive surgery or FES interventions often do not accept the treatment that is offered (Snoek et al. 2004). According to Moberg (1975), over 60% of the tetraplegic population could benefit from reconstructive surgery and it continues to be widely advocated (Snoek et al. 2004). Reconstructive surgeries such as muscle/tendon transpositions of the intact arm or hand muscles are designed to substitute for lost motor function (van Truijl et al. 2002). Despite this, controversy still exists among clinicians as to whether or not to perform reconstructive surgeries and the benefits of reconstructive surgery have not been clarified with good quality randomized clinical trials (Harvey et al. 2001). Gorman et al. (1997) deduced that 11% of the tetraplegic population could be candidates for an implanted FES device (Freehand System). Most implanted FES devices are usually combined with augmentative and substitutional reconstructive surgery (Keith et al. 1996). Using the framework proposed by Murphy and Chuinard (1998), this chapter will be divided into the following sections: acute phase of rehabilitation, sub acute phase of rehabilitation and reconstructive phase. 5.2 Acute Phase of Rehabilitation Rehabilitation and management of the person with a spinal cord injury requires an interdisciplinary team approach during the acute phase of rehabilitation. The level and classification of the injury is determined and the goals of maintaining range of motion (ROM), improving strength, managing tone, spasticity, and the prevention of secondary complications in order to achieve the persons maximum functional ability for independent transfers, activities of daily living and mobility are developed (Haisma et al. 2006; Sipski and Richards 2006; Drolet et al. 1999). Clinicians must be knowledgeable about the change in physical capacity based on level of injury as a prerequisite to developing optimal rehabilitation programs and for setting realistic individual rehabilitation goals.

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5.2.1 Exercise and Strengthening In the acute phase of rehabilitation, the person with a spinal cord injury has a reduced physical capacity because of muscle weakness, loss of autonomic control below the level of injury, reduced activity and subsequent changes in metabolic and vascular function (Haisma et al. 2006). The inability to reach ones maximum potential will result in an increased risk of medical and secondary complications and has been correlated to a reduced level of functioning and quality of life. One of the important goals of rehabilitation is to reverse the debilitative cycle of reduced physical capacity that leads to reduced activity and functioning (Haisma et al. 2006). With shorter hospital lengths of stay, spinal cord injured person have less training opportunities. It is important to determine whether people with SCI can maintain their levels of physical capacity after discharge. There are very few evidence-based analyses of the effectiveness of specific exercise therapies (Sipski and Richards 2006). Most research has only focused on one component of physical capacity (e.g., peak oxygen uptake [VO2 peak] or muscle strength, or respiratory function). Many physical factors have been associated with optimal functional independence individual post-SCI and muscle strength is identified as an important contributor to functional independence (Drolet et al. 1999). Studies by Noreau et al. (1993), Marciello et al. (1995) and Durand et al. (1996) all noted a correlation between the level of the lesion, performance in functional abilities in relationship to peak oxygen intake and level of muscle strength. These associations were significant in individuals with tetraplegia especially in areas of sitting balance, spasticity of the lower limb, hand-grip strength, wrist extensor strength and global upper extremity strength. These functional areas have also been related to Functional Independence Measure (FIM) motor and self-care scores. It was also identified that upper extremity strength must be adequate to support the body weight during transfers and lower limb strength for walking. Optimal recovery of muscle strength following a spinal cord injury is an essential objective of functional rehabilitation of individuals with a SCI (Drolet et al. 1999). Changes in motor function observed six months after an injury may be partially explained by collateral sprouting within the spinal cord (Mange et al. 1990). Changes between 2 to 8 months may be related to peripheral nerve sprouting and muscle fiber hypertrophy after partial denervation (Mange et al. 1990; Yang et al. 1990). Natural muscle strength recovery may occur up to two years post injury, with the recovery rate being more important for the first six months as measured by manual muscle testing (Ditunno et al. 1992; Mange et al. 1992; Waters et al. 1993). Muscle strength gains have been attributed to two different mechanisms in healthy subjects. In healthy subjects, short-term gains (2-4 weeks) might be explained by improved capacity to recruit motor units (neural adaptation) and gains observed after 4 weeks have been attributed to morphological changes within the contractile tissue inducing muscle fiber hypertrophy (Sale 1988). Additional studies regarding cardiovascular and exercise interventions will be discussed in another chapter. Table 5.1 Exercise and Strengthening
Author Year; Country Score Research Design Total Sample Size Needham-Shrophire et al. 1997;USA/CA Pedro=8 RCT Methods Population: age 18-45yrs, gender m=31, f=3, tetraplegia, time since injurymean=3yrs. Treatment: Subjects randomly assigned to 1. Outcome No significant difference was found at the 4-week evaluation between Groups 1 and 2 (p=0.22) or between Groups 2 and 3 (p=0.07).

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Author Year; Country Score Research Design Total Sample Size Initial N=43; Final N=32

Methods one of three groups: Group 1 received 8 wks of neuromuscular stimulation (NMS) assisted arm ergometry exercise Group 2 received 4 wks of NMS assisted exercise, then 4 wks of voluntary arm crank exercise Group 3 (control group) - voluntarily exercise for 8 wks without the application on NMS. Outcome Measures: Manual muscle test. Population: age19-65 yrs; C4-L1; ASIA AD; 1-24 yrs duration Treatment: Experimental group (EX) participated in progressive exercise training twice weekly for 9 months-each session offered on alternative days lasing 90-120 minutes. Outcome Measures: Perceived stress scale, muscle strength, depression, physical self-concept pain, perceived health and Q of L were assessed 2.

Outcome Subjects in Group 1 had a higher proportion of muscles improving one or more muscle grades after 4 weeks of NMS cycling compared with Group 3 (p<0.003). Following the second 4 weeks of training, a significant difference was found between Groups 1 and 3 (p<0.0005) and between Groups 2 and 3 (p<0.03). No statistically difference was found between Groups1 and 2 (p=0.15). Overall 11 in the ex group (exercise adherence 82.5%) and 13 in the control group completed the study No sign differences were noted between the two groups at baseline Following training, EX gr. had significant increases in sub maximal arm ergometry power output (81%; p<0.05) and significant increases in upper body muscle strength (19-34%; p<0.05) EX gr. reported less pain, stress and depression after training + scored higher than CON in indices of satisfaction with physical function, level of perceived health + overall quality of life (p<0.05) Age was related to the PO peak and handheld dynamometry (HHD) score (p<0.05), the older the subject the more improvement in either of these measures was significantly less than it was in younger subjects. Men had greater PO peak, VO2peak and HHD score than women did (p<0.05), thus improvement in men was greater than women. In tetraplegia subjects the PO peak, VO2peak, muscle strength and % of forced vital capacity (FVC) was lower (p<0.05) than it was in paraplegics but tetraplegics improved more in muscle strength and % of forced expiratory flow (FEV1). Those with a complete lesion had greater HHD score and lower % of FVC than those with incomplete lesions (p<0.05). Strength values at admittance were inversely repeated to strengthen changes during rehab (Pearson correlation coefficients ranging from .47 (p=.001 shoulder flexors) to -.73 (p<.001 shoulder adductors). For those with paraplegia the range was from -.48 (p=0.049 shoulder

3.

4. 1. 2. 3.

Hicks et al. 2003; Canada Downs & Black score=20 PEDro=7 RCT Initial N=34; Final N=11

4.

Haisma et al. 2006; Netherlands Downs & Black score=13 Cohort Initial N=186; Final N=42

Population: Age: approx 40 yrs, Gender: 75% male, Level of Injury: both para and tetraplegia; Injury completeness: approx 67.5% complete injuries; Time since injury: approx 105 days Treatment: No treatment provided Outcome Measures: Power output (PO) peak, VO2 peak, strength of upper extremity, respiratory function

1.

2.

3.

4.

Drolet et al. 1999; CA Downs & Black score=15 Pre-post Initial N=40; Final N=31

Population: Gender: m=27, f=4; Age: approx 29.5yrs; ASIA: A-D; length of stay: approx 4.5 months; time since injury: approx 2 months Treatment: Rehab included PT, OT and physical conditioning. There were 4 1hr sessions of each intervention Outcome Measures: Meaning muscle

1.

2.

5-4

Author Year; Country Score Research Design Total Sample Size

Methods strength was assessed for 6 muscle groups 4 times. Muscle strength changes during & after functional rehab

Outcome abductors to -.72 (p=.001 elbow flexors) compared to those with tetraplegia, the correlation coefficients ranged from -.28 (p=.345 elbow extensors) to -.68 (p=.010 shoulder adductors). Patterns of change in muscle strength from admittance to the 15 month follow up differed between the 2 groups. Differences in strength have been observed for: elbow flexors (p=.001) and shoulder extensors (p=0.04) All subjects showed improvement in one or more of their manual muscle score with the most dramatic occurring in the tricep muscle group (average increase 1.1 +/- 0.2 for L triceps, 0.7 +/- 0.1 for R) Results show NMS in combination with resistive exercise can be used safely and assists in the strengthening of voluntary contractions

3. 4. Population: Gender m=10, f=1, age 1845yrs, >1yr post injury, level of injury C4C7, neurologically stable Treatment: Testing of hybrid device, 8 wks of NMS assisted exercise with training sessions 3x/wk Outcome Measures: Manual muscle test scores biceps, triceps, wrist flexors and extensors. 1.

Cameron et al. 1998; USA Downs & Black score=9 Case Series N=11

2.

Discussion The five studies presented address the long-term change of upper limb strength after the spinal cord injured person has returned to community living. Needham-Shophire et al. (1997) found that Neuromuscular stimulation (NMS)-assisted exercise ergometry alone and in combination with voluntary arm crank exercise was effective for strengthening of the upper limb for SCI injured individuals well after injury (mean time since injury 3 years). Hicks et al. (2003) demonstrated all study participants had progressive increases in muscle strength in each of the muscle groups tested and that the change scores were significant from the control group except for the left anterior deltoid. Study participants self-reported decreases in stress, pain, depression, enhanced physical self-concept and overall quality of life. Drolet et al. (1999) conducted one of the first longitudinal studies published in muscle strength changes in individuals with SCI during rehabilitation. Significant improvement of muscle strength during rehabilitation for individuals with both paraplegia and tetraplegia was noted. Significant improvements were noted at the three-month post discharge evaluation period with the tetraplegia group in the four muscle groups (elbow flexors and extensors and shoulder flexors and extensors) and then began to plateau. One year later elbow flexors showed significant improvement in both paraplegia and tetraplegia groups and shoulder extension showed significant gains only on individuals with paraplegia. Large variability was noted indicating the recovery of strength maybe influenced by a variety of individual factors such as level and severity of injury, associated health conditions, age, gender, motivation and physical condition before SCI. Improvements in strength realized in rehabilitation continue to be maintained or improved when the person with a SCI returned to community living.

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Haisma et al. (2006) found positive changes in the different components of physical capacity both during and after inpatient rehabilitation. SCI subjects continued to improve and this study illustrates the importance of regularly assessing the physical capacity of people with SCI after discharge. It is important to create conditions (education, exercise facilities) that facilitate further improvements (Haisma et al. 2006). Cameron et al. (1998) also reported improvements in upper limb strengths in combination with neuromuscular stimulation. Haisma et al. (2006) and Sipski and Richards (2006) recommended further research in this area: Further research is needed to document benefits of exercise interventions post-SCI including optimal methods for strengthening muscles, merits of endurance versus strength training, range of motion, gait, ADL, and transfer training. Due to impact of body composition, age, concomitant medical problems and our limited knowledge of recovery post SCI, research needs to be performed through well-designed multicentre trials. Longitudinal studies are needed to gain more insight into the changes that occur after inpatient rehabilitation and the factors which influence these changes. Exercise and strengthening of the upper limb in both the acute and subacute phase of rehabilitation are important in promoting independence and prevention of injury.

Conclusions For exercise and strengthening of the SCI individual following injury: There is level 1 evidence based on one RCT that physical capacity continues to improve after 1- year post discharge. There is level 2 evidence based on one pre/post study that neuromuscular stimulationassisted ergometry alone and in conjunction with voluntary arm crank exercise was an effective strengthening intervention for chronically injured individuals. There is level 2 evidence based on one study that muscle strength continues to improve up to 15 months post hospital discharge for both tetraplegic and paraplegic individuals. There is level 4 evidence based on one study that neuromuscular stimulation-assisted exercise improves muscle strength over conventional therapy. Neuromuscular stimulation-assisted exercise following a spinal cord injury is effective in improving muscle strength, preventing injury and increasing independence in all phases of rehabilitation. 5.3 Augmented Feedback on Motor Functions Several studies have addressed the use of augmented feedback such as biofeedback with spinal cord injured populations. Van Dijk et al. (2005) conducted a systematic review of RCTs on the effect of augmented feedback on motor function of the affected upper extremity in

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rehabilitation patients. Much of the information about augmented feedback comes from the motor learning literature where it has been noted that feedback combined with practice is a potent variable for affecting motor skill learning (Newell 1991; Schmidt and Lee 1999). There are two types of performance-related information or feedback. The first type of feedback, task intrinsic or inherent feedback, is sensory-perceptual information and is a natural part of performing a skill. The second type of feedback is augmented feedback or information-based extrinsic or artificial feedback. Augmented feedback refers to enhancing task intrinsic feedback with an external source (Schmidt et al. 1999; Magill 2001), such as a therapist or device (biofeedback or timer) (van Dijk et al. 2005). It has been suggested that augmented feedback may have practical implications for rehabilitation therapy since re-acquisition of motor skills is an important part of functional motor recovery (Winstein 1991; Kilduski and Rice 2003; Jarus 1994; Jarus and Ratzon 2005). The ability to use intrinsic feedback to guide performance is impaired in patients with cognitive and perceptual impairments (Flinn and Radomski 2002). In persons who are compromised by neurological sensory impairments, augmented feedback is important (Sabari 2001). van Dijk et al. (2005) systematic review found three randomized clinical control trials which studied augmentative feedback in the SCI population (Klose et al. 1993; Klose et al. 1990 and Kohlmeyer et al.1996). In our literature search we were able to find an additional two other studies with lower level of evidence that studied augmented feedback applications. Table 5.2 Augmented Feedback on Motor Functions
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender m=40, f=5, age mean=39yrs, injury level C4 C6, complete & incomplete injuries, Treatment: Extremities were randomly assigned to 1 of 4 treatment groups: 1. conventional strengthening; 2. electrical stimulation; 3. biofeedback and electrical stimulation; 4. biofeedback. Participation ranged from 5 to 6 weeks post SCI Outcome Measures: manual muscle testscoring and ADL performance 1. Outcome Comparison of Groups (Increment or Decrement or No Change): no relationship between treatment group and observed change; no treatment produced a significantly higher proportion of individuals that improved relative to the proportion showing no change or a decrement; no change between treatment groups. Influence of Initial Muscle Grade: a correlation between the initial muscle grade and increment in muscle grade was seen at the end of treatment; poorer initial muscle grades, more likely to see a larger increment in muscle grade as a result of treatment. Conclusion-biofeedback and electrical stimulation both alone + together did not prove to be more effective than standard therapy for wrist extensor recovery during the acute phase of rehabilitation A great deal of variance between participants in most measures due to low numbers of subjects, no significant differences was found between the Control and Intervention groups.

Kohlmeyer et al. 1996; USA PEDro=10 RCT Initial N=60; Final N=45

2.

3.

Popovic et al. 2005; Canada PEDro=6 RCT N=21

Population: Age: 25-70; ASIA A-D incomplete; Time Since Injury: 15-243 days; acute/subacute; tetraplegic Treatment: The control group received conventional Occupational Therapy; Intervention group received Functional Electrical Therapy and conventional Occupational Therapy

1.

5-7

Author Year; Country Score Research Design Total Sample Size

Methods Outcome Measures: Functional Independence Measure (FIM); Spinal Cord Independence Measure (SCIM); Rehabilitation Engineering Laboratory Hand Function Test (REL Test); Consumer Perceptions. Population: Age 18 to 35 yrs, Gender m=24, f=4, level of injury C5-C7, at least 1yr post injury Treatment: Both groups received 45 mins of aggressive exercise therapy 3/wk for 12 weeks along with 30 min of neuromuscular stimulation to assist with upper extremity muscle strength. EX group also received 12 wks of 30 min EMG biofeedback 3/wk. Outcome Measures: Manual muscle test, functional activities score Population: Age 18-45 yrs, level of injury C4-C6, incomplete injury, at least 1yr post injury Treatment: All received 3days/wk of therapy in 2 consecutive eight week treatment blocks. Treatment blocks were as follows; Group 1: Biofeedback followed by supervised physical therapy exercise (PET) Group 2: Biofeedback followed by neuromuscular stimulation (NMS) Group 3: NMS followed by PET Group 4: 16 weeks PET Outcome Measures: Manual muscle test assessed the biceps, triceps, wrist flexors and wrist extensors. Self care measures looking at feeding, hygiene and dressing. Mobility measure and a muscle electrical activity were also measured Population: Gender m=81, f=19, injury level C2-C6, age 17-63yrs, time since injury 1-29.7yrs. Treatment: EMG biofeedback treatment sessions. Outcome Measures: EMG scores.

Outcome

1.

Klose et al. 1993; USA PEDro=5 RCT Initial N=31; Final N=28

2.

Scores after training indicated no significant differences for the muscle test score and functional activities score between groups. Analysis of the repeated measures factor showed a significant change (p<0.05) for the manual muscle test (F=25.17, df=2, 52) and functional activities score (F=8, 86, df=2, 52). No statistically significant differences were noted between the groups. Differences were noted for the repeated measures of mobility, selfcare, and the left arm muscle test scores (p<0.05). The repeated measures factor was statistically significant in all of the analyses looking at measures of physical function (p<0.01) but not in those that compared EMG values.

1. 2.

3.

Klose et al. 1990; USA PEDro=3 RCT Initial N=43; Final N=39

1.

Brucker & Bulaeva 1996; USA Downs & Black score=18 Pre-post N=100

2.

3.

T-test analysis of the differences before and after initial biofeedback treatment an increase of 19.21% of normal EMG scores for right triceps and increase of 19.59% of normal EMG scores from the left triceps from one biofeedback treatment session, significant (p<.001). T-test analysis of the difference from before initial biofeedback treatments to after additional treatments, increase in percentage of normal EMG scores of 41.55% right triceps and 38.31% left triceps, significant (p<.001). Increases in percentage of normal EMG scores after initial biofeedback treatment to after additional biofeedback treatment 22.3% right triceps and 18.72% for left triceps, significant (p<.001). Correlation coefficient for manual muscle test score and EMG pretest before initial treatment was r=.569 for

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome right triceps and r=.437 for left triceps, significant (p<.001). Increases in percentage of normal EMG before, after, and after additional treatments was significant in right and left triceps regardless of initial manual muscle test.

4.

Discussion All of the studies concluded that there was no firm evidence of the effectiveness of the use of augmented feedback to improve arm function in rehabilitation. van Dijk et al. (2005) in their systematic review recommended the following be considered in future research in this area: future studies need to focus on content, form and timing of the augmented feedback to clarify its importance in rehabilitation studies should recognize the difference between performance and learning effects concerning reacquisition of motor skills by re-examining the study population after a follow up period

Conclusion There is level 1 evidence (from 2 RCTs) that augmented feedback is not effective in improving upper limb function in tetraplegia. Augmented feedback does not improve motor function of the upper extremity in SCI rehabilitation patients.

5.4 Pharmacological Interventions Cervical injuries of the spinal cord frequently lead to hypertonia characterized by disabling spasticity and dystonia involving the upper and lower limb. Spasticity has been defined by Lance (1980) as a velocity exaggerated increase in the tonic stretch reflexes (muscle tone) resulting from hyperactivity of the stretch reflex. The EU-SPASM Thematic Network or Consortium (Support Network for the Assembly of Database for Spasticity Measurement) has presented an updated definition of spasticity that reflects a recent research findings and current clinical interpretations. Spasticity has been re-defined as disordered sensori-motor control, resulting from an upper motor neurone lesion, presenting as intermittent or sustained involuntary activation of muscles (Pandyan et al. 2005).

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Table 5.3 Pharmacological Interventions

Author Year; Country Score Research Design Total Sample Size Methods Population: age 25-64yrs, injury level C4C7, ASIA A-D, length of time since injury 1.2-24yrs. Treatment: Intrathecal baclofen. Outcome Measures: Ashworth Scale; Spasm Frequency Scale; Reflex Scale 1. 2. Outcome Significant decline in UE hypertonia during 12 month follow up period. Average baseline Ashworth score was 2.4 1.1 (SD) compared to 1.8 1.0 (SD) at 12 months (P<0.0001, Friedman). The average spasm score decreased from 2.3 1.6 (SD) to 0.5 0.9 (SD), not significant at P=0.2503 (Friedman test). The difference was significant (P=0.0012 Wilcoxon signed rank test). UE reflexes, average baseline reflex score was 2.3 0.2 (SD) compared to 0.9 0.2 (SD) at 12 months (P<0.0001 Friedman). Dosage requirements increased during the 12-month follow-up period, statistically significant (P<0.0001, Friedman). Statistically significant declines in upper extremity spasm scores (1.8 points, p=0.012), reflex scores (1.4 points, P<0.0001) and Ashworth scores (0.6 points, P<0.0001) for the 1-year follow-up period.

3.

Burns & Meythaler 2001; USA Downs & Black score=16 Case Series N=14

4.

5.

6.

Discussion The management of severe cases of hypertonia can be challenging as it can be refractory to oral medications. Many studies have shown that intrathecal delivery of balcofen has been effective for refractory hypertonia in the lower extremity. Baclofen, 4-amino-3 (p-chlorophenyl) butyric acid works by binding to the inhibitory presynaptic GABA-B receptors in the spinal cord (Meythaler et al. 1999). Intrathecal delivery of the drug facilitates achievement of therapeutic levels in the cerebral spinal fluid (CSF) while minimizing systemic side effects (drowsiness, confusion). Burns and Meythaler (2001) is the only study published which deals with hypertonia involving the upper extremity post-SCI. Further discussion regarding the management of hypertonia can be found in the spasticity chapter. Burns and Meythaler (2001) showed statistically significant decrease in Ashworth (tone) and reflex scores in upper extremity hypertonia due to pathology at the level of the spinal cord. Conclusion There is level 4 evidence that intrathecal baclofen may be an effective treatment for upper extremity hypertonia of spinal cord origin. Intrathecal baclofen may be an effective intervention for upper extremity hypertonia of spinal cord origin.

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5.5 Restorative Strategies 5.5.1 Plasticity of Motor Systems It has been reported that 55% of all spinal cord injured persons are classified as having complete injuries. Through the use of magnetic resonance imaging (MRI) and histopathology indicates that approximately 65% of the traumatic injuries initially classified as neurologically complete (absence of sensory and motor function in lowest sacral segment) show some tissue and axonal sparing across the lesion (Bunge et al. 1997). It is now accepted that the CNS is capable of substantial reorganization, especially in incomplete SCI because cortical, sub cortical and much of the local spinal cord circuitry remains largely intact and still partially interconnected by unlesioned fibres (Raineteau et al. 2001). Information may still pass through the level of the lesion on spared fiber tracts but the information maybe fragmented or distorted (Beekhuizen et al. 2005). Functional recovery can occur for several years after injury in incomplete spinal cord injury, with the degree of recovery dependent upon the reorganization of circuits that have been spared by the lesion (Green et al. 1999). Cortical reorganization occurs after SCI with evidence that the sensorimotor cortex may play a role in the recovery of function in individuals with SCI (Green et al. 1999). Results of neuroimaging and neurophysiological techniques (functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS) and positron emission tomography (PET) demonstrate that changes occur in the cortex following damage to the spinal cord with expansion of cortical areas corresponding to muscles spared after SCI into the cortical areas previously associated with control of muscle reinnervated at spinal cord levels below the level of the lesion (Raineteau et al. 2001; Bruehlmeier et al. 1998; Cohen et al. 1991; Levy et al. 1990). In ISCI, reorganization might occur at two levels; in pre-existing circuits by modifications of synaptic strength (synaptic plasticity) or by new circuits through sprouting or anatomical reorganization, including growth of axonal branches and dendrites (anatomical plasticity) (Raineteau et al. 2001). Laboratory work is currently explaining and researching cortical reorganization, cortical plasticity, sub cortical plasticity, plasticity at the red nucleus, plasticity and spontaneous adaptation of the central pattern generators (CPG) and plasticity of unlesioned descending pathways. The strengthening and weakening of synapses, axonal and dendritic sprouting can occur at different levels of motor system in response to spinal cord lesions, in the cortex, the brainstem, and the spinal descending pathways and in the intraspinal circuits. All interact with each other; therefore it is difficult to interpret functional recovery processes. A spinal cord injury interrupts distinct descending fibre populations. The overall complexity of an incomplete spinal cord injury resides first in the organization of descending spinal tracts. Most of the descending systems terminate on spinal interneurons, but some direct excitatory or inhibitory connections to motor neurons also exist. Different tracts are involved in specific functions. For example, lesions of the cortical and rubrospinal systems lead to more severe and longer lasting deficits for movement of the distal extremities and lesions of the reticulo and vestibulospinal systems affect movements of proximal and axial muscles. Functional outcomes of given spinal cord lesions therefore depends on type of fibres that are interrupted (Raineteau et al. 2001). Functional reorganization is based on two mechanisms; synaptic plasticity in pre-existing circuits and sprouting and anatomical reorganization that leads to the formation of new circuits. The study of animal models provides further understanding of rehabilitation treatments and development of new therapeutic approaches for people with spinal cord injury (Raineteau et al. 2001).

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Two studies were found that tested the use of massed practice, a form of constraint therapy, and repetitive transcranial magnetic stimulation (rTMS) in changing the cortex. Table 4: Restorative Strategies
Author Year; Country Score Research Design Total Sample Size Methods Population: Age: range 22-63 yrs; Gender: m=9, f=1; ASIA score: C N=4, D N=6; Level of injury: C5-C7: time since injury: 12 to 154 mths Treatment: Subjects participated in 2h of massed practice (MP) therapy 5/wk for 3 wks or MP+median nerve somatosensory stimulation (SS). Massed practice training focused on continuous repetitions of the following: gross upper extremity movement, grip, and grip with rotation, pinch and pinch with rotation. Tasks in each block were performed for 25 min before moving to the next category. Outcome Measures: Maximal pinch grip force, Wolf motor function test timed task scores, Jebson hand function test scores, stimulus intensity required to elicit motor threshold response in muscles, and motor evoked potentials amplitude. 1. 2. 3. Outcome Pinch grip scores: differences were noted in the MP+SS group (Z=-2.023, p<0.05) only. The MP+SS group also showed greater increase in pinch grip strength than the MP group (U=2.0, p<0.05). Upper extremity Functional tests: the Pre/post Wolf Motor Function Test timed scores in the MP+SS group showed a difference (Z=-2.023, p<0.05). No statistical differences were noted for the MP group. Timed test scores between the 2 groups were also found to be statistically different (U=1.0, p<0.05). Jebsen test scores: pre and posttest scores were different for the MP+SS group (Z=-2.023, p<0.05). The MP+SS group showed greater improvement than the MP group (U=3.0, p<0.05). Cortical Excitability: No significant differences were noted between the 2 groups. No difference between patients when looking at the assessments done after baseline and after sham intervention. The level of intracortical inhibition was reduced to 37.5 8.0% of pretreatment levels during the week of therapeutic treatment (p<0.05) and returned to 90.2 15% of pretreatment levels during the follow-up period. This was linked to improvements in clinical measures of both motor and pinprick of 4-10% during treatment week. (p<0.05). Subjects also improved perceptual threshold to electrical stimulation of the skin and peg board test scores (p<0.05)

Beekhuizen and FieldFote 2005; USA PEDro=8 RCT N=10

4. 5.

6. Population: gender m=3, f=1, age 4154yrs, time since injury 1.25-8yrs, lesion level C5, ASIA-D Treatment: 5 days of sham repetitive transcranial magnetic stimulation (rTMS) followed by 5 days of therapeutic stimulation (rTMS) Outcome Measures: electrophysiological, clinical - sensory + motor function (ASIA) & Functional - 9 Hole Peg Board 1. 2.

Belci et al. 2004; UK Downs & Black score=13 Prospective Controlled Trail N=4

3.

4.

Discussion Beekhuisen et al. (2005) suggested that massed practice or constraint-induced therapy promotes cortical reorganization that may be an effective rehabilitative tool for improving strength and function in individuals with cervical spinal cord injury. Improvement may be further enhanced by the addition of somatosensory stimulation. Belci et al. 2004 observed clinical changes consistent with the concept that reduced corticospinal inhibition can facilitate functional recovery. Recovery involved increased ASIA

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sensory and motor scores, improved response to cutaneous electrical stimulation over the thenar muscles and possibly improved hand/finger function. This preliminary study demonstrated rTMS treatment in patients with chronic stable incomplete spinal cord injury can produce reductions in corticospinal inhibition detectable using electrophysiological techniques. Additional research studies with appropriate controls are needed to confirm the overall effectiveness of the intervention. There is lack of studies evaluating the efficacy of restorative strategies. In order for these therapies to be successful in everyday clinical practice, the therapy interventions need to be associated with meaningful changes in functional motor performance and incorporate techniques that are available in the clinic and at home (Beekhuizen et al. 2005). Conclusion There is level 1 evidence from one RCT that showed that massed practice (repetitive activity) and somatosensory stimulation (median nerve stimulation) demonstrated significant improvement in grip and pinch strength required for functional activity use. There is level 2 evidence from a before/after study that showed that rTMs treatment in individuals with chronic stable ISCI may produce reductions in corticospinal inhibition that resulted in clinical and functional changes for several weeks after treatment. Afferent inputs in the form of sensory stimulation associated with repetitive movement and peripheral nerve stimulation may induce beneficial cortical neuroplasticity. Restorative therapy interventions need to be associated with meaningful change in functional motor performance and incorporate technology that is available in the clinic and at home. 5.5.2 Complimentary Alternative Therapies (CAM) Acupuncture is an ancient Chinese therapy practiced for more than 2500 years to cure disease and relieve pain (Lee et al. 1990). There are 361 identified acupoints that have been formed into a network of 14 channels called the meridians. Acupuncture therapy has been shown to be effective in improving functional outcomes in hemiplegic stroke patients and in paraplegic spinal cord injured patients (Cheng et al. 1998). In electrical acupuncture therapy, electrical stimulation is provided directly to the acupoint areas. It has been speculated that acupuncture therapy through the correct acupoints and meridians in the acute spinal cord injury episode will assist in the minimization of posttraumatic cord shrinkage and sparing of the ventral horn neurons (Politis et al. 1990; Ran et al. 1992; Tsay 1974; Wu 1990). Table 5.5 Complimentary Alternative Therapies (CAM)
Author Year; Country Score Research Design Total Sample Size Wong et al. 2003; Taiwan PEDro=5 RCT N=100 Methods Population: Age mean=35, gender m=80, f=20, ASIA A-B, tetraplegia (37)/quadriplegia (63). Time since injury: acute, admission to ER after injury Treatment: Acupuncture was administered to the treatment group via 4 x 5 cm 1. Outcome Acupuncture group - sensory, motor + FIM scores improved significantly day of D/C + 1yr after injury (p<0.05). Control group - only motor score significant improvement at 1yr post injury F/U p=0.023

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Author Year; Country Score Research Design Total Sample Size

Methods adhesive surface electrodes at the acupoints of bilateral Hou Has (S13) and Shen Mo (B62). Frequency was set at 75 hz with a pulse duration of 200 usec and the magnitude of stimulation was set at 10 mV Outcome Measures: ASIA (sensory + motor), FIM, before + after therapy 2.

Outcome Comparison of ASIA + FIM scores of both groups not at admission; D/C + 1yr post significant improvement ASIA + FIM in acupuncture vs. control p<0.05 More patients in acupuncture group improved to ASIA grade B + C or better at D/C + 1yr post p<0.05

3.

Discussion With acupuncture thin metal needles are inserted into specific body sites and slowly twisted manually or stimulated electrically. The uncomfortable pain sensation or de qi, a prerequisite for effective acupuncture therapy, is induced by needle manipulation (Wong et al. 2003). The randomized control trial by Wong et al. (2003), studied the use of electrical acupuncture therapy through adhesive surface electrodes and concomitant auricular acupuncture therapy in improving the neurologic or functional recovery in acute traumatic spinal cord injury patients. The study demonstrated that in the acupuncture group all sensory, motor and FIM scores improved significantly when examined on the day of discharge from hospital and one year after injury (p<0.05). The control group (auricular acupuncture) demonstrated only significant improvement in motor score at one-year post injury follow up (p=0.023). At discharge and at one year post injury follow up, the acupuncture group revealed significant improvement in all ASIA and FIM scores when compared to the control group (p<0.05). An inherent bias may have been introduced into this study as the reviewer who assessed the participants was not blinded to the group assignment. Conclusion There is level 2 evidence from one RCT that showed that the use of concomitant auricular and electrical acupuncture therapy may improve the neurological and functional recovery of acutely injured spinal cord individuals. The use of concomitant auricular and electrical acupuncture therapies when implemented early in acute spinal cord injured persons may contribute to neurologic and functional recoveries in spinal cord injured individuals with ASIA A and B.

5.5.3 Splinting of the Hand Splinting of the hand in the management of tetraplegia is a well-accepted therapy intervention and has been an accepted practice for many years in the management of SCI especially in the acute phase of injury (Curtin1994; Krajnik and Bridle1992). The therapeutic goals of splinting are immobilization, protection and support of the joints of the wrist and hand, prevention of joint malalignment, prevention and reduction of soft tissue shortening and contractures, prevention of soft tissue overstretch, counteracting hypertrophic scars, support of weak muscles, improvement of function and pain relief (Paternostro-Sluga and Stieger 2004; Curtin1994; Krajnik and Bridle 1992). There are four most common static hand splints for tetraplegic

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patients; resting pan or paddle splints, wrist extension splints (Futuro-type splint, long opponens splint and dorsal cock-up splint and spiral splint), short hand splints and tenodesis splints (Curtin 1994). Table 5.6 Splinting of the Hand
Author Year; Country Score Level Total Sample Size Methods Population: Age 18 to 42 yrs, gender m=12, f=1, time since injury 68wks Treatment: EX gr. was given long or short orthosis to be worn at night (8hrs) as soon as the subject could tolerate it. Outcome Measure: pinch strength and functional activity use DiPasquale-Lehnerz 1994; USA Pedro=4 RCT Initial N=13; Final N=9 1. Outcome No significant differences were noted between the 2 groups-all subjects demonstrated improvement in hand function and pinch strength. At 8 weeks the 13 subjects showed improvement in their performance on the checkers subtest (F=10.32, df=1, 11, p<0.01), simulated feeding subtest (F=7.58, df=1, 11, p<0.01), and the large light object subtest (F=5.49, df=1, 11, p<0.01). At the 12-week marker, improvement could be seen on the card subtest (F=3.94, df=2, 14, p<0.05). An increase in pinch strength was noted at 8 weeks for all subjects (F=4.41, df=1,11, p<0.05) and at 12 weeks 9 remaining subjects (F=4.46, df=2,14, p<0.05)

2.

3. 4.

Discussion Even though splinting and orthotic fabrication is an accepted practice, there is minimal research data on the effectiveness of this intervention (DiPasquale-Lehnerz 1994; Krajnik and Bridle 1992), although there are numerous anecdotal descriptions of orthotic devices and rationales for orthotic intervention (DiPasquale-Lehnerz 1994). Curtin (1994) and Krajnik and Bridle (1992) also found formal assessments were often not done due to; a lack of time and staff shortages; inconsistent documentation; absence of standardized tests available for spinal cord injured patients; limited funding to purchase equipment; and/or patient declined to participate in formal assessments due to boredom and frustration. Krajnik and Bridle (1992) noted that therapists considered observation of the patient when involved in a functional activity as the most informative assessment although this was not an objective means of documenting a patients status and progress. There appears to be a variety of splints made for similar purposes because there is little research as to what splint is best for the level and stage of SCI (Krajnik and Bridle 1992). In Paternostro-Sluga and Stiegers (2004) review, the therapeutic aims of splinting and the choice of splint depend on the disease and the individual functional problem resulting from the impairment. These authors also concluded that there is insufficient evidence from clinical trials on splinting strategies in CP or spinal cord injury patients. The studies also referred to research looking at hand splints for clients with an acquired brain injury or stroke (Rose and Shah 1987; McPherson et al. 1982). In the only study which met criteria for our review, by DiPasquale-Lehnerz (1994) noted that there was no significant improvement in hand function as it related to passive range of motion, strength of prehension or coordination in subjects with C6 tetraplegia who wore a thumb

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opponens orthoses during sleep as compared to those subjects with C6 tetraplegia who did not wear such an orthosis. The study did show over time a significant improvement of hand function especially pinch strength, and functional use (turning cards, picking up small objects, simulated feeding and holding onto light cans) for those wearing the splint. There are several published surveys that addressed the use of splints in the spinal cord population with the majority of splints being functional use splints (i.e., feeding splint, writing splint, typing splint or an application for an assistive device) (Krajnik and Bridle 1992; Garber and Gregoria 1990). More research is needed in this area. Conclusion There is level 2 evidence based on one RCT that wearing a thumb opponens splint will improve pinch strength and functional use of the hand. There is clinical and intuitive support for the use of splinting for the prevention of joint problems and promotion of function for the tetraplegic hand. However, there is very little research evidence to validate its overall effectiveness. 5.6 Sub Acute Phase of Rehabilitation 5.6.1 Upper Limb Injuries A spinal cord injured individual is forced to rely on their upper extremities for their weight bearing activities such as transfers, mobility needs and activities of daily living (ADLs) using limbs that were designed to place hands in space (Dalyan et al. 1999; Dyson-Hudson et al. 2004; Consortium of Spinal Cord Medicine, 2005). Repeated use of the upper limb for weight bearing activities such as manual wheelchair propulsion, transfers, raised ischial pressure reliefs (weight shifts) and reaching from a seated position in the wheelchair in environments designed for nondisabled individuals places a great deal of stress on the bones, joints and soft tissues of the shoulder complex. This places the structures of the upper limb at significant risk for overuse and subsequent injury (Dyson-Hudson et al. 2004). Pain in the early post injury period is typically due to increased demands on anatomically weakened muscles or muscle weakness induced because of deconditioning. Upper limb pain is known to interfere with a wide range of functional activities, transfers, ambulation, pressure relief, self-care (Curtis et al. 1995, Dalyan et al. 1999); many individuals report alternation/cessation of activities critical to functional independence (Pentland and Twomey 1994; Sie et al. 1992). Shoulder pain may be functionally and economically equivalent to a higher level of lesion (Salisbury et al. 2003). Dalyan et al. (1999) reported that of individuals with upper limb pain, 26% needed additional help with functional activities and 28% reported limitations of independence. Subbarao et al. (1994) and Gerhart et al. (1993) reported that individuals with SCI reported that their dependence in personal care assistants fluctuated with upper limb pain and was a major reason for functional decline. The Consortium of Spinal Cord Medicine (2005) has written clinical practice guidelines Preservation of Upper Limb Function Following Spinal Cord Injury: A Clinical Practice Guideline for Health Care Professionals, as a way to address upper limb problems.

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5.6.1.1 Shoulder Injuries Upper limb pain and injury are highly prevalent in people with SCI and consequences are significant. The Consortium of Spinal Cord Medicine (2005) and Dyson-Hudson and Kirshblum (2004) reported through surveys and cross-sectional studies that shoulder pain in chronic spinal cord injured persons are common in both paraplegia and tetraplegia at a prevalence of 30-73%. In the acute phase after SCI, shoulder pain is reported in approximately 75% of patients (Silfverskiold and Waters 1991; Waring and Maynard 1991), and 33% to 63% of patients in the chronic phase (>6 months) experience shoulder pain (Nepomuceno et al. 1979; Sie et al. 1992; Silfverskiold and Waters 1991). Curtis et al. (1995), Nichols et al. (1979) and Pentland and Twomey (1991) reported in cross sectional studies that 60-100% of long-term wheelchair users experience shoulder pain. Subbardo et al. (1994) and Sie et al. (1992) reported that there is a high prevalence of shoulder pain during the first year after injury, and in individuals 15-20 years post injury. Pain experienced above the injury level during the first 3-6 months after injury is different than the pain experienced 1 year or more after injury (Apple 2001). Pain above the level of injury in chronically injured person assumes the character of overuse syndromes (Apple 2001). Injury involving the shoulder, elbow, wrist and hand are seen at an earlier age in spinal cord injured individuals than in the general population because of the stresses of weight bearing and mobility that are added to the normal use of the upper limb (Pentland and Twomney 1996). Individuals who are older at the time of injury may experience functional changes earlier than people who are injured at a younger age (Thompson 1999). It is also very difficult to determine whether shoulder pain is a function of duration of SCI or simply a part of the normal aging process (Neer and Walsh 1977). The wide variability in these numbers is most likely a reflection of the heterogeneity of participant populations between the studies with respect to duration of injury, age, neurologic level and severity of injury, as well as body mass index. Small sample size, selection bias and variations in participant populations across the different studies with respect to duration of injury, age, gender and neurological level and severity of injury make it difficult to assess the true prevalence of shoulder pain in individuals with shoulder pain (Pentland and Twomey 1991). The incidence of shoulder pain in acute tetraplegia (<6 months post injury) has been reported to range from 51% to 78% (Salisbury et al. 2003). Nichols et al. (1979) was one of the first groups to report an association between chronic SCI and shoulder pain coining the term wheelchair users shoulder. Due to the prevalence of shoulder pain, Curtis et al. (1995) developed a Wheelchair Users Shoulder Pain Index (WUSPI) that measures the severity of pain for 14 functional activities.
The following are the many identified risk factors for the development of injury and pain in the upper limb. The shoulder is the most common joint above the level of injury where pain complaints are reported with persons with paralysis (tetraplegia or paraplegia) (Apple 2001). The shoulder is not well designed to handle the higher intra-articular pressures required for both weight bearing and mobility (Apple 2001). Partial innervation and impaired balance of shoulder, scapular and thoracolumbar muscles place individuals with tetraplegia at a higher risk for developing shoulder pain especially during weight-bearing upper limb activities such as wheelchair propulsion, transfers, and pressure reliefs. Due to differences in trunk postural control, differences may also occur between individuals with high paraplegia (T2-T7) and low paraplegia (T8-T12). Individuals with C1-C4 motor levels of injury are also at risk for shoulder pain SCI severity also may be associated with shoulder pain (Dyson-Hudson and Kirshblum 2004).

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Lack of use of immobilization of the shoulder girdle muscles can limit their active joint movement and lead to muscle shortening and shoulder capsule tightness. The development of pain is associated with decreased shoulder ROM Weakness and paralysis in these muscles can lead to increased reliance on the trapezius, which can result in overuse and pain in this muscle. Shoulder pain can occur from nerve root injury or radicular pain with dysesthesias or phantom sensations People of certain age groups, those with higher cervical lesions and those with shorter lengths of bed rest may be at a greater risk Gender may be associated with shoulder pain in individuals with SCI (Pentland and Twomey 1991). Body mass index (BMI) also may play a role in shoulder injuries in manual wheelchair using individuals with SCI because it directly relates to the amount of physical strain experienced during ADLs in these individuals (Boninger et al. 2001; Jensen et al. 1996). Shoulder pain is more common in individuals with tetraplegia and complete injuries and in women and duration of injury, older age, and higher BMI all may be risk factors for developing shoulder pain and/or abnormalities in persons with SCI (Dyson-Hudson and Kirshblum 2004).

5.6.1.2 Elbow/Wrist and Hand Injuries The prevalence of elbow pain and injury has been reported to be between 5-16% (Consortium of Spinal Cord Medicine, 2005); Sie et al. (1992) found 15% and 16% rates of pain localized in the elbow region in persons with tetraplegia and paraplegia. Dalyan et al. (1999) in their study found 35% complained of elbow pain. The prevalence of carpal tunnel syndrome is reported to be between 40-66% (Consortium of Spinal Cord Medicine 2005). There are four studies done by Aljure et al. 1985; Gellman et al. 1988; Schroer et al. 1996, and Sie et al. 1992 that found an association between length of time since injury and prevalence of carpal tunnel syndrome. Some studies also found median nerve damage without clinical symptoms. The most significant activities causing pain in the wrist and hand were propelling a wheelchair and doing transfers (Subbarao et al. 1994). Table 5.7 Shoulder Treatment Interventions
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=18, f=6, age: 2869yrs, time since injury: 5-33 yrs, SCI; length of shoulder pain: 4mths-22yrs. Treatment: Subjects received either acupuncture treatments (sessions lasted 20 to 30 min) or Trager Psychophysical Integration - sessions lasted approx 45 min. Consisted for both table work and mentastic exercises. Outcome Measures: Intake questionnaire (demographics and medical history), Weekly log, Wheelchair users shoulder pain index (WUSPI), Numeric rating scale, Verbal rating scale (VRS), Range of Motion (ROM). 1. Outcome There was a significant effect of time for both treatments on performance corrected (PC)-WUSPI (Acupuncture p<0.001 and Trager p=0.001). Overall a reduction of the PC-WUSPI could be seen when looking at the data from the beginning of treatment to the end for both groups (p<0.05) There was a significant effect of time for both acupuncture and Trager groups for average pain & most severe pain (p<0.01, p<0.001 respectively), for the least severe pain the acupuncture group showed a significant reduction (p<0.01) compared to the Trager group.

2.

Dyson-Hudson et al. 2001; USA PEDro=7 RCT N=21

3.

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Author Year; Country Score Research Design Total Sample Size

Methods 4. Population: age19-65 yrs; TSCI (C4-L1); ASIA A-D; 1-24 yrs duration Treatment: Experimental group participated in a progressive exercise training twice weekly for 9 months-each session offered on alternative days lasing 90-120 minutes. Outcome Measures: Perceived stress scale, muscle strength, depression, physical self-concept pain, perceived health and Q of L were assessed Population: Gender: m=35, f=7, age: mean=35yrs, duration of wheelchair use: mean=24yrs, Injury level: cervical to lumbar, mixed etiology Treatment: Both groups completed the Wheelchair Users Shoulder Pain Index (WUSPI) q2mos x 6mos. The experimental group attended a 60min educational session where they were instructed in 5 shoulder exercises. Outcome Measures: Self report questionnaire (demographic and medical info), Wheelchair User's Shoulder Pain Index (WUSPI), and a visual analog scale (VAS) used to rate intensity of pain. 1.

Outcome Verbal response scores- there was a statistically significant treatment effect for both groups (p=0.001). EX group reported less pain, stress and depression after training + scored higher than CON in indices of satisfaction with physical function, level of perceived health + overall quality of life (p<0.05). Following training, EX gr. had significant increases in sub maximal arm ergometry power output (81%; p<0.05) and significant increases in upper body muscle strength (19-34%; p<0.05) There were no significant differences between control and experimental group in age, years of wheelchair use or activity levels. When looking at the effect of exercise of intervention on performance corrected (PC) WUSPI, a 2 factor repeated measures ANOVA showed a significant effect of time only (p=0.048).

Hicks et al. 2003; Canada PEDro=6 RCT Initial N=32; Final N=24

2.

1.

2.

Curtis et al. 1999; USA PEDro=5 RCT N=42

Discussion Management of established upper limb pain is very difficult and thus prevention is critical. Evidence-based best practice standards have not been established for the medical, rehabilitative or surgical treatment of upper limb injuries in people with spinal cord injury. In addition, there is little consensus among health-care providers on the best treatment practices for upper limb injuries in the general population. In general, musculoskeletal upper limb injuries in the SCI population are managed in a similar fashion as the unimpaired population. Outcome studies of surgical treatment in SCI also very limited. Two small studies report the outcome of rotator cuff repair one showing relatively poor results (Goldstein et al. 1997) and another study showing relatively good outcomes (Robinson et al. 1993). Both studies recommend non-surgical approaches prior to surgical intervention. One randomized control trial found that supervised exercise produced results similar to arthroscopic surgery for patients with impingement syndrome (Brox et al. 1993), however; this study was not on SCI patients. Exercise has been shown to reduce pain in a randomized control trial in which subtypes of pain were not reported (Hicks et al. 2003). Two studies found an association between restricted ROM and pain, reduced activity and/or injury (Ballinger et al. 2000; Waring and Maynard 1991). A study incorporating stretching into an exercise program for individuals who use manual wheelchairs found stretching exercises were associated with decreased reported pain intensity (Curtis et al. 1999).

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One study demonstrated that acupuncture was no more effective than Trager Treatment in the treatment of shoulder pain (Dyson-Hudson et al. 2001). There are several studies that address the use of complimentary or alternative medicine (CAM) with the spinal cord population, which is used at similar rates to the general population. It was reported that the most common reason CAM was used, was for dissatisfaction with conventional medicine for treatment of chronic pain (Nayak et al. 2001). The only CAM technique evaluated in the SCI population is acupuncture although studies do not provide conclusive evidence of effectiveness (Nayak et al. 2001; DysonHudson et al. 2001; Rapson et al. 2003). Psychological interventions among non-SCI individuals with chronic pain are popular and it has been suggested that selected approaches may be useful for those with SCI (Consortium of Spinal Cord Medicine 2005). Cognitive-behavioural strategies have been found to produce changes in pain experience, increase positive cognitive coping and appraisal skills and reduce pain behaviours (Morley et al. 1999). There are mixed results for the use of relaxation training for relief of chronic pain (Carroll and Seers1998), which may also have secondary beneficial effects on muscle tension and emotional distress (Astin et al. 2002; Luebbert et al. 2001). Cognitive-behavioral interventions have not been subjected to controlled trials as to their effectiveness in the SCI population (Wegener et al. 2001). As identified in the Consortium of Spinal Cord Medicine (2005) document, modification of task performance based on ergonomic analysis has been proven to reduce the incidence of upper limb pain and cumulative trauma disorders of the upper limb in various work settings (Carson 1994; Hoyt 1984; Chatterjee 1992; McKenzie et al. 1985). It is suggested that these same interventions can be used to prevent pain and injury in SCI. Although the number of studies linking activities of individual with SCI to injury may be small, the ergonomics literature provides a strong basis for evidence-based practice.
The Consortium of Spinal Cord Medicine (2005) Clinical Practice Guideline Preservation of Upper Limb Function published the following recommendations regarding the upper limb; Both the spinal cord injured person and the clinician need to be educated about the prevalence of upper limb pain and injury and the potential impact of pain and possible means of prevention Routinely assess the patients function, ergonomics, equipment and level of pain as part of periodic health review Assessment of risk factors, changes in medical status, new medical problems, changes in weight Reduce the number of non level transfers per day Assess work related activities Re-evaluate current exercise program (strengthening, stretching, conditioning)

Dyson-Hudson et al. (2001) in a randomized controlled trial compared acupuncture treatment to Trager Psychosocial Integration performed by a certified Trager practitioner. The authors noted that trager therapy is a form of bodywork and movement re-education to induce relaxation and encourage the patient to identify and correct painful patterns. The theory is that chronically contracted muscles reduced by stress led to pain (Dyson-Hudson et al. 2001). There was a significant effect over time for both treatment groups in reducing shoulder pain, but there was no difference between the two groups. Curtis et al. (1999) in a randomized control trial and Hicks et al. (2003) studied the effectiveness of a six-month exercise and stretching protocol on shoulder pain experienced by wheelchair users. The data supported the effectiveness of this exercise and stretching protocol

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in decreasing the intensity of shoulder pain that was interfering with functional activity of wheelchair users. Further Research The Consortium of Spinal Cord Medicine (2005), Sipski and Richards (2006), Campbell and Koris (1996), Dalyan et al. (1999), and Nichols et al. (1979), have identified the following as important areas of further research in the upper limb:

Research to validate and support the adoption of a standardized classification scheme with accompanying diagnostic procedures and criteria. Research trials could include both primary prevention and treatment of acute and chronic pain. Determine the best methods to treat existing painful shoulder lesions and prevent others so that these individuals are as pain free and independent as possible. Further study is needed to elucidate the mechanisms of pain in this group and to establish why some patients who have pain early in rehabilitation continue to have pain at discharge and others do not. Multicentre RCT of intervention are also needed to reduce the severity and impact of different subtypes of SCI pain. Possible links between pain during rehabilitation and pain in long-term SCI. Detailed investigation of the biomechanics of activities commonly performed by people with tetraplegia to enhance understanding of the stresses placed on the shoulder and the mechanical causes of shoulder pain. Causes of shoulder pain in the acutely injured individual compared to the chronic spinal cord injured person. Implementation of upper limb pain prevention and management programs for persons with SCI- acute and ongoing patient education about basic biomechanical principles on avoiding impingement and overuse Managing the early signs of strain and overuse and knowledge of several alternative techniques of ADL. Education and training in endurance and balanced strengthening of muscles acting around the shoulder and optimizing posture to achieve a normal alignment of shoulder, head, and the spine are critical for avoidance of injuries. Ergonomically designed environmental changes and wheelchair, home and work modifications

Further clinical and biomechanical research to improve the preventative measures and treatment methods of
upper limb pain in SCI persons in order for them to maintain optimal functional status.

Conclusions There is level 1 evidence based on two RCTs that a shoulder exercise and stretching protocol reduces the intensity of shoulder pain post SCI. There is level 2 evidence that general acupuncture is no more effective than Trager therapy in reducing post-SCI upper limb pain. Shoulder exercise and stretching protocol reduces post SCI shoulder pain intensity. Acupuncture and Trager therapy may reduce post-SCI upper limb pain. Prevention of upper limb injury and subsequent pain is critical.

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5.7 Reconstructive Surgery 5.7.1 Hand The loss of upper limb function especially the use of the hand is one of the most significant and devastating losses an individual can experience. Tetraplegia is responsible for many problems in daily living, mostly related to the recovery and/or preservation of independence for the tetraplegic individual (Welraeds et al. 2003). In the study by Hanson and Franklin (1976) showed recovery of hand function was preferred to that of the bladder, bowel or even sexual function among tetraplegics. In a survey of tetraplegic patients, 75% responded that hand function was very important for their independence in activities of daily living (ADL) and to increase their quality of life (Snoek et al. 2004). Reconstructive surgery is one option to attempt to improve the function of the hand and upper limb in persons with tetraplegia. Functionally, the benefit of reconstructive surgery may be evident as improved ability to write, complete catheterizations, dress, self-feed, drive, lift objects, button, turn dials, propel their wheelchair, catch objects overhead, turn in bed and swim are only some of the activities that become possible after surgery (Rabischong et al. 1993). Surgery has been reported to improve quality of life for those people who had little or no upper limb function (Freehafer et al. 1984). As aptly stated by Sterling Bunnell, one of the preeminent surgeons when describing improvements of hand and upper limb function as a result of surgery, When you have nothing, a little is a lot. Despite the many reported studies, over 40 documented studies, hand reconstructive surgery is not common practice in many spinal units and its importance in improving hand function still remains controversial (Forner-Cordero et al. 2003). Guttmann (1976), McSweeney (1969) and Bedbrook (1969) believed that only a small percentage of tetraplegics (5%) benefit from hand surgery because they re-adjust the function of their arm and hands if properly rehabilitated, while other authors like Moberg (1975) state that 75% of tetraplegics can obtain benefit from hand surgery. Reconstructive surgery and tendon transfers are generally performed following an identifiable pattern based on the level of injury and results depend on the patients residual motor and sensory function as identified in each group (Freehafer et al. 1984). In 1978, the International Classification for Surgery of the Hand in Tetraplegia was developed at the International Conference held in Edinburgh and modified in 1984. The classification takes into account the residual motor strength below the elbow, considering that only the muscles graded 4 or 5 according to the Medical Research Council Scale (MRCS) are adequate for muscle transfer, as well as the sensibility in thumb and index. The sensibility was evaluated by the two-point discrimination test in the thumb and the index. If it is lower than 10mm the classification belongs to the group Cutaneous (Cu-) and if it is higher than 10mm and the patient needs visual help it is classified in the group Ocular (O-). Table 8: Modified International Classification for Surgery of the Hand in Tetraplegia
0 1 2 3 4 5 Motor Weak or absent Brachioradialis (BR) grade 3 BR ( grade 4) BR, ECRL BR, ECRL, ECRB BR, ECRL, ECRB, PT BR, ECRL, ECRB, PT, FCR O2 1 3 Sensory Cu1 1 1 4 4 Total 3 1 2 7 4

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Sensory Motor Total OCu6 BR, ECRL, ECRB, PT, FCR, Finger Extensors 7 BR, ECRL, ECRB, PT, FCR, Finger Extensors, Thumb Extensors 1 1 BR, ECRL, ECRB, PT, FCR, Finger Extensors, Thumb Extensors, 8 1 1 Finger Flexors 9 Lacks intrinsics only 1 1 Total 7 13 20 O-: Two-point discrimination in the thumb > 10mm. Cu-: Two-point discrimination in the thumb < 10mm. ECRL: Extensor Carpi Radialis Longus ECRB: Extensor Carpi Radialis Brevis PT: Pronator Teres FCR: Flexor Carpi Radialis The listing of a muscle means that it is functional (grade 4 or better). (McDowell CL, Moberg EA, House JH. The Second International Conference on Surgical Rehabilitation of the Upper Limb in Traumatic Quadriplegia. J Hand Surg 1986; 11A: 604-608.)

Candidates for reconstructive surgery are carefully selected and are followed by a rehabilitation team that includes an orthopedic surgeon, rehabilitation physiatrist, and therapist over a significant period of time. The identified criteria for selection are as follows: At least one year post injury Completed a comprehensive rehabilitation program Neurologically stable Psychologically adjusted to their injury

The measure of outcomes following reconstructive surgery continues to be debated in the literature. Many of the reported studies on surgical outcomes are older, are case series evaluations and lack the rigor of randomized control trials, and have subjective outcomes based on reported client satisfaction. In addition, there is little consensus in the literature on the assessment instruments and tools to be used in this population as their reliability, validity and responsiveness have not been adequately proven. The methodology appears to be a major failing of the various scales and the absence of clear conceptual models forming the basis of their scales. Also, the scales or instruments have been deemed to be too insensitive to document the small but meaningful functional gains made by tetraplegics after functional surgery (Fattal 2004). Many authors state that comparing the post surgical condition is the best way to evaluate results (Freehafer et al. 1984). There have been several articles published that discuss the use of the ICF conceptual framework as a way to interpret hand function outcomes following tendon transfer surgery for tetraplegia (Sinnott et al. 2004; Bryden et al. 2005). The reconstructions of upper limb to obtain functions of pinch and grasp often require multiple procedure and are also individualized to each person. The reconstructions performed are also dependent on what motor muscles/tendons are present and strong enough for transfer. The most commonly performed surgeries for reconstructive pinch are: Key-Pinch Grip: Brachioradialis (BR) to Extensor Carpi Radialis Longus (ECRL), Flexor Pollicis Longus (FPL) split tenodesis. The IP joint of the thumb may need to be stabilized to prevent excessive IP flexion. Key-Pinch Grip with or without Hook Grip: Brachioradialis (BR) to Flexor Pollicis Longus (FPL) with or without Flexor Digitorum Profundus (FDP) tenodesis or Brachioradialis (BR) to Extensor Carpi Radialis Longus (ECRL).

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Key-Pinch Grip and Hook Grip: Brachioradialis (BR) or Pronator Teres (PT) to Flexor Pollicis Longus (FPL) and BR or Extensor Carpi Radialis Longus (ECRL) to Flexor Digitorum Profundus (FDP). Additional procedures to increase thumb pinch and thumb opposition may also be completed. Table 9: Reconstructive Surgery: Pinch Studies
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=13 , f=2; Age: range 20-47 yrs; Injury to operation: range 8 months-18 yrs; Operation to follow-up: range 8-48 months; Treatment: Surgery Outcome Measures: Pinch strength; ADL reports. 1. Outcome Release of the BR and suture to the FPL. In 16/17 hands , fixation of the IP joint of the thumb was obtained with a Moberg screw. 11/17 patients lacked active thumb extension had tenodesis of the thumb extensors to the MCP to prevent excessive flexion of the MCP joint. 2. EPL and EPB were secured to the dorsum of the MC. 6/11 patients did not require tenodesis had sufficient strength in the EPL to extend the thumb. 3. 2/6 EIP was transferred to EPL for active extension. 4. Satisfactory finger flexion present 10 hands. In seven hands: intertendinous suture of all FDP tendons 4 patients who had active flexion in the ulnar profundi of small and ring finger, but could not flex index finger; 5. Transfer of PT to all FDP tendons in 2 patients; transfer of ECRL to all FDP tendons in 1 patient; transfer of FCU to all FDP tendons one patient. 6. Preoperative lateral pinch ranged from 0- 0.15 lbs post operative lateral pinch ranged from 2.2-4 (depending on elbow and wrist position) 7. Residual motor function in triceps (fair plus)(11 patients) and pinch strength; lateral pinch 5.1 lbs, strength fair or less (6patients) 2.0 lbs pinch. 8. 87% (13/15) reported significant improvement; 4 patients wanted stronger pinch; 9. 80% (12/15) could name 4 ADL activities that they were able to perform. 10. 13% (2/15) were dissatisfied. 11. 20% (3/15) reported discomfort tip of thumb. (Follow-up 1-10yrs (average 3.5yrs) 1. All patients reported a significant increase in independent hand function in relation to ADL's, no patient reported hand function was worse after surgery 2. Technique provided a reliable and

Waters et al. 1985; USA Downs &Black score=12 Case Series N=15

House et al. 1992; USA Downs & Black score=11 Case Series N=18

Population: Gender-m=14, f=4, level of injury-C5-C6, Age-16-29yrs, time to surgery-16mths to 12/13 yrs Treatment: Carpal-metacarpal fusion was performed; along with extensor pollicis longus tenodesis and motor transfer to flexor pollicis longus.

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Author Year; Country Score Research Design Total Sample Size

Methods Outcome measures: function of the hand, subjective pain scale, & level of satisfaction with surgery and rehabilitation Population: Gender m=103, f=30, age 858yrs, tetraplegia, follow-up 3-24mths. Treatment: Extrinsic hand reconstruction with intrinsic balancing procedures vs. extrinsic reconstructions without intrinsic balancing procedures Outcome Measures: Pre and postoperative assessments of grip strength (on the second position of the Jamar dynamometer) and a patient questionnaire evaluating 31 activities of daily living

Outcome reproducible key pinch All patients had significant improvement in functional activities of daily living and highly satisfied with results of surgery All patients had preoperative grip strength of 0. At an average follow-up period of 31 months, the average final grip strength was 69N (7kg) and the ADL improvement score averaged 35.5 Patients who underwent an intrinsic procedure had a statistically stronger grip (72N) than patients who did not undergo an intrinsic procedure (p=0.026). OCU group 5 patients with an intrinsic procedure had a statistically stronger grip than patients without an intrinsic procedure (p=0.028). With the exception of OCU group 7 in which 8 patients did not undergo an intrinsic procedure due to their ability to balance tension between the extensors and flexors, all other OCU groups with an intrinsic reconstruction showed stronger grip than patients without an intrinsic reconstruction. ADL improvements scores were higher but not statistically significant for those with intrinsic rebalancing versus those without rebalancing. There was significant difference between the hands treated by FDS lasso and those treated by intrinsic tenodesis when patients were stratified by OCU level. There was also no significant difference in grip strength results between the FDS lasso versus the intrinsic tenodesis procedures when stratified by both OCU level and type of extrinsic reconstruction, both surgical techniques were effective in improving strength and ADL.

3.

1.

2.

3.

4. McCarthy et al. 1997; USA Downs & Black score=10 Pre-post N=135 5.

6.

7.

Summary Table 5.10 Pinch Studies

Author N 15 patients (17 procedures) Intervention BR to FPL (lateral pinch) with thumb IP joint stabilization (16 hands) 11 patients also had EPL tenodesis and EPB to metacarpal joint; 2/17 patients EIP to EPL procedure CMC fusion EPL tenodesis Main Outcome(s) +ve lateral pinch strength in all test positions +ve ADL functions +ve direct correlation between pinch strength and amount of residual triceps and wrist extensor strength +ve pinch strength +ve ADL and functional use

Waters et al. 1985

House et al. 1992

18 patients (21 procedures)

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Intervention BR 0r ECRL or ECRI to FPL As indicated: stabilization of thumb IP joint and Zancolli Lasso procedure 135 patients Extrinsic reconstruction with Intrinsic (183 procedures) Balancing vs. without Intrinsic McCarthy et al. 1997 Balancing FDS Lasso vs. Intrinsic Tenodesis for Intrinsic Balancing + positive outcome, = no difference, - negative outcome

Author

Main Outcome(s)

+ve grip strength with intrinsic balancing = ADL and functional use = grip strength = ADL and functional use

Pinch and Grasp (Key-Pinch and Hook Grip) The most commonly performed surgeries to obtain key-pinch and hook grip are; Wrist Extension: If the person does not have adequate wrist extension, Brachioradialis (BR) to Extensor Carpi Radialis Brevis (ECRB) is performed prior to any surgery for pinch reconstruction. Key-Pinch and Hook Grip: Extensor Carpi Radialis Longus (ECRL) to Flexor Digitorum Profundus (FDP). This is a synergistic transfer in which dorsiflexion of the wrist potentiates the effects of the transfer. The amplitude of excursion provides strong flexion of the fingers into the palm. Brachioradialis (BR) is also transferred to Flexor Pollicis Longus (FPL). The aim of these transfers is to provide mass finger flexion for grasp and independent thumb flexion for key-pinch against the side of the middle phalanx of the index finger. Adjustment of tension in these transfers is also completed (Lamb and Chan 1983). Table 5.11 Reconstructive Surgery: Pinch and Grip Studies
Author Year; Country Score Research Design Total Sample Size Meiners et al. 2002; Germany Downs & Black score=10 Case Series Initial N=24; Final N=22 Methods Population: Gender f=3, m=21, age 2157yrs, time since injury 9-59months Methodology: Surgery Outcome Measures: ADL questionnaire, Satisfaction Survey, Key grip and lateral force grip Population: Age: 19-60 yrs Age at injury: 15-46 yrs; Injury to operation: 1-17 yrs; Follow-up post op: 1-17 yrs ; Gender: 17 m, 7 f; Level of injury; 3 in group III, 11 in group IV, 7 in group V, 4 in group VI. Intervention: surgery Outcome Measures: Not specified Kelly et al. 1985; USA Downs & Black score=9 Case Series N=24 Outcome No statistical findings reported. 1. Operative interventions on the tetraplegic hand brings gains in cylindrical and lateral grip and improvement in ADL 2. Subjective acceptance is high 3. Complication rate is high 4. Long duration of treatment 1. 7 extremities had had post deltoid to triceps transfer before opponensplasty; 24 patients, 11 (46%) had bilateral opponensplasty. 2. 35 opponensplasties were done. 22 flexor tendon transfers were done for voluntary grasp and then opponensplasty. 3. 14 patients (22 extremities) evaluated. 4. Subjects reported that they would have the operation again (95% of the extremities) and had improved function (91%). 5. One patient reported that function was unchanged; 1 was dissatisfied. Overall value of key pinch 35 extremities was 1.47 +/- 1.29 kg (mean +/- SD).

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Author Year; Country Score Research Design Total Sample Size

Methods 6.

Outcome Grasp measured in 20 extremities; 2.81 +/- 2.89 kg (mean +/-SD) (range trace to 10kg). 7. Palmar pinch; 9 of 20 extremities (45%) achieved palmar pinch (1.04 +/1.02 kg; mean +/- SD) (range 0.20-3.0 kg). Palmar pinch achieved in 17% of the extremities in group III, 71% in group IV, and 33% in group V. No statistical results reported. 1. Self assessment questionnaire results indicated: power decreased since surgery in all patients. No statistical results reported. 1. All reported they would have surgery again. 2. Key pinch strength in non-op limbs was 1.0 1.3 kg, in surgically treated arms it was 1.2 1.1 kg. 3. Minnesota rate of manipulation: nonoperative limbs were 1 min 29 secs 15 secs, post operative limbs was 2 min 56 secs 1 min 56 secs. No statistical results reported 1. 6 of 8 subjects were evaluated. Subjects indicated they were pleased with the surgery. 2. Hand function tests indicated an improvement (16-49% improvement). 5 of 6 subjects showed key grip strength remained constant. No statistical results reported-8 pts interviewed, 5 completed questionnaire. 1. Conclusion-transfer of brachioradialis tendon provides key pinch and grip of sufficient quality to improve the activities of daily living in patients with loss of flexion of the thumb and fingers 1. Strength: key-pinch strength average of 17.2 kPa (5-50 kPa); grasp strength average 18.8 kPa (3-45 kPa). 2. No relation found between the activities of daily living test and the key=pinch strength (P=O.7976) or grasp strength (P=0.6948). 3. Modification of ADL questionnaire; excellent (3) 21.4%; good (7) 50.0%; fair (2) 14.3 %; poor (2) 14.3%. Scores ranged from 54-122 points. No statistical analysis reported 1. Passive range of motion of the elbow and wrist remained unchanged post surgery. Functional active flexion of the fingers was gained in 10 of 11 subjects. 2. Improved performance of ADLs was reported.

Rieser & Waters 1986; USA Downs & Black score=8 Case Series N=23

Lo et al. 1998; CA Downs & Black score=7 Case Series N=9

Population: Age: mean=23.6yrs; age at time of surgery: mean=29.8yrs, time from injury to operation 6.2 yr, follow-up time of this study: 7.4 yrs Intervention: Surgery Outcome Measures: Not specified Population: at least 1 yr post injury, C5-6 spared quadriplegia Intervention: Surgery Outcome Measures: not specified

Colyer & Kappelman 1981; USA Downs & Black score=7 Case Series N=8

Population: Age: 16-36yrs, time post injury: 4mths-18yrs Intervention: Surgery Outcome measures: Not specified

Faillia et al. 1990; USA Downs & Black score =6 Case Reports N=8

Population: age 9-58yrs, tetraplegia Treatment: Surgery Outcome Measures: key pinch, grip strength, function in ADL

Forner-Cordero et al. 2003; Spain Downs & Black score=5 Retrospective Follow-up Initial N=15; Final N=14

Population: age at first operation 2062yrs, level of injury C4-C7, time from injury to operation 15-239 months. Treatment: Surgical reconstruction. Outcome Measures: Increased hand movement and strength; improvement in ADL; patient's satisfaction, fulfillment of patient's expectations, surgical complications. Population: age at time of surgery 20-47 yrs. Intervention: Surgery. Outcome Measures: Not specified

Gansel et al. 1990; USA Downs & Black score=4 Case Series N=19

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Summary Table 5.12 Pinch and Grip Studies

Author N 22 patients (23 hands) Intervention FCR to FDP ECRL to FDP Main Outcome(s) +ve lateral and cylindrical grip +ve satisfaction with surgery +ve ADL and functional use

Meiners et al. 2002

Kelly et al. 1985

24 patients (57 procedures)

Reiser and Waters 1986

9 patients (10 procedures)

7/24 also had PD to Triceps Opponensplasty- FDS to APB Flexor tendon transfers: BR (also used PT, FCR, ECRL, FCU, PL) to FDP 22/35 Flexor tendon transfer BR to FDP (also used PT, FCR, ECRL) Tenodesis of FPL, thumb IP joint stabilization 6/9 MP joint tenodesis of extensor tendons of thumb 2/9 BR to wrist extensor 7/9 tenodesis of EPL and EPB

+ve satisfaction with surgery +ve ADL functional use +ve key-pinch, palmar pinch and grip strength

-ve result, bowstringing of FPL across MP joint -ve grasp and lateral pinch strength +ve satisfaction with surgery +ve key-pinch and grip strength +ve ADL functional use +ve improved pinch strength -ve finger flexion +ve ADL and functional use +ve key-pinch and grip strength +ve ADL and functional use

Lo et al. 1998

8 patients (12 procedures)

ERCL to FDP and BR to FPL

Colyer and Kappleman 1981

6 patients (8 hands)

FPL tenodesis 2 also had ECRL to FDP BR to FDP or FPL BR or ECRL to FPL PD to Triceps BR to ECRB Tenodesis of FPL APL to CMC joint or arthrodesis of CMC joint BR or ECRL or PT to EDC and EPL or tenodesis of extensor tendons BR or ECRL or ECRB to FPL PT or ECRL or BR to FDP Zancolli Lasso of FDS 11/11 PT to FDP 10/11 BR to FPL 1/11 BR to FDS

Faillia et al. 1990

8 patients (9 hands)

Forner-Cordero et al. 2003

15 patients (20 limbs)

+ve key-pinch strength +ve grip strength = ADL and functional use +ve patient satisfaction -ve patient expectation

Gansel et al. 1990

11 patients

+ve finger flexion +ve key-pinch strength +ve ADL functional use

+ positive outcome, = no difference, - negative outcome

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5.7.2 Elbow Extension The most commonly performed surgery for elbow extension is using the posterior third of the deltoid (PD) to motor the triceps. This converts the transferred portion of the deltoid into a two joint muscle but causes no functional loss at the shoulder (Moberg 1975). Table 13: Reconstructive Surgery: Elbow Extension Studies (Posterior Deltoid to Triceps)
Author Year; Country Score Research Design Total Sample Size Methods Population: age-mean 33.6yrs, level of lesion-C6, time since injury 28-173 months, time prior to sugery-34.5yrs, time since surgery-46.1 months Treatment: The arm and forearm were locked in position and a force transducer was used to assess the torque output isometrically. The muscle was tested at 6 different lengths with the shoulder abducted at 900 Outcome Measures: Maximal torque and absolute values. 1. Outcome The muscle was tested at 6 different lengths (130, 110, 90, 70, 45 and O degrees of elbow flexion) with the shoulder abducted at 90. 2. When compared, the absolute values (dimension of torque) were significantly different between groups (0.00001<p<0.002. 3. The expression of this relation (% of maximum values) revealed significant statistical differences (p<0.002) at 90 and 70 degree of elbow flexion; peak torque was at 130 degrees in experimental group and 110 degrees in control group with a plateau between 110 and 70 degrees. 4. Length-tension relationship was fairly similar among control group, but great differences in experimental group. 1. Straight Arm Raising-statistically significant decrease in maximal shoulder abduction (mean 57 SEM 12 before, 14 SEM 6 after surgery) 2. Shoulder flexion increased after deltoid-to-triceps transfer by 42% (mean 113 SEM 11), remained significantly lower (121 SEM 12) than control group (P<0.0001) 3. Hand-to-nape-of-neck-movement-no significant improvements were noted after surgery 4. Conclusion-peaks of shoulder and elbow flexion speed are almost normal, indicating the importance of restoring elbow extension torque for improving the whole kinematic picture of the upper limb 1. FIM scores: both groups scored identically 2. Mobility: no significant differences were noted (p=0.256, and p=0.432 3. Questionnaire: answered only by the treatment group-clients gave positive response to the questions. No statistical results reported: No statistically significant differences between pre and post operative stages. 1. Activities that were noted as improved

Rabischong et al. 1993; France Downs & Black score=16 Prospective Controlled Trial N=12

Remy-Neris et al. 2003; France Downs & Black score=13 Pre-post N=17

Population: gender m=11, f=5, age mean 27yrs, ASIA score 16-20 Treatment: Surgery. Control group members sat on a chair, while the tetraplegics sat in a wheelchair. All were asked to perform 2 movements; a straight arm lateral and maximal raising and return Outcome Measures: Straight Arm Raising & Hand-to-nape-of-neck movement

Dunkerley 2000; UK Downs & Black score=13 Case-Control Initial N=15; Final N=11 Lacey et al. 1986; USA Downs & Black score=7 Case Series N=10

Population: Age: 23-38yrs; Time since injury: 5-16 yrs; Age at time of injury: 18-27 yrs. Treatment: Surgery. Outcome Measures: Questionnaire; FIM; 10 m push and the figure of 8 push Population: Level of injury: C6 or C7; time since injury: average 24 mths, time to operation: approx 32 months Treatment: Surgery

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Author Year; Country Score Research Design Total Sample Size

Methods Outcome Measures: Not specified Population: Time since injury: average 10242 mths, 64.1 mths to surgery. Treatment: Surgery Outcome Measures: ADLs, use of wheelchair

Outcome were: the overhead use of the arms, use of arms while lying supine and eating. No statistical analysis reported. 1. 15 of 18 reported function improvement after surgery, 13 felt they gained an increase in independence. 2. Functional improvements and grooming was noted. 3. Improvements were noted in subjects ability to relieve ischial pressure from their wheelchair, writing improved, and driving in a small percentage was positively affected.

Raczka et al. 1984; USA Downs & Black score=4 Case Series Initial N=22; Final N=18

Summary Table 5.14 Elbow Extension (Posterior Deltoid to Triceps)

Author Rabischong et al. 1993 Remy-Neris et al. 2003 N Gr 1- 8 pts/11 elbows Gr 2-control 9 R hand (female) 5 pts 17 limbs 5 elbows, 6 controls 10 pts/16 procedures 18pts/19transfers Intervention PD to triceps PD to triceps Main Outcome(s) = initial tension pt transfer at time of surgery is important for torque output + ve ADL and functional use + ve straight arm raise +ve speed of movement = surgical/control gr: FIM (adapted) 13 items =surgical/control gr: W/C propulsion 8m&10 m push +ve elbow function indicated on questionnaire +ve satisfaction with surgery +ve ADL and functional use +ve elbow extension strength +ve ADL and functional use

Dunkerley 2000

PD to triceps

Lacey et al. 1986 Raczka et al. 1984

PD to triceps PD to triceps

+ positive outcome, = no difference, - negative outcome

5.7.2.1 Elbow Extension (Biceps to Triceps) A biceps to triceps transfer can be used to create elbow extension in patients who have active supinator and brachialis muscles to provide for the lost functions of the transferred biceps (Kuz et al. 1999). Table 5.15 Reconstructive Surgery: Elbow Extension Studies (Biceps to Triceps Transfer)
Author Year; Country Score Research Design Total Sample Size Kuz et al. 1999; USA Downs & Black score=7 Case Series N=3 Methods Population: Tetraplegic Treatment: Surgery Outcome Measures: Not specifed Outcome No statistical results reported: 1. subjects indicated they were satisfied with the surgery. 2. Activities that required precision hand placement had improved. 3. Elimination of the need for some adaptive aids was possible post surgery.

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Summary Table 5.16 Reconstructive Surgery: Elbow Extension Studies (Biceps to Triceps Transfer)
Author Kuz et al. 1999 N 3 patients 4 elbows Intervention Biceps to Triceps Main Outcome(s) +ve elbow extension +ve functional improvements through ability to place the hand in space +ve satisfaction with surgery

+ positive outcome, = no difference, - negative outcome

5.7.3 Multiple Reconstructions The following studies report results from multiple procedures to reconstruct the upper limb. Table 5.17 Reconstructive Surgery: Multiple Reconstructions
Author Year; Country Score Research Design Total Sample Size Methods Population: Age: mean age 42.9 years; Mean time since injury: 20.5 years; Mean time since surgery: 15.1 years; 22/24 right handed; Level of Injury: 01: 6 hands; 02: 3 hands; 03: 5 hands; 0Cu2: 2 hands; 0Cu3: 6 hands; 0Cu4: 17 hands; 0Cu5: 8 hands; 0Cu6: 1 hand; Tetraplegia Treatment: surgery Outcome Measures: Lamb and Chan questionnaire with additional 10 Burwood questions; Swanson sphygmomanometer (hook grip); Preston Pinch Meter (key pinch); Quadriplegic index of Function (QIF); Digital Analyzer (key and grip pinch) 1. Outcome Elbow Extension: bilateral surgery 9/11 subjects; Hook Grip; 17 right hands (av. Grip 46.2 mm Hg in 1991; improved slightly, not statistical significant (p=0.30)) Left hand: 15 hands: significant increase (p=<0.001), av. 28.7 mmHg to 53.2 mmHg; no statistical significance between right and left hook grip as measured by SGM and DA in 2001 (p=0.93 and p=0.97). Key Pinch: av. key pinch 20 right thumbs in 1991 25.8 N and decreased in time to av. 13.9 N (significant decrease p=<0.001); average pinch strength 18 left thumbs decreased from 17.7 to 8.8 N (significant decrease p=<0.001). Average pinch strength measured by DA, increase in key pinch when compared to 1991, significant for both right (p=0.01) and left (p=0.01) thumbs. Active Transfer Vs. Tenodeses: hook grip: active transfers 2x strength of tenodeses in 1991 (p=0.05) and 2001 (p=0.03). Pinch grip: similar to 1991 data (p=<0.001), 2001 data does not follow trend. 2001 DA data did not reach significance (p=0.06); Longitudinal Comparison: hook grip strength 25 hands with active transfers significant increase 42.1 to 60.2 mm Hg (p=<0.001) and pinch grip increase from 24.0 to 38.4 N in 31 thumbs that had active transfers using 2001 DA data (p=0.03). Hook strength obtained from a tenodesis in 7 hands did not weaken over time (p=0.05) but pinch strength in 7 thumbs significantly increased (p=<0.001) using 2001 DA data.

2.

Rothwell et al. 2003; New Zealand Downs & Black score=20 Case Series Initial N=29; Final N=24

3.

4.

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Author Year; Country Score Research Design Total Sample Size

Methods 5.

Outcome Questionnaire results; Lamb and Chan activity measure: showed perceived improvement of functional activities significantly lower in 2001 (p=<0.001). QIF scores of current functional independence was significantly better (p=0.004). Additional Burwood questionnaire showed levels of satisfaction, perceived expectation, gratification and opportunity enhancement were maintained over time (p=0.281). Elbow Function: 10/16 elbows (10 patients): full extension; 2/16 elbows 20 degree flexion contracture; 4/16 15 degrees of extension lag. All 10 patients considered the procedure beneficial. Hand Function: 48 hands (assessed only 27 patients). 5 rated as excellent; 28 rated good; 11 rated as fair; 4 graded as poor. No patient had any impairment of hand function after operation. ADL: 29 patients assessed. No one considered their functional capability deteriorated after operation. Most significant improvement in basic activities such as washing, eating and using the toilet, hold glasses and cups, wash limbs and brush hair, turn on taps, improve bladder compression, insertion of suppositories, change from complete reliance on other for selfcare, more mobile, 7 able to drive a car. Improvement in UL function facilitated development of personal interests. No statistical analysis providedgestural ability improved in more than 80% of the patients and functional gain was important in more than half. 43 procedures; Atypical procedures (2) good: 2; Moberg procedures (18) good: 17; poor: 1; Deltoid/triceps (12) good: 7; fair 3; poor 2; Additional procedures (11) good: 7; fair: 3; poor: 1. Subjective Assessment: obtained for 86% of the patients, av. Follow up of 37 months (range 5-86 months); 70% reported good or excellent results; 22% fair; 8% poor. Simultaneous surgery for key-grip and hook grip strength 96% good or excellent results. Objective Results: over 70% of patients, av. follow up of 32 months;

Population: Age: 21-59 years (av. 29 years); Gender: 38 male; 3 female; Complete injuries. Av. Follow up after operation: 6 months- 25 years; Tetraplegia Treatment: Surgery Outcome Measures: Elbow strength; Hand function (assessment checklist developed); ADL (developed checklist)

1.

2.

Lamb & Chan 1983; UK Downs & Black score=14 Case Series N=41

3.

Walreads et al. 2003; Belgium Downs & Black score=12 Case Series N=25

Population: Age at time of injury-mean 30yrs, age at time of operation-mean37yrs, time between injury and surgery 7-356 months, injury level C5-C8 Treatment: Upper limb surgery Outcome measures: Functional testing.

1.

2.

Mohammed et al. 1992 New Zealand Downs & Black score=12 Case Series N=57

Population: Age: av. age at first operation 27 years (5-55 years); Gender: 51 males, 6 females; Level of Injury: 00:4; 01: 6; 02: 4; 03: 6; 0X: 3; Cu3: 6; Cu 4: 24; Cu 5: 10; Cu 6: 3; Cu X: 3; Tetraplegia Treatment: Surgery Outcome Measures: Subject assessment of ADL by questionnaire; Objective assessment of key pinch (Preston Pinch Meter); Hook-grip strength (modified

1.

2. 3.

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Author Year; Country Score Research Design Total Sample Size

Methods Sphygmomanometer); Elbow extension: MRC grading system

Outcome Key Pinch 52/68 cases (76%); av. strength was 2.1 kg. Hook grip measured in 42/58 cases (72%), thumb included av. strength was 42 mmHg; thumb excluded 29 mmHg. Elbow extension measured in 71% of patients, obtained grade 3 or 4 strength. One hundred forty two transfers were performed on 68 subjects. No upper limbs were made worse. Four remained unimproved, all others that had tendon transfers improved.

4. Population: age at time of surgery 1561yrs, time since injury to surgery 1-17yrs, tetraplegics, Treatment: Surgical reconstruction Outcome Measures: Comparison of the post surgical with the pre surgical condition Population: Age: born between 19181962; Gender: 7 female, 36 male; Level of Injury: 0:1 9 pts; 0:2 2 pts; 0Cu:1 4 pts; 0Cu:2 13 pts; 0Cu:3 9 pts; 0Cu:4 5 pts; 0Cu:6 1 pt. re-examined 1-14 yrs after the last operation. Treatment: Surgery Outcome Measures: Questionnaire of 55 ADL tasks; opinion of the effect of surgery to perform these ADL tasks; elbow extension (evaluation of extension deficit or holding a sand bag in hand); key grip pinch (Preston Pinch Guage); finger flexion (Martin Vigorimeter) 1. 2. 3. 1.

Freehafer et al. 1984; USA Downs & Black score=12 Case Series N=68

Ejeskar & Dahllof 1988; Sweden Downs & Black score=11 Case Series N=43

Freehafer 1998; USA Downs & Black score=10 Case Series N=285

Population: Neurological levels C5-C8. Treatment: Surgical reconstruction. Outcome Measures: Not specified

Hentz et al. 1983; USA Downs & Black score=4 Case Series Initial N=30; Final N=23

Population: level of injury OCu 1,2,3 Treatment: Reconstruction of key grip and active elbow extension. Outcome Measures: interview and/or questionnaire (self-care, communication, mobility), objective measurements - pre + post op strength, ROM wrist + elbow extension, strength of key pinch, range of passive wrist flexion + functional testing

Elbow Extension: 30 elbows in 23 patients; (23/30 with free tendon graft;7/30 Castro-Sierra and LopezPita method); 5/23 with free tendon graft 1/23 full ext.; 8/23 lack ext. against gravity of max. 60; 10/23 lack even more ext.; 6/7 ext. deficit greater than 60. 2. Key Grip: 50 hands/40 patients; Strength 0-3.5 kg (av. 0.7 kg); 15 case had minimum of 1.0 kg. 3. Finger Flexion: 14 hand/13 patients (ECRL to profundi II-V); grip 0-0.27 kP (av. 0.13 kP); 5/14 minimum strength 1.0 kg. 4. 4 patients reported no improvement (1 severe spasticity, 2 BR muscle transferred to wrist; 1 operation on weaker hand); 4/43 could not state how much they had improved, 35/43 average improved capacity to perform 23/55 ADL tasks; 3/43 patients a functional deterioration. 1. Opponens transfers were done 180 times; transfers for finger flexion-161 times; posterior deltoid transfers-59 times; transfers for wrist extension-17 times. 2. 13 out of 285 stated that they were no better, and no patient said they were worse. No statistically significant findings reported Subjective client reports.

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Summary Table 5.18 Multiple Reconstructions

Author Rothwell et al. 2003 N 24 patients (48 reconstructions) Intervention BR to FPL or BR and tenodesis FPL ECRL to FDP PD to Triceps PD to Triceps Biceps to Triceps Hand Grip: ECRL to FDP BR to FPL Key-Pinch: FPL tenodesis or FPL tenodesis plus ECRL to FDP Other: EPB to ECU, FCR to FDS, APB to EDM PD to Triceps ECRL to FDS BR to FDS PD to Triceps Key-Pinch: BR or PT to ECRL; FPL tenodesis and IP stabilization Hook Grip: BR or ECRL to FDP Variation of all procedures PD to Triceps Tenodesis FPL, thumb IP joint stabilization ECRL to Profundus iv Opponens transfer: 180 times Transfers to finger flexors: 161 times PD to Triceps: 59 times Transfers for wrist extension: 17 times PD to Triceps or Biceps to Triceps FPL tenodesis BR to ECRB EPL and EPB tenodesis Main Outcome(s) +ve key-pinch and hook grip +ve ADL and functional use

Lamb and Chan 1983

41 patients (57 reconstructions)

+ve elbow extension and function -ve elbow extension (biceps to triceps) +ve hook grip and key pinch and ADL and functional use

Walreads et al. 2003

25 patients (43 procedures)

+ve elbow extension +ve key grip and grasp +ve ADL and functional use + hook grip strength +ve ADL and functional use +ve key-pinch and grip strength +ve elbow extension +ve ADL and functional use -ve elbow extension +ve key-grip and finger flexion +ve ADL and functional use

Mohammed et al. 1992

57 patients (97 transfers)

Freehafer et al. 1984

68 patients (142 transfers) 43 patients (94 transfers)

Ejeskar and Dahllof 1988

Freehafer 1998

285 patients (417 transfers)

Review of surgical procedures and recommendations.

Hentz et al. 1983

30 patients (40 limbs)

+ve satisfaction with surgery +ve pinch and grip strength

+ positive outcome, = no difference, - negative outcome

Discussion In reviewing the identified studies as a whole, the operative interventions on the tetraplegic hand and upper limb bring definite gains in pinch force, cylindrical grasp, and the ability to reach above shoulder height that result in an improvement in ADL function and quality of life for the individual with tetraplegia. Despite the level of evidence (grade 4) the subjective acceptance among patients who have had reconstructive surgery is high. One of the reported downsides of surgery is the high complication rate (infection, torn attachments) and the extended period of time post surgery for rehabilitation and increased need for personal care (Meiners et al. 2002).

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Many Spinal Cord Injury Centres do not offer or have access to reconstructive surgery or neuroprothesis interventions. It is also debated whether the overall cost of surgery or use of neuroprostheses is more beneficial to the client, as the client has to relearn new movement strategies in order to perform activities of daily living (ADL) (van Truijl et al. 2002). Conclusion There is level 4 evidence from multiple studies that support the use of reconstructive surgery for the tetraplegic upper limb for the improvement of ADL and quality of life. Reconstructive surgery appears to improve pinch, grip and elbow extension functions that improve both ADL performance and quality of life in tetraplegia.

5.8 Neuroprostheses A neuroprostheses for grasping is a device designed to improve or restore the grasping, holding and reaching functions in individuals with stroke and SCI (Baker et al. (1993); Cornwall et al. 2004). The neuroprostheses applies functional electrical stimulation (FES) in which paralyzed muscles are electrically stimulated to produce movement (Shimada et al. 1996A). The FES uses bursts of short electrical pulses (pulse widths 0-250 mSec and pulse amplitude 0-150 mA) to generate muscle contraction by stimulating motoneurons or reflex pathways. The key element for achieving synergistic activity of muscles that results with reaching and grasping is the appropriate sequencing of bursts of electrical pulses. For continuous contraction of the arm and hand muscles (tetranization), a FES system has to deliver at least 16 stimulation pulses per second to elicit action potentials (AP) in the motor nerve, causing the corresponding muscles to contract. FES enables the patients with high spinal cord injury to reconstruct grasp movements such as palmar and lateral grasps of the upper extremity (Shimada et al. 2003). The palmar grasp is used to hold bigger and heavier objects such as cans and bottles and the lateral grasp is used to hold smaller and thinner objects such as keys, paper and CDs (Popovic et al. 2002). It has been reported to be useful in improving ADL functions (Shimada et al. 1996A; Popovic et al. 2001). FES is also applied to generate elbow extension by stimulating the triceps brachii in combination with voluntary biceps contraction used to augment reaching (Grill and Peckham 1998; Popovic et al. 1998). Elbow and shoulder FES systems have not been developed into practical clinical devices. The motor nerves can be stimulated using surface (transcutaneous), percutananeous or implanted electrodes (Mortimer 1981). Transcutaneous stimulation is performed with selfadhesive or non-adhesive electrodes that are placed on the subjects skin in the vicinity of the motor point of the muscle that needs to be stimulated (Baker et al. 1993; Mortimer et al. 1981). Percutaneous and fully implanted electrodes are placed close to the entry point of the motor nerve to the muscle which should be stimulated, either epimysial or intramuscular (Cameron et al. 1997; Hoshimiya and Handa 1989). Individuals with C5-C7 complete SCI and with no major degree of motoneuron or nerve root damage of the stimulated muscles benefit the most from neuroprosthesis. The use of an implanted FES system can only be applied once the patient reaches stable neurological status, which usually occurs two or more years post SCI. The use of surface FES systems can be introduced during the early rehabilitation period, as the patient does not have to be neurologically stable. 5-35

Gorman et al. (1997) and Cornwall and Hausman (2004) have presented guidelines for patient selection for consideration of for an implantable neuroprosthesis. They are as follows: Anatomic: Stable tetraplegia with C5 or C6 motor level with international classification motor scores of 0, 1, 2 or an impairment scale level of A, B, C (ASIA) Physiologic: Presence of adequate ROM in joints of the shoulder, arm, forearm, wrist and hand Medical: Free of overwhelming medical problems Psychosocial factors: Sufficient motivation to learn its use and use it Adequate caregiver and/or family support One year post injury, plateau of functional recovery. Need for sufficient vision to provide visual feedback during training and use sufficient cognitive ability Contraindications to neuroprothesis use include: Cardiac disease Arrhythmias Pace makers Chronic systemic infections Diabetes Immune disease 5.8.1 Types of Neuroprostheses There are several existing neuroprostheses and these include implanted FES systems such as the Freehand System and the NEC FESMate System and surface stimulation electrode systems such as the Handmaster NMS-1, Bionic Glove, ETHZ-ParaCare Neuroprosthesis and systems developed by Rebersek and Vodonik and Popovic et al. 5.8.1.1 Freehand System The Freehand System from Cleveland, OH, USA is an implantable neuroprothesis intended to restore hand function in C5 and C6 level tetraplegics. The Freehand system can stimulate eight different muscles in order to produce a useful grip and key pinch in tetraplegic individuals. It is the only FDA approved (1997) implantable upper extremity neuroprothesis. The system consists of a surgically implanted receiver/stimulator unit and electrodes with an external controller and power supply/microprocessor. It was first implanted in 1986 (Cornwall and Hausman 2004). The NeuroControl Freehand System consists of an active receiver/stimulator that is placed in the chest wall and has eight leads that come from the receiver/stimulator and pass under the skin to a connector site in the upper arm. At this point they are joined to epimyseal electrode leads that are passed under the skin from the forearm and hand. Power and control signals from the unit are passed through the skin to the receiver/stimulator from a skin-mounted coil. The patient controls the device by movement of the opposite shoulder that uses a skin surface mounted position detector. The lateral grasp is generated by first flexing the fingers to provide opposition, which is followed by thumb flexion. Palmar grasp is generated by first forming the opposition between the thumb and palm, followed by simultaneous flexion of both the thumb and fingers. Stimulating the flexor digitorum superficialis and profundus muscles performs finger flexion and finger extension is obtained by stimulating the extensor communis digitorum. Stimulation of the thumb thenars muscle or median nerve produces thumb flexion. Hand opening and closure strength are proportional to the distance moved by the shoulder. Both

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palmar and lateral grasps are possible by pressing a button on the shoulder controller. Taylor et al. (2002) and Keith et al. (1996) reported that most clients with require several surgical procedures are needed for each client for optimal use of the device. The most common surgeries performed are brachioradialis to extensor carpi radialis for voluntary wrist extension and posterior deltoid to triceps for elbow extension (Taylor et al. 2002; Keith et al. 1996). The 1st generation of the Freehand System is no longer available from NeuroControl Corporation. There are devices still available on a selective basis in several centres (Cornwall et al. 2004). Table 5.19 Freehand System
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender m=26, f=8; Age: 1353 yrs; Age at implantation: 16-57yrs; Tetraplegia; One year post survey, including 6 months of home use Treatment: Implemented with a hand neuroprosthesis that provides grasp and release Outcome Measures: Functional Evaluations: standardized test of grasp and release, measurements of pinch strength and range of motion & satisfaction survey 1. Outcome General Satisfaction: 87% were positive agree or strongly agree, 97% would recommend neuroprosthesis to others, 90% were satisfied with neuroprosthesis, 90% stated neuroprosthesis was reliable, 87% would have surgery again, 80% felt the neuroprosthesis met their expectations, & 77% would pay for the neuroprosthesis if they had the money Life Impact: 88% responses were positive for life impact; 90% stated neuroprosthesis improved their quality of life; 87% positive impact on their life (90% reported did not make a negative impact); 83% provided a benefit ADL; 87% responses regarding changes in ADL were positive; 93% participants could perform ADL easier; 93% could perform ADL such as painting and shaving; 90% had increased confidence when performing ADL; 83% could perform ADL more normally; 73% could perform ADL faster Independence: 81% of responses were positive; 87% reported they were able to function more independently; 83% used less adaptive equipment; 87% required less assistance from others; 67% felt more comfortable out in the community alone Occupation: 57% of responses to occupation questions were positive Appearance: 87% felt their hand appearance was unchanged or improved Usage: used prosthesis median of 5.5 days/week - ranged from 15 participants (44%) who donned the neuroprosthesis 7 days per week to 5 participants (15%) who used it less than 1 day/week; 24/34 participants (71%) used it 4 or more days/week; range of usage C4/C5, C5/C5, C6/C6 levels was the same (0 to 7 days/week) C5/C6 group - used it

2.

Wuolle et al. 1999; USA Downs & Black score=22 Case Series Initial N=42; Final N=30

3.

4. 5. 6.

5-37

Author Year; Country Score Research Design Total Sample Size

Methods

Outcome most regularly 4 to 7 days/week with most participants 8/10 reporting daily use Activities: most frequently reported activities included eating, drinking, shaving, brushing teeth, brushing hair, writing, operating a computer, playing games Quality of Life: 18/34 positive comments; 1/34 responded neutrally; 1/34 responded negatively Improvements: Additional stimulus channels, an implanted command source, smaller, lighter external control unit - easier to don, improve hand and arm function, make device operable if user is confined to bed When the neuroprosthesis was activated all participants increased their pinch force in lateral pinch (p<0.001) and some increased their pinch force in palmar grasp (p<0.001). 98% of participants moved at least 1 object with the neuroprosthesis (p<0.001) and 37 improved by moving at least 3 more objects (p<0.001). Disability was reduced in 49 of 50 participants as measured by the ADL abilities or ADL assessment tools.

7.

8. 9.

Peckham et al. 2001; USA/UK/Australia Downs & Black score=16 Cohort Initial N=51; Final N=50

Participants: gender m=42, f=9, age at implant 16-57yrs, level of injury C5=C6, time from injury 4.6yrs (median), follow-up3-13.9yrs Treatment: Participants were trained to use the neuroprosthesis and to use it for functional activities. Once they were satisfied with their ability to perform daily activities or when they reached a plateau in proficiency then rehab was complete. Outcome Measures: Pinch strength, active ROM, Grasp-Release Test, Activities of Daily Living (ADL) Abilities Test, ADL Assessment Test, user satisfaction survey. Population: Age: 31-48 Gender: m=7: f=1; Level: C4-6 Time Since Injury: 43-430 months; Time Since Surgery: 8-53 months Treatment: Interviews- reviewing use of Neuro Control Freehand System Outcome Measures: Amount of Care & The System

1.

2.

3.

Taylor et al. 2001; UK 2001 Downs & Black score=16 Case Series Initial N=9; Final N=8

No statistical results reported 1. Care-all users had come from outside agencies (mean 11.5 h a day, range 324 hrs); 4 users had additional care from family members (mean 3.4 h a day, range 2-5 hrs); no users claimed that care given by family members had decreased 2. System-donning external components 5-10 min; most users reported no significant problems fitting the external equipment; 2 users had problems locating the coil; 3 locating the shoulder controller; 1 had persistent problems maintaining the position through the day d/t the adhesive tape used becoming detached (4 reported this as an occasional problem); 4 users had problems with skin allergy to the tape or double sided adhesive rings; 2 users reported that the system made transfers more difficult; 3 users never stopped using the system d/t system failure; some problems with equipment reliability; no change in paid caregiver time; 6 users felt more

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome confident when using the system; 7 felt their quality of life had improved Variation in elbow moment across subjects significantly greater than the variance within subjects (ANOVA p< 0.001). 10/11 elbows tested elbow moment generated by triceps stimulation at different elbow angles, elbow moment weakest with elbow in more extended position (30 degrees flexion) and peaked with elbow at 90 flexion, significant ANOVA p<0.001. Elbow moment generated by triceps stimulation at 90 and 120 degrees elbow flexion was significantly greater than elbow moment produced by tendon transfer (ANOVA p<0.05), no difference between elbow extension methods at 30 degrees elbow flexion. Triceps stimulation and posterior deltoid together provided a greater elbow moment than each method separately, difference significant at each elbow position p<0.05, except at 90 degrees. Quantitative workspace assessment done on 5 arms, more successful with triceps stimulation, significant for each subject, chi square p<.05). Average acquisition time with triceps stimulation less than without stimulation 4/5 arms (3.2-6.4 seconds) and significant in 3/5 arms (unpaired ttest p<0.01) and not for one p=0.076. 7/9 use Freehand System daily Provided an active grip of some strength which allowed many functional activities Increase in self confidence Over 80% of their selected ADL goals - user preferred to be independent with their Freehand system than use previous method or have activity performed by caregiver Pinch force ranged from 8 to 25 N, with stimulation and greater than tenodesis grasp alone; all demonstrated functional grasp patterns and were able to manipulate at least 3 more objects with the neuroprosthesis; had increased independence and were able to use the neuroprosthesis at home on a regular basis; the implanted stimulator proved to be safe and reliable.

Population: Level of injury C5-C6. Treatment: Epimysial or intramuscular electrodes were implanted on the triceps. Following surgery standard stimulation exercise regimens were followed. Outcome Measures: elbow extension moments at different elbow positions, performance in controllable workspace experiments, comparison to an alternative method of providing elbow extension in these individuals (posterior deltoid to triceps tendon transfer) Memberg et al. 2003; USA Downs & Black score=14 Case Series N=22

1.

2.

3.

4.

5.

6.

Hobby et al. 2001; UK Downs & Black score=14 Cohort N=9

Population: Tetraplegia; Age:16-55 Treatment: The patients, using an external stimulator, built up the muscles strength in the hand and forearm, to ensure the muscles were in good condition at the time of surgery Outcome Measures: Grip Strength, ADL

1. 2. 3. 4.

Kilgore et al. 1997; USA Downs & Black score=13 Case Series N=5

Population: Age: 28-57 years; Time from injury to insertion of implant: 2 years 2 months to 9 years; Clinically complete at C5 or C6; Chronicity: 2 years 2 months to 9 years Treatment: Implanted neuroprosthesis. Outcome Measures: Grasp force; GraspRelease Test; Tests of ADL (functional independence); Usage Survey

1.

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Author Year; Country Score Research Design Total Sample Size

Methods Population: age-16-18yrs, level CC6, >1yr post injury. Treatment: Surgery Outcome Measures: Grasp Release Test & ADL Test before and after implementation of the implanted FES hand system 1.

Outcome 40 electrodes implanted, 37 continued to work, all implant stimulators have functioned without problems with follow up ranging between 16 and 25 months 2. Grasp Release Test-lateral pinch and palmar grasp forces - Wilcoxon test, FES forces were significantly greater than tenodesis forces for both grasps (P=0.043) 1. Grasp release test results: increase in the types of tasks that subjects could perform (pre n=1.4) and post implantation (n= 5.1 p=0.011). 2. One year post implantation the types of tasks performed was 5.5 p=0.027, without the system it was 1.2 (p=0.028). 3. Number of repetitions increased post implantation from 12.7 to 37.4 (p=0.028) and with out the implant post-implantation (20.2, p=0.046). 4. At one year number of repetitions was increase to 50.5, p=0.046 with the system and without 24.3, p=0.28. 1. No predicted difference between electrodes in intrinsic and extrinsic muscles (P=0.93) 2. Significant differences were predicted between exit sites (P=0.016) + across muscle groups (P=0.047) 3. Survival likelihoods poorer for electrodes exiting dorsally 4. At 90 days after implant survivals probabilities of the finger + thumb extensors + thumb abductors (P=0.8) were smaller than that of thumb adductor + flexor muscle groups (P>0.9) No statistical analysis was complete. 1. Passive elbow extension was within normal limits. 2. With stimulated triceps subjects attained full elbow extension; without it full range was not met

Mulcahey et al. 1997; USA Downs & Black score=13 Pre-post N=5

Taylor et al. 2002; UK Downs & Black score=12 Case Series N=9

Population: age-mean 38.4yrs, gender m=7, f=1, level-C4-C6, time since injurymean 10.1 yrs. Treatment: no-it was assessment of the Freehand System Outcome Measures: Grasp Release Test, Grip Strength, Activities of Daily Living, Sensory ability (static 2 pt discrimination)

Smith et al. 1994; USA Downs & Black score=12 Case Series N=5

Population: age-13-19yrs, gender m=5, level of injury C5-C6, # of mths in study 1238, time since injury 3-72mths Treatment: Intramuscular electrodes were implanted in the upper extremity muscles Outcome measures: The Breslow Test - a non-parametric linear rank test used to compare survival chances across subgroups 95% confidence limit used to reject the null hypothesis

Bryden et al. 2000; USA Downs & Black socre=12 Case Series N=4

Smith et al. 1996; USA Downs & Black score=11 Case Series N=5

Population: Age 23-48yrs, level of injuryC5-C6 Treatment: Participants were implanted with an upper extremity neuroprothesis including a triceps electrode to provide stimulated elbow extension. Participants exercised triceps 4-6 hr/session using a programmed electrical stimulation exercise regimen that includes breaks. Participants exercised either nightly or every other night-whatever was best for maintaining an optimal amount of strength Outcome Measures: 5 overhead reaching tasks, amount of assistance required to complete the task & survey of home use. Population: age-13-19yrs, gender m=3, f=2, level of injury C5, time since injury 3 72mths. Treatment: FNS vs. Tenodesis

FNS vs. Tenodesis 1. With FNS and tenodesis each case of improved performance in later sessions was significantly better as

5-40

Author Year; Country Score Research Design Total Sample Size

Methods Outcome Measures: CWRU Hand System (Case Western Reserve University), Grasp and Release Test

Outcome compared to the initial session. (p<0.05). The average grasp forces with FNS increased; the range was from 8.9N (SD+5.2) to 22.5N (SD+8.6) and the palmar grasp forces increases from 2.1N (SD+2.9) to 11.1N (SD+6.0). No statistical results are reported. No perioperative complications reported. Subjects began Freehand System use between 2 = 5 days after implantation Muscle Strength-no subject gained significant strength in any key muscle on their freehand limb Pinch Force-with Freehand System each subject realized significant improvement in pinch force Upper Extremity Capacity-first 11 questions - no difference with or without Freehand-last set of questions Freehand System improved scores Quadriplegic Index of Function-all subjects increased their level of independence Freehand System Open-ended Questions-all subjects would repeat implantation

2.

Mulcahey et al. 2004; USA Downs & Black score=6 Case Series N=4

Population: Age-13-16years, tetraplegia, injury to surgery 4-16 weeks. Treatment: The following muscles were implanted with intramuscular electrodes: Extensor digitorum profundus, extensor pollicis longus, flexor pollicis longus, adductor pollicis, and opponens pollicis for each subject. Outcome Measures: Muscle StrengthPinch Force & Hand Function, Performance of ADL, Satisfaction with + without the Freehand System (COPM), Upper Extremity Capacity, Quadriplegic Index of Function

1. 2. 3. 4. 5. 6.

7. 8.

SummaryTable5. 20 Implanted Neuroprostheses (Freehand System and CWRU)

Author N Intervention Main Outcome(s) +ve satisfaction (87%) +ve life impact (90%) +ve ADL (87%) +ve independence (81%) +ve occupation (74%) +ve appearance +ve usage (5.5 d/week median) +ve activities +ve QOL +ve lateral pinch +ve palmar grasp +ve Grasp Release Test +ve satisfaction = no change in ability and long term stability and function = no change in level of personal care assistance -ve system failure +ve ADL and functional use

Wuolle et al. 1999

34

Implanted Freehand System and 31 had adjunctive surgeries

Peckham et al. 2001

51 implanted (50 evaluated)

Implanted Neuroprosthesis and adjunctive surgeries

Taylor et al. 2001

Implantation of Freehand System 5/11 Implanted Freehand System 6/11 CWRU 6/11 tendon transfer surgery for elbow extension 4 arms triceps electrode 11 triceps electrodes/10 UL

Memberg et al. 2003

10

+ve elbow extension +ve workspace assessment

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Author

Intervention

Hobby et al. 2001

Implanted Freehand System and adjunctive surgeries

Taylor et al. 2002

Implantation of Freehand System Implanted Neuroprosthesis and adjunctive surgeries Implanted Freehand System and adjunctive surgeries Implanted Neuroprosthesis Implantation of Freehand System with electrode to triceps Implanted Neuroprosthesis

Kilgore et al. 1997 Mulcahey et al. 1997 Smith et al. 1994 Bryden et al. 2000 Smith et al. 1996

5 5 5 4 (5 limbs) 5

Mulcahey et al. 2004

Implanted Freehand System

Main Outcome(s) +ve ADL and functional use (80%) +ve lateral grasp +ve palmar grasp +ve 5 finger grasp -ve several electrode failures; stimulator failure; medical complications 7/9 use device daily +ve Grasp Release Test +ve Grip Strength +ve ADL Assessment +ve pinch force +ve grasp strength +ve Grasp Release Test +ve ADL and functional use +ve Grasp Release Test +ve ADL and functional use -ve electrode failure +ve elbow function (strength, ROM) +ve ADL and functional use +ve unilateral grasp and release abilities with FNS = UE strength +ve ADL: QIF scores +ve Satisfaction: COPM +ve lateral and palmar pinch = UE capacity: UEC

+ positive outcome, = no difference, - negative outcome

5.8.1.2 HandMaster-NMS-1 The Handmaster developed by Nathan et al., and produced by Neuromuscular Electrical Stimulator Systems, Raanana, Israel. It has been FDA approved for use with stroke patients. It is predominantly used as an exercise tool for stroke subjects and is commercially available in a limited number of countries (Popovic et al. 2001). The Handmaster has three surface stimulation channels used to generate grasping function in tetraplegic and stroke subjects. One channel is used to stimulate extensor digitorum communis muscle at the volar side of the forearm. The second channel stimulates the flexor digitorium superficialis and profundus muscles. The third stimulation channel generates thumb opposition. The system is controlled with a push button that triggers the hand opening and closing functions. The system is easy to don and doff. However, it does have some limitations in its design. The system is limited by not enough sufficient flexibility to vary the position of the electrodes for stimulation of the finger flexors for grasp; it is a stiff orthosis that fixes the wrist joint angle and prevents full supination of the forearm (Popovic et al. 2001). Table 5. 21 Handmaster-NMS-1
Author Year; Country Score Research Design Total Sample Size Alon & McBride 2003 USA Downs & Black score=12 Case Series N=7 Methods Population: Gender m=7, level of injury C5-C6, 6mths post injury Treatment: Subjects practiced with the neuroprothesis daily to regain grasp, hold, and release ability and to restore selected functions of 1 of the 2 paralyzed hands. Outcome No statistical results reported. 1. All were 100% successful in using the handmaster in the studied ADL and grasp (hold and release) tasks. 2. Improvements were noted in strength (.57 98N to 16.5 4.4N, finger linear

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Author Year; Country Score Research Design Total Sample Size

Methods Subjects were observed 2 to 3 times weekly for 3 wee Outcome Measures: Hand function was evaluated by a series of upper limb measures: 3 ADL tasks, 3 hand impairment measures, 2 grasp and release tests. Population: Gender: m=8, f=2; Age range: 20 to 65; Level of injury: C4 to C6; Classification: 3-Cu n=3, 1-O n=5, 2-O n=1, 0-O n=1; Fitted hand: Right n=6, Left n=4 Treatment: Training for use of Handmaster Outcome Measures: not specified

Outcome motion (0.0cm to 8.4 3.2cm) and Fugi-Meyer scores (p<0.05)

Snoek et al. 2000; Netherlands Downs & Black score=8 Case Series Initial N=10; Final N=4

No statistical results were reported. 1. 6 people left the study for various reasons (>50%). Over all the 4 remaining were able to perform several tasks with the Handmaster that they were not able to without it ( e.g.: 3/4 were able to put the splint on independently)

Summary Table 5. 22: Handmaster-NMS-1

Author Alon and McBride 2003 Snoek et al. 2000 N 7 Intervention NESS Handmaster Main Outcome(s) +ve ADL use +ve Grasp Release Test +ve grip strength = finger motion -ve poor compliance, only 4 completed the training period

10 patients Handmaster (7 at end) + positive outcome, = no difference, - negative outcome

5.8.1.3 Bionic Glove Developed by Prochazka and colleagues at the University of Alberta the Bionic Glove improves hand function in people with SCI. This device uses three channels of electrical stimulation to stimulate finger flexors, extensors and thumb flexors. The control signal comes from a wrist position tranducer mounted in the garment. The actual functioning of the device can be described as greatly augmenting tenodesis (Prochazka et al. 1997; Popovic et al. 2005). The Bionic Glove is designed to enhance the tenodesis grasp in subjects that have a voluntary control over the wrist (flexion and extension). Stimulates finger flexors and extensors during tenodesis grasp, enhances strength of grasp. The Bionic Glove is available at the University of Alberta, Alberta, Canada and used primarily for clinical evaluation. A modified version of this device will be called Tetron (Popovic et al. 2002). Overall acceptance rate for long-term use is reported in 30% of potential users. Functions of power grasp and handling of big objects were significally improved (Popovic et al. 2002). There have been several identified concerns with the device that include damage to the stimulator located on the forearm that is frequently damaged through accidental contact during functional activities and the transducer mechanism is delicate and has to be replaced frequently (Popovic et al. 2001). Table 5.23 Bionic Glove
Author Year; Country Score Level Total Sample Size Popovic et al. 1999; Methods Population: 12 people with SCI at C5-7 1. Outcome QIF: mean was 19.0 +/- 6.5 at the

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Author Year; Country Score Level Total Sample Size Yugoslavia Downs & Black score=13 Case Series N=12

Methods who had used the device 6 months or more Age: 26.5 +/- 8.3 years (18-38 yr) 10 complete; 1 central cord; 1 BrownSequard Time post injury; 2+ years: 7; 1+ year: 3; 6 months+: 1; 3 months: 1 Treatment: Taught how to use the device Outcome Measures Quadriplegia Index of Function; Functional Independence Measure; Upper Extremity Function Test; Goniometric Measurements

Outcome beginning; at the end 28.4 +/- 5.2, improvement of 49.5%. FIM: 63.8 +/- 10.4 at the beginning; 79.0 +/- 8.9 after 6 months. When 3 clients excluded who had 120 points on FIM scores were beginning 44.4 +/13.5 and 64.8 +/- 16.6 after 6 months (increase of 20.4 points/46%). Functional task completion: 6 subjects continued to use the device. Average was .745 or 75% of the functions were performed better after 6 months of use. 6/12 (50%) did not continue to use the device C6-C7 individuals may find the device beneficial enough to use it as an assistive device. Technical improvements specifically cosmetics, positioning of the electrodes, donning/doffing. Best candidates are individuals with complete C6-C7 tetraplegia; FIM score between 25-50 (up to 75), QIF between 0-13 (up to 27), are motivated to use it, can demonstrate efficient grasp. Mean peak force of tenodesis grasp in the nine subjects increased from 2.6 N 3.8 N (passive) to 11.3 N 7.4 N (glove active), significant than Fp (P= 0.0064, t-test), and significant at end of 5th grasp 6.8 N 4.2 N, P= 0.0064, Mann-Whitney rank sum test. Most manual tasks improved significantly with the use of the glove

2.

3.

4. 5. 6.

Prochazka et al. 1997; Canada Downs & Black score=12 Case Series N=9

Population: Gender m=8, f=1, age-2242yrs, level of injury-C6-C7, time post injury-16mths-22yrs. Treatment: Use of bionic glove Outcome Measures: Mean peak force of tenodesis grasp, qualitative ratings of manual tasks.

1.

2.

Summary Table 5.24 Bionic Glove

Author Popovic et al. 1999 Prochazka et al. 1997 N 12 9 Intervention Bionic Glove Bionic Glove Main Outcome(s) +ve QIF +ve FIM +ve UE Function Test +ve grasp +ve compliance (60%)

+ positive outcome,= no difference, - negative outcome

5.8.1.4 ETHZ-ParaCare System The ETHZ-Para Care System was developed collaboratively between ParaCare, the University Hospital Zurich, the Rehabilitation Engineering Group at Swiss Federal Institute of Technology Zurich and Compex SA, Switzerland. The system was designed to improve grasping and walking function in SCI and stroke patients. Surface stimulation FES system is programmable, 4 stimulation channels, can be interfaced with any sensor or sensory system. The system provides both palmar and lateral grasps. The device has some reported disadvantage that includes a lengthy time to don and doff the device (7-10 minutes) and it is not commercially available. The next generation of the device will be called the Compex Motion (Popovic et al. 2001; Popovic et al. 2005). The Compex Motion device is currently available in clinical trials 5-44

with approximately 80 units available. The Compex Motion stimulator was designed to serve as a hardware platform for the development of diverse FES systems that apply transcutaneous (surface) stimulation technology. One of the main designs in this system is that it is easily programmable (Popovic et al. 2005). Table 5.25 ETHZ ParaCare and Compex Motion Systems
Author Year; Country Score Research Design Total Sample Size Methods Population: gender m=9, f=2, age 1570yrs, level of injury C5-C7, ASIA A-D, FES applied 1-67 mths post injury Treatment: FES was carried out with a stationary stimulation system and 2 portable systems (ETHZ-Paracare FES system, and Complex Motion) Outcome Measures: videos of functional tasks: hand function tests, self-designed functional tests, f/u query-assessment of muscle strength Outcome No statistical results. Case Reports. 1. Cervical SCI patients can benefit from transcutaneous FES of hand muscles during rehabilitation with respect to muscle strengthening, facilitation of voluntary muscle activity and improvements of ADL functions 2. Surface FES system is more flexible in its application and does not need surgical procedures 3. High flexibility in electrode placement, stimulation programmes, and FES control devices is required in order to adapt the system to individual needs

Mangold et al. 2005; Switzerland Downs & Black socre=10 Case Series N=11

Summary Table 5.26: ETHZ ParaCare and Compex Motion Systems

Author Mangold et al. 2005 N 11 Intervention ETHZ-ParaCare FES System and Compex Motion Main Outcome(s) +ve Training Programme +ve Functional exercises in therapy = ADL function in rehab centre -ve ADL use at home

+ positive outcome, = no difference, - negative outcome

5.8.2 Other Surface or Percutaneous Neuroprosthesis Systems 5.8.2.1 NEC-FES System The Sendai FES team in corporation with NEC Inc. 1994 developed the NEC-FES System. The system is to restore both grasping and walking abilities. It is an implanted FES system with 16 stimulation channels. It is used almost exclusively for research purposes and is not available outside Japan. 5.8.2.2 Neuroprosthesis developed by Rebersek and Vodovik (1973) This is one of the first FES systems developed for grasping three decades ago. The device has three stimulation channels (2 stimulation electrodes per channel) that are used to generate the grasping function by stimulating finger flexors and extensors and thumb flexors. The user can control the stimulation intensity via different sensory interfaces such as EMG sensor, sliding resistor and pressure sensors. The main reported disadvantages of the system are the long donning and doffing times and the selectivity of stimulation is low. This device is not commercially available (Popovic et al. 2001).

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5.8.2.3 Belgrade Grasping-Reaching System (BGS) The BGS as proposed by Popovic et al. (1998) is a neuroprosthesis device designed for grasping and it also provides a reaching function. The device has four stimulation channels (three for generating grasping function and fourth to stimulate triceps brachii muscle for elbow extension). The grasping function is controlled via a push button that triggers hand opening and closing. The motion of grasp is performed in three phases; prehension that forms the correct aperature of the hand, a relaxation phase that allows the hand to get into good contact with the object and closure of the hand by opposing either the palm and the thumb or side of index finger and thumb. The act of hand release is completed in two stages; opening of the hand and resting. Measuring the subjects shoulder velocity with a goniometer and then generating a synergistic elbow motion by stimulation of the triceps brachii muscle achieves the reaching function of the upper limb. It is reported that the BGS system requires more time to place electrodes compared to Handmaster system, and it is not commercially available (Popovic et al. 2002). 5.8.3 Reported Benefits of Neuroprosthesis Use There have been many documented and reported benefits of neuroprosthesis use with the spinal cord injured person. The training required to use the device leads to short and long-term changes within the central nervous system (Popovic et al. 2002). A neuroprosthesis can be used as a neurorehabilitation system that promotes recovery and better hand function in incomplete SCI and stroke subjects or as a permanent orthotic device for complete cervical lesion SCI subjects to augment the grasp and manipulation functions required for typical ADLs. 5.8.4 Clinical Results of Neuroprosthesis Use The following are the reported clinical results of neuroprosthesis use; Clinical trials show improvement in grasping functions in stroke and SCI subjects FES technology facilitates a comfortable and secure grasp that allows the individual to hold and manipulate various objects All except the Bionic Glove were able to facilitate both palmar (power) grasp and lateral (fine) grasp The Handmaster-NMS-1, the BGS system, and the ETHZ-ParaCare neuroprostheses have been applied successfully as rehabilitation tools to restore grasping function in SCI individuals instead of being used as permanent orthotic systems To control the neuroprosthesis, subjects are using either an on-off type of switch or have to apply simple analog sensors to generate desired control commands There is a delay of 1-2 seconds from time command is issued and moment that grasp is executed which restricts the speed that an individual can grasp and release objects Neuroprosthesis for grasping can only be used for slower grasping tasks The most widely used and accepted neuroprostheses for grasping are the Freehand System and the Handmaster-NMS-1 and all of the other neuroprostheses mentioned are mainly used in experimental trials for research purposes 5.8.5 Challenges in Neuroprosthesis Use There are several reported challenges in neuroprosthesis use: There is a general perception within the clinical community that neuroprosthesis technology is not fully matured and the application of its use is labour intensive

5-46

Patients and families have over expectations from assistive systems as aspirations and results do not match Acceptance of the device depends on the specific needs of the client Complicated by variety of age and lifestyle factors represented in patients with UE paralysis Complacent (feel comfortable, safe and happy with home and workplace adaptation and with attendant care) Waiting for cure (refuse any other intervention) Afraid of technology Degree of cognitive interaction they require high levels of attention to their neuroprosthesis may interfere with social interaction Impact in clinical applications is limited Reasons for poor acceptance is can be technical, cultural and psychological FES technology requires intensive maintenance and skilled technician Found to be effective in hospitals with strong engineering support Attempts to simplify neuroprosthesis systems and reduce the systems donning and doffing time resulted in less technical support needed but the devices then failed to address the needs of a wider population Inadequate reliability of use (breakage of wires, electrode failure, accidental damage) The grasping functions are robotic quality of stimulated motions and in order to design a more dexterous hand motion it would require a more complicated system Overall cosmetics of the device Implanted neuroprosthesis require additional surgery and it is recommended that tendon transfers be performed to augment the system Extensive training is required to learn how to use the device, which is expensive in terms of staffing and resources Efforts to increase reliability of system components, data on long-term reliability not yet available Simple systems for powered tenodesis grip for individual with lesions at C6 or lower have not been fully explored in deference to volitional tendon transfer surgery (Popovic et al. 2002; Triolo et al. 1996)

Discussion The use of neuroprosthesis whether implanted or surface electrodes appear to benefit persons with C5-C7 level tetraplegia. The studies consistently demonstrate improvements in pinch (lateral and palmar), grip strength, and ADL functioning and general satisfaction with the use of the device, although the study subject numbers are relatively small. Ongoing compliancy and use of the devices on a long-term basis continue to be problematic. Reasons for discontinuing the use of the device are with length of time and the amount of assistance required to don and doff the device, and if using the device can provide enough of a difference in overall level of functioning. The studies also consistently report both mechanical/electrode failure and adverse medical complications. Many of the devices are only available in specialized rehabilitation centres where access to rehabilitation engineering is available. In addition, many of the devices continue to be only available in clinical trials. The overall cost to use the device continues to be great when factors such as cost of the device, the extensive training period required and staff to support the programme.

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Conclusion There is level 4 evidence from multiple studies that support the use of neuroprostheses for persons with C5-C6 complete tetraplegia in the improvement of pinch and grip strength and ADL functioning. However, many devices are only available in clinical trials in specialized rehabilitation centres and the overall cost of the device continues to be expensive. The use of neuroprostheses appears to have a positive impact on pinch and grip strength and ADL functions in C5-C6 complete tetraplegia, however, access to the devices are limited and continue to be expensive in use.

5.9 Summary The treatment and management of the upper limb in persons with a spinal cord injury can be rewarding yet very challenging. Secondary complications related to repetitive strain injury, pain and hypertonicity in addition to aging presents numerous challenges for both the injured individual and the clinician. In reviewing the critical evidence of treatment interventions it was surprising that there was few studies on the effectiveness of traditional interventions such as strengthening, exercise, splinting and management of hypertonicity. The majority of research for the upper limb has been focused on reconstructive surgery and the use of neuroprosthesis. Advancements in understanding the mechanisms related to spinal cord injury has led to restorative treatment interventions especially in the management of the incomplete SCI person. This chapter outlined the importance in the prevention of upper limb dysfunction and the impact of an injury in ones overall level of basic independence in the areas of self-care and mobility. Further research and consensus is needed in how we assess and document upper limb function especially hand function in an effort to establish objective, reliable and measurable outcomes. Other areas for further research have been identified throughout the chapter. There is level 1 evidence based on one RCT that physical capacity continues to improve after 1- year post discharge. There is level 2 evidence based on one pre/post study that neuromuscular stimulationassisted ergometry alone and in conjunction with voluntary arm crank exercise was an effective strengthening intervention for chronically injured individuals. There is level 2 evidence based on one study that muscle strength continues to improve up to 15 months post hospital discharge for both tetraplegic and paraplegic individuals. There is level 4 evidence based on one study that neuromuscular stimulation-assisted exercise improves muscle strength over conventional therapy. There is level 1 evidence (from 2 RCTs) that augmented feedback is not effective in improving upper limb function in tetraplegia. There is level 4 evidence that intrathecal baclofen may be an effective treatment for upper extremity hypertonia of spinal cord origin.

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There is level 1 evidence from one RCT that showed that massed practice (repetitive activity) and somatosensory stimulation (median nerve stimulation) demonstrated significant improvement in grip and pinch strength required for functional activity use. There is level 2 evidence from a before/after study that showed that rTMs treatment in individuals with chronic stable ISCI may produce reductions in corticospinal inhibition that resulted in clinical and functional changes for several weeks after treatment. There is level 2 evidence from one RCT that showed that the use of concomitant auricular and electrical acupuncture therapy may improve the neurological and functional recovery of acutely injured spinal cord individuals. There is level 2 evidence based on one RCT that wearing a thumb opponens splint will improve pinch strength and functional use of the hand. There is level 1 evidence based on two RCTs that a shoulder exercise and stretching protocol reduces the intensity of shoulder pain post SCI. There is level 2 evidence that general acupuncture is no more effective than Trager therapy in reducing post-SCI upper limb pain. There is level 4 evidence from multiple studies that support the use of reconstructive surgery for the tetraplegic upper limb for the improvement of ADL and quality of life. There is level 4 evidence from multiple studies that support the use of neuroprostheses for persons with C5-C6 complete tetraplegia in the improvement of pinch and grip strength and ADL functioning. However, many devices are only available in clinical trials in specialized rehabilitation centres and the overall cost of the device continues to be expensive.

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Schmidt RA, Lee TD. Motor control and learning: a behavioral emphasis. 3rd Edn. Champaign, IL: Human Kinetics, 1999. Schroer W, Lacey S, Frost FS, Keith MW. Carpal instability in the weight-bearing upper extremity. Journal of Bone and Joint Surgery 1996; 78:1838-43. Shimada Y, Chida S, Matsunaga T, Misawa A, Ito H, Sakuraba T, Sato M, Kazutoshi H, Itoi E. Grasping power by means of functional electrical stimulation in a case of C6 complete tetraplegia. Tohoku J. Exp. Med. 2003;201:91-96. Shimada Y, Sato K, Abe E, Kagaya H, Ebata K, Oba M, Sato M. Clinical experience of functional electrical stimulation in complete paraplegia. Spinal Cord 1996a;34:615-619. Sie IH, Waters RL, Adkins RH, Gellman H. Upper extremity pain in the post rehabilitation spinal cord injured patient. Arch Phys Med Rehabil 1992; 73:44-47. Silfverskiold J, Waters RL. Shoulder pain and functional disability in spinal cord injury. Clin Orthop. 1991; 272:141-145. Sinnott KA, Dunn JA, Rothwell AG. Use of the ICF conceptual framework to interpret hand function outcomes following tendon transfer surgery for tetraplegia. Spinal Cord 2004; 42:396-400. Sipski ML, Richards JS. Spinal cord injury rehabilitation: State of science. Am J Phys Med Rehabil 2006; 85:310-342. Smith BT, Betz RR, Mulcahey MJ, Triolo RJ. Reliability of percutaneous intramuscular electrodes for upper extremity functional neuromuscular stimulation in adolescents with C5 tetraplegia. Arch Phys Med Rehabil 1994; 75: September, 939-945. Smith BT, Mulcahey MJ, Betz RR. Quantitative comparison of grasp and release abilities with and without functional neuromuscular stimulation in adolescents with tetraplegia. Paraplegia 1996; 34: 16-23. Snoek GJ, Ijzerman MJ, FACG in t Groen, Stoffers TS, Zilvold G. Use of the NESS Handmaster to restore hand function in tetraplegia: clinical experiences in 10 patients. Spinal Cord 2000; 38: 244-249. Snoek GJ, Ijzerman MJ, Hermens HJ, Biering-Sorensen F. Survey of the needs of patients with spinal cord injury: impact and priority for improvement in hand function in tetraplegics. Spinal Cord 2004; 42; 526-532. Snoek GJ, Ijzerman J, Post MW, Stiggelbout AM, Roach MJ, Zilvold G. Choice-based evaluation for the improvement of upper-extremity function compared with other impairments in tetraplegia. Arch Phys Med Rehabil 2005; 86: August, 1623-1630. Subbarao JV, Klopfstein J, Turpin R. Prevalence and impact of wrist and shoulder pain in patients with spinal cord injury. J Spinal Cord Med. 1994;18(1):9-13. Taylor P, Esnouf J, Hobby J. Pattern of use and user satisfaction of Neuro Control Freehand system. Spinal Cord 2001; 39: 156-160. Taylor P, Esnouf J, Hobby J. The functional impact of the freehand system on tetrapleic hand function. clinical results. Spinal Cord 2002; 40:560-566. Thompson L. Functional changes in persons aging with spinal cord injury. Assistive Technology II 1999: 123-9. Triolo R, Nathan R, Handa Y, Keith M, Betz RR, Carroll S, Kantor C. Challenges to clinical deployment of upper limb neuroprostheses. Rehabil Res Dev 1996; 33: 111-122. Tsay RC. Textbook of Chinese acupuncture medicine: general introduction to acupuncture. Wappinger Falls, Association of Chinese Medicine and East-West Medical Centre, 1974; 1:40-52. Van Dijik H, Jannink JA, Hermens HJ. Effect of Augmented feedback on motor functions of the affected upper extremity in rehabilitation patients: a systematic review of randomized controlled trials. J Rehabil Med 2005; 37: 202-211. Van Tuijl JH, Janssen-Potten YJM, Seelen HAM. Evaluation of upper extremity motor function tests in tetraplegia. Spinal Cord 2002; 40: 51-64. 5-57

Waring WP, Maynard FM. Shoulder pain in acute traumatic quadriplegia. Paraplegia 1991; 29: 37-42. Waters RL, Adkins RH, Yakura JS, Sie I. Motor and sensory recovery following complete tetraplegia. Arch Phys Med Rehabil 1993; 74:242-247. Waters R, Moore KR, Graboff SR, Paris K. Brachioradialis to flexor pollicis longus tendon transfer for active lateral pinch in the tetraplegic. J Hand Surg 1985; 10A:385-391. Waters RL, Sie IH, Gellman H, Tognella M. Functional hand surgery following tetraplegia. Arch Phys Med Rehabil 1996; 77:86-94. Wegener S, Haythornthwaite JA. Psychological and behavioral issues in the treatment of pain after spinal cord injury. Top Spinal Cord Inj Rehabil 2001; 7:73-83. Welraeds D, Ismail AA, Parent A. Functional reconstruction of the upper extremity in tetraplegia. Application of Mobergs and Allieus procedures. Acta Orthopaedica Belgica 2003; 69(6): 537-545. Winstein CJ. Knowledge of results and motor learning- implications for physical therapy. Phys Ther 1991;71:140-149. Wong AMK, Leong CP, Su TY, Yu SW, Tsai WC, Chen CPC: Clinical trial of acupuncture for patients with spinal cord injuries. Am J Phys Med Rehabil 2003; 82:21-27. Wu D. Acupuncture and neurophysiology. Clin Neurol Neurosurg 1990;92:13-25. Wuolle SK, Van Doren CL, Bryden AM, Peckham PH, Keith MW, Kilgore KL, Grill JH. Satisfaction with and usage of a hand neuroprosthesis. Arch Phys Med Rehabil 1999; 80:2, 206-213. Wuolle SK, Van Doren CL, Thrope GB, Keith MW, Peckham PH. Development of a quantitative hand grasp and release test for patients with tetraplegia using a hand neuroprosthesis. J Hand Surg 1994; 19A:209-218. Yang JF, Stein RB, Jhamandas J, Goordon T. Motor unit numbers and contractile properties after spinal cord injury. Ann Neurol 1990;28:496-502. Zancolli E. Surgery of the quadriplegic hand with active strong wrist extension preserved: a study of 97 cases. Clin Orthop 1975; 112: 101-113

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CHAPTER SIX
Lower Limb Rehabilitation Following Spinal Cord Injury
Tania Lam, PhD, PT Dalton L Wolfe, PhD Jane TC Hsieh, MSc Maura W Whittaker, PT Janice J Eng, BSc (PT/OT), PhD

Key Points Patterned Electrical Stimulation (PES) programs are beneficial in preventing and restoring lower limb muscle atrophy as well as improving lower limb muscle strength and endurance. Functional Electrical Stimulation (FES)-assisted exercise programs are beneficial in preventing and restoring lower limb muscle atrophy as well as improving lower limb muscle strength and endurance. For patients less than 6 months post-SCI, body weight supported treadmill training has equivalent effects on gait outcomes to conventional rehabilitation consisting of overground mobility practice. Body weight-support gait training strategies can improve gait outcomes in chronic, incomplete SCI, but no body weight-support strategy (overground, treadmill, with FES) is more effective. There is little evidence that any pharmacological agent is significantly beneficial in directly improving ambulation in individuals with SCI. FES-assisted walking can enable walking or enhance walking speed in incomplete SCI or complete (T4-T11) SCI. Regular use of FES in gait training or activities of daily living can lead to improvement in walking even when the stimulator is not in use. There is limited evidence that bracing alone does not enable significant gains in functional ambulation for people with complete SCI. The advantages of bracing appear largely restricted to the general health and well-being benefits related to practice of standing and the ability to ambulate short-distances in the home or indoor settings. The benefits of bracing-alone on functional ambulation are primarily with people with incomplete spinal lesions. There is limited evidence that a combined approach of bracing and FES results in additional benefit to functional ambulation in paraplegic patients with complete SCI. Locomotor training programs are beneficial in improving lower limb muscle strength although in acute SCI similar strength benefits can be obtained with conventional rehabilitation. The real benefit of locomotor training on muscle strength may be realized when it is combined with conventional therapy. This should be further explored in acute, incomplete SCI where better functional outcomes may be realized with the combination of therapies.

Table of Contents
6.1 Introduction ......................................................................................................................6-1 6.2 Electrical Stimulation to Enhance Lower Limb Muscle Function................................6-2 6.2.1 Patterned Electrical Stimulation (PES) ...........................................................................6-2 6.2.2 Functional Electrical Stimulation .....................................................................................6-4 6.3 Gait Retraining to Achieve Functional Measures of Overground Ambulatory Capacity ............................................................................................................................6-7 6.3.1 Body-weight supported treadmill training (BWSTT) ........................................................6-8 6.3.1.1 BWSTT in Acute/Sub-acute SCI ..................................................................................6-8 6.3.1.2 BWSTT in Chronic SCI ..............................................................................................6-10 6.3.2 Special Case Report: Spinal Cord Stimulation Combined with BWSTT .......................6-12 6.3.3 Pharmacological Interventions......................................................................................6-12 6.3.4 Functional Electrical Stimulation (FES).........................................................................6-15 6.3.5 Orthoses/Braces ...........................................................................................................6-18 6.3.5.1 Bracing alone in SCI ..................................................................................................6-18 6.3.5.2 Bracing Combined with FES in SCI ...........................................................................6-22 6.3.6 Enhancing Strength Following Locomotor Training ......................................................6-24 6.4 Summary.........................................................................................................................6-26 References..............................................................................................................................6-29

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Lam T, Wolfe DL, Hsieh JTC, Whittaker M, Eng JJ (2006). Lower Limb Rehabilitation Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 6.1-6.34. www.icord.org/scire

Lower Limb Rehabilitation Following Spinal Cord Injury

6.1 Introduction The rehabilitation of lower extremity function after spinal cord injury has generally focused on the recovery of mobility. In individuals with paraplegia, the recovery of trunk stability and walking function are cited as the highest priorities after sexual and bladder/bowel function. Among people with tetraplegia, the return of arm/hand function is by far the greatest concern, but trunk stability and walking movement do appear among their priorities (Anderson 2004). Indeed, the basic capacity to stand upright and interact with others at eye-level is an important ability that many able-bodied individuals take for granted. Improvements in emergency and acute medical care for spinal cord injury have translated into improved survival rates in people who suffer such trauma (Frankel et al. 1998; O'Connor 2005). Concomitant with this change is also the finding that there is a trend towards less severe lesions, increasing the number of incomplete spinal cord injuries (Tator et al. 1993). The chance that a person can be ambulatory following a spinal cord injury is greatly increased when the severity of the spinal lesion is less (Burns et al. 1997; Curt & Dietz 1997). Thus, with the trend towards increased survival rates and decreased lesion severity, there is an increasing need for ambulatory rehabilitation treatments to maximize function and mobility for people with spinal cord injury. Conventional rehabilitation strategies for enhancing lower limb function after spinal cord injury have focused on range of motion and stretching, active exercises, electrical stimulation to strengthen functioning musculature, and functional training in daily mobility tasks (e.g. transferring, bed mobility, sitting). After SCI, it is well established that muscles experience deconditioning, especially those denervated following complete SCI. The most visible effect of deconditioning is muscle atrophy, characterized by a reduction in size of individual muscle fibers (Castro et al. 1999a; Castro et al. 1999b). Deconditioning is also associated with a complex cascade of biochemical events and alterations over time in muscle composition such as changes to muscle fiber type (Stewart et al. 2004; Round et al. 1993). Functionally, these changes are manifest as loss of strength and endurance of muscular contractions and have been targets for various interventions. Muscular contractions have the added potential of improving the well known loss of bone density following SCI. It should be noted that there might be additional benefits to enhancing muscle structure and function in addition to the immediate functional consequences of enhancing strength and endurance. For example, Anderson (2004) noted that future treatments developed for chronic SCI may require the reversal of muscle atrophy in order for benefits of the treatment to be detectable. Others have noted the potential health benefits (e.g., reduction in secondary conditions) that may be associated with reducing muscle atrophy and enhancing muscular strength and endurance (Shields & Dudley-Javoroski 2006). Various rehabilitation techniques have been focused on reducing or reversing these detrimental changes to the muscles of the lower limb following SCI. Standing and overground ambulation training are also important components of conventional rehabilitation using various bracing and assistive devices such as walkers (O'Sullivan & Schmitz 1994; Somers 1992). In the last several years, we have also seen exciting advances in technology applications for facilitating or augmenting gait rehabilitation strategies, such as

6-1

robotic devices for treadmill gait retraining (Colombo et al. 2001; Hesse et al. 2004) and the introduction of microstimulators for activating paralyzed muscles (Weber et al. 2004). 6.2 Electrical Stimulation to Enhance Lower Limb Muscle Function A variety of electrical stimulation techniques have been employed to enhance lower limb muscle structure and function in people with SCI. These typically involve delivering a series of electrical pulse trains to the muscle (or nerve supplying the muscle) over time such that it simulates the normal exercise experience. Specific stimulation parameters (i.e., pulse width, train duration, between train interval, method of application) and other exercise-related variables (i.e., frequency, duration, intensity, program length) may each be varied to attain an optimal training stimulus. Given the number and variety of these factors, it is not surprising that there is considerable heterogeneity among the specific electrical stimulation interventions that have been investigated to date. In the present review we focus on two strategies: patterned electrical stimulation (PES) and functional electrical stimulation (FES). Whereas both methods typically employ cyclical patterns of electrical stimulation that simulate natural muscular activity, FES is directed towards the attainment of purposeful movement such as cycling or walking. PES, on the other hand, is focused on producing muscle contractions that may be used to generate muscle force such as in an isometric condition. In some applications, PES techniques have been used as a training stimulus to prepare muscles for a subsequent FES training condition (e.g., Kern et al. 2005; Hjeltnes & Lannem 1990). In situations where increased muscle torque and endurance are primary goals to improve function, for example in the quadriceps in an incomplete SCI, the outcomes of these experimental studies have direct clinical relevance. 6.2.1 Patterned Electrical Stimulation (PES) Table 6.1 PES Studies Examining Muscle Function and Morphology
Author Year; Country Score Research Design Total Sample Size Methods Population: 26 subjects within 15 weeks SCI, traumatic, motor complete, thoracic or cervical SCI, mean ages from 25.0 to 28.2 years, 67.5-80% males. Treatment: Random assignment to 3-6 months of 1. FES-assisted cycle ergometry (n=8), 30 min, 3X/week; 2. PES-assisted isometric exercise group (n=8) (same muscle groups as FES group) for 1 hr, 5X/week and 3. control group (n=9) with no stimulation. Outcome Measures: lean body mass lower lim . Population: 7 men with complete SCI (ASIA class A), C5-T10, 6 weeks postinjury, ages 21-43. Treatment: PES exercise to unilateral ankle plantarflexion (untrained leg served as a control). Four 4 min exercise bouts, 5 days/week for 1.87-3.05 years. Outcome Measures: Stimulated ankle torque and soleus twitch profiles at baseline and every 6 months up to 3 years. 1. 2. Outcome Lean body mass increased with FES-cycling at all regions and declined for control and PES group. With respect to total body lean mass, lower limb lean mass and gluteal lean mass, controls lost an average of 6.1%, 10.1%, 12.4% after 3 months and 9.5%, 21.4%, 26.8% after 6 months.

Baldi et al. 1998; USA PEDro=5 RCT N=26

Shields et al. 2006; USA Downs & Black score=17 Prospective Controlled Trial N=7

Compared to the untrained side, stimulated limb had: 1. strength ( peak stimulated ankle torque and higher torque-time integrals (p<0.05). 2. More resistant to fatigue (muscle fatigue indexes), (p<0.05). 3. Increased twitch difference (indicative of force generating capacity) (p<0.05), especially with successive stimulation trains. 4. Greater trabecular bone mineral

6-2

Author Year; Country Score Research Design Total Sample Size

Methods

Outcome density at some sites but not others.

Hjeltnes & Lannem 1990; Norway Downs & Black score=11 Pre-post N=4

Kayaga et al. 1996; Japan Downs & Black score=9 Pre-post N=5

Population: 4 subjects with SCI; Frankel A (3 chronic T7-T12; 1 with recent injury at T5); age range 20-36; 3 females, 1 male; 3 months-5 years post-injury. Treatment: PES, 4 weeks, 2x/day, 510mins, isokinetic resistance to quadriceps muscles followed by 4 weeks, 30 min, 2X/day, 4-5X/day of integrated training of rising and standing. Outcome Measures: Knee extension torque, thigh circumference, creatine kinase collected monthly. Population: 5 male patients, complete paraplegia (T5-L2), 19 to 68 years of age, 3-60 months post-injury. Treatment: Subcutaneous PES to various lower limb nerves and muscles for 6 months. Applied at 10 min, 3X/day and gradually increased to 60 min, 3X/day at 10 weeks. Outcome Measures: Muscle crosssectional area (CT scan), manual muscle test, stimulated muscle torque.

1.

2.

No group statistics done. At least 2 subjects had knee extension torque, muscular endurance, thigh circumference, elevated CK (indicator of muscle injury) on occasion. The more acute subject stopped training due to muscle spasms. One subject progressed to the planned stage of FNS-assisted ambulation training. No group statistical analysis performed, limited by heterogeneity across subjects. All cross-sectional muscle areas except gluteus maximus increased (p<0.05 to <0.001). Muscle torques generally increased after PES. Manual muscle tests generally increased (p<0.001) for muscles initially assessed as poor-minus or greater.

1. 2. 3. 4.

Discussion In general, all studies reviewed involving PES produced beneficial results on muscle functions such as strength and endurance or muscle structure such as increased muscle size (i.e., reduced muscle atrophy). The study with the strongest design was conducted by Shields and Dudley-Javorski (2006), who employed an experimental non-RCT design to examine the effect of long-term (up to 3 years) PES exercise to unilateral ankle plantarflexor muscles with the untrained leg serving as a control. This study examined 7 ASIA class A males with relatively recent injuries (~6 weeks post-injury). Peak stimulated ankle torque (i.e, non-voluntary) was found to be significantly greater in the stimulated leg as compared to the untrained leg. Trained limbs also generated significantly higher torque-time integrals than untrained limbs (p<0.05). Pre-post study designs of PES-assisted exercise also found increased stimulated muscle forces or torques following training although the subjects involved in these studies were generally more chronic (Kagaya et al. 1996; Hjeltnes & Lannem 1990). In addition, Bajd et al. (1999) showed increases in voluntary and stimulated isometric knee joint torques in 4 of 7 subjects with incomplete SCI (2 months to 8 years post-injury) with a 5th subject showing an increase in the stimulated response only. In addition to enhancing muscle bulk, most interventions are focused on improving muscle function, most notably strength and endurance, but also contractile speed and muscle fatigue. PES-assisted exercise, in particular, has been studied and shown to benefit the property of strength in the lower limb. All but one (i.e., Bajd et al. 1999) of the studies assessing outcome measures associated with strength evaluated this in individuals with complete or motor complete SCI (Shields & Dudley-Javoroski 2006; Kagaya et al. 1996; Hjeltnes & Lannem 1990).

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Shields and Dudley-Javorski (2006), also demonstrated a beneficial effect with their protocol of PES-assisted exercise to the plantarflexors in more recently injured individuals with ASIA A SCI. Conclusion There is level 2 evidence that a program of PES-assisted isometric exercise reduces the degree of lower limb muscle atrophy in individuals with recent (~10 weeks post-injury) motor complete SCI, but not to the same extent as a comparable program of FESassisted cycling exercise. There is level 4 evidence that programs of PES-assisted exercise partially reverses the lower limb muscle atrophy found in individuals with long-standing (>1 year post-injury) motor complete SCI. There is level 2 evidence that a program of PES-assisted exercise increases lower limb strength and muscular endurance.

PES programs are beneficial in preventing and restoring lower limb muscle atrophy as well as improving lower limb muscle strength and endurance.

6.2.2 Functional Electrical Stimulation Table 6.2 FES Studies Examining Muscle function and Morphology
Author Year; Country Score Research Design Total Sample Size Methods Population: 26 subjects within 15 weeks SCI, traumatic, motor complete, thoracic or cervical SCI, mean ages from 25.0 to 28.2 years, 67.5-80% males. Treatment: Random assignment to 3-6 months of 1. FES-assisted cycle ergometry (n=8), 30 min, 3X/week; 2. PES-assisted isometric exercise group (n=8) (same muscle groups as FES group) for 1 hr, 5X/week and 3. control group (n=9) with no stimulation. Outcome Measures: lower limb lean body mass. Population: 9 subjects (1 female, 8 males), aged 20-49, complete traumatic conus cauda equina lesions, at least .8 years post-injury. Treatment: Progressive PES to FES program for quadriceps to FES-assisted standing (n=4 trained 2.4 years); untrained controls (n=5). Outcome Measures: Muscle biopsy of vastus lateralis (mean fiber diameter, % area covered by muscle fibers, adipocytes, connective tissue). 1. 2. Outcome Lean body mass increased with FES-cycling at all regions and declined for control and PES group. Controls lost an average of 6.1%, 10.1%, 12.4% after 3 months and 9.5%, 21.4%, 26.8% after 6 months in total body lean mass, lower limb lean mass and gluteal lean mass, respectively.

Baldi et al. 1998; USA PEDro=5 RCT N=26

1.

Kern et al. 2005; Austria Downs & Black score=14 Pre-post N=9

2.

Overall mean fiber diameter of trained group was increased vs untrained group (p<0.001) and also had similar values to normal sedentary adults. Proportion of total cross-sectional area covered by muscle fibers increased with training whereas the area covered by adipocytes and connective tissue significantly decreased.

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Author Year; Country Score Research Design Total Sample Size

Methods Population: 6 tetraplegic, 4 paraplegic, complete, aged 27-45, 5 sedentary controls, age 30-39. Treatment: 18-month FES-assisted cycling ergometry (First training period: 30 min, 3X/week, 1 year; Second training period:1X/week, 6 months). Outcome Measures: Muscle morphology and protein measurement (type IV collagen, total collagen, muscle proteins). 1.

Outcome Total collagen content (as indicated by hydroxyproline concentration) was increased with first training period (p=0.05) and second training period (p=0.05) and even more so compared to able-bodied controls. No difference in Type IV collagen content between groups. This result combined with the changes seen with the other muscle proteins suggest accelerated type IV collagen turnover in skeletal muscle. Work output as training progressed (p=0.019). More fatigue-resistant: force decrement during quadriceps fatiguing stimulations (p=0.012). No change in contractile speed (using maximal rate of rise force), mean Rt (p=0.014) and the degree of fusion diminished (p=0.006). Force responses at low stimulation frequencies. No change in thigh circumference. cross-sectional area including: rectus femoris, sartorius, adductor magnus-hamstrings, vastus lateralis, vastus medialisintermedius (all p .025). No change in cross-sectional area of adductor longus and gracilis muscles. No correlations between total number of sessions and magnitude of muscle hypertrophy. There were significant increases in the muscle/adipose tissue ratio (p<0.05), muscle tissue in the thigh and leg (p<0.05) but no changes in the adipose tissue. Total work performed increased (p<0.05) after training. Paralysed vastus lateralis muscle was altered with type IIA fibres, type IIX fibres MHC IIx and MHC IIA (p<0.05). Total mean fibre cross-sectional area increase of 129%, crosssectional area of type IIA and IIX fibres (p<0.05). Number of capillaries surrounding each fibre (p<0.05). Citrate synthase and hexokinase activity (p<0.05).

Koskinen et al. 2000; Finland Downs & Black score=14 Pre-post N=15

2.

Gerrits et al. 2000; UK Downs & Black score=16 Pre-post N=7

Scremin et al. 1999; USA Downs & Black score=16 Pre-post N=13

Population: 7 male subjects with motorcomplete spinal lesions, aged 28-61, (5 ASIA A, 2 ASIA B), C5-T8, from 1-27 years post-injury. Treatment: FES leg cycle ergometry training, 3 - 30 minutes sessions/week for 6 weeks. Outcome Measures: Thigh girth, work output, contractile speed and fatigue resistance characteristics, including half relaxation time ( Rt) and degree of fusion of electrically stimulated isometric contractions. Population: 13 males, ASIA class A, aged 24-46, C5-L1, 2-19 years post-injury. Treatment: A 3-phase, FES-assisted cycle ergometry exercise program leading to FES-induced cycling for 30 minutes. Average program was 2.3X/week for 52.8 weeks. Outcome Measures: CT-scan of legs to assess muscle cross-sectional area and proportion of muscle and adipose tissue collected (pre-test, midpoint and post-test).

1. 2. 3.

4. 5. 1.

2. 3.

Crameri et al. 2002; Denmark Downs & Black score=14 Pre-post N=6

Population: 6 subjects with complete paraplegia (T4-T12) at least 8 years postinjury, 5 males, 1 female, age 28-43. Treatment: FES leg cycle ergometry training, 3 - 30 min/week for 10 weeks. Outcome Measures: Incremental exercise leg test to muscle fatigue (total work output), histological assessment, myosin heavy chain (contractile protein) (MHC), citrate synthase (a mitochondrial enzyme) and hexokinase (enzyme needed to produce muscle glycogen).

1. 2.

3.

4. 5.

6-5

Discussion In general, all studies reviewed involving FES produced beneficial results on muscle functions such as strength and endurance or muscle structure such as increased muscle size (i.e., reduced muscle atrophy). FES may have additional benefits over PES alone. In particular, the study by Baldi et al. (1998) should be highlighted as it was the only randomized, controlled trial (n=26) which compared FES (cycle ergometry exercise), PES (isometric exercise) and an untrained control group. These investigators assessed lean body mass in 3 distinct body areas (i.e., total body, lower limb, gluteal) as a marker of muscle atrophy in recently injured (10 weeks) individuals with motor complete SCI. Their results demonstrate that the FES-assisted cycling program is effective in reducing atrophy and resulted in relative increases in lean body mass in all areas after 3 and 6 months of participation. The PES-assisted isometric exercise group also reduced muscle atrophy but had intermediate results between FES and no treatment (their control group actually loss lean mass). Reversal of muscle atrophy also appears feasible in more longstanding complete or motorcomplete SCI (i.e, > 2 years post-injury) SCI as shown by increases in muscle cross-sectional area and the muscle/adipose tissue ratio using FES-cycling (Crameri et al. 2002; Scremin et al. 1999). However, controlled trials in chronic SCI are lacking. Note that PES is often used to strengthen the atrophied muscles to some extent prior to FES (Kern et al. 2005) and in some cases, FES is not possible unless PES is first used. Kern et al. (2005) used a progressive PES - FES program for quadriceps building eventually leading to FES-assisted standing in people with longstanding complete cauda equina injuries (>1.2 years post-injury). These investigators demonstrated increases to the overall mean fiber diameter and the proportion of total cross-sectional area covered by muscle fibers with training as compared to an untrained group. However, the feasibility of providing life-long stimulation therapy to subjects with denervation injuries is uncertain. There was one null finding associated with muscle atrophy in that Gerrits et al. (2000) employed a relatively shorter program of 6 weeks of FES-assisted cycling exercise in people with longstanding motor complete SCI (> 1 year post-injury) and found no change in muscle size. These non-significant results might be due to the measure of thigh circumference which may not have been sufficiently sensitive to change, especially with the short intervention period and the absence of a control group for comparison purposes. In addition to improving muscle properties, FES-cycling can improve work output and endurance (Crameri et al. 2002; Gerrits et al. 2000). For example, Gerrits et al. (2000) used a short (6 weeks) pre-post trial of FES-assisted cycling intervention in people with motor complete SCI and found an increase resistance to fatigue in the quadriceps muscle and greater work output. Some mechanistic investigations have been conducted which help to explain some of these adaptations to muscle morphology and function with ongoing electrical stimulation exercise programs. For example, using FES-assisted cycling, Koskinen et al. (2000) demonstrated an increase in total collagen content as well as up- and down-regulation of proteins consistent with muscle-building activity. Others have noted an adaptive response to FES-assisted cycling exercise that serves to limit or alter the shift in the oxidative properties or fibre type composition of muscles that typically occurs following SCI (Crameri et al. 2002)

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Conclusion There is level 2 evidence that a program of FES-assisted cycling exercise prevents and reverses lower limb muscle atrophy in individuals with recent (~10 weeks post-injury) motor complete SCI and to a greater extent than PES. There is level 4 evidence that programs of FES partially reverses the lower limb muscle atrophy found in individuals with long-standing (>1 year post-injury) motor complete SCI. There is level 4 evidence that a program of FES-assisted cycle exercise increases lower limb muscular endurance. FES-assisted exercise programs are beneficial in preventing and restoring lower limb muscle atrophy as well as improving lower limb muscle strength and endurance.

6.3 Gait Retraining to Achieve Functional Measures of Overground Ambulatory Capacity There are several approaches to measure overground functional ambulation, as opposed to neurophysiological or biomechanical measures of gait. These include objective measures of walking speed or distance, or the use of qualitative functional scales or categories to describe ambulatory capacity. Walking speed is typically calculated from the time required for the subject to walk over 10 m (10-m walk test, or 10MWT). Walking speed has also been calculated by measuring the total distance traversed over a 2-minute period (Field-Fote 2001; Field-Fote et al. 2005). Walking endurance is typically assessed by measuring the total distance traversed within 6 minutes (6-minute walk test, or 6MWT). This test was developed to assess fitness capacity in patients with cardiopulmonary illnesses, but is now also often used to assess walking endurance in patients with spinal cord injury e.g. (Hornby et al. 2005; Thomas & Gorassini 2005; Wirz et al. 2005; Dobkin et al. 2006). Recently, both the 10MWT and the 6MWT have been shown to be valid and reliable measures for assessing walking function in ambulatory individuals with SCI (Van Hedel et al. 2005). Ambulatory capacity may also be qualitatively described by the type of ambulatory aid used during overground walking. The Walking Index for Spinal Cord Injury (WISCI) (Ditunno et al. 2000) and its current revision (the WISCI-II) (Dittuno & Dittuno 2001) is a 20-point scale that measures the level of assistance and type of ambulatory aid required to walk 10-m. A score of 0 corresponds to an inability to stand or walk with assistance while the maximum score of 20 is given when the subject can ambulate 10m without any personal or physical assistance (Dittuno & Dittuno 2001). This measure has been shown to be a valid measure of ambulatory capacity in patients with SCI (Ditunno et al. 2000). There are other functional ambulatory scales in use by various investigators to describe walking capacity in people with SCI. The Wernig Scale of Ambulatory Capacity (Wernig et al. 1995; Wernig et al. 1998; Hicks et al. 2005; Effing et al. 2006) classifies people according to the amount and type of assistance required to walk 5 steps, with classification levels ranging from no walking capability to free walking for more than 5 steps. The Garrett Scale of Walking classifies subjects according to their functional ambulatory status, ranging from a physiological walker (hospital ambulation) to unlimited community ambulator (Scivoletto et al. 2000; Protas et al. 2001).

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6.3.1 Body-weight Supported Treadmill Training (BWSTT) It has been more than a decade now since it was first demonstrated that body-weight supported treadmill training (BWSTT) in animals can enhance locomotor activity after spinal cord transection (Barbeau & Rossignol 1987; Edgerton et al. 1991). In this approach, partial body weight support is provided by a harness suspended from the ceiling or a frame while limb stepping movements are assisted by a moving treadmill belt. Since then, BWSTT strategies has been introduced as a promising approach to improve ambulatory function in people with spinal cord injury (Barbeau & Blunt 1991). This area of research has raised much excitement and interest among rehabilitation specialists and neuroscientists. In this review, we focus on the BWSTT intervention studies that report functional ambulation outcome measures (such as walking speed). These studies tend to focus on individuals with incomplete SCI lesions. There are a few studies reporting the effects of treadmill training on the locomotor pattern in people with complete SCI lesions (Dietz et al. 1994; Dietz et al. 1995; Wernig et al. 1995; Dietz et al. 1998; Wirz et al. 2001; Dietz & Muller 2004; Grasso et al. 2004). While there is modulation of muscle (EMG) activity during body weight support treadmillassisted stepping in individuals with complete SCI lesions, there has not been any evidence for functional ambulatory gains in this sub-population. In people with incomplete SCI, much motor recovery already occurs within the first 2 months post-injury; the rate of further recovery then decelerates over the next 3 to 6 months (Burns & Ditunno 2001). However, it is possible for motor function to continue to improve up to 2 years post-injury. For ease of interpretation, the studies reviewed in this section separate those that investigated subjects <6 months post-injury (acute/sub-acute) from those that studied subjects who were >6 months post-injury (chronic). In studies that used both types of subjects, the results were divided by subject chronicity. In addition, only results from studies with more than 3 subjects of a given chronicity were included. Therefore, some studies that investigated both chronic and acute SCI subjects may appear only in Table 6.4 because they had >3 chronic subjects, but <3 acute subjects (e.g. Thomas & Gorassini 2005). 6.3.1.1 BWSTT in Acute/Sub-acute SCI Table 6.3 Studies Using BWSTT in Acute/sub-acute SCI (<6 months post-injury)
Author Year; Country Score Research Design Total Sample Size Methods Population: 117 men and women (completed study), age 16-69 years, ASIA B-D; up to 8 weeks post-injury. Treatments: BWSTT (manual) vs. conventional rehabilitation with overground mobility training. BWSTT group also practiced overground walking. Gait training was 5X/week, 9-12 weeks, 30-45 min/session. Follow-up at 3 and 6 months post-training. Outcome measures: primary: Locomotor Scale of the Functional Independence Measure (ASIA B & C, n=108), walking speed (ASIA C & D, n=72); secondary: 6MWT, WISCI. Population: Study 1: 0-4.5 months post injury. Study 2: 2-30 weeks post-injury. 1. Outcome No difference in Functional Independence Measure Locomotor Scale (ASIA B & C) or walking speed (ASIA C & D) between groups. ASIA C & D subjects in both groups improved walking function. No improvement in walking function in the ASIA B subjects with either intervention, except in subjects who improved to ASIA C within 8 weeks after injury.

2.

Dobkin et al. 2006; USA PEDro=7 RCT N=117

Wernig et al. 1995; Germany

1.

Study 1 (BWSTT): 7 initially nonambulatory tetraplegic subjects

6-8

Author Year; Country Score Research Design Total Sample Size Downs & Black score=9 Case Control N=97

Methods Treatment: Study 1: BWSTT (manual, no parameters presented) (n=12). Study 2: BWSTT (n=45), 2-22 weeks versus conventional rehab (n=40) (historical controls). Outcome measures: Wernig Scale of Ambulatory Capacity.

Outcome progressed to walk with assistance or with rollator. Five subjects progressed from walking with aids to walking independently. Study 2: Of the non-ambulatory subjects, 33/36 progressed to walking with aids or independently after BWSTT, but only 12/24 improved to functional walking with conventional rehab. 29/37 initially non-ambulatory subjects improved to walking with aids. Follow-up (6 months to 6 years post-training): 15 subjects showed continued improvement, 26 had no change in ambulatory status

2.

Wernig et al. 1998; Germany Downs & Black score=12 Pre-post N=41

Population: 41 subjects, incomplete, 3-16 weeks post-injury. Treatment: BWSTT (manual). 30-60 min, 5X/week, 3-22 weeks. Outcome measures: Wernig Scale of Ambulatory Capacity.

1. 2.

Discussion For acute/sub-acute (< 6 months) incomplete SCI, there were 3 studies (n>3) reporting the effects of locomotor training in subjects with using functional measures of ambulatory capacity (Table 6.3). The general finding across these studies is that BWSTT with manual assistance beginning during the acute/sub-acute post-injury period provides improvements in ambulatory capacity in people with incomplete SCI. The studies of Wernig (Wernig et al. 1995; Wernig et al. 1998) showed that 87% (87/98) of their incomplete SCI subjects achieved improvements in functional ambulation with BWSTT in the acute phases of injury. The lack of ambulatory change in 13 subjects may be related to severe flaccid paralysis, high cervical lesion, or proprioceptive disturbances (Wernig et al. 1995). Although lower levels of study design (non-randomized, non-blinded) suggest that BWSTT in acute/sub-acute SCI yields better outcomes than conventional rehabilitation (Wernig et al. 1995), there exists strong evidence from a single-blind RCT (Dobkin et al. 2006) (n=146) that there are no differences in effects between BWSTT and overground mobility practice (standard of care) in incomplete SCI during inpatient rehabilitation for walking speed or distance. In both groups, improvements in walking function were particularly notable in subjects with ASIA C (92%) or D (100%). Among the subjects who were initially classified as ASIA B, those who improved to ASIA C within 8 weeks post-injury showed improved walking function. In addition, subjects who entered the trial earlier (< 4 weeks post-injury) had faster walking speeds and endurance post-training. This was particularly the case for subjects who improved in their ASIA classification within 4 to 6 weeks post-injury. The fact that both subjects in both treatment groups were provided with task-specific locomotor training (on a treadmill or overground) may account for the lack of any difference in functional outcomes observed (Dietz 2006). Both groups experienced similar durations of body loading during therapy, either as a function of practicing standing or walking between parallel bars or ambulatory aids overground, or practicing upright locomotion with body weight support and a treadmill (Dobkin et al. 2006). In the older study that reported improved outcomes with BWSTT compared to conventional rehabilitation (Wernig et al. 1995), the conventional rehabilitation was not well defined. The disparate results between these two sets of data may be accounted for by the shift in recent years towards more intensive and task-specific rehabilitation therapy.

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Conclusion There is level 2 evidence using historical controls that BWSTT is effective in improving ambulatory function. However, stronger evidence from one level 1RCT demonstrates that BWSTT has equivalent effects to conventional rehabilitation consisting of overground mobility practice for gait outcomes in acute/sub-acute SCI. For patients less than 6 months post-SCI, body weight supported treadmill training has equivalent effects on gait outcomes to conventional rehabilitation consisting of overground mobility practice. 6.3.1.2 BWSTT in Chronic SCI Table 6.4 Studies Using BWSTT in Chronic SCI (>1 year post-injury)
Author Year; Country Score Level Total Sample Size Methods Population: 27 men and women, age 2164 years, incomplete, C3-T10. Treatment: Randomized to 4 gait training strategies, 45-50 min, 5X/week, 12 weeks: 1) BWSTT (manual leg movement) (n=7); 2) BWSTT+FES (common peroneal nerve) (n=7); 3) overground body weight support walking+FES (n=7); 4) Lokomat (robotic gait device with body weight support) (n=6). Outcome measures: walking speed and distance, step length, step symmetry. Population: 44 subjects with para and tetraplegia. BWSTT (manual leg movement). Treatment: Study 1: 30-60 min, 5X/week, 3-20 weeks. Study 2: 29/44 subjects of study 1 compared with 24 chronic subjects who underwent conventional rehab (historical controls). Outcome measures: Wernig Walking Capacity Scale. Population: 14 men and women, age 2053 years, ASIA B (n=2) & C (n=12), C4-L1. Treatment: BWSTT (robotic). Up to 45 min, 3X/week, 144 sessions (12 months). Outcome measures: Walking Capacity Scale (Wernig). Population: 20 men and women, age 1664 years (mean 40, SD 14), ASIA C (n=9) & D (n=11), C3-L1. Treatment: BWSTT (robotic). Up to 45 min, 3-5X/week, 8 weeks. Outcome measures: WISCI II, 10MWT, 6MWT. Population: 19 men and women, mean age 31.7 (SD 9.4) years, ASIA C, paraand tetraplegia. 1. Outcome No difference in outcome between groups, but a trend towards better improvement in groups who received FES (groups 2 & 3). Subjects with slower initial walking speed (< 0.1 m/s) had greater percent increase in walking speed compared to those with faster initial walking speeds. Study 1: 25/33 initially nonambulatory could walk after BWSTT. At 6 months post-training, 18/21 ambulatory patients maintained abilities. Study 2: 14/18 initially nonambulatory subjects could walk after BWSTT, compared with only 1/14 in the conventional rehab group. 6/14 subjects improved in walking capacity, but only 3 maintained improvements at 8 months posttraining. 3/10 initially non-ambulatory subjects could walk (with assistance) post-training. No statistical change in WISCI II. Among initially-ambulatory subjects, there was an overall significant increase in 10MWT and 6MWT. Significant increase in walking speed (median: 77%).

Field-Fote et al. 2005; USA PEDro=6 RCT N= 27

2.

1.

Wernig et al. 1995; Germany Downs & Black score=9 Case Control N=68

2.

1.

Hicks et al. 2005; Canada Downs & Black score=18 Pre-post N=14 Wirz et al. 2005; Switzerland Downs & Black score=17 Pre-post N=20 Field-Fote 2001; USA Downs & Black score=15 Pre-post

2. 1. 2.

1.

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Author Year; Country Score Level Total Sample Size N=19

Methods Treatment: BWSTT + common peroneal nerve FES. Up to 90 min, 3X/week, 12 weeks. Outcome measures: gait speed. Population: 14 men and women, age 1850 years, ASIA C, C4-T7. Treatment: BWSTT + common peroneal nerve FES. Up to 90 min, 3X/week, 12 weeks. Outcome measures: overground gait speed. Population: 6 men and women, age 29-78 (mean 54.4, SD 14.8) years, ASIA C (n=4) & D (n=2), C5-L1. Treatment: BWSTT (manual). Up to 60 min, 3-5X/week, 10-23 weeks. Outcome measures: 10MWT, 6MWT, WISCI II. Population: 35 men and women, age 1970, C4-T12. Treatment: BWSTT (manual). 30-60 min, 5X/week, 8-20 weeks. Outcome measures: Wernig Walking Capacity Scale.

Outcome

1.

Field-Fote & Tepavac 2002; USA Downs & Black score=13 Pre-post N=14 Thomas & Gorassini 2005; Canada Downs & Black score=12 Pre-post N=6

All subjects showed increase in walking speed (ranging from 0.01 to 0.2 m/s increase). Subjects with slower walking speeds showed the greater % improvement. Significant improvement in WISCI II score, 6MWT, and 10MWT and improvements correlated with the increase in corticospinal connectivity. 20/25 initially non-ambulatory improved to walking with aids. 2/10 ambulatory patients improved functional class, but all improved speed and endurance. At follow-up (0.5-6.5 years later) all ambulatory patients remained ambulatory, with changes only in functional class.

1.

1. 2. 3.

Wernig et al. 1998; Germany Downs & Black score=12 Pre-post N=35

Discussion Across 8 studies, there was a total of 158 chronic incomplete subjects (C3-L1) enrolled in some form of body-weight supported gait retraining therapy. Gait retraining strategies were typically performed with a treadmill and the assistance of therapists or the Lokomat, which is a robotic gait device. The training protocols ranged from 30 to 90 minutes per day, occurred 3 to 5 times/week and lasted for 8 weeks to 12 months. All studies (and 82% of all subjects) reported overall improvements in functional walking ability. Subjects with initially-slower walking speeds (< 0.10 m/s walking speed) tend to make the most improvements in locomotor function. Subjects with initially high walking capacity (> 0.10 m/s gait speed) or severely impaired, initially non-ambulatory subjects tend to show little improvement after gait retraining (Wernig et al. 1995; Wernig et al. 1998). Note that a large percent improvement from an initially low walking speed can be a result of the mathematics. Of greater clinical utility is an understanding of how gains in walking speed translate to everyday function. For people with paraplegia, it has been suggested that an overground walking speed of at least 0.9 m/s is necessary for community ambulation (Cerny et al. 1980). None of the studies showed attainment of walking speeds greater than 0.5 m/s. Nevertheless, even modest gains in walking speed after treadmill training have been reported to translate into meaningful enhancements in daily function (Field-Fote et al. 2005). BWSTT with FES of the common peroneal nerve results in improvements in overground walking speed in chronic incomplete SCI (Field-Fote 2001; Field-Fote & Tepavac 2002). However, there is only a non-significant trend for better outcomes when electrical stimulation was combined with

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treadmill or overground body weight support gait training in chronic SCI subjects compared with locomotor training alone (Field-Fote et al. 2005). Conclusion There is Level 4 evidence from pre-test/post-test studies that BWSTT is effective for improving ambulatory function in people with chronic, incomplete SCI. There is Level 1 evidence from 1 RCT that different strategies for implementing body weight support gait retraining all yield similar ambulatory outcomes in people with chronic, incomplete SCI. It is recommended that therapists may choose a body weight support gait retraining strategy based on available resources (Field-Fote et al. 2005). Body weight-support gait training strategies can improve gait outcomes in chronic, incomplete SCI, but no body weight-support strategy (overground, treadmill, with FES) is more effective.

6.3.2 Special Case Report: Spinal Cord Stimulation Combined with BWSTT There are 2 published reports (Herman et al. 2002; Carhart et al. 2004) describing the effects of epidural spinal cord stimulation combined with gait training in a single subject (male with incomplete tetraplegia, 43 years old, injury level C5-C6, ASIA C, 3.5 years post-injury). The subject first underwent 12 weeks of BWSTT that resulted in some significant improvements in treadmill gait parameters although overground ambulation remained limited. Subsequently, the subject underwent surgical implantation of an epidural stimulation system placed over the T10T12 vertebral level. BWSTT and overground gait training in combination with epidural stimulation commenced after surgical healing. The combination of epidural spinal cord stimulation with gait training resulted in a substantial improvement in treadmill gait parameters as well as in overground ambulation. The subject reported a decreased sense of effort, a doubling in walking speed, and increased walking endurance when assisted by spinal cord stimulation. This was associated with improved community and indoor functional ambulation. Obviously, controlled trials of this specific intervention are required before spinal cord stimulation combined with locomotor training can be recommended as a useful rehabilitation strategy. Nevertheless, this special case report highlights one of the innovative and exciting possibilities of technology. 6.3.3 Pharmacological Interventions Drugs such as clonidine (a noradrenergic agonist), cyproheptadine (a serotonergic antagonist), baclofen (GABA agonist), GM-1 ganglioside and 4-aminopyridine have been used in association with attempts to improve ambulation in individuals with SCI. The results from animal studies indicate that such drugs may act on the receptors in the spinal cord which facilitate interaction with a locomotor central pattern generator (spinal circuits which produce coordinated locomotor movement) (Barbeau et al. 1990; Chau et al. 1995; Rosssignol et al. 1996). Although not conclusive, there is some evidence that similar central pattern generator circuits exist in humans (Calancie et al. 1994; Illis 1995; Bussel et al. 1988; Bussel et al.1996a, 1996b) and provide the rationale for clinical use of these drugs.

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Table 6.5 Studies of Pharmacological Interventions for Enhancing Locomotion in SCI

Author Year; Country Score Research Design Total Sample Size Methods Population: SCI, chronic, ambulatory (ASIA D). Treatment: Double-blind, placebocontrolled, crossover design: 4Aminopyridine (4-AP): 1 week of uptitration prior to 2 weeks of 10 mg 4x/day stable dosing of 4-AP (n=15) versus Placebo (n=14) and then switch conditions. Outcome measures: Isometric muscle force, gait analysis. Population: chronic, incomplete. Treatment: Double-blind, placebocontrolled, crossover design: 4 weeks of 15-45 mg, immediate-release 4Aminopyridine capsules or Placebo. 2 week washout between conditions. Outcome measure: walking speed. Population: chronic paraplegia, complete and incomplete. Treatment: Double-blind, placebocontrolled, crossover design: Two periods of 4 weeks of medication (Clonidine or Placebo, randomly assigned) separated by a 2 week washout period. Outcome measures: Kinematic measures during body weight support gait, spasticity, adverse effects. 1. Outcome Some positive effects for both placebo and 4-AP treatment when compared to baseline, but no changes between groups were not significant.

Deforge et al. 2004; Canada PEDro=10 RCT N=29

1.

Van der Bruggen et al. 2001; Netherlands PEDro=10 RCT N=20

No significant differences were found between groups, period, cross over design, or treatment effects.

1.

2.

Stewart et al. 1991; Canada PEDro=8 RCT N=9

3.

Walker & Harris 1993; USA PEDro=8 RCT N=9

Wainberg 1990; Canada PEDro=7 RCT N=15

Remy-Neris et al. 1999; France Downs & Black score=15 Pre-post N=11

Population: Chronic. Treatment: Double-blind, placebocontrolled crossover study design: Intravenous GM-1 ganglioside (Sygen), 6 days per week. 6 month physical therapy preceding 4 months of trial. Outcome measures: Motor Score Walking distance and velocity. Population: spastic paraparesis of spinal origin, motor incomplete. Treatment: Randomized, double-blind cross-over design: Oral Cyproheptadine (n=8) or placebo tablets (n=7) over 3 weeks (1 week each at 2mg, 4mg and 8mg 5x/day) with a 1 week washout in between. Outcome measures: Kinematic and leg muscle activity (EMG) during gait, spasm severity, spasticity diary. Population: sub-acute to chronic (0.5-16 years post injury). Treatment: Intrathecal Clonidine 60g test dose (n=11) followed by 3 doses (15 to 90 g) and a placebo injection (n=4). Outcome measures: Ashworth spasticity

1.

1/3 ambulatory patients had marked improvement in locomotor function resulting from Clonidine compared to Placebo. Spasticity (#Improvement/deterioration/nochange resulting from Clonidine): Ankle reflexes 5/2/2, Knee reflexes 5/0/2, spasticity visual analog scale 6/1/2, Daily spasms 2/0/2, Daily clonus 4/0/1. Side effects of clonidine (8/9 patients): dry eyes and mouth, lethargy, mild hypotension and constipation. Irrespective of treatment order, GM-1 resulted in motor scores, walking distance, walking velocity.

1. 2.

1.

2.

Descriptive results only. Compared to control, Cyproheptadine resulted in 1) gait changes ( forward trunk flexion but no change in EMG, walking speed, %stance time, %double support duration; 2) spasticity: all subjects reported a decrease in the severity and frequency of involuntary movements. Only 5/8 ambulatory subjects could stand up and walk after 60 ug clonidine dose (2 showed improvements). One subject showed overground speed (P>0.03), stride length

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Author Year; Country Score Research Design Total Sample Size

Methods scores, H-reflex, ambulation parameters, flexion reflexes. 3. Population: male, chronic, 6 tetraplegics, 3 paraplegics. Treatment: 4-Aminopyridine (single 10mg immediate-release capsule). Comparison of means at baseline and at intervals over 24-hour follow-up. Outcome measures: Ambulation parameters. Population: chronic, incomplete, traumatic. Treatment: 3 different oral tablets in order of convenience: Clonidine (0.25 mg/day) or Cyproheptadine (24 mg/day) or Baclofen (80mg/day): each drug trial had incremental increase to maximum dose and stable dosing over 3 weeks followed by incremental decrease from maximum dose and washout over 2 weeks. Outcome measures: Surface EMG and kinematic gait analysis during treadmill walking. No statistical analysis. 1.

Outcome (P>0.0009) but not cycle duration and higher doses impaired gait. Ashworth score in all subjects. No change seen in H-reflex. Flexion reflex not enhanced with low doses. Improvements in gait velocity ( by 36% from 24.1 16.5 m/min to 32.7 22.9 m/min; (p 0.04); in stride length ( from 0.9 0.3 meters to 1.0 0.3 meters, p 0.02); cadence and gait cycle duration, but not significant. Gait changes began 6 hours after drug administered and persisted the 24 hour follow-up. 7/12 subjects had evaluations of all 3 drugs; adverse effects for 4/5 subjects prevented completion of all conditions. The greatest effects in more severely disabled subjects. Cyprohyeptadine resulted inneed for assistance, in maximum treadmill speed and clonus. Clonidine resulted in maximal treadmill speed and a generally more upright posture. Baclofen resulted in minor changes in walking. Maximal treadmill speed increases and other changes were often retained following washout of drugs.

Segal & Brunneman; 1998; USA Downs & Black score=14 Pre-post N=9

2. 1.

2.

Norman et al. 1998; Canada Downs & Black score=13 Pre-post N=12

Discussion The interactions of these pharmacological interventions are complex and appear to affect walking ability and spasticity to varying effects. The studies on clonidine (oral or intrathecal), cyproheptadine and baclofen demonstrate improvements in various aspects of gait (i.e. walking speed, posture, spasticity), but no improvements led to significant functional improvements in walking. Norman et al. (1998) found the greatest improvements in more severely disabled subjects and in many cases, the drug effects were retained following washout of drugs. Bradycardia and hypotension, common side-effects of oral clonidine can be ameliorated with intrathecal injection of clonidine (150-450g) (Filos et. al. 1994). The combined effect of different drugs has not been well explored. One very small study (not tabled due to its small sample size of 2 subjects) (Fung et al. 1990) showed that a combination of Clonidine, Cyproheptadine and treadmill training improved SCI locomotion in 2 subjects. Conflicting evidence exists on the use of GM-1 ganglioside for neurologic recovery for walking in SCI. The small RCT conducted by Walker and Harris in 1993 (N=9) concluded that the use of GM-1 ganglioside improved motor scores, walking distance and walking speed in chronic SCI subjects. A recent large scale multicenter RCT (n=760) (Geisler et al 2001) suggested that although GM-1 treatment may have accelerated initial SCI recovery (at 8 weeks), it did not improve the final extent of recovery (26 weeks). However, walking ability was not assessed given the subjects who ranged from ASIA A to D. 6-14

The effects of immediate release, 4-aminopyridine capsules on ambulation are conflicting with 2 RCTs suggesting no benefit (vander Bruggen et al. 2001, n=20; Deforge et al. 2004, n=15). However, the van der Bruggen et al. (2001) hypothesis was not directed solely at exploring the effects on walking and therefore the heterogenous nature of the subject groups may have confounded the ambulation results. Furthermore, differences in intervention (i.e. 10mg single dose, 15-45mg/day over 4 weeks in the Deforge et al. study versus 10mg 4X/day for 8 days in the Van der Bruggen et al study and the lack of consistent clinically relevant outcome measures complicates the interpretation of the available evidence. Conclusion In summary, level 1 evidence describes limited and indirect improvements in aspects of walking (i.e. spasticity, speed and posture) but do not translate into significant functional walking gains as a result of clonidine and cyproheptadine. Limited and non-functional improvements in walking as a result of baclofen are only supported by level 4 evidence. Conflicting evidence provides little guidance with respect to the use of GM-1 and 4aminopyridine for the improvement of ambulation in spinal cord injury. Scientifically robust studies with consistent clinically relevant outcome measures are needed for pharmacological intervention studies of ambulation after spinal cord injury.

There is little evidence that any pharmacological agent is significantly beneficial in directly improving ambulation in individuals with SCI.

6.3.4 Functional Electrical Stimulation (FES) The idea of compensating for paralyzed function using electrical stimulation was introduced as early as the 1960s (Liberson et al. 1961). Functional electrical stimulation of the common peroneal nerve was found to be effective in assisting foot clearance during the swing phase (Liberson et al. 1961). There has also been a report of attempts to stimulate the ankle plantarflexor muscles to assist push-off at the end of stance and enhance the initiation of the swing phase in subjects with incomplete SCI (Bajd et al. 1999). Approaches that focus on swing phase activity are more suitable for less severely disabled individuals who have adequate balance to support their stance leg during gait. There are also more complex systems that involve several channels of stimulation that support proper extension as well as foot clearance during swing (e.g. Sigmedics 2000). These are more suitable for patients who require assistance in standing as well as gait, such as those with neurologically complete SCI. FES systems such as the Parastep or ALT-2 provide stimulation of thigh extensor muscles (quadriceps, gluteal muscles) to support extension and standing, as well as stimulation of the common peroneal nerve to assist with swing phase movements. FES may also be combined with bracing to counter trunk and hip instability (Solomonow et al. 1997a). One of the limitations of surface FES is possible skin irritation, discomfort under the electrodes, or difficulties with proper positioning of the electrodes. With improvements in electronics technology, FES systems are becoming smaller and more amenable for everyday use. In addition, some patients have opted for implanted FES systems that may be inserted without surgery. These systems offer a more precise delivery of stimulation, enabling greater muscle selectivity, and the ability to access deeper muscles, such as the hip flexors (Kobetic et al.

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1997). Percutaneous electrodes, which are inserted through the skin with a hypodermic needle, offer one possibility to circumvent complications with surface electrodes (Marsolais & Kobetic 1986; Kobetic et al. 1997). However, there may be complications due to infection or irritation at the site of insertion, and electrode movement or breakage (Agarwal et al. 2003). More recently, there was a case study reporting positive effects with a BION microstimulator in an incomplete tetraplegic subject with drop-foot (Weber et al. 2004). Thus, preliminary reports of the use of such innovative FES technology are promising, but further study is warranted to determine the long-term stability and efficacy of such implanted systems. Table 6.6 Studies Using Functional Electrical Stimulation to Improve Locomotor Function
Author Year; Country Score Research Design Total Sample Size Methods Population: 15 men and women, age 1647 years, T3-T11, Frankel A, B (n=1), and C (n=1), 6-240 months post-injury (some same subjects as Gallien et al. (1995). Treatment: Surface FES: Parastep 6 channels (bilateral common peroneal nerve, quadriceps, glutei/lumbar muscles), mean of 20 sessions. Outcome measures: ambulatory status, walking distance and speed (with FES). Population: 14 (but only 10 subjects analyzed), age 25-49 years, C3-L1, incomplete, 1.8-19.1 years post-injury. Treatment: Surface FES: bilateral or unilateral common peroneal nerve, home use as much as possible ~1 year (26 and 56 weeks), 2 subjects also had bilateral quadriceps. Outcome measures: temporal gait measures. Population: 16 men and women, mean age 28.4 (SD 6.6) years, T4-T11, complete, 0.7-9.0 years post-injury. Treatment: Surface FES: ParastepI: 6 channels (bilateral common peroneal nerve, quadriceps, glutei). 3X/week, 32 sessions (once subjects had sufficient strength to stand). Outcome measures: walking distance and speed (with FES). Population: 6 men and women, age 20-40 years, C3-L1, Frankel C & D, 2 to 18 years post-injury. Treatment: Surface FES: quadriceps, hip abductors, hamstrings, erector spinae, common peroneal nerve, home program >30 min, 5X/week, 3 months. Outcome measures: walking speed, stride length, cadence. 1. Outcome 13 subjects completed training. All could ambulate independently with the Parastep system after ~14 sessions. The mean walking distance without a rest was 52.8 m (SD 69 m; range: 1-350 m). The mean speed was 0.15 m/s (SD 0.14 m/s; range: 0.03-0.4 m/s). 5/10 patients with a 3 year follow-up continued to use the system at home. Mean increase of 0.10 m/s in walking speed (over the first year of FES-use (measured with and without FES).

Brissot et al. 2000; France Downs & Black score=17 Post-test N=15

2.

1.

Ladouceur & Barbeau; 2000a; Canada Downs & Black score=16 Pre-post N=14

1.

Klose et al. 1997; USA Downs & Black score=15 Pre-post N=16

Most subjects improved endurance and gait speed. Longest distance walked with FES was between 12 to 1707 m (mean: 334 m; SD 402 m).

1. 2.

Granat et al. 1993; Scotland Downs & Black score=14 Pre-post N=6

Significant mean increase in stride length, but not speed or cadence. 3 to 4 subjects had significant individual increases in gait speed, stride length and cadence.

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Author Year; Country Score Research Design Total Sample Size

Methods Population: 14 (but only 10 subjects analyzed), age 25-49 years, C3-L1, incomplete, 1.8-19.1 years post-injury (same subjects as in Ladouceur & Barbeau 2000a). Treatment: Surface FES: bilateral or unilateral common peroneal nerve, 2 subjects also had bilateral quadriceps, home use as much as possible ~1 year. Outcome measures: temporal gait measures. Population: 31, mean age 36 (SD 2) years, injury level above lumbar levels, incomplete, mean 6 (SD 1) years postinjury, 4 centres. Treatment: Surface FES: common peroneal nerve; some subjects also received FES to hamstrings, quadriceps, gluteus medius, duration of FES ranged from 3 months to over 3 years. Outcome measures: walking speed, stride length, cycle time. Population: 13 men and women, age 1742 years, T4-T10, complete, 5-240 months post-injury. Treatment: Surface FES: Parastep: 6 channels (bilateral common peroneal nerve, quadriceps, glutei). Outcome measures: walking distance and speed (with FES). Population: age 20-44 years, C2-T10, incomplete, 2.5-10 years post-injury. Treatment: Surface, percutaneous, or implanted FES of common peroneal nerve, and sometimes quadriceps, glutei, and psoas. Outcome measures: speed, gait parameters 1.

Outcome All subjects showed an improvement in functional mobility. 7/14 subjects showed improvement based on type of ambulatory device. When walking with FES, 13/14 subjects improved gait speed. Ambulatory improvements were still evident when the FES was turned off during walking in12/14 subjects, suggesting a training, or carryover, effect with long-term FES-use. Overall improvement in gait speed which persisted even when subjects walked without FES. Mean increase in speed was 0.14 m/s (SE: 0.03 m/s) (although mixed stroke and SCI results). Greatest % improvements particularly for the initially slow walkers.

Ladouceur & Barbeau 2000b; Canada Downs & Black score=14 Pre-post N=14

2.

1. 2.

Wieler et al. 1999; Canada Downs & Black score=13 Pre-post N=31

1.

Gallien et al. 1995; France Downs & Black score=6 Post-test N=13

2.

Independent ambulatory distances 2 to 350m (mean 73.25 m, SD 102 m) and speed 0.2 to 0.6 m/s (mean: 0.2 m/s, SD 0.1 m/s). Poorer performances were observed in more chronic subjects. All subjects improved gait speed when FES was on (mean change was 4 m/min), particularly significant for more disabled subjects.

1.

Stein et al. 1993; Canada Downs & Black score=6 Pre-post N=10

Discussion To date, there are no randomized controlled or blinded assessments of the efficacy of any form of FES to improve mobility after SCI. Results from the experimental pre-test/post-test studies reviewed here show that almost all the participants showed improvements in gait parameters (walking speed or distance) when FES was used. This is not surprising, given that the FES could compensate for weakened or paralyzed muscle function during gait. Of greater interest is the finding of carryover effects after FES training. After completion of an FES-training program, improvements in gait function persisted even when the stimulator was turned off (Wieler et al. 1999; Ladouceur & Barbeau 2000; Johnston et al. 2003). This suggests that neuroplastic changes may have taken place in response to regular use of FES during walking. Indeed, it has been shown in non-disabled human subjects that the combination of treadmill walking and FES led to an acute increase in corticospinal excitability that persists even after the cessation of FES

6-17

(Kido Thompson & Stein 2004). Improved muscle strength and conditioning after regular use of FES could also contribute to carryover effects in walking function (Granat et al. 1993). Although laboratory studies advocate the efficacy of FES systems for improving ambulatory function in patients with SCI, the effectiveness of any technology is only as good as its acceptance by the intended users. Wieler et al (Wieler et al. 1999) reported that the majority of their subjects found they could use the FES device easily on a regular basis and that they walked better with the FES. Those who reported difficulties reported problems with finding the proper stimulation site or technical difficulties with the leads, switches, or electrodes. There have also been reports of musculoskeletal complications such as ankle sprain, calcaneum fracture, back pain, or falls with FES use (Gallien et al. 1995; Brissot et al. 2000). Some of these complications may have been associated with commencement of upright exercise (gait) after a period of being non-ambulatory. Anecdotal reports found in several studies suggest that most subjects mainly use FES indoors or at home, for short distance walking, to prevent complications due to prolonged immobilization, and to enhance physical fitness rather than functional community ambulation (Gallien et al. 1995; Klose et al. 1997; Brissot et al. 2000). Subjects who do use FES outdoors for community ambulation tend to be the less severely impaired (Granat et al. 1993; Brissot et al. 2000). The functional benefits derived from FES are also quite variable. For instance, Stein et al. (Stein et al. 1993) report that most subjects showed a modest improvement in gait speed (average: 4 m/min), which was more significant for the more severely disabled subjects. Higher-functioning subjects felt that this small benefit in gait speed did not warrant the daily use of FES. In contrast, (Ladouceur & Barbeau 2000) reported that there was a tendency for the subjects with initially faster gait speed to have greater absolute improvements. Thus, outcomes from FES-use also seem to be quite variable in terms of walking speed (Stein et al. 1993; Ladouceur & Barbeau 2000) or distance (Klose et al. 1997). Conclusion There is Level 4 evidence that FES-assisted walking can enhance walking speed and distance in complete and incomplete SCI. There is also Level 4 evidence from 3 independent laboratories that regular use of FES in gait training or activities of daily living leads to persistent improvement in walking function that is observed even when the stimulator is not in use.

FES-assisted walking can enable walking or enhance walking speed in incomplete SCI or complete (T4-T11) SCI. Regular use of FES in gait training or activities of daily living can lead to improvement in walking even when the stimulator is not in use.

6.3.5 Orthoses/Braces 6.3.5.1 Bracing alone in SCI There are several available devices used for bracing the legs in order to support standing and walking function, particularly for people with complete SCI. These range from single-joint bracing (e.g. ankle-foot orthosis), usually for individuals with low, incomplete spinal lesions, to whole-leg/long-leg braces that extend from the lower back to the ankle. Among the most common long-leg braces studied in the literature are the purely mechanical Parawalker (Rose 6-18

1979) or the Reciprocating Gait Orthosis (RGO) (Douglas et al. 1983). These devices may also be combined with FES to augment gait function and efficiency (Nene and Patrick 1990; Yang et al. 1996; Marsolais et al. 2000). These devices must be used with a walking aid (e.g. crutches or walker) for functional ambulation. Table 6.7 Studies of Bracing Interventions in SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: 10 men and women, mean age 37 years (SD 8.4), T9-T12, motor complete, 4-19 years post-injury. 1 Treatment: Walkabout Orthosis (WO ) vs. Isocentric Reciprocal Gait Orthosis (IRGO 2): training with first orthosis 2-3 hours, 2-3X/week for 6-8 weeks, followed by 3-month home trial period. 2-month wash-out period (no orthosis) followed by other orthosis. Outcome measures: functional skills (e.g., curbs, stairs, donning/doffing, sit-stand), Functional Independence Measure, gait speed over flat and inclined surfaces. 1. Outcome No differences between orthoses re: donning/doffing (independent), stairs and curbs (stand-by or minimal), or level gait (independent or stand-by). Tendency for better performance with IRGO for flat walking, ramp walking, and stairs. Faster gait with IRGO on flat (mean IRGO=0.34 m/s 0.18, mean WO=0.14 m/s 0.12; p=.002) and on inclined surfaces. IRGO allowed more independent gait; WO easier to go from sit-stand and stand-sit. Neither orthosis enabled subjects to be fully independent in the key skills necessary for functional ambulation after 8 weeks of training. The orthosis enabled all subjects to independently ambulate with canes. All 3 subjects increased gait speed from 0.13, 0.22, 0.37 m/s to 0.20, 0.35, 0.43 m/s, respectively. 11/24 patients had stopped using RGO at 1-year follow-up, but there was no difference between the RGO-users and RGO-non-users in terms of gait speed, stair climbing, or use of ambulatory aid. However, the RGO-users achieved a higher functional ambulatory capacity (Garrett Scale) than non-users. RGO-users achieved home ambulation with limitations or home ambulation (Level 2-3) while nonusers achieved hospital ambulation or home ambulation with limitations (Level 1-2). No one reached community ambulation levels.

2.

Harvey et al. 1997; Australia Downs & Black score=17 Post-test N=10

3.

Nakazawa et al. 2004; Japan Downs & Black score=14 Pre-post N=3

Scivoletto et al. 2000; Italy Downs & Black score=14 Post-test N=24

Population: 3 men, age 22 to 28 years, T8 -T12, complete (ASIA A), 8-12 months post-injury. Treatment: Weight bearing control orthosis (WCBO), a long-brace reciprocating gait orthosis: training occurred 1 hour, 5X/week for 12 weeks. Outcome measures: walking speed. Population: 24 men and women, mean age 33.6 years (SD 3.2), T1-T12, complete (ASIA A), mean 5.3 years (SD 2.1) postinjury. Treatment: RGO: training provided and then subjects given braces for home-use for 1 year. Outcome measures: gait speed, going up and down stairs, use of walker or crutches, Garrett Score (out of 6; 6 = community ambulation with no limitations; 1=hospital ambulation).

1. 2.

1.

2.

3.

1
2

Similar model to the MSH-KAFO Successor model to the RGO (uses a central pivot bar and tie rod arrangement instead of crossed-cable to couple hip flexion/extension). The IRGO is thought to be less fatiguing for subjects compared to RGO Winchester et al. (1993).

6-19

Author Year; Country Score Research Design Total Sample Size

Methods Population: 5 men, age 26-36 years, T5L1, 4 complete (Frankel A) and 1 incomplete (Frankel C), 8.4-70 months post-injury. Treatment: Medially-placed Single-axis Hip joint with long-leg hip-Knee-Ankle-Foot Orthosis (MSH-KAFO). Patients were trained to stand and walk using device daily for 2 weeks, followed by an exercise program 1-2 times/week. Outcome measures: walking speed and distance. Population: multicentre, 74 men and women, mean age 27 years, T1-T12, complete (Frankel A & B), mean 37 years post-injury. Treatment: Orthoses: RGO (n=53), Advanced RGO (RGO with links between mechanical hip joints and hip and knee joints) (n=17), and Hip Guidance Orthosis (HGO) (n=4). Individual treatment included practice at don/doff device and functional mobility. Follow-up at hospital discharge and 6 months later. Outcome measures: Garrett Score, ability to climb up and down 12 steps. Population: 22 men and women, age 21 to 44 years, T3-T12. Treatment: Hip Guidance Orthosis (HGO), also known as Parawalker combined with crutches vs. Reciprocating Gait Orthosis (RGO) combined with rollator walker. Groups matched for age and level of injury. Practice period followed by 4 month home use before being switched to the second orthosis. Outcome measures: walking speed, cadence, stride length. 1. 2. 3.

Outcome 4 of 5 were able to stand without crutches with MSH-KAFO (1 subject needed parallel bars). 3/5 could climb stairs with crutches and rail. Donning and doffing brace took only 3-4 minutes. After 3-10 months of therapy, gait speed improved from 0.05-0.2 m/s to 0.17-0.63 m/s) and walking distance ranged from 300 to 4000 m. At discharge, 28 patients could climb stairs (13 with crutches, 15 with a walker). The ability to climb stairs or Garret score at discharge was associated with continued orthosis-use. 31 patients achieved functional gait (Garrett = 2-5) and 9 achieved community ambulation (Garrett=45). 19 used orthosis only for exercise (Garrett=1).

Saitoh et al. 1996; Japan Downs & Black score=10 Pre-post N=5

1. 2.

Franceschini et al. 1997; Italy Downs & Black score=12 Post-test N=74

1. 2. 3.

Whittle et al. 1991; UK Downs & Black score=12 Post-test N=22

4.

No significant differences between the orthoses in terms of gait speed, cadence, and stride length. Mean walking speed with either orthosis was 0.24 m/s. The HGO was much quicker to put on and to take off. The RGO was quicker on most of the other ergonomic tests, but this was significant only for standing up and climbing up a curb. At the end of the trial 12 subjects chose to keep the RGO, 4 the HGO, and 6 kept neither. The rollator prescribed for use with the RGO may have influenced subjects preference to keep the RGO system.

Discussion The level 4 (primarily pre-test/post-test studies) reviewed here indicate that these devices facilitate the ability of people with sub-acute (as low as 4 months post-injury) or chronic complete paraplegia to rise from sitting to standing independently and to achieve some modest gains in ambulation (Thoumie et al. 1995; Saitoh et al. 1996; Harvey et al. 1997; Scivoletto et al. 2000). In general, however, the use of any of the braces investigated in these studies did not greatly enhance the ability of complete paraplegic subjects to be fully independent for functional community ambulation (Hong et al. 1990; Harvey et al. 1997; Scivoletto et al. 2000), although community ambulation was reported in some subjects in one study (Franceschini et al. 1997).

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Maximum walking speeds achieved with orthosis-use range from 0.14 to 0.63 m/s, which is 13 to 57% of the optimal speed (1.1 m/s) required for successful community ambulation (Robinett & Vondran 1988). In a few studies, some subjects demonstrated the ability to climb up and down stairs with the assistance of crutches or walker (Whittle et al. 1991; Franceschini et al. 1997; Harvey et al. 1997). Thus, the greatest benefit derived from orthosis/brace-use is from enhanced home or indoor mobility, for general exercise and health benefits, and psychological benefits from attaining upright posture and standing (Mikelberg & Reid 1981; Hong et al. 1990; Sykes et al. 1996). The successful use of orthoses/braces is also dependent on other more individual and practical factors. It has been recommended that orthoses or braces are best for people who are wellmotivated, with complete SCI at T9 or below or incomplete SCI at any level, with good postural control and good level of fitness (Hong et al. 1990; Thoumie et al. 1995; Franceschini et al. 1997). Medical problems such as limited thoraco-lumbar mobility or mechanical back pain, or any musculoskeletal problems that make standing upright uncomfortable tend to interfere with successful use of these orthoses/braces (Harvey et al. 1997; Middleton et al. 1997). The ability for a patient to don/doff the orthosis without difficulty and relatively quickly (e.g. <5 minutes) also appears to enhance the probability of their acceptance (Mikelberg & Reid 1981; Hong et al. 1990; Thoumie et al. 1995; Saitoh et al. 1996; Franceschini et al. 1997; Harvey et al. 1997; Scivoletto et al. 2000). Frequent reports of technical problems (e.g. mechanical breakdown at the hinges, improper fitting) across many studies (Mikelberg & Reid 1981; Whittle et al. 1991; Thoumie et al. 1995; Harvey et al. 1997; Scivoletto et al. 2000) suggest that appropriate technical support of these mechanical devices is necessary to enhance ongoing use of these braces (Whittle et al. 1991). Overall, it appears that most subjects feel that the difficulties and inconvenience encountered with orthoses/braces and the modest increase in function do not warrant their acceptance for regular, daily use in functional activities (Mikelberg & Reid 1981; Hong et al. 1990; Sykes et al. 1996; Harvey et al. 1997). It has been suggested that the therapeutic benefits of orthosis-use (e.g. health benefits from standing practice) should be stressed to patients rather than setting forth an expectation that they will enhance functional ambulation and be a replacement for wheelchair-use (Franceschini et al. 1997). However, it must be noted that for people with incomplete SCI, bracing (AFO-use) alone during walking can enhance gait speed and endurance compared to walking without an AFO (Kim et al. 2004). Conclusion None of the studies investigating the efficacy of brace/orthotic devices for upright support and mobility are randomized or blinded, but that is in part due to the ethical dilemma of providing safe and appropriate bracing and the fact that participants will be able to distinguish which device they received. There is weak evidence from post-test studies that bracing alone results in significant gains in functional ambulation for people with complete SCI. Only 2 studies reported pre-test/post-test results (total n = 8) that the use of long-leg braces could enhance gait speed and endurance in people with complete SCI.

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There is limited evidence that bracing alone does not enable significant gains in functional ambulation for people with complete SCI. The advantages of bracing appear largely restricted to the general health and well-being benefits related to practice of standing and the ability to ambulate short-distances in the home or indoor settings. The benefits of bracing-alone on functional ambulation are primarily with people with incomplete spinal lesions.

6.3.5.2 Bracing Combined with FES in SCI Energy expenditure of walking facilitated by bracing alone in spinal cord injury is extremely high and contributes to its low use. Hybrid systems combine conventional bracing with FES to activate large lower extremity muscles in the hopes of improving the gait pattern and reduce upper extremity exertion. The additional FES is used to improve trunk and hip stability and to facilitate forward progression. Table 6.8 Studies of Bracing Interventions combined with FES in SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: 26 men and women, age 2053 years, C8-T11, complete, 9-144 months post-injury. Treatment: RGO-II orthosis: long-leg brace with reciprocal hip joint combined with FES to the quadriceps and hamstrings. 4-6 weeks of gait training with orthosis alone followed by RGO-II+FES (hybrid) program (total program time: 2-5 months inpatients, 3-14 months outpatients). Outcome measures: walking distance and speed with RGO and with RGO+FES. 1. Outcome 21/26 completed the training program, 19 were able to stand up alone. Following program, walking distance ranged from 200-1400 m with hybrid orthosis, 150-400 m with RGO II. Maximal walking speed with the hybrid orthosis (mean 0.32 m/s; SD 0.02; range 0.21-0.45 m/s) was not significantly different from that with orthosis alone (mean 0.29 m/s; SD 0.03; range 0.22-0.41 m/s). A two-month follow-up study revealed that, out of 15 patients using the hybrid orthosis, 11 were home users. After training, 57 patients could walk at least 180 m (19 could walk >450 m). 77% of patients could walk independently on different surfaces (grass, ramps, curbs).

Thoumie et al. 1995; France Downs & Black score=19 Pre-post N=26

2.

3.

Solomonow et al. 1997b; USA Downs & Black score=12 Post-test N=70

Marsolais et al. 2000; USA Downs & Black score=11 Pre-post N=6

Population: 70 men and women, age 16 to 50+, C6-T12, 1-10+ years post-injury. Treatment: RGO +/- FES. Orthosis-use and gait training of 1-3 hours, 3X/week for 6 weeks. In patients with injury level above T10, FES was added (bilateral quadriceps and hamstrings) with up to 6 more weeks of gait training. Outcome measures: walking ability, 180m walk. Population: 6 men and women, age 22-50 years, C7-T12, severity not reported, 2.520.6 years post-injury. Treatment: Case-Western Reserve University Hybrid Gait Orthosis: IRGO combined with FES to various muscles (combination of 8-16 muscles). Outcome measures: walking speed and distance.

1.

1.

Subjects who were unable to use RGO alone could ambulate with hybrid system. 3 subjects (all paraplegics) who were previously ambulatory with either RGO or FES alone showed improvement in walking distance with the hybrid system (from 3-90 m to 200-350 m).

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Author Year; Country Score Research Design Total Sample Size

Methods 2. Population: 3 subjects, age 28-42 years, C6 -T8 (tetraplegic incomplete, paraplegics complete), 3-15 years post-injury. Treatment: RGO FES. RGO with and without FES to common peroneal nerve stimulation. Outcome measures: walking speed, stride length. Population: 5 subjects, age 24-37 years, C2 -T6 (2 tetraplegics ASIA A & C, 3 paraplegics ASIA A & B), 8-14 years postinjury. Treatment: RGO and FES. 20-40 weeks of RGO use at home followed by hybrid system (RGO combined with FES. bilaterally to quadriceps and hamstrings). Outcome measures: RGO pedometer measured number of steps over 18 months. 1.

Outcome 2 of the subjects were capable of stair-climbing with the hybrid system. Use of the RGO with FES was associated with modest (nonsignificant) increase in walking speed and stride length compared with RGO with no FES. When subjects walked with the RGO+FES, average walking speed was 13% faster and stride length was 5% longer. Number of steps taken per week varied between 306 and 1879 steps (=99-845 m/week). Use of the RGO was low and no increase in use or function after hybrid system supplied. 1 subject (ASIA C) was already a community ambulator and showed most frequent use of RGO but across all subjects, RGO-use was variable, intermittent and generally poor.

Yang et al. 1996; UK Downs & Black score=11 Pre-post N=3

2. 3. 1. 2. 3.

Sykes et al. 1996; UK Downs & Black score=13 Observational N=5

Discussion There does not seem to be much further benefit of combining FES with orthosis-use in terms of maximal walking speed (Thoumie et al. 1995; Sykes et al. 1996; Yang et al. 1996), although greater walking distance may be achieved (Thoumie et al. 1995; Marsolais et al. 2000). Biomechanical studies (not included in the summary tables if they did not have a training period) provide some insight into the relative benefits of FES versus bracing. One study that has compared FES-alone with bracing-alone found that FES provides a particular advantage in facilitating sit-to-stand movements and donning the system in young (<18 years old) patients with chronic motor complete SCI (Bonaroti et al. 1999). However, mobility (e.g. walking, stairs) once standing was achieved was not found to be different between FES and bracing. In incomplete SCI, FES-use was found to result in greater benefits in terms of walking speed while bracing alone (with an AFO) was found to be particularly advantageous for improving walking distance (Kim et al. 2004). However, the combination of AFO with FES provided improved gait benefits than either device used alone (Kim et al. 2004). Conclusion There is Level 4 evidence that a combined approach of bracing and FES results in additional benefit to functional ambulation in paraplegic patients with complete SCI. However, in subjects who are achieve little benefit from bracing alone, the addition of FES appears to help improve standing or short-distance walking function (Marsolais et al. 2000). In incomplete SCI, however, there is some indication that a combination of bracing and FES provides greater ambulatory function than either approach alone (Kim et al. 2004).

6-23

There is limited evidence that a combined approach of bracing and FES results in additional benefit to functional ambulation in paraplegic patients with complete SCI.

6.3.6 Enhancing Strength Following Locomotor Training Much research is focused on the development of effective therapies directed at enhancing locomotion. Typically, as noted earlier in this chapter, the majority of these investigations focus on individuals with incomplete SCI and also predominately employ ambulation-related outcome measures. However, some investigators have also examined the effect of locomotor training on enhancing lower limb strength as a secondary measure, or in other cases have examined the relationship between changes in lower limb strength and walking ability. For the most part, these therapies include a form of body-weight supported treadmill training (also termed Laufband Therapy). In these therapies, the patients limb movements may also be assisted by any (or a combination) of the following: therapist, appropriately timed stimulation (i.e., FES) or a robotically controlled servo-mechanism (Wernig et al. 1995; Wernig et al. 1998; Field-Fote 2001; Hornby et al. 2005; Wirz et al. 2005). In other locomotor studies involving strength measures, locomotor training consisted of overground walking assisted by FES (Johnston et al. 2003; Granat et al. 1993) or a combination of this with treadmill and biofeedback training (Petrofsky 2001). In the present section, the outcomes associated with the strength benefits of these studies will be presented. Table 6.9 Locomotor Training Studies Examining strength Measures
Author Year; Country Score Level Total Sample Size Methods Population: 10 male patients with incomplete SCI, paraplegia T3-T12, aged 22-30, asymmetrical impairment with Trendelenburg gait; could walk without an assistive device. Treatment: The control group (n=5) had 2hour daily conventional physical therapy, including 30 min biofeedback of more affected gluteus medius for 2 months. Experimental treatment (n=5) had same program and used a portable home biofeedback device. Outcome Measures: Muscle strength (isometric strain gauge transducer) and gait analysis. Population: 153 patients overall, 89 (44 chronic, 45 acute) locomotor training, 64 (24 chronic, 40 acute) control. Treatment: Body-weight supported treadmill locomotor training (BWSTT) (Laufband therapy) vs conventional rehabilitation. Specific parameters for each were not described or appeared to vary within and between groups. Outcome Measures: Manual muscle testing, walking function and neurological examination pre and post training. 1. Outcome Gains in strength (in quadriceps, gluteus medius and hamstring) were seen for both groups but were greater for the experimental group than controls (p<0.05). After 2 months of therapy the reduction in Trendelenburg gait was greater for the experimental group than for the control group (p<0.01) and the experimental group showed almost normal gait.

Petrofsky 2001; USA Downs & Black score=12 Prospective Controlled Trial N=10

2.

1.

Wernig et al. 1995; Germany Downs & Black score=9 Case Control N=153

2. 3.

6 /20 chronic individuals initially nearly paralysed gained bilateral muscle strength ( manual muscle testing) For acute patients, no differences in strength gains between BWSTT and conventional rehab. Authors noted that locomotor gains had little correlation with strength gains.

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Author Year; Country Score Level Total Sample Size

Methods Population: 19 subjects, 13 men and 6 men, mean age 31.7 (ASIA class C), > 1 year post-injury, asymmetrical lower extremity function. Treatment: Body weight-supported treadmill walking with peroneal nerve FES of the weaker limb for 1.5 hours, 3X/week, 3 months. Outcome Measures: Lower extremity motor score (LEMS), Gait outcomes. Population: 6 incomplete SCI (3 males, 3 females), aged 20-40, 2-18 years post injury, C4 to L1, 3 Frankel C, 3 Frankel D. Treatment: FES-assisted locomotor training to quadriceps, hip abductors, hamstrings, erector spinae, common peroneal nerve, minimum 30 min, 5 days/week. Outcome Measures: Manual muscle tests, maximum voluntary contraction (MVC), upright motor control, spasticity, balance and gait outcomes. Population: 3 adolescents (age 12-17), incomplete SCI, 1-3 years post-injury, 1 male, 2 females, all ASIA C, C6, C7 and L2 injury levels. Treatment: 1 year percutaneaous intramuscular FES system preceded by 4 week stimulated exercise and FES gait training period. Outcome Measures: Manual muscle test scores, gait outcomes. Population: 2 males, 1 female, ASIA C, 5 weeks/ 6 weeks/ 18 months post-injury. Treatment: Therapist and Roboticassisted, body-weight-supported treadmill training (parameters varied between subjects). Outcome Measures: Lower extremity motor scores (LEMS), functional mobility outcomes. Population: 76 SCI patients (35 chronic, 41 acute), strength data reported for 25 chronic only who returned to clinic for follow-up. Treatment: Body-weight supported treadmill locomotor training (Laufband therapy). 1-2X/day for 30 minutes, 5 days/week for 8-20 weeks. Outcome Measures: Voluntary muscle scores and walking function. 1.

Outcome LEMS had median increases of 3 points in both the FES-assisted leg and the non-stimulated leg (p<.005). ASIA lower limb motor scores in 15 of 19 incomplete SCI (ASIA C) (p<.005).

Field-Fote 2001; USA Downs & Black score=15 Pre-post N=19

2.

1. 2.

Granat et al. 1993; UK Downs & Black score=14 Pre-post N=6

strength ( hip flexors and knee extensor manual muscle test, p<0.05). strength as indicated by increased quadriceps torque with MVC (p<0.05).

1. 2.

Johnston et al. 2003; USA Downs & Black score=14 Pre-post N=3

No group statistics. Voluntary strength for all subjects in 12/13 stimulated muscles by ~1 manual muscle grade. The greatest gains were in hip extension and hip abduction.

1. 2.

Hornby et al. 2005; USA Downs & Black score=12 Pre-post N=3

No group statistics ASIA lower limb motor scores in 2/3 subjects in acute phase (5 & 6 weeks) which cannot be separated from natural recovery. No changes seen in 3rd person initiated at 18 months. No group statistics. All subjects showed increases in cumulative muscle scores (i.e., 8 muscles summed) indicative of increased strength.

1.

Wernig et al. 1998; Germany Downs & Black score=12 Pre-post N=76

Discussion Measures of strength were employed as a secondary outcome measure to the primary outcome of ambulation. In general, investigators have noted significant increases of lower limb strength 6-25

following locomotor training despite variations between training protocols and specific methods employed. Outcome measures have included manual muscle testing of individual lower limb muscles in incomplete SCI or summated scores of several muscles (Granat et al. 1993; Wernig et al. 1995; Wernig et al. 1998; Field-Fote 2001; Johnston et al. 2003; Hornby et al. 2005; Wirz et al. 2005). Most recent studies have adhered to ASIA international guidelines for the manual muscle testing (Field-Fote 2001; Hornby et al. 2005; Wirz et al. 2005). Others have employed muscle torque measurements by employing strain gauge transducers (Granat et al. 1993; Petrofsky 2001;). All investigators have reported increases in lower limb muscle strength in individuals with chronic SCI. However, several investigators have noted that enhanced walking capability did not necessarily demonstrate parallel increases in strength (Wernig et al. 1995; Wernig et al. 1998; Field-Fote 2001; Wirz et al. 2005). Furthermore, the clinical relevance of the small strength gains following locomotor training is questionable when considering the duration and complexity of the intervention (Field-Fote 2001). However, there is weak evidence (from 1 study, n = 3) that significant improvements in muscle strength may be realized when locomotor training is combined with conventional therapy (Hornby et al. 2005). Detecting group differences in strength gains during the acute phase may be more challenging given the natural recovery. Wernig et al. (1995) found no differences between those provided locomotor training versus those treated conventionally in muscle strength gains. However, specific subject characteristics were inadequately described other than stating that body-weight supported treadmill training was initiated within a few weeks (i.e., 2-20 weeks, median 7 weeks) following injury. There was also a lack of standardized assessment, further confounding the findings. Conclusion There is level 4 evidence that most forms of locomotor training (i.e., including body weight supported treadmill training with various assists and FES-assisted overland training) increase lower limb muscle strength in chronic SCI as indicated by overall increases in total lower extremity motor scores. There is level 3 evidence that body weight supported treadmill training is not significantly different than conventional rehabilitation therapy in enhancing lower limb muscle strength in acute SCI, although these studies are confounded by the natural recovery that may take place in the acute period.

Locomotor training programs are beneficial in improving lower limb muscle strength although in acute SCI similar strength benefits can be obtained with conventional rehabilitation. The real benefit of locomotor training on muscle strength may be realized when it is combined with conventional therapy. This should be further explored in acute, incomplete SCI where better functional outcomes may be realized with the combination of therapies.

6.4 Summary There is level 2 evidence that a program of PES-assisted isometric exercise reduces the degree of lower limb muscle atrophy in individuals with recent (~10 weeks post-injury)

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motor complete SCI, but not to the same extent as a comparable program of FESassisted cycling exercise. There is level 4 evidence that programs of PES-assisted exercise partially reverses the lower limb muscle atrophy found in individuals with long-standing (>1 year post-injury) motor complete SCI. There is level 2 evidence that a program of PES-assisted exercise increases lower limb strength and muscular endurance. There is level 2 evidence that a program of FES-assisted cycling exercise prevents and reverses lower limb muscle atrophy in individuals with recent (~10 weeks post-injury) motor complete SCI and to a greater extent than PES. There is level 4 evidence that programs of FES partially reverses the lower limb muscle atrophy found in individuals with long-standing (>1 year post-injury) motor complete SCI. There is level 4 evidence that a program of FES-assisted cycle exercise increases lower limb muscular endurance. There is level 2 evidence using historical controls that BWSTT is effective in improving ambulatory function. However, stronger evidence from one level 1RCT demonstrates that BWSTT has equivalent effects to conventional rehabilitation consisting of overground mobility practice for gait outcomes in acute/sub-acute SCI. There is Level 4 evidence from pre-test/post-test studies that BWSTT is effective for improving ambulatory function in people with chronic, incomplete SCI. There is Level 1 evidence from 1 RCT that different strategies for implementing body weight support gait retraining all yield similar ambulatory outcomes in people with chronic, incomplete SCI. It is recommended that therapists may choose a body weight support gait retraining strategy based on available resources (Field-Fote et al. 2005). In summary, level 1 evidence describes limited and indirect improvements in aspects of walking (i.e. spasticity, speed and posture) but do not translate into significant functional walking gains as a result of clonidine and cyproheptadine. Limited and non-functional improvements in walking as a result of baclofen are only supported by level 4 evidence. Conflicting evidence provides little guidance with respect to the use of GM-1 and 4aminopyridine for the improvement of ambulation in spinal cord injury. Scientifically robust studies with consistent clinically relevant outcome measures are needed for pharmacological intervention studies of ambulation after spinal cord injury. There is Level 4 evidence that FES-assisted walking can enhance walking speed and distance in complete and incomplete SCI. There is also Level 4 evidence from 3 independent laboratories that regular use of FES in gait training or activities of daily living leads to persistent improvement in walking function that is observed even when the stimulator is not in use. None of the studies investigating the efficacy of brace/orthotic devices for upright support and mobility are randomized or blinded, but that is in part due to the ethical dilemma of providing safe and appropriate bracing and the fact that participants will be able to distinguish which device they received. There is weak evidence from post-test studies that bracing alone results in significant gains in functional ambulation for people with complete SCI. Only 2 studies reported pre-test/post-test results (total n = 8) that the use of long-leg braces could enhance gait speed and endurance in people with complete SCI.

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There is Level 4 evidence that a combined approach of bracing and FES results in additional benefit to functional ambulation in paraplegic patients with complete SCI. However, in subjects who are achieve little benefit from bracing alone, the addition of FES appears to help improve standing or short-distance walking function (Marsolais et al. 2000). In incomplete SCI, however, there is some indication that a combination of bracing and FES provides greater ambulatory function than either approach alone (Kim et al. 2004). There is level 4 evidence that most forms of locomotor training (i.e., including body weight supported treadmill training with various assists and FES-assisted overland training) increase lower limb muscle strength in chronic SCI as indicated by overall increases in total lower extremity motor scores. There is level 3 evidence that body weight supported treadmill training is not significantly different than conventional rehabilitation therapy in enhancing lower limb muscle strength in acute SCI, although these studies are confounded by the natural recovery that may take place in the acute period.

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CHAPTER SEVEN
Cardiovascular Health and Exercise Following Spinal Cord Injury
Darren ER Warburton, PhD Shannon Sproule, PT Andrei Krassioukov, MD, PhD Janice J Eng, BSc (OT/PT), PhD

Key Points There is limited evidence that BWSTT can improve indicators of cardiovascular health in individuals with complete and incomplete SCI. Tetraplegics and paraplegics can improve their cardiovascular fitness and physical work capacity through aerobic exercise training which are of moderate intensity, performed 20-60 min day, at least three times per week for a minimum of six to eight weeks. Resistance training at a moderate intensity at least two days per week also appears to be appropriate for the rehabilitation of persons with SCI. It remains to be determined the optimal exercise intervention for improving cardiovascular fitness. Interventions that involve FES training a minimum of 3 days per week for 2 months can improve muscular endurance, oxidative metabolism, exercise tolerance, and cardiovascular fitness. Aerobic and FES exercise training may lead to clinically significant improvements in glucose homeostasis in persons with SCI. Preliminary evidence indicates that a minimum of 30 min of moderate intensity training on 3 days per week is required to achieve and/or maintain the benefits from exercise training. Aerobic and FES exercise training may lead to improvements in lipid lipoprotein profile that are clinically relevant for the at risk SCI population. The optimal training program for changes in lipid lipoprotein profile remains to be determined. However, a minimal aerobic exercise intensity of 70% of heart rate reserve on most days of the week appears to be a good general recommendation for improving lipid lipoprotein profile in persons with SCI.

Table of Contents
7.1 Introduction ......................................................................................................................7-1 7.2 The Risk for Cardiovascular Disease in Persons with SCI ..........................................7-2 7.3 Physical Inactivity and the Risk for Cardiovascular Disease in Persons with SCI....7-3 7.4 Exercise Rehabilitation and Cardiovascular Fitness ...................................................7-3 7.4.1 Treadmill Training ...........................................................................................................7-4 7.4.2 Arm, Mixed Arm and Wheelchair Ergometry...................................................................7-6 7.5 Functional Electrical Stimulation (FES).........................................................................7-9 7.5.1 FES Leg Cycle Ergometry ..............................................................................................7-9 7.5.2 Hybrid FES (Combined Leg and Arm Ergometry).........................................................7-11 7.5.3 Other Electrically-Assisted Training Programs .............................................................7-12 7.6 Glucose Homeostasis ...................................................................................................7-14 7.7 Lipid Lipoprotein Profiles .............................................................................................7-17 7.8 Summary.........................................................................................................................7-19 References..............................................................................................................................7-23

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Warburton DER, Sproule S, Krassioukov A, Eng JJ (2006). Cardiovascular Health and Exercise Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 7.1-7.28. www.icord.org/scire

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Warburton DER, Sproule S, Krassioukov A, Eng JJ (2006). Cardiovascular Health and Exercise Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 7.1-7.28. www.icord.org/scire

Cardiovascular Health and Exercise Following Spinal Cord Injury

7.1 Introduction Persons with SCI currently have an increased life expectancy owing to improvements in medical treatment (Bauman et al. 1992a). The majority of all SCI (80%) occur in individuals who are under 30 years of age (ICORD 2003). Therefore, persons with SCI will be susceptible to the same chronic conditions across the lifespan as able-bodied persons. In fact, cardiovascular disease (CVD) is the leading cause of death in both able-bodied individuals (Health Canada 1999) and persons with SCI (Bauman et al. 1992a, Whiteneck et al. 1992). In the general population, it is estimated that approximately one in four Canadians has some form of CVD. However, there appears to be an earlier onset of CVD and/or and increased prevalence of CVD in individuals with SCI in comparison to the general population (Yekutiel et al. 1989, Whiteneck et al. 1992, DeVivo et al. 1993, Bauman et al. 1999b). The prevalence of asymptomatic CVD has been shown to be between 60-70% in persons with SCI (Bauman et al. 1993, Bauman et al. 1994). This is an alarming statistic, which places a significant burden upon the patient, his/her family and society as a whole. Physical inactivity is a major independent risk factor for CVD and premature mortality (Blair & Brodney 1999, Booth et al. 2000, Katzmarzyk et al. 2000). As reviewed later, persons with SCI are commonly inactive and exhibit low levels of cardiovascular fitness (Hoffman 1986). Also, it appears that the ordinary activities of daily living are not adequate to maintain cardiovascular fitness in persons with SCI (Hoffman 1986). Extremely low levels of physical activity and fitness (as a result of wheelchair dependency) may explain directly the increased risk for CVD in individuals with SCI. Moreover, a reduction in cardiovascular fitness may also lead to a vicious cycle of further decline, which results in a reduction in functional capacity and the ability to live an independent lifestyle. The current chapter summarizes briefly the literature regarding the risk for CVD in persons with SCI. This chapter also evaluates critically the level of evidence regarding the effectiveness of varied forms of exercise rehabilitation in increasing cardiovascular fitness and attenuating the risk for CVD in persons with SCI. Table 7.1 contains a definition of the commonly used terms and/or abbreviations in this chapter (Warburton et al. 2006a). Table 7.1 Description of Commonly Used Terms
Term Spinal Cord Injury (SCI) Cardiovascular Disease (CVD) Physical Activity Exercise Aerobic Training Heart Rate Reserve Definition Refers to persons who have sustained a spinal cord injury. Refers to diseases affecting the circulatory system (i.e., heart and/or blood vessels) including acute myocardial infarction, coronary artery disease, arteriosclerosis, heart valve disease, heart failure, high blood pressure, peripheral vascular dysfunction, congenital heart disease, stroke, and arrhythmias. Refers to all leisure and non-leisure body movements resulting in an increased energy output from the resting condition. Refers to structured and repetitive physical activity designed to maintain or improve physical fitness. Refers to an exercise program that incorporates activities that are rhythmic in nature, using large muscle groups at moderate intensities for 3 to 5 days per week. Refers to the difference between maximal heart rate (HRmax; predicted or determined

7-1

Term (HRR)

MET Moderate Intensity Exercise Current General Exercise Recommendation Activities of Daily Living (ADLs) Cardiovascular (Aerobic) Fitness Maximal Aerobic Power (VO2max) Health-related Physical Fitness Quality of Life

Definition directly) and resting HR. The %HRR formula takes into account resting and maximal HR to provide an appropriate target HR (or range) for training. Training Heart Rate = [(HRmax HRrest) x 40-85%] + HRrest Refers to an estimate of resting metabolic rate while sitting quietly. 1 MET = 3.5 mLkg-1min-1 or 1 kcalkg-1h-1 Exercise performed at relative intensities of 40-59% HRR, approximately 4-6 METs, or 55-69% of HRmax. Moderate intensity exercise for 20-60 min day on most days of the week.

Refers to the activities in which one engages during daily life. Refers to the ability to transport and utilize oxygen during prolonged, strenuous exercise or work. It reflects the combined efficiency of the lungs, heart, vascular system and exercising muscles in the transport and utilization of oxygen. The maximum amount of oxygen that can be transported and utilized by the working muscles. Also, known as maximal oxygen consumption. Involves the components of physical fitness that are related to health status including cardiovascular fitness, musculoskeletal fitness, body composition and metabolism. Refers to an overall satisfaction and happiness with life, and includes the facets of physiological, emotional, functional and spiritual well-being.

7.2 The Risk for Cardiovascular Disease in Persons with SCI The majority of CVD events are the result of atherosclerosis (i.e., narrowing and hardening of the arteries) (Grey et al. 2003). Persons with SCI appear to be particularly susceptible to the development of atherosclerotic disease (Bravo et al. 2004). Researchers have revealed that persons with SCI exhibit a series of risk factors for atherosclerotic disease and thus CVD (as shown in Table 7.2). A healthy endothelium (interior lining of blood vessels) is essential for the protection against atherosclerosis (Anderson 2003). Relatively limited data exists regarding the vascular health of individuals with SCI (de Groot et al. 2005). However, the majority (if not all) of the risk factors for CVD in persons with SCI will have a significant negative impact upon endothelial function. As such, it would appear that vascular dysfunction is also a central step in the development of CVD in persons with SCI. Table 7.2 Risk Factors for Cardiovascular Disease in Persons with SCI
Risk Factor Abnormal lipoprotein profiles Literature Support Brenes et al. 1986, Dearwater et al. 1986, Bauman et al. 1992b, Krum et al. 1992, Maki et al. 1995, Dallmeijer et al. 1997, Bauman et al. 1998, Bauman et al. 1999a, Bauman et al. 1999b Myllynen et al. 1987, Bauman & Spungen 2001 Bauman et al. 1999c, Spungen et al. 2003 Wecht et al. 2000, Wecht et al. 2003, de Groot et al. 2005 Miranda & Hassouna 2000 Vaidyanathan et al. 1998, Kahn 1999, Roussi et al. 1999, Kahn et al. 2001, Frost et al. 2005, Lee et al. 2005 Bauman et al. 2001 Claus-Walker & Halstead 1982b, Bauman & Spungen 2000

Abnormal glucose homeostasis Increased relative adiposity, elevated body fat and/or reduced lean body mass Reduced peripheral vascular function and/or endothelial dysfunction Increased risk for deep vein thrombosis Abnormal haemostatic and inflammatory markers Excessive homocysteine Depressed endogenous anabolic hormone levels (e.g. serum testosterone and growth hormone)

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Risk Factor Increased activation of the renin-angiotensinaldosterone system Hypertension Reduced aerobic fitness

Literature Support Claus-Walker & Halstead 1982a Lee et al. 2006 Hoffman 1986

7.3 Physical Inactivity and the Risk for Cardiovascular Disease in Persons with SCI The separation of the autonomic nervous system from the superior brain centres after injury results in a series of changes that markedly affect the cardiovascular health of persons with SCI (Bravo et al. 2004). Adrenergic dysfunction, poor diet, and physical inactivity are thought to play key roles in the elevated risk for CVD in SCI. Physical inactivity is prevalent amongst persons with SCI. In fact, persons with SCI often lead relatively sedentary lives leading to marked deconditioning (Jacobs & Nash 2004). In the general population, deconditioning has been associated with a pronounced reduction in cardiovascular fitness (Warburton et al. 2006a) and an increase in the risk for CVD and premature mortality (Warburton & Mathur 2004). Not only is physical inactivity a major independent risk factor for CVD and premature mortality (Warburton et al. 2006a), it also plays a key role in the development of the majority of the other commonly observed risk factors for CVD in persons with SCI. For instance, cross-sectional investigations have shown that the extreme inactivity (associated with SCI) is related to lower HDL cholesterol levels (Brenes et al. 1986, Dearwater et al. 1986, Shetty et al. 1992, Schmid et al. 2000, Manns et al. 2005), elevated LDL cholesterol (Schmid et al. 2000), triglyceride (Schmid et al. 2000, Manns et al. 2005), and total cholesterol levels (Schmid et al. 2000), abnormal glucose homeostasis (Myllynen et al. 1987, Elder et al. 2004, Manns et al. 2005), increased adiposity (Elder et al. 2004, Manns et al. 2005), and excessive reductions in aerobic fitness (Eriksson et al. 1988, Schmid et al. 2000, Manns et al. 2005). It is important to note, that SCI presents additional risk for CVD above that seen in able-bodied individuals owing to the marked decrease in physical activity and injury-related changes in metabolic function (Bravo et al. 2004). The major abnormalities observed in SCI are reduced physical activity/fitness, abnormal glucose homeostasis, and deteriorated lipid lipoprotein profiles. Based on the available literature, it is clear that effective exercise interventions are required to slow the progression of multiple risk factors for CVD and other chronic diseases (e.g. obesity, type 2 diabetes) in persons with SCI. 7.4 Exercise Rehabilitation and Cardiovascular Fitness Exercise rehabilitation has been shown to be an effective means of attenuating or reversing chronic disease in persons with SCI. Similar to the general able-bodied population (Warburton et al. 2006a), habitual physical activity (beyond activities of daily living) can lead to numerous health benefits that significantly reduce the risk for multiple chronic conditions (in particular CVD) and premature mortality in persons with SCI. Although research is increasingly evaluating the health benefits of physical activity in persons with SCI, this body of information is relatively low in comparison to the general population and other clinical conditions (such as chronic heart failure) (Warburton et al. 2006a).

7-3

The research conducted within the field of SCI has examined predominantly the effects of aerobic exercise and/or functional electrical stimulation (FES) training. In the following sections we will review the literature regarding to the effects of varied exercise interventions on the risk for CVD in persons with SCI. Particular attention will be given to the changes in cardiovascular fitness, glucose metabolism, and lipid lipoprotein profiles that occur after training interventions in persons with SCI. Aerobic fitness is a strong predictor of multiple chronic diseases, the capacity for activities of daily living, and premature mortality in the general population (Warburton et al. 2006a). Moreover, exercise training commonly results in significant improvements in aerobic fitness (i.e., VO2max) in the general population (Warburton et al. 2006a, 2006b). There is increasing evidence illustrating the important association between the risk for chronic disease (in particular CVD) and cardiovascular fitness in persons with SCI. Recent work has also revealed the importance of maintaining high levels of health-related physical fitness for the capacity of performing activities of daily living in able-bodied and disabled populations (including persons with SCI) (Sloan et al. 1994, Warburton et al. 2006a). Moreover, aerobic fitness (and other components of health-related physical fitness) have been positively associated with the gainful employment of paraplegics (Noreau & Shephard 1992). Both tetraplegic and paraplegic persons appear to benefit from regimented exercise interventions that improve health-related physical fitness. We found at total of 41 studies in our search of the literature for investigations evaluating cardiovascular fitness before and after an exercise intervention. This included investigations related to treadmill training (2 studies; n = 14), arm exercise (20 studies; n = 278), and FES (18 studies; n = 233) training. 7.4.1 Treadmill Training Body-weight supported treadmill training (BWSTT) is an exercise protocol that has been used to potentially affect a number of domains, including motor recovery, bone density, cardiovascular fitness, respiratory function as well as quality of life. Traditional BWSTT requires participants to step on a treadmill while supporting some of their body weight on two parallel bars. Significant resources are often required with BWSTT as the majority of individuals will require one or two assistants to manually move the limbs forward. Limited data exists regarding the changes in cardiovascular fitness and health that occur with BWSTT (Table 7.3). Table 7.3 Effects of Bdy-weight Sported Treadmill Training on Cardiovascular Fitness and Health
Author Year; Country Score Research Design Total Sample Size Methods Population: 6 participants (4 male, 2 female), ASIA A and B, C4-T12, mean age 37.7 yrs, mean 6.7 years post-injury, motor complete. Treatment: Body weight supported treadmill training, 15 min/day (3 bouts of 5 min), 3 days/week for 4 months. Outcome Measures: BP, HR, HR variability, BP variability, arterial diameters and mean blood velocities, and arterial blood flow. Outcome 1. No changes in femoral or carotid artery cross sectional area, blood flow, or resistance post-training 2. An improvement in femoral artery compliance. 3. No change in resting BP, mean arterial blood pressure, resting HR or HR and blood pressure variability after training. 4. 3/6 patients had changes in HR and blood pressure variability reflective of increased vagal predominance.

Ditor et al. 2005a; Canada Downs & Black score=14 Pre-post N=6

7-4

Author Year; Country Score Research Design Total Sample Size

Methods Population : 8 participants (6 males, 2 females), ASIA B-C, C4-C5, incomplete, mean age 27.6 yrs, mean 9.6 years postinjury. Treatment: Progressive, body weightsupported treadmill training, 3 day/week for 6 months. Outcome Measures: HR and BP variability, LF/HR ratio (low to high frequency heart spectrum and is indicative of balanced sympathetic/parasympathetic tone and reduced risk for cardiovascularrelated mortality).

Outcome 1. Significant decrease in resting HR (10.0%) after training. 2. No changes in resting systolic, diastolic, or mean arterial BP after training. 3. Significant reduction in the resting LF/HF ratio after training. 4. There were no significant effects of training on HR and/or blood pressure variability during an orthostatic challenge (60 head up tilt).

Ditor et al. 2005b; Canada Downs & Black score=14 Pre-post N=8

Discussion The two level 4 papers are by the same Canadian research group (Ditor et al. 2005a, Ditor et al. 2005b). They reported that BWSTT did not have substantial group effects on HR and blood pressure in motor complete subjects, but did reveal a significant reduction in resting HR in the study with incomplete tetraplegics. There is also evidence that improvements in HR and blood pressure variability may occur after BWSTT in incomplete SCI and a subset of participants with complete SCI. These changes reflected an increased predominance of the parasympathetic nervous system control of HR and blood pressure. The changes in HR variability are indicative that beneficial changes in cardiac autonomic balance can occur in SCI. This research group also revealed the potential for improvements in vascular health (e.g. arterial compliance) after BWSTT in individuals with motor-complete SCI. There was no indication of the effects of BWSTT on VO2peak. In both papers, two trainers assisted the participants with the gait cycle, while a third trainer assisted with weight shifting, balance and overall safety. The mechanisms responsible for the improvement in markers of cardiovascular health and regulation in individuals with incomplete SCI remain to be determined. Both weight-bearing and the passive movement of the limbs may contribute to the improvement in cardiovascular health in these studies. Conclusion There is Level 4 evidence that BWSTT can reduce resting heart rate in individuals with incomplete, but not complete SCI injuries. There is Level 4 evidence that BWSTT can result in improvements in cardiac autonomic balance in persons with incomplete tetraplegia. There is Level 4 evidence that BWSTT can result in improvements in cardiac autonomic balance in a subset of individuals with motor-complete SCI who respond to ambulation with moderate to large increases in heart rate. There is Level 4 evidence that BWSTT can improve arterial compliance in individuals with motor-complete SCI.

There is limited evidence that BWSTT can improve indicators of cardiovascular health in individuals with complete and incomplete SCI.

7-5

7.4.2 Arm, Mixed Arm and Wheelchair Ergometry Given the motor loss of the lower limbs, upper extremity exercise is a logical choice. Improving cardiovascular fitness can be challenging using the smaller mass of the arms especially when muscle fatigue can often occur before endurance training targets are met. From our search, we found one level 1, five level 2, and fourteen level 4 studies. Given the large number of studies which have looked at upper extremity exercise, we have tabled only those studies which included an SCI control group. Table 7.4 Effects of Arm, Mixed Arm, and Wheelchair Ergometry Training on Cardiovascular Fitness and Health
Author Year; Country Score Research Design Total Sample Size Methods Arm Ergometry Population: 4 male, 2 female, C5-L1, ASIA A (n=1), B (n=1), C (n=4), mean age 36 yrs. Treatment: Interval training (3 min exercise of arm cranking, boxing, push ups and ball throwing followed by 2 minutes rest for 1 hour), 1h/day, 3 days/wk for 8 weeks. Randomized to low intensity (5060% HRR) or high intensity (70-80% HRR) group. Outcome Measures: VO2peak, maximal power output. Population: 24 men with spinal lesions: 8 spina bifida, 16 traumatic, ages 17-42 yrs. Treatment: Random assignment to 1) control or 1 of 3 arm ergometry programs 2 days/week for 24 weeks: 1) high-intensity long duration (40 min at 70% of VO2peak) exercise training, 2) high-intensity short duration (20 min at 70% of VO2peak) exercise training, and 3) low-intensity short duration (20 min at 50% of VO2peak) training. Outcome Measures: cardiac output, HR, VO2peak, power output, stroke volume. Participants: 14 sedentary, disabled males (n=9 exercise group, n=5 control group), ages 20-39. Treatment: 16 week arm ergometry aerobic training at 50-70% of VO2peak for 20-40 min/day, 3 days/week. Outcome Measures: BP, HR, power output, VO2peak, resting left ventricular dimensions, cardiac function. Outcome

de Groot et al. 2003; Netherlands PEDro=7 RCT N=6

1. Training resulted in a significant improvement in VO2peak and peak power output in the entire group. 2. The changes in VO2peak were significantly greater in the high intensity (59%) versus low intensity group (17%).

Davis et al. 1991; Canada PEDro=4 RCT N=24

1. Training increased VO2peak in the 3 arm ergometry groups (about 21%). 2. Significant increases in submaximal stroke volume and cardiac output with training in the high intensity long and the low intensity long training groups. 3. In contrast, the low intensity short duration training and control groups exhibited small, but non-significant decrements in SV. 1. Training was associated with a significant improvement in VO2peak (31%) and HR (-9.5%) 2. During isometric handgrip exercise, rate pressure product (20%), stroke volume (12-16%) 3. No changes in echocardiographic responses at rest or during isometric handgrip exercise.

Davis et al. 1987; Canada PEDro=4 RCT N=14

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Author Year; Country Score Research Design Total Sample Size Hjeltnes & WallbergHenriksson 1998; Norway Downs & Black score=16 Prospective Controlled Trial N=27

Methods Population: 27 participants: Exercise group: 10 tetraplegia, C6-8, 7 ASIA A & 3 ASIA B, 99 days post-injury; Control: 10 paraplegia, T7-11, all ASIA A. Treatment: Exercise group: standard rehabilitation + Arm ergometry, 30 min/day, 3 day/week for a 12-16 week period; Control: standard rehabilitation. Outcome Measures: power output, cardiac function, HR, VO2, systolic blood pressure, lactate levels, muscular strength, ability to perform activities of daily living. Mixed Arm and Other Exercise Population: 34 participants (18 tetraplegic and 16 paraplegic), ASIA A-D, C4-L1, ages 19-65 yrs. Treatment: The exercise group: 90-120 min/day, 2 days/wk for 9 months of aerobic (arm ergometry, 15-30 mins, at ~70% VO2max) and whole-body, circuit resistance exercise (wall pulley, free and machine weights) components. Control group: bimonthly education session on topics including exercise physiology, osteoporosis, and relaxation. Outcome Measures: muscular strength, power output, HR, quality of life ratings. Wheelchair Ergometry Population: low-intensity group n=6, C5T7, moderate-intensity group n=5, C5-T9. Treatment: Wheelchair ergometry 20 min/day, 3 days/week for 8 weeks. The low-intensity group trained at 50-60% max HR reserve (HRR); Moderate intensity group trained at 70-80% max HRR. Outcome Measures: HR, power output, blood lactate, VO2max, Rating of Perceived Exertion (RPE), lipid profiles.

Outcome 1. Peak workload increased (45%) significantly, while VO2peak did not change in the tetraplegics after training. 2. Peak workload (45.5%) and VO2peak (27.7) increased significantly in the paraplegics after standard rehabilitation. 3. No change in peak HR, systolic BP, submaximal exercise stroke volume or cardiac output in either SCI group.

Hicks et al. 2003; Canada PEDro=5 RCT N=23

1. Power output increased by 118% and 45% after training in the tetraplegic and paraplegic groups, respectively. 2. There were progressive increases in strength over the 9 months of training (ranging from 19-34%). 3. There was a significant decline in the HR to power output ratio (an indicator of improved aerobic fitness) after training.

Hooker & Wells 1989; USA Downs & Black score=9 Prospective Controlled Trial N=8

1. Neither group had changes in maximal HR, maximal power output, maximal blood lactate, or VO2max. The mean change in VO2max was 10 and 24%, respectively, for the low-intensity and high-intensity training groups. 2. The moderate-intensity group had significantly lower post-training submaximal HR, lactate, and RPE but no changes in oxygen consumption. 3. 70% maximal HRR appears to be the beneficial training threshold.

Discussion The reported improvements in aerobic capacity after aerobic arm training in SCI are approximately 20-30%; however, it is not uncommon for improvements in excess of 50%. For instance, researchers (DiCarlo 1988) revealed a 99% improvement in VO2max after aerobic arm cycle training. The majority of aerobic training investigations have evaluated the effectiveness of moderate (40-59% HRR or 55-69% of maximum HR) to vigorous (60-84% HRR or 70-89% of maximum HR) intensity exercise. These studies have used arm ergometry, wheelchair ergometry, and swimming based interventions (Jacobs & Nash 2004). Based on the current level of literature, it appears that moderate intensity exercise performed 20-60 min per day, at least 3 days per week 7-7

for a minimum of 6 weeks is effective for improving cardiovascular fitness in persons with SCI. Therefore, the general recommendations provided by Health Canada, the Canadian Society for Exercise Physiology, and the American College of Sports Medicine are appropriate for improving the cardiovascular fitness of persons with SCI. It is important to note that an exercise intensity threshold of 70% maximal HRR has been advocated for the attainment of training benefits when a minimal training duration (20 min) is the standard (Hooker& Wells 1989, Tordi et al. 2001, Bizzarini et al. 2005). It is also important to note that improvements in exercise capacity and functional status may occur after training without significant improvements in VO2peak, particularly in tetraplegic patients (Hjeltnes & Wallberg-Henriksson 1998). Questions remain regarding the primary mechanisms of importance for improvements in aerobic fitness after training. It is unclear whether central (heart and lung) or peripheral (skeletal muscle) adaptations are of key importance. Improvements have been observed in peripheral muscle function. For instance, investigators have shown intrinsic cellular adaptations that facilitate oxidative metabolism (level 4) (Stewart et al. 2004). Only limited investigations, however, have shown an improvement in cardiac function after aerobic exercise training. It could therefore be argued that peripheral adaptations are of primary importance to the improvement in aerobic capacity after aerobic exercise interventions. However, this statement is somewhat misleading as the majority of investigations have not directly evaluated cardiac output during maximal/peak exercise. This is owing to the fact that the assessment of maximal cardiac output during exercise is one of the most difficult and expensive procedures in clinical exercise physiology (Warburton et al. 1999a, 1999b). When exercise measures of cardiac function have been taken, improvements in central function have been observed (Davis et al. 1987). Further research examining the primary mechanism(s) of importance for the improved cardiovascular fitness and exercise capacity seen in SCI after aerobic exercise training is warranted. Less is known about the effects of resistance training on cardiovascular fitness. However, as reviewed by Jacobs and Nash (2004) the incorporation of resistance training into the treatment of persons with SCI appears to be essential. In fact, muscle weakness and dysfunction are key determinants of pain and functional status in persons with SCI. Investigators have evaluated the effects of resistance training on cardiovascular fitness in persons with SCI. For instance, hydraulic resistance training has also been shown to lead to significant improvements in VO2max (Cooney & Walker 1986). Furthermore, circuit resistance training has resulted in increases in VO2peak, time to fatigue, peak power output, and musculoskeletal fitness (Jacobs et al. 2001). The general health guidelines for resistance training appear to be appropriate for the rehabilitation of persons with SCI. This includes 1-2 sets of 8-10 different resistance exercises with large muscle groups for 8-12 repetitions (moderate intensity), on 2-4 days per week (Warburton et al. 2006b). Circuit weight training is also likely appropriate as it provides a significant stress to the cardiovascular and musculoskeletal systems. Conclusion There is Level 1 evidence that arm exercise at a moderate to vigorous intensity (50-80% HRR), 3 days/week for at least 2 months improves cardiovascular fitness. There is Level 1 evidence that high intensity (70-80% HRR) exercise leads to greater improvements in peak power and VO2peak than low intensity (50-60% HRR) exercise. There is Level 1 evidence that aerobic exercise training is effective in improving exercise capacity/tolerance in persons with SCI.

7-8

It is uncertain whether aerobic training can improve cardiac function in persons with SCI. Based on the changes observed in VO2max and findings from able-bodied individuals, a consensus was derived stating that aerobic training may be effective in improving the ability to extract oxygen at the periphery in persons with SCI. Tetraplegics and paraplegics can improve their cardiovascular fitness and physical work capacity through aerobic exercise training which are of moderate intensity, performed 20-60 min day, at least three times per week for a minimum of six to eight weeks. Resistance training at a moderate intensity at least two days per week also appears to be appropriate for the rehabilitation of persons with SCI. It remains to be determined the optimal exercise intervention for improving cardiovascular fitness.

7.5 Functional Electrical Stimulation (FES) Computer-assisted FES during leg cycling has been shown to be an important and practical means of exercising a relatively large muscle mass in persons with SCI (Hooker et al. 1992). These devices also permit the activation of the skeletal muscle pump during leg cycling. For these reasons, FES training has been widely advocated as an effective treatment strategy for SCI. It is important to note, that the physiological responses to FES training appear to be distinct from arm ergometry training. For instance, arm exercise has been shown to lead to faster VO2 kinetics (at a constant workload), greater changes in HR, and lower post-exercise blood lactates than FES leg cycling (Barstow et al. 2000). 7.5.1 FES Leg Cycle Ergometry Table 7.5 Effects of Functional Electrical Stimulation on Cardiovascular Fitness
Author Year; Country Score Research Design Total Sample Size Methods Population: 6 tetraplegia at C6, 4 paraplegia at T4, all complete, ages 2745 yrs, 3-23 yrs post-injury. Treatment: One-year exercise training using an FES cycle ergometer (30 min/day, 3 days/week). Outcome Measures: VO2max, total work output, blood lactate, muscle properties. Population : 16 male, 3 females (7 paraplegics T4-T10, 12 tetraplegics C4C7), ages 19-47 yrs, 2-17yrs post-injury. Treatment: Phase I: quadriceps stimulation with dynamic knee extensions against increasing resistance, 3 days/week for 4 weeks. Phase II: leg-cycle FES, 15-30 mins/day, 3 days/week for 12 weeks. Outcome Measures: HR, work, BP, and VO2peak. Population: 17 males, 1 female, 10 tetraplegia (C5-C7), 8 paraplegia (T4-T11), 7 incomplete, mean age 30.6 yrs, mean 1. 2. 3. Outcome 4 fold increase in total work output and 12% increase in thigh muscle mass over the training program. VO2max increased 17.5% (6 months) and 19.2% (12 months). Shift towards more fatigue resistant contractile proteins, which was accompanied by a doubling of citric synthase activity. Most participants showed an increase in strength and endurance. The average resistance increased by 50.4%. VO2peak increased non-significantly (14.9%) after training.

Mohr et al. 1997; Denmark Downs & Black score=14 Pre-post N=10

1.

Ragnarsson et al. 1988; USA Downs & Black score=14 Pre-post N=19

2.

Hooker et al. 1992; USA Downs & Black score=13 Pre-post

1.

Increase in power output (45%), VO2peak (23%), cardiac output (13%), HR (11%), and a reduction in total

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Author Year; Country Score Research Design Total Sample Size N=18

Methods 6.1yrs post-injury. Treatment: FES leg cycle training 10-30 min/day, 2-3 days/week for 12-16 weeks. Outcome Measures: VO2peak, power output, cardiac output, stroke volume, total peripheral resistance, and HR.

Outcome peripheral resistance (-14%) during peak FES leg cycle. No changes in stroke volume (6%), mean arterial BP (-5%), or arteriovenous oxygen difference (+10%). No differences during peak arm cranking exercise for any of the cardiovascular variables therefore no carry-over effect from leg training. The isometric-trained leg showed significantly larger mean increases in force, increase in type 1 fibres, fibre cross-sectional area, capillaryto-fibre ratio, citrate synthase activity and relative oxygenation after static training in comparison to baseline and the dynamically trained leg. These changes reflect the importance of load in the amount of adaptation to FES. VO2peak increased (70%) during FES leg cycling, but not during arm cycling. Increase in lean body mass (3.0%) and a decrease in body fat (6.4%). Increase in muscle cross-sectional area (21.3%). Training significantly increased VO2peak (10.9%), peak work rate (46.5%), and peak oxygen pulse (12.6%). HR was unaffected both at rest or peak exercise. resting HR and systolic blood pressure in the tetraplegics, while systolic, diastolic and mean arterial BP in the paraplegics after training. exercise power output after training in both groups. In both groups, submaximal exercise HR and blood pressure and stroke volume after training. After training, submaximal cardiac output increased significantly in the paraplegic group. work output (300%) over training. No change HR and systolic BP. common femoral artery diameter (8%), no change common carotid artery diameter. Blood flow to the paralyzed limbs was increased.

2.

3.

Crameri et al. 2004; Denmark Downs & Black score=12 Pre-post N=6

Population: all paraplegic, complete, C6T7, ages 26-54yrs, 3-21yrs post-injury. Treatment: FES training 45 min/day, 3 days/week, for 10 weeks. One leg: dynamic cycle ergometry involved bilateral quadriceps and hamstring stimulation; Contralateral leg: isometric contractions. Outcome Measures: muscle biopsies, capillary-to-fibre ratio, muscle proteins, and oxygenation. Population: 5 males, complete chronic lesions, 2 C5, 2 C6, 1 C7; 4 ASIA A, 1 ASIA A/B, mean age 35yrs, mean 10.2yrs post-injury. Treatment: 8 weeks of FES leg cycling, 7X/week. Outcome Measures: DXA (Body composition), VO2peak. Population: 9 males, 2 tetraplegia, 7 paraplegia, all ASIA A, mean age 34.4yrs, mean 10.1yrs post-injury. Treatment: FES leg cycle exercise, 30 min (minimum of 24 sessions, 3X/week). Outcome Measures: work rate, VO2peak, oxygen pulse. Population: 6 paraplegics (5 complete), 7 tetraplegics (all incomplete), C4-C7 and T4-T10, mean age 30.5yrs, mean 8yrs post-injury. Treatment: FES leg cycle, 3X/week for about 12 weeks. Outcome Measures: BP, power output, HR, VO2peak, stroke volume, and cardiac output.

1.

2. 1. 2. 3. 1.

Hjeltnes et al. 1997; Norway Downs & Black score=12 Pre-post N=5

Barstow et al. 1996; USA Downs & Black score=12 Pre-post N=9

2. 1.

Faghri et al. 1992a; USA Downs & Black score=12 Pre-post N=13

2. 3. 4.

Gerrits et al. 2001; Netherlands Downs & Black score=11 Pre-post N=9

Population: C4-C6 and T4-T8, ASIA A (5), B (3) and C (1), ages 26-61yrs, 1-27yrs post-injury. Treatment: FES leg cycle ergometry, 30min/day, 3day/wk for 6 weeks. Outcome Measures: BP, end-diastolic velocity, HR.

1. 2. 3.

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7.5.2 Hybrid FES (Combined Leg and Arm Ergometry) Table 7.6 Effects of Hybrid FES Training on Cardiovascular Fitness and Health
Author Year; Country Score Research Design Total Sample Size Methods Population: 9 males, 1 female, T1-T12, 9 complete, mean age 39.2yrs, 1-20yrs post-injury. Treatment: simultaneous FES cycle ergometry and voluntary arm ergometry, 30 mins/day, 2-3 days/wk for 4 weeks. Outcome Measures: VO2peak, blood flow and vascular resistance, and echo Doppler (diameter and flow-mediated dilation (FMD) after 13 min of ischemia). Population: all male, C4-T10, 4 paraplegia, 2 tetraplegia, ages 23-41yrs, 5-24yrs post-injury. Treatment: Phase I: FES leg cycle, 3 days/week for 6 weeks. Phase II: FES leg cycle with simultaneous, voluntary arm ergometry, 3 days/week for 6 weeks. Phase III: 8 weeks of detraining inactivity. Outcome Measures: VO2peak, submaximal and maximal HR. Population: all male, complete ASIA A, C5-6 to T12-L1, mean 35.6yrs, mean 9.7yrs post-injury. Treatment: 3 phases of exercise training (FES-Leg cycle ergometry): Phase I progressive FES-Leg Cycle Exercise (FESLCE) to 30 min of exercise; Phase II approximately 35 sessions of FES-LCE, and Phase III approximately 41 sessions (30 min each) of combined FES-LCE and arm ergometry. Outcome Measures: VO2peak and submaximal physiological parameters (VO2, HR, blood lactate). Population: 7male, 1 female, 7 paraplegia, 1 tetraplegia, mean age 32yrs, mean 13yrs post-injury. Treatment: 2 phase program. Phase I: FES leg cycle for 6 weeks, 3 days/week. Phase II: FES leg cycle plus simultaneous, voluntary arm ergometry for a 6 week period. Outcome Measures: VO2peak, HR, workload, peak lactate. Population: 7 male and 4 female, C4-C6 and T2-T6, complete motor lesions, ages 18-54yrs, 6-132 months post-injury. Treatment: 3 phase program over 13-28 weeks. Phase I: quadriceps stimulation for knee extension. Phase II: FES leg cycle with 0-1 kp resistance. Phase III: loaded FES leg cycle, 3 days/week for 3 weeks. 1. Outcome Training resulted in increased thigh resting (43.5%) and peak blood flow (17.1%), decreased thigh resting vascular resistance (31.8%), and increased common femoral artery diameter in the stimulated thigh tissue. Forearm and calf arterial parameters and FMD, in both superficial femoral and brachial artery, did not change. After training, there was an increase in maximal workload (6.8%), VO2peak (6.1%), and resistance to fatigue. VO2peak (81.7%) and workload with FES leg cycle. 8 week detraining period, peak workload returned to baseline levels; however VO2peak was still higher than baseline.

Thijssen et al. 2005; Netherlands Downs & Black score=14 Pre-post N=10

2. 3. 1. 2.

Gurney et al. 1998; USA Downs & Black score=12 Pre-post N=6

1.

Mutton et al. 1997; USA Downs & Black score=12 Pre-post N=11

2.

In response to FES-LCE training both VO2peak and peak work rate during graded FES leg exercise (but not graded arm ergometry) testing improved with training. As a result of the hybrid exercise training, VO2peak (13%) and peak power output (28%) were significantly increased during graded hybrid testing, but not during graded arm or graded FES leg testing alone.

1. 2. 3. 4. 1. 2.

Krauss et al. 1993; USA Downs & Black score=12 Pre-post N=8

After Phase 1, arm ergometer VO2peak (21.9%) and FES leg ergometer VO2peak (62.7%). After Phase 2, the hybrid exercise VO2peak increased 13.7%. Peak HR only increased with training in FES leg ergometry. There were no significant changes in peak lactate with training. Resting measures of VO2, HR, and oxygen pulse did not significantly change with training. There were significant increases in endurance time (288%), VO2peak (95.9%) and HR (16.8%), and decreases in diastolic blood pressure (31.5%) with training.

Pollack et al. 1989; USA Downs & Black score=11 Pre-post N=11

7-11

Author Year; Country Score Research Design Total Sample Size

Methods Outcome Measures: BP, HR, oxygen consumption. 3.

Outcome There was a non-significant increase (59.7%) in oxygen pulse with training.

7.5.3 Other Electrically-Assisted Training Programs Table 7.7 Effects of Other Electrically Assisted Training Programs on Cardiovascular Fitness and Health
Author Year; Country Score Research Design Total Sample Size Wheeler et al. 2002; Canada Downs & Black score=17 Pre-post N=6 Methods Population: C7-T12, 5 ASIA A, 1 ASIA C, mean age, 42.5yrs, mean 13.8yrs post-injury. Treatment: FES (quadriceps) with arm rowing 30 min/day, 3 days/week, for 12 weeks at 70-75% of VO2peak. Outcome Measures: VO2peak, rowing distance, and peak oxygen pulse. Population: all male, complete ASIA A, C5-T10, mean age 35.6yrs, mean 13.4yrs post-injury. Treatment: Home-based electrical stimulation (4 sets of 10 dynamic knee extensions with 3 mins rest between, increasing resistance with weight), 2X/week for 18 weeks. Outcome Measures: Doppler echo ultrasound (blood velocity and flow, femoral artery diameter), muscle fatigue, and muscle mass. Population: all paraplegia, no other details given. Treatment: 3 hours per week for 14 weeks with the Reciprocating Gait Orthosis. Outcome Measures: muscle hypertrophy, cholesterol, LDL, cardiac output, and stroke volume. Population: SCI: 3 male, 3 female, T4L2, all complete ASIA A/B, mean age 43 yrs, mean 14.5yrs post-injury; Controls: 8 able-bodied individuals (4 male, 4 female), mean age 41yrs. Treatment: Unilateral surface stimulation of the quadricep, tibial anterior and gastrocnemius muscles, 30 min/day, daily for 4 weeks (isometric training, as the leg was fixed in a sitting position with a knee angle of ~90) Outcome Measures: leg circumference, total limb volume, resting mean red blood cell velocity and vessel diameter and blood pressure. 1. Outcome Training resulted in significant increases in rowing distance (25%), VO2peak (11.2%), and peak oxygen pulse (11.4%).

1.

Sabatier et al. 2006; USA Downs & Black score=15 Pre-post N=5

2. 3.

Training resulted in significant increases in weight lifted and muscle mass, and a decrease in muscle fatigue (-60%). There was no change in femoral artery diameter with training. Resting, reactive hyperaemia, and exercise blood flow did not change significantly with training.

1. 2.

Solomonow et al. 1997; USA Downs & Black score=13 Pre-post N=70

There was a non-significant increase in cardiac output (7.1%) and stroke volume (5.0%) after training. There was a significant increase in knee extensor torque (78.2%). There was an increase in arterial compliance and a decrease in the flow-mediated dilation response in the femoral artery of the trained leg, with no changes in these vascular parameters in the femoral artery of the untrained leg, the carotid artery, and the brachial artery. There were no significant trainingrelated changes in resting vessel diameter, blood flow or shear rate in the femoral, carotid, and brachial arteries. No significant training-related changes occurred in blood pressure or leg volumes.

1.

de Groot et al. 2005; Netherlands Downs & Black score=10 Pre-post N=6

2.

3. 4.

7-12

Discussion There is a growing body of literature indicating that FES exercise training is effective in improving cardiovascular health, peak power output, and exercise tolerance/capacity in persons with SCI (Table 7.5). This research generally employs a cycling motion, although rowing and bipedal ambulation have also been evaluated. It appears that moderate-to-vigorous intensity FES training (relative to baseline capacity) is effective to improve cardiovascular fitness in persons with SCI. The majority of the investigations are pre-post designs (level 4) with investigations reporting marked changes in VO2max or VO2peak after FES training. Similar to aerobic training, 20-40% changes in aerobic capacity are often observed after FES training. However, it is not uncommon for improvements in excess of 70% (Table 7.5). For instance, researchers (Faghri et al. 1992) found a 260% increase in VO2peak after FES training. Investigations with FES training have also shown an improvement in musculoskeletal fitness and health. Similar to arm exercise training, limited investigations have shown an improvement in cardiac function after FES training. A recent investigation has also revealed that the degree of muscular adaptation that can be achieved via FES exercise is dependent upon the load that is applied to the paralyzed muscle (Crameri et al. 2004). Researchers have also revealed that hybrid exercise training (FES-leg cycling combined with arm ergometry) may elicit greater changes in peak work rates and VO2max/VO2peak than FESleg cycling exercise alone (Krauss et al. 1993, Mutton et al. 1997). Moreover, it appears that the physiological adaptations to combined FES-leg cycling and arm ergometry training are maintained partially following 8 weeks of detraining (Gurney et al. 1998). Furthermore, other interventions (Table 7.7) that make use of FES training have also been shown to improve the exercise capacity and cardiovascular health status of persons with SCI. A series of intrinsic muscle adaptations can also occur after FES training that enhance the ability for oxidative metabolism at the cellular level, which in turn facilitate improved endurance, exercise tolerance and functional capacity. Key intrinsic muscle adaptations that have been observed include an increase in the proportion of type 1 fibres, an enhancement in crosssectional fibre area, an increase in capillary-to-fibre ratio, a shift towards more fatigue resistant contractile proteins, and an increase in citrate synthase activity. Given the recently established importance of musculoskeletal fitness for health and functional status (Warburton et al. 2001a, 2001b, Warburton et al. 2006b), further research is clearly warranted with persons with SCI. Randomized, controlled exercise interventions (both arm and/or FES training) that evaluate concurrent changes in musculoskeletal fitness and health status are particularly needed. Conclusion There is Level 4 evidence FES training for a minimum of 3 days per week for 2 months can improve muscular endurance, oxidative metabolism, exercise tolerance, and cardiovascular fitness. There is Level 4 evidence that FES training is effective in improving exercise cardiac function in persons with SCI. Based on the changes observed in VO2max and findings from able-bodied individuals a consensus (Level 5; Expert Opinion) was derived stating that aerobic training is effective in improving the ability to extract oxygen at the periphery in persons with SCI.

7-13

Interventions that involve FES training a minimum of 3 days per week for 2 months can improve muscular endurance, oxidative metabolism, exercise tolerance, and cardiovascular fitness.

7.6 Glucose Homeostasis Glucose intolerance and decreased insulin sensitivity are independent risk factors for CVD (Hurley & Hagberg 1998). Abnormal glucose homeostasis is associated with deteriorated lipidlipoprotein profiles and an increased risk for the development of hypertension and type 2 diabetes (Hurley & Hagberg 1998, Warburton et al. 2001a, 2001b). It is well-established that habitual physical activity is an effective primary preventative strategy against insulin resistance and Type 2 diabetes in the general population (Warburton et al. 2006a). Although comparatively less information is available for SCI, it appears that exercise training programs are effective in improving glucose homeostasis (Hjeltnes et al. 1998, Chilibeck et al. 1999, de Groot et al. 2003, Phillips et al. 2004, Mahoney et al. 2005). Table 7.8 Glucose Homeostasis
Oral Glucose Tolerance Test (OGTT) Insulin Sensitivity Blood Glucose Blood Insulin Glucose Transporters (GLUT-4) Glycogen Synthase Hexokinase Citrate Synthase Phosphofructokinase Involves the ingestion of glucose and the subsequent serial blood analysis of glucose levels to determine the rate of blood glucose removal. Common test used in the diagnosis of diabetes. Refers to the sensitivity of target cells (muscle, hepatic cells and adipose) to insulin. Refers to blood levels of glucose (a simple sugar, carbohydrate). High fasting blood glucose levels reflects pre-diabetic or diabetic conditions. Refers to blood levels of insulin (a hormone that regulates carbohydrate metabolism). Glucose transporters are important membrane proteins that facilitate the transport of glucose through the cellular membrane. GLUT4 is an insulin-regulated glucose transporter located in adipose and muscle tissues. Enzyme involved in the synthesis of glycogen from glucose. An enzyme that acts during carbohydrate metabolism. In the first step of glycolysis, hexokinase phosphorylates (transfers phosphate from ATP) glucose to prepare it for subsequent breakdown for use in energy production. Citrate synthase is an important enzyme in the Citric Acid Cycle (Krebs cycle). Phosphofructokinase (PFK) is an important regulatory enzyme of glycolysis.

Table 7.9 Effects of Exercise Training on Glucose Metabolism in Persons with SCI
Author Year; Country Score Research Design Total Sample Size de Groot et al. 2003; Netherlands PEDro=7 RCT N=6 Methods Population: 4 male, 2 female, C5-L1, ASIA A (n=1), B (n=1), and C (n=4), mean age 36yrs, mean 116 days post-injury. Treatment: Randomized to low intensity (50-60% HRR) or high intensity (70-80% HRR) arm ergometry. 20 min/day, 3 days/week for 8 weeks. Outcome Measures: VO2peak, insulin Outcome 1. There was a significant difference in insulin sensitivity between groups, with a non-significant decline in the high intensity group and a significant improvement in the low intensity group with training. 2. A significant positive correlation between VO2peak and insulin

7-14

Author Year; Country Score Research Design Total Sample Size

Methods sensitivity, blood glucose. Population: 5 males, complete SCI, C5T10, ASIA grade A, mean age 35.6yrs, mean 13.4yrs post-injury. Treatment: Home-based neuromuscular electric stimulation-induced resistance exercise training, 2 days/week for 12 weeks. Outcome Measures: quadriceps femoris muscle cross-sectional area, plasma glucose, insulin.

Outcome sensitivity (r=0.68, p=0.02) was found for the group as a whole. 1. Quadriceps femoris muscle crosssectional area increased in both thighs (~37%) after training. 2. All participants had normal fasting glucose levels before and after training. 3. There were no significant changes in blood glucose or insulin with training. However, there was a trend towards reduced plasma glucose levels (p=0.074). 4. There was a progressive increase in muscular strength over the 12 week program. 1. After training, insulin-mediated glucose disposal was increased by 33%. There was an associated 2.1 fold increase in insulin-stimulated glucose transport activity. 2. Training led to marked increases in protein expression of GLUT4 (glucose transporter) (378%), glycogen synthase (526%), and hexokinase II (204%) in the vastus lateralis muscle. 3. Hexokinase II activity increased 25% after training. 4. A small increase in percentage type I muscle fibres and signs of transformation from type IIb to IIa muscle fibres were noted in 4/5 participants. 1. Decrease in the external supported proportion of body weight and increase in session length and walking velocity. 2. Reduction in the area under the curve for glucose (-15%) and insulin (-33%). 3. The oxidation of exogenous (ingested) glucose and endogenous (liver) glucose increased (68% and 36.8%, respectively) after training. 4. Training resulted in increased muscle glycogen, GLUT-4 content (glucose transporter) (126%), and hexokinase II enzyme activity (49%). 1. There were significantly lower (14.3%) 2h OGTT glucose levels after 8 weeks of training. 2. Glucose utilization was higher for all 3 participants and insulin sensitivity was higher for 2 of the 3 participants during post-training 2h clamp test.

Mahoney et al. 2005; USA Downs & Black score=17 Pre-post N=5

Hjeltnes et al. 1998; Sweden Downs & Black score=13 Pre-post N=5

Population: 5 males, C5-C7, all complete ASIA A, mean age 35yrs, mean 10yrs postinjury. Treatment: Electrically stimulated leg cycling exercise, 7 days/week for 8 weeks. Outcome Measures: peripheral insulin sensitivity, whole body glucose utilization, glucose transport, phosphofructokinase, citrate synthase, hexokinase, glycogen synthase, blood glucose, plasma insulin.

Phillips et al. 2004; Canada Downs & Black score=12 Pre-post N=9

Population : 8 male, 1 female, incomplete ASIA C, C4-T12, mean 8.1yrs post-injury. Treatment: Body-weight supported treadmill walking, 3 days/week for 6 months. Outcome Measures: whole-body dualenergy X-ray absorptiometry, GLUT4 protein abundance, hexokinase activity, oral glucose tolerance tests, glucose oxidation, CO2 breath analysis.

Jeon et al. 2002; Canada Downs & Black score=11 Pre-post N=7

Population: 5 male, 2 female, motor complete, C5-T10, ages 30-53yrs, 3-40yrs post-injury. Treatment: FES leg cycle training, 30 min/day, 3 day/week for 8 weeks. Outcome Measures: oral glucose tolerance test (OGTT), glucose and insulin

7-15

Author Year; Country Score Research Design Total Sample Size

Methods levels, glucose utilization, insulin sensitivity and levels. Population : 8 male, 2 female, 6 tetraplegia, 4 paraplegia, C6-T4, mean age 35yrs, mean 12yrs post-injury. Treatment: FES cycling, 30 min/day, 3 day/wk for 12 months. 7 participants completed an additional 6 months (at 1 day/week). Outcome Measures: insulin-stimulated glucose uptake, oral glucose tolerance test (OGTT), GLUT 4 glucose transporter protein.

Outcome

Mohr et al. 2001; Denmark Downs & Black score=10 Pre-post N=10

Chilibeck et al. 1999; Canada Downs & Black score=10 Pre-post N=5

Population: 4 male, 1 female, motor complete C5-T8, ages 31-50yrs, 3-25yrs post-injury. Treatment: FES leg cycle ergometry training, 30 min/day, 3 day/week for 8 weeks. Outcome Measures: glucose transporters (GLUT-4, GLUT-1), oral glucose tolerance test, citrate synthase.

1. Insulin-stimulated glucose uptake rates increased after intensive training. 2. With the reduction in training, insulin sensitivity decreased to a similar level as before training. GLUT 4 increased by 105% after intense training and decreased again with the training reduction. The participants had impaired glucose tolerance before and after training, and neither glucose tolerance nor insulin responses to OGTT were significantly altered by training. 1. Training resulted in increases in GLUT-1 (52%) and GLUT-4 (72%). 2. There was a training-induced increase in citrate synthase activity (56%) and an improvement in the insulin sensitivity index as determined from oral glucose tolerance test.

Discussion The majority of the data is from experimental non-randomized controlled trials. A search of the literature revealed 7 investigations (n = 47). This included 1 randomized controlled trial (RCT) and 6 experimental non-randomized controlled trials. The RCT involved the randomization to two different forms of exercise, and as such an exercise condition served as the control. The majority (5) of these trials examined the effectiveness of FES training in comparison to aerobic training (2 investigations). Similar to other studies in the field of SCI research, this area of investigation is limited by the lack of quality RCT. Moreover, the majority of the research relates to the effects of FES training. Limited work has been conducted using aerobic and/or resistance exercise training. As a whole, however, these studies are consistent and reveal several important findings. For instance, the improvements in glucose homeostasis may be the result of increased lean body mass (which leads to enhancd insulin sensitivity), and increased expression of GLUT4, glycogen synthase, and hexokinase in exercised muscle. Consistent with findings in able-bodied individuals (Warburton et al. 2001a, 2001b), the improvement in glucose homeostasis after exercise interventions (such as aerobic training or FES) does not appear to be solely related to decreases in body adiposity and/or increases in VO2max. This is due to the fact that significant improvements in glucose homeostasis can occur with minor changes in body composition and/or aerobic fitness. It is also important to note that there appears to be a minimal volume of exercise required for improvements in glucose homeostasis. For instance, Mohr et al. (2001) revealed that a reduction of FES training was not sufficient to maintain the beneficial changes in insulin sensitivity and GLUT4 protein observed during a 3 day/week FES training program.

7-16

Conclusion There is Level 4 evidence that aerobic exercise training programs (performed 30 min/day, 3 day per week for 6 weeks or more) are effective in improving glucose homeostasis in persons with SCI. There is Level 4 evidence that FES training programs (performed 30 min/day, 3 day per week for 6 weeks or more) are effective in improving glucose homeostasis in persons with SCI. There is Level 4 evidence that the changes in glucose homeostasis after aerobic or FES training are clinically significant for the prevention and/or treatment of type 2 diabetes. Aerobic and FES exercise training may lead to clinically significant improvements in glucose homeostasis in persons with SCI. Preliminary evidence indicates that a minimum of 30 min of moderate intensity training on 3 days per week is required to achieve and/or maintain the benefits from exercise training.

7.7 Lipid Lipoprotein Profiles Abnormal lipid-lipoprotein profiles have been associated with an increased risk for CVD (Hurley & Hagberg 1998, Warburton et al. 2001a, 2001b, Warburton et al. 2006a, 2006b). Routine physical activity has been shown to enhance lipid lipoprotein profiles, e.g., reduced triglycerides (TG), greater levels of high-density lipoprotein (HDL) cholesterol and lower low/high density lipoprotein ratios (LDL/HDL) (Brenes et al. 1986, Tell & Vellar 1988, DuRant et al. 1993, Taimela et al. 1994, O'Connor et al. 1995, Halle et al. 1996, Berg et al. 1997, Warburton et al. 2001a, 2001b) in the general population (Warburton et al. 2006a). Although limited, similar findings have been observed in persons with SCI (Table 7.9). The following table describe the common measurements of lipid profiles. Table 7.10 Lipid Lipoprotein Profiles
Low-density lipoprotein (LDL) Lipid protein complex that transports cholesterol from the liver to other tissues within the body. LDL is often referred to as the bad cholesterol. LDL levels above 160 mg/dL (4.1 mmol/L) are considered to be high. Lipid protein complex that transports cholesterol from the tissues to the liver for excretion and re-utilization. HDL is often referred to as the good cholesterol. HDL levels of <40 mg/dL (<1.03 mmol/L) are associated with an increased risk for CVD. Total amount of all cholesterol in the blood (TC related to risk for CVD) High energy fatty acids which form much of the fat stored by the body

High-density lipoprotein (HDL) Total cholesterol (TC) Triglycerides (TG)

Table 7.11 Effects of Exercise Training on Lipid Lipoprotein Profiles in Persons with SCI
Author Year; Country Score Research Design Total Sample Size de Groot et al. 2003; Netherlands PEDro=7 RCT N=6 Methods Population: 4 male, 2 female, C5-L1, ASIA A (n=1), B (n=1), and C (n=4), mean age 36yrs, mean 116 days post-injury. Treatment: Randomized to low intensity (50-60% HRR) or high intensity (70-80% Outcome 1. The TC/HDL and triglycerides decreased significantly more in the high intensity versus the low intensity group.

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Author Year; Country Score Research Design Total Sample Size

Methods HRR) arm ergometry. 20 min/day, 3 days/week for 8 weeks. Outcome Measures: lipid profiles including total cholesterol (TC), HDL, LDL, triglycerides (TG). Population: 5 SCI: lesion below T10, mean age 32 years; 7 AB controls: mean age 31 years. Treatment: Arm ergometry, 30 min/day (at 60-65% VO2peak), 3 day/week for 12 wks. Outcome Measures: VO2peak, peak HR, peak workload, TC, triglycerides, HDL. Population: all paraplegia, no other details given. Treatment: 3 hours per week for 14 weeks with the Reciprocating Gait Orthosis. Outcome Measures: cholesterol, LDL, HDL Population: 5 males, complete lesions T6L1, mean age 37.8yrs, mean 4.8yrs postinjury. Treatment: Circuit resistance training, 3 days/week for 12 weeks, with resistive load of 50-60% 1RM. Outcome Measures: VO2peak, time to fatigue, TC, triglycerides, HDL, LDL. Population: 8 male, 1 female, incomplete lesions ASIA C, C4-T12, mean 8.1yrs postinjury. Treatment: Body weight-supported treadmill training, 3 day/week for 6 months. Outcome Measures: ambulatory capacity (Wernig Walking Scale), cholesterol, HDL, LDL, triglycerides Population: low-intensity group: n=6, 3 male, 3 female, C5-T10, ages 26-36yrs, 3months-19yrs post-injury; moderateintensity group: n=5, 3 male, 2 female, C5T9, ages 23-30yrs, 2-19yrs post-injury. Treatment: Two SCI groups performed wheelchair ergometry 20 min/day, 3 days/week for 8 weeks. The low-intensity group trained at 50-60% max HRR and the moderate intensity group trained at 70-80% max HRR. Outcome Measures: total cholesterol (TC), triglycerides, HDL, LDL.

Outcome

El-Sayed et al. 2005; UK Downs & Black score=13 Pre-post N=12

1. There was a significant increase in peak workload (10.1%) and VO2peak (8.6%). 2. Training did not alter TC or triglycerides. 3. Training improved HDL. 1. There were significant reductions in total cholesterol, LDL, LDL/HDL, and TC/HDL in 8 patients with initially high total cholesterol levels (>200 mg/dL). 2. 20 patients with initially normal cholesterol levels did not exhibit a statistically significant change in total cholesterol, HDL, or LDL levels. 1. There were significant increases in VO2peak, time to fatigue and peak power output after training. 2. There were significant decreases in LDL, LDL/HDL and TC/HDL after training. 1. Treadmill velocity and session length increased by 135% and 55%, respectively, while amount of externally supported weight decreased as the result of training. 2. Functional locomotor capacity improved in 4 subjects. 3. There were significant reductions in TC (-11.2%), LDL (-12.9%) and total cholesterol/HDL (-19.8%). 1. Blood lipid levels remained unaltered in the low-intensity group, while the moderate-intensity group exhibited significant increases in HDL and decreases in triglycerides, LDL, and the TC/HDL ratio. 2. It appears that 70% maximal HRR was the threshold intensity needed to elicit training benefits in SCI persons.

Solomonow et al. 1997; USA Downs & Black score=13 Pre-post Initial N=70; Final N=33

Nash et al. 2001; USA Downs & Black score=11 Pre-post N=5

Stewart et al. 2004; Canada Downs & Black score=10 Pre-post N=9

Hooker & Wells 1989; USA Downs & Black score=9 Prospective Controlled Trial N=8

Discussion The information regarding the effects of exercise training on lipid lipoprotein profile is derived from one level 1 study, 1 level 2 and several level 4 studies (N = 105). The majority (6) of the investigations examined a form of aerobic training (either arm ergometry or assisted-treadmill 7-18

walking). The other investigation examined the effects of reciprocating gait orthosis powered with electrical muscle stimulation. These findings generally support the importance of exercise in the reduction of atherogenic lipid lipoprotein profiles and the reduction of the risk for CVD in persons with SCI. It appears that a minimal threshold of training exists for changes in lipoprotein profile. For instance, a few authors reported that 70% of maximal HRR is the threshold necessary to achieve significant improvements in lipid lipoprotein profiles. Future research is warranted, however, to quantify the effects of varying forms of exercise (including aerobic exercise, resistance exercise, and FES) on lipid lipoprotein profiles in persons with SCI. Conclusion There is Level 4 evidence to suggest that aerobic exercise training programs (performed at a moderate to vigorous intensity 20-30 min/day, 3 days per week for 8 weeks) are effective in improving the lipid lipoprotein profiles of persons with SCI. Preliminary evidence (Level 4) also indicates that FES training (3 hours/week, for 14 weeks) may improve lipid lipoprotein profiles in SCI.

Aerobic and FES exercise training may lead to improvements in lipid lipoprotein profile that are clinically relevant for the at risk SCI population. The optimal training program for changes in lipid lipoprotein profile remains to be determined. However, a minimal aerobic exercise intensity of 70% of heart rate reserve on most days of the week appears to be a good general recommendation for improving lipid lipoprotein profile in persons with SCI. 7.8 Summary There is a growing body of evidence to suggest that persons with SCI are at an increased risk for CVD. The evidence is summarized for the management of the risk of cardiovascular disease with aerobic exercise training (Table 7.12) and with FES (Table 7.13). Table 7.12 Management of the Risk for Cardiovascular Disease in Persons with SCI through Aerobic Exercise Training Interventions
Risk Factor Strength of Evidence Literature Support Gass et al. 1980, DiCarlo et al. 1983, DiCarlo 1988, Hjeltnes & WallbergHenriksson 1998, Jacobs et al. 2002, Sutbeyaz et al. 2005 Gass et al. 1980, DiCarlo et al. 1983, Cooney & Walker 1986, DiCarlo 1988, Jacobs et al. 2002, de Groot et al. 2003, El-Sayed et al. 2004, Sutbeyaz et al. 2005. Davis et al. 1987, Davis et al. 1991

Cardiovascular Fitness

Increased exercise tolerance

Level 1

Increased VO2max

Level 1

Increased cardiac output

Level 4

7-19

Risk Factor Reduced submaximal exercise heart rate Increased maximal heart rate Increased stroke volume Decreased total peripheral resistance

Strength of Evidence Level 4 Level 4 Level 4 Level 4

Literature Support DiCarlo 1988 Sutbeyaz et al. 2005 Davis et al. 1987, Davis et al. 1991 Davis et al. 1987, Davis et al. 1991 Cooney & Walker 1986, DiCarlo 1988, Hjeltnes & Wallberg-Henriksson 1998, Jacobs et al. 2002, de Groot et al. 2003, Hicks et al. 2003, Sutbeyaz et al. 2005 Stewart et al. 2004 Hooker & Wells 1989, Nash et al. 2001, El-Sayed & Younesian 2005 Hooker & Wells 1989, Nash et al. 2001, de Groot et al. 2003, Stewart et al. 2004 de Groot et al. 2003 Hooker & Wells 1989, de Groot et al. 2003, Stewart et al. 2004 de Groot et al. 2003

Increased power output

Level 1

Intrinsic cellular adaptations that facilitate oxidative metabolism Increased HDL cholesterol Lipid Lipoprotein Profile Reduced LDL cholesterol Reduced triglycerides Reduced total cholesterol Glucose Homeostasis Increased insulin sensitivity, decreased insulin resistance, and/or improved glucose tolerance.

Level 4 Level 4 Level 4 Level 4 Level 4 Level 4

Table 7.13 Management of the Risk for Cardiovascular Disease in Persons with SCI through Functional Electrical Stimulation Training Interventions
Risk Factor Strength of Evidence Level 4 Literature Support Pollack et al. 1989, Hooker et al. 1992, Barstow et al. 1996, Mohr et al. 1997, Wheeler et al. 2002, Thijssen et al. 2005 Pollack et al. 1989, Hooker et al. 1992, Barstow et al. 1996, Hjeltnes et al. 1997, Mohr et al. 1997, Wheeler et al. 2002, Thijssen et al. 2005 Hooker et al. 1992 Faghri et al. 1992 Faghri et al. 1992 Faghri et al. 1992 Faghri et al. 1992, Hooker et al. 1992, Thijssen et al. 2005 Andersen et al. 1996, Mohr et al. 1997, Crameri et al. 2002, Crameri et al. 2004 Solomonow et al. 1997 Solomonow et al. 1997 Jeon et al. 2002

Increased exercise tolerance

Increased VO2max Cardiovascular Fitness Increased cardiac output Reduced submaximal exercise heart rate Increased stroke volume Decreased total peripheral/vascular resistance

Level 4 Level 4 Level 4 Level 4 Level 4 Level 4 Level 4 Level 4 Level 4 Level 4

Increased power output Intrinsic cellular adaptations that facilitate oxidative metabolism Lipid Lipoprotein Profile Glucose Homeostasis Reduced LDL cholesterol Reduced total cholesterol Increased insulin sensitivity, decreased insulin resistance, and/or improved glucose tolerance.

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Marked physical inactivity appears to play a central role in this increased risk. Accordingly, exercise interventions are effective in leading to significant reductions in the risk for CVD and multiple comorbidities (such as type 2 diabetes, hypertension, obesity). Both exercise and FES training are effective in attenuating and/or reversing abnormalities in glucose homeostasis, lipid lipoprotein profiles, and cardiovascular fitness in persons with SCI. Future well-designed randomized controlled trials are required to firmly establish the primary mechanisms by which exercise interventions elicit these beneficial changes in health status. There is Level 4 evidence that BWSTT can reduce resting heart rate in individuals with incomplete, but not complete SCI injuries. There is Level 4 evidence that BWSTT can result in improvements in cardiac autonomic balance in persons with incomplete tetraplegia. There is Level 4 evidence that BWSTT can result in improvements in cardiac autonomic balance in a subset of individuals with motor-complete SCI who respond to ambulation with moderate to large increases in heart rate. There is Level 4 evidence that BWSTT can improve arterial compliance in individuals with motor-complete SCI. There is Level 1 evidence that arm exercise at a moderate to vigorous intensity (50-80% HRR), 3 days/week for at least 2 months improves cardiovascular fitness. There is Level 1 evidence that high intensity (70-80% HRR) exercise leads to greater improvements in peak power and VO2peak than low intensity (50-60% HRR) exercise. There is Level 1 evidence that aerobic exercise training is effective in improving exercise capacity/tolerance in persons with SCI. It is uncertain whether aerobic training can improve cardiac function in persons with SCI. Based on the changes observed in VO2max and findings from able-bodied individuals, a consensus was derived stating that aerobic training may be effective in improving the ability to extract oxygen at the periphery in persons with SCI. There is Level 4 evidence FES training for a minimum of 3 days per week for 2 months can improve muscular endurance, oxidative metabolism, exercise tolerance, and cardiovascular fitness. There is Level 4 evidence that FES training is effective in improving exercise cardiac function in persons with SCI. Based on the changes observed in VO2max and findings from able-bodied individuals a consensus (Level 5; Expert Opinion) was derived stating that aerobic training is effective in improving the ability to extract oxygen at the periphery in persons with SCI. There is Level 4 evidence that aerobic exercise training programs (performed 30 min/day, 3 day per week for 6 weeks or more) are effective in improving glucose homeostasis in persons with SCI.

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There is Level 4 evidence that FES training programs (performed 30 min/day, 3 day per week for 6 weeks or more) are effective in improving glucose homeostasis in persons with SCI. There is Level 4 evidence that the changes in glucose homeostasis after aerobic or FES training are clinically significant for the prevention and/or treatment of type 2 diabetes. There is Level 4 evidence to suggest that aerobic exercise training programs (performed at a moderate to vigorous intensity 20-30 min/day, 3 days per week for 8 weeks) are effective in improving the lipid lipoprotein profiles of persons with SCI. Preliminary evidence (Level 4) also indicates that FES training (3 hours/week, for 14 weeks) may improve lipid lipoprotein profiles in SCI.

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DuRant RH, Baranowski T, Rhodes T, Gutin B, Thompson WO, Carroll R, et al. Association among serum lipid and lipoprotein concentrations and physical activity, physical fitness, and body composition in young children. J Pediatr 1993;123(2):185-92. Elder CP, Apple DF, Bickel CS, Meyer RA, Dudley GA. Intramuscular fat and glucose tolerance after spinal cord injury--a cross-sectional study. Spinal Cord 2004;42(12):711-6. El-Sayed MS, Younesian A, Rahman K, Ismail FM, El-Sayed Ali Z. The effects of arm cranking exercise and training on platelet aggregation in male spinal cord individuals. Thromb Res 2004;113(2):129-36. El-Sayed MS, Younesian A. Lipid profiles are influenced by arm cranking exercise and training in individuals with spinal cord injury. Spinal Cord 2005;43(5):299-305. Eriksson P, Lofstrom L, Ekblom B. Aerobic power during maximal exercise in untrained and well-trained persons with quadriplegia and paraplegia. Scand J Rehabil Med 1988;20(4):141-7. Faghri PD, Glaser RM, Figoni SF. Functional electrical stimulation leg cycle ergometer exercise: training effects on cardiorespiratory responses of spinal cord injured subjects at rest and during submaximal exercise. Arch Phys Med Rehabil 1992;73(11):1085-93. Frost F, Roach MJ, Kushner I, Schreiber P. Inflammatory C-reactive protein and cytokine levels in asymptomatic people with chronic spinal cord injury. Arch Phys Med Rehabil 2005;86(2):312-7. Gass GC, Watson J, Camp EM, Court HJ, McPherson LM, Redhead P. The effects of physical training on high level spinal lesion patients. Scand J Rehabil Med 1980;12(2):61-5. Grey E, Bratteli C, Glasser SP, Alinder C, Finkelstein SM, Lindgren BR, et al. Reduced small artery but not large artery elasticity is an independent risk marker for cardiovascular events. Am J Hypertens 2003;16(4):265-9. Gurney AB, Robergs RA, Aisenbrey J, Cordova JC, McClanahan L. Detraining from total body exercise ergometry in individuals with spinal cord injury. Spinal Cord 1998;36(11):782-9. Halle M, Berg A, von Stein T, Baumstark MW, Konig D, Keul J. Lipoprotein(a) in endurance athletes, power athletes, and sedentary controls. Med Sci Sports Exerc 1996;28(8):962-6. Health Canada. Statistical report on the health of Canadians. Ottawa: Health Canada; 1999. Hicks AL, Martin KA, Ditor DS, Latimer AE, Craven C, Bugaresti J, et al. Long-term exercise training in persons with spinal cord injury: effects on strength, arm ergometry performance and psychological well-being. Spinal Cord 2003;41(1):34-43. Hjeltnes N, Aksnes AK, Birkeland KI, Johansen J, Lannem A, Wallberg-Henriksson H. Improved body composition after 8 wk of electrically stimulated leg cycling in tetraplegic patients. Am J Physiol 1997;273(3 Pt 2):R1072-9. Hjeltnes N, Galuska D, Bjornholm M, Aksnes AK, Lannem A, Zierath JR, et al. Exercise-induced overexpression of key regulatory proteins involved in glucose uptake and metabolism in tetraplegic persons: molecular mechanism for improved glucose homeostasis. Faseb J 1998;12(15):1701-12. Hjeltnes N, Wallberg-Henriksson H. Improved work capacity but unchanged peak oxygen uptake during primary rehabilitation in tetraplegic patients. Spinal Cord 1998;36(10):691-8. Hoffman MD. Cardiorespiratory fitness and training in quadriplegics and paraplegics. Sports Med 1986;3(5):312-30. Hooker SP, Figoni SF, Rodgers MM, Glaser RM, Mathews T, Suryaprasad AG, et al. Physiologic effects of electrical stimulation leg cycle exercise training in spinal cord injured persons. Arch Phys Med Rehabil 1992;73(5):470-6. Hooker SP, Wells CL. Effects of low- and moderate-intensity training in spinal cord-injured persons. Med Sci Sports Exerc 1989;21(1):18-22. Hurley BF, Hagberg JM. Optimizing health in older persons: aerobic or strength training? Exercise and Sport Science Reviews 1998;26:61-89.

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Jacobs PL, Mahoney ET, Nash MS, Green BA. Circuit resistance training in persons with complete paraplegia. J Rehabil Res Dev 2002;39(1):21-8. Jacobs PL, Nash MS, Rusinowski JW. Circuit training provides cardiorespiratory and strength benefits in persons with paraplegia. Med Sci Sports Exerc 2001;33(5):711-7. Jacobs PL, Nash MS. Exercise recommendations for individuals with spinal cord injury. Sports Med 2004;34(11):727-51. Jeon JY, Weiss CB, Steadward RD, Ryan E, Burnham RS, Bell G, et al. Improved glucose tolerance and insulin sensitivity after electrical stimulation-assisted cycling in people with spinal cord injury. Spinal Cord 2002;40(3):110-7. Kahn N, Sinha A, Bauman W. Impaired platelet prostacyclin receptor activity: a monozygotic twin study discordant for spinal cord injury. Clin Physiol 2001;21(1):60-6. Kahn NN. Platelet-stimulated thrombin and PDGF are normalized by insulin and Ca2+ channel blockers. Am J Physiol 1999;276(5 Pt 1):E856-62. Katzmarzyk PT, Gledhill N, Shephard RJ. The economic burden of physical inactivity in Canada. CMAJ 2000;163(11):1435-40. Krauss JC, Robergs RA, Depaepe JL, Kopriva LM, Aisenbury JA, Anderson MA, et al. Effects of electrical stimulation and upper body training after spinal cord injury. Med Sci Sports Exerc 1993;25(9):1054-61. Krum H, Howes LG, Brown DJ, Ungar G, Moore P, McNeil JJ, et al. Risk factors for cardiovascular disease in chronic spinal cord injury patients. Paraplegia 1992;30(6):381-8. Lee MY, Myers J, Abella J, Froelicher VF, Perkash I, Kiratli BJ. Homocysteine and hypertension in persons with spinal cord injury. Spinal Cord 2006;44(8):474-9. Lee MY, Myers J, Hayes A, Madan S, Froelicher VF, Perkash I, et al. C-reactive protein, metabolic syndrome, and insulin resistance in individuals with spinal cord injury. J Spinal Cord Med 2005;28(1):20-5. Mahoney ET, Bickel CS, Elder C, Black C, Slade JM, Apple D, Jr., et al. Changes in skeletal muscle size and glucose tolerance with electrically stimulated resistance training in subjects with chronic spinal cord injury. Arch Phys Med Rehabil 2005;86(7):1502-4. Maki KC, Briones ER, Langbein WE, Inman-Felton A, Nemchausky B, Welch M, et al. Associations between serum lipids and indicators of adiposity in men with spinal cord injury. Paraplegia 1995;33(2):102-9. Manns PJ, McCubbin JA, Williams DP. Fitness, inflammation, and the metabolic syndrome in men with paraplegia. Arch Phys Med Rehabil 2005;86(6):1176-81. Miranda AR, Hassouna HI. Mechanisms of thrombosis in spinal cord injury. Hematol Oncol Clin North Am 2000;14(2):401-16. Mohr T, Andersen JL, Biering-Sorensen F, Galbo H, Bangsbo J, Wagner A, et al. Long-term adaptation to electrically induced cycle training in severe spinal cord injured individuals. Spinal Cord 1997;35(1):1-16. Mohr T, Dela F, Handberg A, Biering-Sorensen F, Galbo H, Kjaer M. Insulin action and longterm electrically induced training in individuals with spinal cord injuries. Med Sci Sports Exerc 2001;33(8):1247-52. Mutton DL, Scremin AM, Barstow TJ, Scott MD, Kunkel CF, Cagle TG. Physiologic responses during functional electrical stimulation leg cycling and hybrid exercise in spinal cord injured subjects. Arch Phys Med Rehabil 1997;78(7):712-8. Myllynen P, Koivisto VA, Nikkila EA. Glucose intolerance and insulin resistance accompany immobilization. Acta Med Scand 1987;222(1):75-81. Nash MS, Jacobs PL, Mendez AJ, Goldberg RB. Circuit resistance training improves the atherogenic lipid profiles of persons with chronic paraplegia. J Spinal Cord Med 2001;24(1):2-9.

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National Spinal Cord Injury Association. Stats and facts. Spinal cord injury statistics. [Online]. 2003 [cited 2006 Sept 5]. Available from: URL:http://www.spinalcord.org/html/factsheets/spinstat.php Noreau L, Shephard RJ. Return to work after spinal cord injury: the potential contribution of physical fitness. Paraplegia 1992;30(8):563-72. O'Connor GT, Hennekens CH, Willett WC, Goldhaber SZ, Paffenbarger RS, Jr., Breslow JL, et al. Physical exercise and reduced risk of nonfatal myocardial infarction. Am J Epidemiol 1995;142(11):1147-56. Phillips SM, Stewart BG, Mahoney DJ, Hicks AL, McCartney N, Tang JE, et al. Body-weightsupport treadmill training improves blood glucose regulation in persons with incomplete spinal cord injury. J Appl Physiol 2004;97(2):716-24. Pollack SF, Axen K, Spielholz N, Levin N, Haas F, Ragnarsson KT. Aerobic training effects of electrically induced lower extremity exercises in spinal cord injured people. Arch Phys Med Rehabil 1989;70(3):214-9. Roussi J, Bentolila S, Boudaoud L, Casadevall N, Vallee C, Carlier R, et al. Contribution of DDimer determination in the exclusion of deep venous thrombosis in spinal cord injury patients. Spinal Cord 1999;37(8):548-52. Schmid A, Halle M, Stutzle C, Konig D, Baumstark MW, Storch MJ, et al. Lipoproteins and free plasma catecholamines in spinal cord injured men with different injury levels. Clin Physiol 2000;20(4):304-10. Shetty KR, Sutton CH, Rudman IW, Rudman D. Lipid and lipoprotein abnormalities in young quadriplegic men. Am J Med Sci 1992;303(4):213-6. Sloan KE, Bremner LA, Byrne J, Day RE, Scull ER. Musculoskeletal effects of an electrical stimulation induced cycling programme in the spinal injured. Paraplegia 1994;32(6):407-15. Solomonow M, Reisin E, Aguilar E, Baratta RV, Best R, D'Ambrosia R. Reciprocating gait orthosis powered with electrical muscle stimulation (RGO II). Part II: Medical evaluation of 70 paraplegic patients. Orthopedics 1997;20(5):411-8. Spungen AM, Adkins RH, Stewart CA, Wang J, Pierson RN, Jr., Waters RL, et al. Factors influencing body composition in persons with spinal cord injury: a cross-sectional study. J Appl Physiol 2003;95(6):2398-407. Stewart BG, Tarnopolsky MA, Hicks AL, McCartney N, Mahoney DJ, Staron RS, et al. Treadmill training-induced adaptations in muscle phenotype in persons with incomplete spinal cord injury. Muscle Nerve 2004;30(1):61-8. Sutbeyaz ST, Koseoglu BF, Gokkaya NK. The combined effects of controlled breathing techniques and ventilatory and upper extremity muscle exercise on cardiopulmonary responses in patients with spinal cord injury. Int J Rehabil Res 2005;28(3):273-6. Taimela S, Viikari JS, Porkka KV, Dahlen GH. Lipoprotein (a) levels in children and young adults: the influence of physical activity. The Cardiovascular Risk in Young Finns Study. Acta Paediatr 1994;83(12):1258-63. Tell GS, Vellar OD. Physical fitness, physical activity, and cardiovascular disease risk factors in adolescents: the Oslo Youth Study. Prev Med 1988;17(1):12-24. Thijssen DH, Heesterbeek P, van Kuppevelt DJ, Duysens J, Hopman MT. Local vascular adaptations after hybrid training in spinal cord-injured subjects. Med Sci Sports Exerc 2005;37(7):1112-8. Tordi N, Dugue B, Klupzinski D, Rasseneur L, Rouillon JD, Lonsdorfer J. Interval training program on a wheelchair ergometer for paraplegic subjects. Spinal Cord 2001;39(10):532-7. Vaidyanathan S, Soni BM, Singh G, Mansour P, Watt JW, Sett P, et al. Recurrent urinary infection, raised serum levels of C-reactive protein, and the risk of cardiovascular disease in patients with spinal cord injury: a hypothesis. Spinal Cord 1998;36(12):868-9. Warburton DE, Gledhill N, Quinney A. Musculoskeletal fitness and health. Can J Appl Physiol 2001b;26(2):217-37. 7-27

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CHAPTER EIGHT
Respiratory Management Following Spinal Cord Injury
A William Sheel, PhD W Darlene Reid, BMR (PT), PhD Andrea F Townson, MD FRCPC Najib Ayas, MD FRCPC, MPH

Key Points For exercise training to improve respiratory function the training intensity must be relatively high (70-80% of maximum heart rate) performed three times per week for six weeks Ideal training regimes have not been identified. There is limited evidence that inspiratory muscle training improves respiratory muscle strength or endurance in people with SCI. The use of bronchodilators should be considered in subjects with tetraplegia who demonstrate an element of obstructive airway impairment. The effects of other medications commonly used in the management of SCI such as baclofen and oxybutynin should be considered when reviewing airway hyperreactivity in subjects with tetraplegia The short-term use of oxandrolone should be considered to improve pulmonary function in subjects with tetraplegia. Progressive ventilator free breathing protocol should be considered for ventilator dependent subjects with tetraplegia who are appropriate for ventilator weaning. Resistance and endurance training should be considered in subjects who are candidates for ventilator weaning. Case by case consideration should be given to tracheostomy decannulation in subjects with SCI. The indications and criteria for tracheostomy decannulation have not been established in SCI. Abdominal binding can be used to achieve immediate improvements in respiratory function, but long term effects have not been established. Chest wall vibration may improve pulmonary function while the vibration is applied, but carry-over effects when the vibration is not in use has not been evaluated. There is limited evidence that immersion to shoulder-deep 33-34 Celsius water may improve pulmonary function, but carry-over effects following immersion has not been evaluated. Patients with SCI have a high prevalence of obstructive sleep apnea, and therapy may improve quality of life and other outcomes. Therefore, we recommend vigilance for suggestive signs and symptoms (e.g., snoring, obesity, witnessed apneas, daytime sleepiness) and further testing in patients with suggestive symptoms/signs (with overnight oximetry or polysomnography). There is limited evidence that suggests that improving inspiratory and expiratory muscle force is important to maximize expiratory flow during cough. Cough effectiveness can be enhanced by a variety of methods including manual assistance by a caregiver and/or electrical stimulation triggered by the person with SCI. Hand-held expiratory pressure devices may enhance secretion removal in people with SCI.

Table of Contents
8.1 Introduction ......................................................................................................................8-1 8.2 Exercise Training .............................................................................................................8-3 8.3 Inspiratory Muscle Training ............................................................................................8-6 8.4 Pharmaceutical Interventions.......................................................................................8-10 8.4.1 Airway Hyperresponsiveness and Bronchodilators.......................................................8-10 8.4.2 Anabolic Agents ............................................................................................................8-14 8.4.3 Other pharmaceuticals..................................................................................................8-15 8.5 Assistive Devices...........................................................................................................8-15 8.5.1 Mechanical Ventilation and Weaning Protocols............................................................8-15 8.5.2 Other methods of ventilation .........................................................................................8-17 8.5.3 Tracheostomy Decannulation .......................................................................................8-17 8.5.4 Girdle/abdominal Binder ...............................................................................................8-18 8.5.5 Vibration........................................................................................................................8-19 8.5.6 Immersion .....................................................................................................................8-20 8.6 Obstructive Sleep Apnea in SCI ...................................................................................8-21 8.6.1 Prevalence and Risk Factors ........................................................................................8-22 8.7 Secretion Removal.........................................................................................................8-23 8.8 Summary.........................................................................................................................8-25 Reference................................................................................................................................8-27

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Sheel AW, Reid WD, Townson AF, Ayas N (2006). Respiratory Management Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 8.1-8.30. www.icord.org/scire

Respiratory Management Following Spinal Cord Injury

8.1 Introduction The respiratory system, including the lung, respiratory muscles, and neural control system, is a complex integrated physiological system that is not yet fully understood. The respiratory system is unique in that it must operate in a cyclical and highly coordinated fashion for 24 hours per day in order to sustain life. Respiratory complications continue to be one of the leading causes of morbidity and mortality in people with spinal cord injury (SCI), especially among cervical and higher thoracic injuries. This continues to be the case despite recent advances in SCI patient care where acute and long-term mortality rates have been significantly reduced (DeVivo et al. 1993; 1999). Respiratory system complications can be exacerbated by pre-existing medical conditions, history of smoking, advanced age and by therapeutic measures to manage the resuscitation phase of the injured patient. Respiratory dysfunction resulting from cervical SCI depends on the level of injury and the extent of innervation. The higher level lesions result in denervation of progressively more of the expiratory and inspiratory muscles as illustrated in Figure.8.1. Although the primary consequence of SCI is dennervation of the respiratory pump, secondary consequences occur within the lungs because of the inability to effectively distend and inflate the lung to its full capacity. As a consequence, the compliance of the lungs diminishes with increasing time after SCI. Figure 8.1 Innervation of the respiratory muscles

Primary Muscles of Inspiration Diaphragm C3-C5 Scalenes C2-C7

Accessory Muscles of Inspiration & Muscles of Expiration Sternomastoid Accessory Nerve & C2-C3

Intercostals T1-T11

Abdominal Muscles especially Transversus Abdominus T7-L1

Complete paralysis of all muscles involved with respiration occurs when the lesion is above C3; this type of injury requires immediate and permanent ventilatory support in order to sustain life. The primary goal of ventilatory support is to ensure arterial blood gas homeostasis. When the

8-1

injury is between C3 to C5 (innervation of the diaphragm), respiratory insufficiency occurs via respiratory muscle dysfunction. Although primary and some accessory muscles of inspiration are fully innervated with injuries below cervical lesions, the ability to ventilate at higher levels is still compromised because the intercostals and other chest wall muscles do not provide the integrated expansion of the upper chest wall as the diaphragm descends during inspiration. Furthermore, ventilation during exercise can be greatly compromised. The expiratory muscles actively contract in healthy people whereas partial or fully denervated expiratory muscles in those with SCI will diminish exercise ventilation and ventilatory reserve. Lung volumes reflect these diminished capacities for full inspiration and forced expiration in people with SCI. These pulmonary function measures are derived by having the person breathe normally followed by full inspiration and full expiration in and out of an apparatus that measures lung volumes (Figure 8.2). As expected lung volumes like the inspiratory capacity (IC) and expiratory reserve volume (ERV), are progressively smaller in higher cervical lesions versus lower thoracic and lumbar lesions (Baydur et al. 2001). Figure 8.2 Measurement of lung volume

Lung Capacities
Inspiratory capacity (IC): maximal volume of air that can be inhaled (sum of VT and IRV). Functional residual capacity (FRC): volume of air remaining in the lungs at the end of an ordinary expiration, i.e. at the resting level or end-expiratory level. Vital Capacity (VC): maximum volume of air that can be expelled after a maximum inspiration, i.e. from total lung capacity (TLC) to residual volume. Total Lung Capacity (TLC): total amount of air in the lungs after a maximal inspiration. TLC= RV + ERV + VT (TV) + IRV.

Lung Volumes
Tidal volume (VT but also known as TV): volume of air inhaled or exhaled during breathing (at rest or during exercise). Inspiratory reserve volume (IRV): maximum volume of air that can be inhaled to total lung capacity over and above the tidal volume. Expiratory reserve volume (ERV): maximum volume of air that can be exhaled from the endexpiratory level or from functional residual capacity (FRC) to residual volume. Residual volume (RV): volume of air remaining in the lungs after a maximal expiration.

The forced expiratory volume in one second (volume of air that can be exhaled in the first second = FEV1) and forced vital capacity (maximum volume of air that can be exhaled = FVC) are usually measured in apparently healthy people to detect airways obstruction. Due to reduced inspiratory muscle force, these measures are diminished in people after SCI with higher lesions and especially in people with tetraplegia (Linn et al. 2000; Baydur et al. 2001) and demonstrate moderate correlation with injury level (Baydur et al. 2001). Longer duration of injury and smoking are two factors associated with greater loss while incomplete lesions

8-2

(compared to complete lesions) have less loss of forced expiratory measures of FEV1 and FVC (Linn et al. 2000). People with SCI at most levels affect innervation of the abdominal muscles (Figure 8.1), which severely compromises the ability to generate cough and clear respiratory secretions. Cough generation is accomplished primarily by the expiratory intercostals muscles (thoracic roots) and the abdominal muscles (T4-L1). Cough is important as a defense mechanism to prevent respiratory tract infections and atelectasis. The respiratory system has other important roles such as speaking and posture-related activities which can also be negatively impacted by the SCI, especially with higher lesions. In summary, the respiratory consequences of SCI are readily apparent and are largely dependent on the level of injury. Additional large-scale cross sectional and longitudinal studies are required to fully characterize pulmonary function in SCI. Secondary respiratory complications related to other respiratory pathologies (i.e., chronic obstructive pulmonary disease, asthma) are not well described. In particular, the consequences of aging on pulmonary function are not well defined in SCI. With healthy aging there is a decline in lung function, primarily because of a loss of elastic recoil. Moreover, additional age-related changes that are known to negatively affect gas exchange are decreased surface area of the lung, decreased pulmonary capillary blood volume, increased dead space ventilation and decreased distensibility of the pulmonary arterial vasculature. A greater understanding of the interactions between SCI, aging and the respiratory system are necessary for comprehensive patient management. While it is clear that the respiratory system can be compromised with SCI, the salient question is: what intervention strategies are known to be effective in patient management? The subsequent sections are divided into commonly used respiratory-related interventions used for the respiratory management of the patient with SCI. The following commonly used respiratory abbreviations are used:
IMT MVV SIP FEV1 FVC TLC IC ERV PEFR inspiratory muscle training maximal voluntary ventilation sustained inspiratory pressure forced expiratory volume in the first second forced vital capacity total lung capacity inspiratory capacity expiratory reserve volume peak expiratory flow rate PaCO2 PaO2 RV MIP MEP VE VT (TV) fb Ti/Ttot partial pressure of arterial carbon dioxide partial pressure of arterial oxygen residual volume maximal inspiratory pressure maximal expiratory pressure minute ventilation tidal volume frequency of breathing inspiratory duty cycle; inspiratory time/total time for one breath

8.2 Exercise Training As with able-bodied individuals, there is strong evidence in support for the use of exercise training for improving cardiovascular health among people this SCI (see Chapter 7). This is important because there is a high incidence of physical inactivity in individuals with SCI and as such they are at increased risk of secondary conditions such as cardiovascular disease, diabetes, osteoporosis and obesity. There is clear evidence that the cardiovascular and skeletal muscle systems adapt positively to exercise training in both able-bodied and SCI people. However, the lungs and airways do not change appreciably in response to exercise training. It is likely that exercise is not sufficiently stressful to warrant an adaptive response. This may be even more so when considering the small muscle mass used in wheelchair propulsion or arm 8-3

cranking exercise. On the other hand, respiratory muscles are both metabolically and structurally plastic and they respond to exercise training. This statement is based largely on direct evidence from animal models and indirect evidence from able bodied humans. Exercise training may influence the control of breathing and respiratory sensations (i.e., dyspnea). It is generally accepted that exercise training results in a lower minute ventilation at any given absolute oxygen consumption or power output. This is likely due to a reduction in one or more of the mechanisms (neural and/or humoral) purported to cause the hyperpnea (increased respiratory rate) associated with exercise. As such, the positive effects of exercise training in SCI may reside in an increase in respiratory muscle strength and endurance as well as a reduced ventilatory demand during exercise. A lower ventilation and/or sensation of dyspnea during exercise would lower the work of breathing and prevent early termination of exercise respectively. Table 8.1 Exercise training
Author Year; Country Score Research Design Total Sample Size Methods Population: 24 subjects (12 paraplegics, 12 able-bodied individuals), median age SCI: 31 yrs (range 22-54), control: 30 (range 22-52), T1-T12, all ASIA A, >3 yrs after injury. Treatment: Arm cranking aerobic training: 30 mins, 3x/wk x 6 wks. Outcome measures: Spirometry. 1. Outcome

After aerobic training, SCI subjects showed significant in FVC (P<0.05) and the ventilatory muscle endurance (P<0.001), so that max Silva et al. 1998; Brazil voluntary venilitation at 70% time Downs & Black score=16 values post-training were not Pre-post different from the initial values of N=24 able bodied individuals. 2. Severely limited ventilatory muscle endurance in people with paraplegia can be improved by arm cranking. Population: 20 people with SCI (12 men, 8 1. After training, FVC, FEV1, and VC, were significantly higher than the women), 14 complete, 6 incomplete (T6baseline values T12), 3.85.8 yrs, Mean age 31.318.17 2. Exercise testing showed increased Sutbeyaz et al. 2005; years. Treatment: Ventilatory and upper extremity peak VE and peak workload and a Turkey reduction in the ratio of physiological Downs & Black score=15 muscle exercise: 1h, 3x/wk x 6 wks; dead space to tidal volume Diaphragmatic, pursed lip breathing for Pre-post compared to baseline values. N=20 15min; Air shifting for 5min; voluntary isocapneic hypernea 10min; arm-crank exercise. Outcome measures: Spirometry. Population: 6 subjects (5 male, 1 female), 1. At maximal exercise, peak VE (75%), peak fb (-13.4%), peak VT T6- & T11/12, age 2914 years (range:18(+28.9%), and the ventilatory 54), Mean time since injury: 94 days reserve (12.9%) improved after (range:73-137 days). 1training. The oxygen cost of VE Treatment: Wheelchair Interval-training significantly decreased (-20%) after Program 30 min (6 x 5 min bouts: 4 min Le Foll-de-Moro et al. training. moderate intensity and 1 min of high 2005; France 2. For the wheelchair test, at the same intensity) 3x/wk for 6 wks; Progressed Downs & Black score=14 workload after training, VE and fb throughout training program to achieve 50% Pre-post and VT consistent with improved and 80% of heart rate. N=6 ventilatory efficiency and greater Outcome measures: Spirometry. reliance on aerobic capacity after training. 3. Spirometric values and lung volumes showed small trend towards improvement after training.

8-4

Author Year; Country Score Research Design Total Sample Size

Methods Population: 8 SCI (4 males, 4 females), 1. Low intensity group: C5-T7 (age range 2636yrs), Moderate Intensity group: C5-T9 (age range 2. 23-36yrs) Treatment: Aerobic training: WC ergometry 20 min 3 x/wk for 8 wk 3. Low Intensity exercised at a power output = 50-60% of maximal heart rate. Moderate Intensity exercised at a power output = 7080% maximal heart rate. Outcome measures: maximal oxygen uptake, peak power.

Outcome After training, no changes to maximal oxygen uptake or peak power. No detectable changes during submaximal or maximal exercise were detected. Training intensity was insufficient, subjects did not comply with the program, or study was underpowered due to small sample size and heterogeneity of subject responses.

Hooker & Wells 1989; USA Downs & Black score=12 Pre-post N=8

Discussion Evidence for exercise training for the respiratory management of the SCI person includes four experimental, non-randomized control trials. Studies describing the acute responses to exercise in people with SCI were not included nor were those studies concerned with competitive athletes with SCI. Of the studies included, they were difficult to interpret because of woefully small sample sizes, differences in exercise modality (wheelchair vs. arm crank exercise) as well as inconsistency in the frequency, intensity and duration of exercise training. Although one study included a control group (Silva et al. 1998), the control group consisted of able-bodied subjects which was used for the normative values, but cannot be considered a true control group for SCI subjects. There is insufficient evidence to strongly support exercise training as a means to improve pulmonary function or ventilatory responses to exercise in SCI people. There is some evidence (Le Foll-de-Moro et al. 2005) to demonstrate that following exercise training that peak VE, VT and ventilatory reserve improve. However, the training intensity needs to be relatively high (7080% of maximum heart rate at a minimum of 3X/week for 6 weeks) as lower intensities have not been shown to be effective (Hooker & Wells 1989). Additional well-designed randomized controlled trials are necessary to elucidate if exercise training is an effective means by which to improve pulmonary function at rest and during exercise. Nonetheless, from the limited SCI data and the well-known able bodied response to upper limb training it appears that changes to exercise ventilation and ventilatory efficiency can be positively changed. Conclusion There is Level 4 evidence to support exercise training as an intervention that might improve resting and exercising respiratory function in people with SCI. For exercise training to improve respiratory function the training intensity must be relatively high (70-80% of maximum heart rate) performed three times per week for six weeks. Ideal training regimes have not been identified.

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8.3 Inspiratory Muscle Training As expected, the loss of inspiratory muscle function is related to the level of injury as illustrated in Figure 8.1. Dyspnea, defined as a subjective report of breathlessness or shortness of breath, is common in people with SCI and is greatest in people with tetraplegia (Ayas et al. 1999). Approximately two-thirds of the prevalence of dyspnea in this group is attributed to the inspiratory muscle loss (Spungen et al. 1997). Improved inspiratory muscle strength and endurance could potentially improve cough and maximal exercise ventilation in addition to decreasing dyspnea. The inspiratory muscles can be trained similar to the limb muscles with inexpensive devices that increase the resistive or threshold inspiratory load on the inspiratory muscles (Reid et al. 2004). Table 8.2 outlines common measures that are indicative of respiratory muscle strength and endurance. In neuromuscular disorders like SCI, maximal lung volumes that measure inspiratory capacity also can reflect increased inspiratory muscle strength. Table 8.2 Measures of respiratory muscle strength and endurance
Term Maximal Inspiratory Pressure Maximal Expiratory Pressure Abbreviation MIP or PImax MEP or PEmax Definition Estimate of inspiratory muscle force as reflected by the maximal pressure exerted by the inspiratory muscles measured at the mouth. Estimate of expiratory muscle force as reflected by the maximal pressure exerted by the expiratory muscles measured at the mouth. Maximum ventilation in 15 seconds, which reflects the sprint capacity of the respiratory muscles. The maximum ventilation can be measured over several minutes - between 4 and 15 minutes which is more reflective of the endurance of the respiratory muscles. Maximum mouth pressure sustained during a 10 minute period of threshold loading which is usually lower than the MIP. This is an estimate of the endurance of the inspiratory muscles. The endurance time while breathing on a resistive or threshold trainer at a defined level of the MIP The maximal load (usually defined as an inspiratory mouth pressure) attained on an incremental threshold loading test whereby the load is progressively increased every 2-3 minutes.

Maximum voluntary ventilation

MVV

Maximal sustainable mouth pressure Endurance time sustained on training load Maximal incremental threshold load

SIP Tlim TLmax

Commercially available hand-held devices can be used for inspiratory muscle training. The two main types of devices are the resistive and threshold trainers (Figure8.3). Both of these devices have a one-way valve that closes during inspiration so that the subject must breathe through a small diameter hole for the resistive trainer or against a spring loaded valve for the threshold trainer. The one-way valve opens during expiration such that no load is imposed during the expiratory phase of respiration. Evidence showing decreased dyspnea and improved strength and endurance after IMT is well documented in people with other health conditions like chronic obstructive pulmonary disease (COPD) (Reid et al. 2004; Geddes et al. 2005). Two main types of commercially available trainers are used to improve the strength and endurance of the inspiratory muscles. Both trainers have a one way valve that opens during expiration such that no load is imposed during the expiratory phase of respiration.

8-6

Figure 8.3 Inspiratory muscle trainers

Threshold trainer (top) has an adjustable spring-loaded valve that imposes the inspiratory load. The inspiratory load can be increased by winding the spring more tightly. Advantage of this trainer is that the same load is imposed on the inspiratory muscles regardless of breathing pattern. Resistive trainer (bottom) has holes of different diameters. The inspiratory load can be increased by setting the dial to holes of lesser diameter. Disadvantage of this trainer is that the subject can reduce the inspiratory load by breathing more slowly. If this device is used for training, a target must be used. Various targets have been designed that set a breathing rate (flow and/or inspiratory pressure) for the subject. Threshold and P-Flex trainers available from Respironics HealthScan Inc., 41 Canfield Rd., Cedar Grove, NJ7, 0009-1201. 1-800-962-1266.

Table 8.3 Inspiratory Muscle Training

Author Year; Country Score Research Design Total Sample Size Methods Population: 12 subjects with complete motor loss below C6-C7 (n=6 control, n=6 training) >1yr post injury, Age IMT:314.1 yrs, Controls: 3512 yrs. Treatment: Resistive IMT without target at 85% SIP for 15 minutes twice daily, 5 days per wk 8 wks. Outcome measures: Spiropmetry. Outcome 1. MIP and Maximal sustainable mouth pressure (SIP) in both the control group (30%19% and 31%18% respectively), and IMT group (42% + 24% and 78%49% respectively) but no difference in post-training improvements between groups. 2. The increased MIP and SIP resulted in a slower and deeper breathing pattern and a significantly shorter inspiratory time:total time of respiratory cycle in both trainers and control subjects. 1. Pre-post % change of vital capacity (VC) and total lung capacity (TLC) in IMT group was greater compared to change in control values. 2. MIP improved in both groups which might be due to natural progression of improvement from SCI, learning to do the maneuver, and/or insufficient length of training. 1. Significant improvements within both groups in forced vital capacity (FVC), maximal voluntary ventilation (MVV), peak expiratory flow rate (PEFR) and Maximal Inspiratory Pressure (MIP) (p<0.001 to 0.05) between week 1 and week 7. 2. No significant differences between treatment groups for any of the

Loveridge et al. 1989; Canada PEDro=5 RCT N=12

Liaw et al. 2000; Taiwan Pedro=4 RCT N=30

Derrickson et al. 1992; USA PEDro=3 RCT N=40

Population: 30 men & women with SCI (C4-C7, 30-134 post-injury); 20 subjects completed (13 control,17 IMT group), 8M:2F in each group, age RIMT:30.9+11.6yrs; control:36.5+11.5yrs Treatment: Target resistive IMT or control; 15-20min 2x/day 6wks; other rehab activities continued. Outcome measures: Spiropmetry, MIP.. Population: 40 subjects met admission criteria; 11 subjects completed (9 males, 2 females), neurologically complete, C4-C7; 2-74 days post-injury, studied at >24hrs after spontaneous breathing, Age:28.55.6 yrs. Treatment: Resistive IMT without target (n=6) and (n=5) breathing with abdominal weights, 5 days per wk 7 wks.

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Author Year; Country Score Research Design Total Sample Size

Methods Outcome Measures: Spiropmetry.

Outcome improvements in pulmonary variables; however, mean changes between week 1 and 7 tended to be larger for the IMT group. TLmax, a measure of inspiratory muscle endurance increased after both sham training and IMT (p<0.05 and p=0.01, respectively). No significant improvement in MIP for either group or differences in post-training change between groups. Significant in peak power, VT and oxygen consumption during maximal exercise test at 6-12wks of IMT (p<0.05). During training, progressive and significant increases in MIP and the critical mouth pressure that resulted in EMG signs of diaphragm fatigue.

Uijl et al. 1999; Netherlands Downs & Black score=14 Prospective Controlled Trial N=10

Gross et al. 1980; Canada Downs & Black score=12 Pre-post N=6

Population: 10 men and women began, M:F= 8:2; 9 subjects completed (8 males, 1 female), all tetraplegic C3-C7, 2-27yrs post-injury; ASIA A (n=3), B (n=3), C and D (n=3); Age: mean 34.4 yrs (range 20-49 yrs) Treatment: No resistance sham training (6 weeks) then Target flow IMT (6 weeks). 15 min twice daily for each phase of 6 wks. Outcome measures:.Spirometry, MIP, Maximal incremental threshold load (TLmax). Population: 4 males:2 females; age range:18-41 yrs; >1 yr post injury Treatment: Resistive IMT without target 30 min per day, 6 days per wk 16 wks. Outcome measures: MIP Population: 20 (2F:18M) in acute posttraumatic phase; 10 tested at 4 months, 10 others were discharged, non-compliant or had medical complications. Treatment: Resistive IMT without target 15min 2x/day 6wks. Outcome measures: MIP. Population: 9 people after SCI C4-C7, > 1 yr since injury; Age: 24-65 yrs with mean 36 yrs Treatment: Resistive IMT without target 15 min twice daily 8 wks. Outcome measures: MIP, spirometry.

1.

2.

3.

1.

Hornstein & Ledsome 1986; Canada Downs & Black score=11 Case Series N=20

1. Four months after IMT began, 10 subjects showed improvement in MIP from 45+4.1 mmHg to 59+6.8 mm Hg but no statistics were performed on data. 2. Two case reports showed improvement in MIP and decreased dyspnea. 1. Significant in MIP and lung volumes after IMT 2. At 6 months, 4 months after training stopped, trends towards baseline and repeat measures in 7 of 8 subjects showed no difference between baseline and 6 months outcomes. 3. Compliance ranged between 48 and 100% of IMT sessions. 1. Number of respiratory infections decreased from 3 to 2 2. Number of respiratory infections requiring acute care hospitalization decreased from 2 to 0. 3. MIP from 10 to 42 cm H2O. 4. Daily suctioning 10x daily to intermittent suctioning not required daily.

Rutchik et al. 1998; USA Downs &Black score=10 Pre-post N=9

Ehrlich et al. 1999; Canada Downs & Black score=7 Case Series N=1

Population: 26 yr old male,C3-C4 Treatment: Threshold IMT and Positive expiratory pressure value (Peripep) for one year. Outcome measures: MIP, infection number.

Discussion There is insufficient evidence to strongly support IMT for people with SCI. Most studies are not comparable and could not be combined in a meta-analysis (Brooks et al. 2005) because of research design, heterogeneity of subject characteristics or differences in training techniques. None of the studies that used an RCT design incorporated an optimal IMT protocol. In 8-8

particular, several used an inspiratory resistive device with no target to control for decreasing resistance with slower flows so the training methods may have induced an alteration in breathing pattern towards slower inspiratory flows rather than a training response against higher inspiratory pressures. The few studies that utilized a RCT design also showed improvement in both control (or sham) and training groups. Comparable improvement in measures of inspiratory muscle and lung function in the control and IMT groups may reflect learning of testing maneuvers, benefit from other rehabilitation or lifestyle activities, and/or natural progression of improvement after SCI. Some of the pre-post design studies showed improvement in inspiratory strength and endurance measures, however, this type of design can show an exaggerated treatment effect. The single subject report by Ehrlich et al. (1999), utilized the threshold trainer, which imposes a constant inspiratory load regardless of breathing pattern. Given that threshold IMT has consistently shown improvements in inspiratory muscle strength and endurance in people with chronic obstructive pulmonary disease, this technique warrants a larger RCT to determine its benefit for people after SCI. Future research to determine a potential treatment effect of IMT after SCI, should utilize: 1) larger samples; 2) a research design that controls for the influence of learning or recovery from SCI on IMT outcome measures of inspiratory muscle strength and endurance, and dyspnea; 3) optimal training techniques of threshold loading, targeted resistive devices, or isocapnic hyperpnea, (see Reid et al. 2004 for details of these training techniques); 4) outcomes of inspiratory muscle strength and endurance; dyspnea; quality of life; daily function; 5) a comparison of the effectiveness of IMT relative to or as an adjunct to other rehabilitation interventions. Until more solid research is performed to further delineate the most effective IMT protocols and criteria for responders and non-responders, prescription of IMT should be approached cautiously. Other types of exercise training and rehabilitation interventions may provide more benefit. Of equal importance, overly aggressive prescription of IMT has the potential to fatigue and injure the inspiratory muscles, which can increase the persons predisposition to respiratory compromise. The article by Reid et al. (2004) provides a table that outlines parameters to monitor during IMT in order to avoid untoward responses such as muscle fatigue and hypercapnia. For inspiratory muscle training to improve ventilation, decrease dyspnea, and to improve daily function after SCI, parameters to optimize IMT are only available for people with other respiratory conditions. For people with chronic obstructive pulmonary disease, the optimal IMT protocol should utilize threshold or targeted resistive trainers, at an intensity of 30-70% of MIP, for a duration up to 30 minutes per session, performed continuously or in intervals, 4-6 days/week and be continued indefinitely (Geddes et al. 2006). Progression of intensity (MIP) should not exceed 5% per week. Conclusion There is Level 4 evidence to support IMT as an intervention that might decrease dyspnea and improve inspiratory muscle function in some people with SCI

8-9

T There is limited evidence that inspiratory muscle training improves respiratory muscle strength or endurance in people with SCI.

8.4 Pharmaceutical Interventions 8.4.1 Airway Hyperresponsiveness and Bronchodilators Subjects with spinal cord injuries have a restrictive ventilatory impairment that is dependent upon the level and completeness of injury. However, there is also a body of evidence that patients with cervical spinal cord injuries have a component of obstructive ventilatory impairment. Subjects with tetraplegia demonstrate bronchial hyperresponsiveness to multiple agents including methacholine, histamine and distilled water (Dicpinigaitis 1994a; Singas 1996; Fein 1998; Grimm 1999; Singas 1999). There are several potential mechanisms for hyperresponsiveness in tetraplegia including loss of sympathetic autonomic input with relatively unopposed parasympathetic input, (Dicpinigaitis 1994a; Grimm 1997; Singas 1999), altered mechanical lung properties with decreased deep breathing and stretching of airways (Singas 1999) and nonspecific airway hyperresponsiveness similar to subjects with asthma (Grimm 1997). Despite evidence regarding the presence of airway hyperresponsiveness in tetraplegia, the use of anticholinergic bronchodilators such as ipratropium and beta 2 selective agonists such as metaproterenol in SCI has not been well studied. The use of bronchodilators is routinely recommended as add-on therapy in other conditions with airway hyperreactivity such as chronic obstructive pulmonary disease (COPD) and asthma, but it is not clear if these recommendations can be generalized to the SCI population. For mechanically ventilated subjects, bronchodilators are routinely administered to relieve dyspnea and reverse bronchoconstriction. They can be administered by metered-dose inhaler (MDI) or by nebulizer. Again, the long-term use of bronchodilators and the best route of administration in mechanically ventilated subjects with SCI have not been studied. The measurement of airway responsiveness with inhaled bronchoconstrictor stimuli such as methacholine or histamine involves the patient inhaling increasing doses or concentrations of a stimulus until a given level of bronchoconstriction is achieved, typically a 20% fall in forced expired volume in one second (FEV1). Airway responsiveness is then expressed as the dose or concentration of the stimulus required to achieve this degree of bronchoconstriction (PD20 and PC20, respectively). Table 8.4 Bronchodilators
Author Year; Country Score Research Design Total Sample Size Schilero et al. 2004; USA Downs & Black score=13 Pre-post N=10 Methods Population: 5 tetraplegia (C4-C7), 2 complete, 3 incomplete, age:4516 yrs, 178 yrs post-injury; 5 paraplegia (below T5), 2 complete, 3 incomplete, age:409 yrs, 1910 yrs post-injury. Outcome 1. In subjects with tetraplegia, inhaled metaproterenol resulted in significant increase in specific airway conductance and significant increases in FEV1 and forced

8-10

Author Year; Country Score Research Design Total Sample Size

Methods Treatment: Inhalation of 0.3 mL of 5% solution of metaproterenol sulfate via nebulizer Outcome Measures: Spirometry and specific airway conductance as measured by body plethysmography pre- and postbronchodilator. Population: tetraplegia (C4-C7); all male, age range 23-57 years, 6 on chronic oral baclofen and 8 controls Treatment: Administration of increasing concentrations of nebulized methacholine. Outcome Measures: Spirometry, PC20.

Outcome expiratory flow 25-75%. 2. In subjects with paraplegia, inhaled metaproterenol resulted in significant increase in specifc airway conductance although the increase was considerably less than that seen in tetraplegia. There was no significant change in FVC, FEV1 and forced expiratory flow 25-75%. 1. 8 out of 8 control subjects showed significant bronchoconstrictor response to methacholine (mean PC20= 1.421.6) 2. 2 out of 6 baclofen subjects had borderline to mild bronchoconstrictor response to methacholine. 4/6 baclofen subjects did not respond to methacholine (mean PC20= 15.09.1 for baclofen group). There was no correlation between PC20 and dosage or duration of baclofen. 1. 48% of subjects had a positive bronchodilator response (6/10 smokers and 6/15 non-smokers). 2. There were no significant correlation between the response to ipratropium and dyspnea at rest, smoking history, or sensory completeness of cord lesion. 1. 12/15 subjects had a significant bronchoconstrictor response to aerosolized histamine (geometric mean PC20 1.27 mg/mL). 2. There were no significant differences in FVC and FEV1 values between responders and nonresponders. 3. All 12 subjects initially responsive to histamine were again hyperresponsive at the time of rechallenge following ipratropium (geometric mean PC20 1.50 mg/mL). 1. All 13 control subjects (methacholine and histamine) and all 6 oxybutyninhistamine subjects had a significant bronchoconstrictor response (PC20<8 mg/mL). 2. The oxybutynin-methacholine subjects had a normal response to methacholine. (PC20>=25 mg/mL).

Dicpinigaitis et al. 1994b; USA Downs & Black score=12 Prospective Controlled Trial N=14

Almenoff et al. 1995; USA Downs & Black score=11 Pre-post N=25

Population: 25 tetraplegia: 6 complete,19 incomplete, all male, age: 433yrs, 112 yrs post-injury. Treatment: Administration of 72 mcg ipratropium bromide by inhaler with spacer Outcome Measures: Spirometry pre- and post-bronchodilator (improvement in FVC or FEV1>=12%) Population: 15 tetraplegia (C4-C7): 5 complete and 10 incomplete, all male, age range:24-64yrs, time since injury range:331 yrs Treatment: Increasing inhaled concentrations of aerosolized histamine diphosphate. Responders to histamine were retested on a separate day after pretreatment with ipratropium bromide 72 mcg. Outcome Measures: Spirometry, PC20. Population: 25 tetraplegia (C4-C7): 10 complete & 15 incomplete, all males, age range:23-63yrs, 1-40yrs post-injury, 12 maintained on oral oxybutynin & 13 agematched controls. Treatment: 6/12 oxybutynin subjects were challenged with methacholine, & 6/12 with histamine; 7/13 control subjects were challenged with methacholine & 6/13 with histamine. Increasing concentrations of aerosolized histamine or methacholine were administered. Outcome Measures: Spirometry, PC20.

Fein et al. 1998; USA Downs & Black score=10 Pre-post N=15

Singas et al. 1999; USA Downs & Black score=9 Prospective Controlled Trial N=25

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Author Year; Country Score Research Design Total Sample Size

Methods Population: 9 tetraplegia (C4-C7) and 6 paraplegia (T9-L1), 4 complete & 11 incomplete, all male, age:25-61yrs, 4-32yrs post-injury Treatment: Increasing duration of exposure time to ultrasonically nebulized distilled water (UNDW). 5 subjects responding to UNDW returned on a separate day for UNDW challenge following the inhalation of aerosolized ipratropium bromide. Outcome Measures: Spirometry, PD20 Population: tetraplegia: 34 males, all motor complete, non-smokers mean age:405 yrs, smokers mean age:483 yrs, 11.81.6 yrs since injury Treatment: Inhalation of 2.5 ml metaproterenol sulfate inhalation solution. Outcome Measures: Spirometry pre- and post-bronchodilator (improvement in FEV1>=12%

Outcome 1. 8/9 tetraplegic subjects (known histamine response positive) had a significant bronchoconstrictor response to UNDW (PD20 7.76 +/7.67 mL). 2. 0/6 paraplegic subjects (known histamine response negative) demonstrated a response to UNDW (PD20 24 mL). 3. 5/5 tetraplegic responders to UNDW no longer responded after pretreatment with ipratropium bromide. 1. 41% of subjects demonstrated a significant response in FEV1 to inhaled metaproterenol (5/12 non-smokers and 9/22 smokers). 2. In the non-smokers, the correlation of FVC and FEV1 with level of lesion was positive and significant prior to administration of bronchodilator and became more significant postbronchodilator. 3. In the smokers, FVC and FEV1 failed to significantly correlate with level of lesion. 1. 11/14 subjects on baclofen and 8/10 control subjects had significant bronchoconstrictor response to histamine. 2. There was no significant difference in mean PC20 between the baclofen and control groups (mean PC20= 2.912.3 and PC20 =2.181.9, respectively). 3. The methacholine and histamine PC20 were almost identical in controls. balcofen subjects had significantly different responses to methacholine and histamine.

Grimm et al. 1999; USA Downs & Black score=9 Pre-post N=15

Spungen et al. 1993; USA Downs & Black score=9 Pre-post N=34

Grimm et al. 1997; USA Downs & Black score=9 Prospective Controlled Trial N=24

Population: tetraplegia (C4-C7), all male, age range:23-65, time since injury range:229 yrs, 14 on chronic oral baclofen and 10 age-matched controls Treatment: Administration of histamine by inhaler in 14 baclofen subjects and 10 controls. Administration of methacholine in 4 baclofen subjects and 5 controls. Outcome Measures: Spirometry, PC20

Discussion Both ipratropium and metaproterenol have been studied in SCI. Both drugs have shown a positive effect with improvements in FEV1 in subjects with tetraplegia. Almenoff et al. (1995) showed that 48% of tetraplegic subjects given inhaled ipratropium bromide responded with greater or equal to 12% improvement in FEV1 and/or FVC. In a study looking at the effects of metaproterenol in tetraplegia, 41% of tetraplegic subjects responded to metaproterenol with a greater or equal to 12% improvement in FEV1 (Spungen et al. 1993). Schilero et al. (2004) also found a significant improvement in FEV1 in tetraplegic subjects treated with metaproterenol. In the short-term, both ipratropium and metaproterenol appeared to be effective in improving pulmonary function. There are concerns that ipratropiums anticholinergic effects could cause thickening of secretions and block release of surfactant 8-12

which could compromise its ultimate effects on respiratory function (Consortium for Spinal Cord Medicine 2005). Although these studies only provide level 4 evidence for the use of bronchodilators in SCI, they cannot be considered in isolation of the large body of literature regarding bronchodilators in other conditions. The recommendations for the use of bronchodilators in asthma and chronic obstructive pulmonary disease are well supported by the literature and there is a strong likelihood that SCI shares some clinical and pathophysiologic similarities to those conditions. Nevertheless, it is important to recognize that literature in SCI remains lacking. In addition to traditional bronchodilators, there is evidence that airway hyperresponsiveness in tetraplegia can be modulated by medications used for other conditions in SCI, such as baclofen and oxybutynin. Baclofen, a GABA agonist, is commonly used to treat spasticity. GABA receptors have been found in peripheral tissue, including lung, raising the possibility that baclofen may have the potential to affect airway hyperreactivity. Oxybutynin, a medication used to treat bladder spasms, has the potential to affect airway hyperreactivity through its anticholinergic properties. The effects of both baclofen and oxybutynin have been studied in small controlled trials in tetraplegia. In each study, the study group was a group of subjects who were already maintained on the medications for the usual indications. The studies did not look at the bronchodilator effects of the medications, but focused on their ability to block bronchoconstrictor challenges to methacholine and histamine. Pre-treating tetraplegic subjects with inhaled ipratropium bromide blocked hyperresponsiveness to methacholine (Dicpinigaitis 1994a). Baclofen and oxybutynin also decreased hyperresponsiveness to methacholine (Dicpinigaitis 1994b; Grimm 1997; Singas 1999). In contrast to the findings with methacholine, pre-treating tetraplegic subjects with inhaled ipratropium bromide did not block hyperresponsiveness to histamine (Fein 1998). Similarly, oxybutynin and chronic oral baclofen did not block hyperresponsiveness to histamine in tetraplegia (Grimm 1997; Singas 1999). Although these results are intriguing, the results of these small studies cannot necessarily be extrapolated to the clinical situation where a bronchodilator effect is required. There are no long-term studies on the use of bronchodilators in SCI. Further studies on the selection of bronchodilators, route of administration and role in long-term mechanical ventilation in SCI should be undertaken. Studies looking at the clinical effects of other commonly used SCI medications with potential bronchodilator effects such as baclofen and oxybutynin are warranted. Conclusion There is level 4 evidence that ipratropium and metaproterenol have a positive effect on pulmonary function in subjects with tetraplegia. There is level 2 evidence that chronic oral baclofen and chronic oxybutynin and level 4 evidence that ipratropium bromide decrease or block hyperresponsiveness to methacholine, but not histamine in tetraplegia.

8-13

The use of bronchodilators should be considered in subjects with tetraplegia who demonstrate an element of obstructive airway impairment. The effects of other medications commonly used in the management of SCI such as baclofen and oxybutynin should be considered when reviewing airway hyperreactivity in subjects with tetraplegia. 8.4.2 Anabolic Agents Anabolic steroids are derivatives of testosterone. Their exact physiologic effects on the respiratory system are unclear, but they have been studied as a possible treatment in chronic obstructive pulmonary disease, especially for their role in potentially increasing muscle mass. Anabolic steroids have potentially serious side effects, including effects on liver function, lipid profile and the reproductive system. The long-term safety of anabolic steroids such as oxandrolone in SCI has not been established. Table 8.5 Anabolic steroids
Author Year; Country Score Research Design Total Sample Size Methods Population: 10 tetraplegia (C4-5), motor complete, all male, mean age: 419 yrs, 168 yrs post-injury Treatment: Administration of oxandrolone 20 mg/day for 1 month. Outcome Measures: Weight gain, spirometry, MIP, MEP, resting self-rate of dyspnea (Borg scale), serum lipid profiles and liver function tests. 1. 2. 3. Outcome On average, subjects gained 1.41.5 kg (22% p=0.01). A significant improvement was seen in combined measures of spirometry (92% p<0.005). A significant improvement was seen in MIP (107% p<0.001. The improvement in MEP was not significant (913%). Borg scale an average of 3728% p<0.01.

Spungen et al. 1999; USA Downs & Black score=16 Pre-post N=10

4.

Discussion There is one study in the literature on the effects of anabolic steroids on pulmonary function in SCI. Spungen et al. (1999) treated 10 male subjects with motor complete C4-C5 tetraplegia with a one month course of oxandrolone, an oral anabolic steroid. Following oxandrolone, significant improvements were seen in weight gain, forced vital capacity, FEV1 and forced inspiratory vital capacity. There was a significant increase in maximal inspiratory pressure (PI max) from baseline and a non-significant increase in maximal expiratory pressure (PE max). Subjects experienced a significant decrease in subjective dyspnea. There was no long-term follow-up of subjects to see if any of the improvements were permanent. Conclusion There is level 4 evidence that the short-term use of oxandrolone improves pulmonary function in subjects with tetraplegia.

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The short-term use of oxandrolone should be considered to improve pulmonary function in subjects with tetraplegia.

8.4.3 Other pharmaceuticals There are many other medications with potential benefit for the treatment of pulmonary function in SCI. The use of anticoagulants for the prevention of deep vein thrombosis and pulmonary emboli is covered in Chapter 15. Other medications used in the treatment of asthma and/or chronic obstructive pulmonary disease such as cromolyn sodium, methylxanthines and inhaled corticosteroids have not been studied in SCI. 8.5 Assistive Devices 8.5.1 Mechanical Ventilation and Weaning Protocols The indications for mechanical ventilation and the acute management of respiratory issues in SCI are outside the scope of this review which focuses on rehabilitation. However, the longterm complications associated with chronic ventilator dependency need to be mentioned in order to highlight their importance. The overall life expectancy for individuals with SCI who are ventilator dependent has been increasing, especially for those individuals who survive the first year following injury. (DeVivo 1995) Despite advances, mortality for individuals with ventilator dependency remains high. (DeVivo 1995). In general, subjects with complete neurologic injuries at C2 and above have no diaphragmatic function and are ventilator dependent. Subjects with complete neurologic injuries at C3 or C4 have variable diaphragmatic function. Although they may have the potential for ventilator weaning, it is difficult to predict whether they will ultimately be successfully weaned. Subjects with complete injuries at C5 and below have intact diaphragmatic function. They may require ventilatory support initially post-injury, but are usually able to wean from the ventilator. The approach to ventilator weaning in SCI remains an important and somewhat neglected issue. The PVA Consortium for Spinal Cord MedicineRespiratory management following spinal cord injury: a clinical practice guideline for health-care professionals (2005) suggest the consideration of progressive ventilator free breathing over synchronized intermittent mandatory ventilation. Table 8.6 Weaning protocols
Author Year; Country Score Research Design Total Sample Size Peterson et al. 1994; USA Downs & Black score=16 Case Series N=52 Methods Population: tetraplegia (C3-C4), ventilator dependent Treatment: Retrospective review of 82 ventilator weaning attempts in 52 subjects using intermittent mandatory ventilation(IMV), progressive ventilator free breathing (PVFB) or a combination of other ventilator weaning techniques Outcome Measures: Successful ventilator Outcome 1. 26/82 weaning attempts used IMV, 34/82 used PVFB and 22/82 used a combination of various techniques. 2. PVFB weaning success rate was 67.6 % (23/34) and IMV was 34.6% (9/26) (p=0.02) and other techniques was 11/22. 3. Overall 43/52 (83%) of subjects were successfully weaned. 6/52

8-15

Author Year; Country Score Research Design Total Sample Size weaning.

Methods

Outcome were partially weaned. 2/52 subjects died. 1. Subjects with low tetraplegia achieved significant gains in inspiratory & and expiratory muscle strength, VC, mean on-ventilator endurance & off-ventilator endurance. 2. Subjects with high tetraplegia had non-significant improvements in inspiratory & expiratory muscle strength and VC and were able to discontinue mechanical ventilation. 3. 4/5 low tetraplegic subjects with low tetraplegia were weaned from the ventilator. 1/5 low tetraplegic subjects died.

Gutierrez et al. 2003; USA Downs & Black score=14 Pre-post N=7

Population: 7 tetraplegia: C2(n=2), C4C7(n=5), incomplete, all male, age range: 45-68 years, time on ventilator: 4-36 months Treatment: Implementation of an evidence-based resistance endurance protocol (REP) designed to help discontinue mechanical ventilation by improving ventilatory muscle strength and endurance Outcome Measures: Pulmonary function tests; on-ventilator endurance and offventilator endurance.

Discussion Peterson et al. (1994) retrospectively compared weaning methods in 52 subjects with C3 and C4 SCI. Overall 83% of subjects were successfully weaned with progressive ventilator free breathing (PVFB, also known as T-piece weaning) being the most successful technique. However, most of the PVFB trials occurred at a single institution and in subjects who were longer post-injury whereas most of the intermittent mandatory ventilation trials (IMV) occurred in a variety of institutions in subjects who were earlier post-injury. Gutierrez et al. (2003) developed an evidence based resistance and endurance protocol to improve ventilatory muscle strength and endurance in subjects with ventilator-dependent cervical SCI. The evidence was based on SCI literature where possible, but was also derived from the general respiratory literature where required. The protocol included 4 daily phases with rests in between each phase: pre-training optimization (Trendelenberg positioning, trachea suctioning, bronchodilator use, and lung hyperinflation); inspiratory/expiratory resistance training; on-ventilator endurance training; and off-ventilator endurance training. Although the pilot study only included 7 subjects, it did show promising results with respect to increasing inspiratory pressure, expiratory pressure and vital capacity and ultimately ventilator weaning, especially in subjects with low tetraplegia (C4-C7) (Gutierrez et al. 2003). Prospective studies on weaning protocols are required to determine the best way to assess, treat and wean subjects requiring mechanical ventilation following SCI. Conclusion There is level 4 evidence that progressive ventilator free breathing (PFVB) protocol is more successful for weaning subjects with C3 and C4 spinal cord injuries than intermittent mandatory ventilation (IMV). There is level 4 evidence that a resistance and endurance protocol increases inspiratory pressure, expiratory pressure and vital capacity especially in low tetraplegia (C4-C7).

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Progressive ventilator free breathing protocol should be considered for ventilator dependent subjects with tetraplegia who are appropriate for ventilator weaning. Resistance and endurance training should be considered in subjects who are candidates for ventilator weaning. 8.5.2 Other methods of ventilation Non-invasive ventilation (Bach 1990), phrenic nerve stimulation (Glenn et al. 1972) and diaphragmatic stimulation (Onders 2004, Di Marco 2006) are all potential alternatives to traditional mechanical ventilation following SCI. Complication rates, cost and quality of life are among the many important factors to consider in all forms of assisted ventilation. The evidence for various methods of assisted ventilation will be addressed in a future edition. The evidence for traditional mechanical ventilation, non-invasive ventilation, phrenic nerve stimulation and diaphragmatic stimulation will be addressed in a future edition. 8.5.3 Tracheostomy Decannulation Subjects with SCI often undergo tracheostomy if it is anticipated that they are going to require ventilatory support for longer than 3 weeks. Evidence for the decannulation of subjects with SCI is lacking. Subjects may not meet the traditional criteria for decannulation and should be assessed on an individualized basis (Bach 1990; Ross & White 2003). Table 8.7 Tracheostomy decannulation
Author Year; Country Score Research Design Total Sample Size Ross & White 2003; Australia Downs & Black score=15 Case Series N=4 Methods Population: tetraplegia (n=3) and paraplegia (n=1), level:C5-T9, ASIA A (n=3) & B(n=1), age: 20-71 yrs Treatment: Interdisciplinary evaluation and assessment Outcome Measures: Successful decannulation. Outcome 1. 4 subjects who had evidence of aspiration were successfully decannulated after assessment by a multidisciplinary team. 2. None experienced respiratory deterioration.

Discussion Ross and White (2003) describe a case series of 4 subjects with SCI who were successfully decannulated despite the presence of traditional contraindications for decannulation such as evidence of aspiration. These 4 subjects were carefully selected by a multidisciplinary team who opted for decannulation after assessing the overall risks of decannulation versus the risks of prolonged tracheostomy. Further studies examining the criteria for decannulation of subjects with SCI are required. Conclusions There is level 4 evidence that decannulation can be successful in subjects with evidence of aspiration.

8-17

Case by case consideration should be given to tracheostomy decannulation in subjects with SCI. The indications and criteria for tracheostomy decannulation have not been established in SCI. 8.5.4 Girdle/abdominal Binder Abdominal binders are used to prevent the abdominal contents from falling forward in upright subjects with SCI. Abdominal binders are most commonly used in subjects with loss of abdominal wall strength (generally lesions above T6). Some early work (primarily level 4 studies) looking at the effects of abdominal binders on respiratory function in SCI was done prior to 1980 but was not included in this review. Studies on the effects of abdominal binders need to include positioning information as position greatly influences lung volumes in tetraplegia. In addition to being used as a respiratory intervention, abdominal binders are used as an intervention in subjects with postural hypotension (see chapter 16). Table 8.8 Abdominal binding
Author Year; Country Score Research Design Total Sample Size Methods Population: 7 tetraplegia, 3 paraplegia, mean age: 35.8 yrs, age range:18-56 yrs, 3-27 months post-injury, post-traumatic SCI levels: C5-T6, ASIA A, Treatment: Custom girdle, designed to provide truncal stability and abdominal support Outcome measures: Spirometry Outcome Abdominal binding resulted in: 1. decrease in respiratory effort measured by Borg scale (4.31.8 to 2.31.8; p=0.02). 2. increase in inspiratory capacity and forced vital capacity, 3. decrease in functional residual capacity ; 4. increase in diaphragm pressuretime product - a measure of diaphragm work; 5. increases in twitch and maximal transdiaphragmatic pressure measures of diaphragm force. Abdominal binding in SCI resulted in: 1. increase inspiratory capacity in all positions, and total lung capacity in the tilted and sitting positions 2. decrease in functional residual capacity in all positions 3. an increase in rib cage dimensions at TLC. Strapping the abdomen in SCI resulted in: 1. Increase in vital capacity; 2. Decrease in FRC and residual volume. 3. Small but inconsistent increases in maximal esophageal pressure and expiratory flow rate that might not improve cough.

Hart et al. 2005; France Downs & Black score=16 Pre-post N=10

McCool et al. 1986; USA Downs & Black score=10 Prospective Controlled Trial N=13

Population: 13 tetraplegia (C4-C7), 9 able-bodied controls, all male, age:29.911.4 yrs Treatment: 3 Body Positions: supine, head-up tilted (37o) and seated w/ & w/o abdominal binders Outcome measures: Spirometry Population: 8 subjects with SCI; Age range: 21-41 years; level of injury C5-C8; length of injury: 6-200 months Treatment: Abdominal strapping Outcome measures: Spirometry

Estenne et al. 1998; USA Downs & Black Score=10 Pre-post N=8

8-18

Discussion Well-designed studies demonstrate that abdominal binders in tetraplegia significantly increase inspiratory capacity or vital capacity, and decrease FRC in all positions (McCool et al. 1986; Estenne et al. 1998; Hart et al. 2005). One study examining a small sample (n=10) showed that a custom girdle reduces the sensation of respiratory effort as measured by the Borg Rating of Perceived Exertion (Hart et al. 2005). Abdominal binding does not appear to consistently improve expiratory flow rates to enhance cough (Estenne et al. 1998). Worthy of further study, the diaphragmatic pressure-time product increases after abdominal binding which may represent enhanced diaphragmatic force production but does not provide information about enhanced efficiency of breathing. All studies on abdominal binding examined short-term response of measures that relate to lung volumes, expiratory flow rates, and/or inspiratory muscle force. No studies have examined the long-term effects of abdominal binding over several hours or intermittent use over several days. Appreciation of the long-term effects of abdominal binding is essential in order to provide evidence-based clinical guidelines. Important outcomes to evaluate are comfort of intervention, sensation of breathlessness, inspiratory muscle efficiency, inspiratory muscle fatigue, and overall fatigue after several hours of abdominal binding. Some of these outcomes may adapt or show deleterious effects over several days or weeks of daily sessions of abdominal binding; such knowledge about repetitive use of the binder will also guide clinical practice. Interventions to increase abdominal pressure and decrease the laxity of abdominal chest wall, which in turn affects diaphragm length and position, have been used in other patient groups. The acute impact on lung volumes and inspiratory muscle force has been documented in small samples of people with SCI. Abdominal binding for people with SCI should be introduced cautiously and be rigorously assessed because of the potential for alteration of diaphragm length to result in mechanical inefficiency, increased dyspnea, and inspiratory muscle fatigue. There is a lack of literature and only anecodotal evidence on the intermediate or long-term effects of abdominal binding on people with SCI above T6. Positioning and using other interventions that increase abdominal pressure in other chronic respiratory conditions improve diaphragm force production but also can induce diaphragm fatigue and have variable influence on dyspnea reduction. The clinical outcomes of abdominal binding should be carefully evaluated for each individual. Abdominal binding could potentially have positive or deleterious effects on inspiratory muscle efficiency and dyspnea in different people after SCI. Conclusions: There is level 2 evidence that abdominal binding in tetraplegic individuals has immediate improvement in respiratory function, but longer term effects have not been studied. Abdominal binding can be used to achieve immediate improvements in respiratory function, but long term effects have not been established.

8.5.5 Vibration Vibration of the muscle tendon to enhance muscle contractile force has been studied in healthy people and in people after SCI. This modality may have the potential to decrease disuse 8-19

atrophy in some people after SCI who have partial voluntary control of muscle and is described as being more comfortable than electrical stimulation (Ribot-Ciscar et al. 2003). Alternatively, vibration also has been considered as an intervention to diminish involuntary muscle contraction after SCI (Butler et al. 2006). The literature on the use of vibration to improve inspiratory and expiratory muscle contraction or to control unwanted spasm of these muscles after spinal cord injury is almost non-existent. One early report examining the physiologic response to this modality in people with spinal cord injury is outlined in the following table. Table 8.9 Vibration
Author Year; Country Score Research Design Total Sample Size Methods Population: 13 people after SCI (11 males, 2 females), ages:17-49 yrs, C4-T1 lesions, 1 incomplete, 12 complete); 19-49 months post-injury Treatment: Application of vibratory stimulus to the 1) parasternal intercostal spaces; 2) 7th -10th intercostal spaces anterior to midaxillary lines; 3) Inspiratory and expiratory vibrations were combined to produce alternating in phase vibration. Outcome measures: Spirometry. 1. Outcome Inspiratory, expiratory and combined in-phase vibrations increased VT and VE while decreasing fb. The combined-alternating in-phase vibration increased VT more than inspiratory or expiratory in-phase vibration alone.

Homma et al. 1981; USA Downs & Black score=9 Pre-post N=13

2.

Discussion One report has shown that alternating in-phase vibration applied during inspiration (over the parasternal intercostals) or during expiration (applied over the 7th-10th intercostal spaces) significantly increased tidal volume (VT) and minute ventilation (VE) with an even greater effect on these two variables when in-phase vibration was applied during inspiration and expiration. Further study is required to examine the long-term utility and compliance of this modality to enhance ventilation in people with SCI. Further, the specific parameters of vibration that enhance versus diminish muscle excitation and contraction needs to be explored in people with different levels and types of SCI. Conclusion There is level 4 evidence that the use of chest wall vibration increases tidal volume and minute ventilation in subjects with tetraplegia. Chest wall vibration may improve pulmonary function while the vibration is applied, but carryover effects when the vibration is not in use has not been evaluated. 8.5.6 Immersion The effects of immersion in shoulder-deep water on spirometry in SCI have been studied. While immersion in water does not represent a treatment modality for pulmonary function, the effects of immersion are important to note from a clinical perspective because many subjects with SCI undergo pool-based therapy that exposes them to shoulder-deep immersion in water.

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Table 8.10 Immersion

Author Year; Country Score Research Design Total Sample Size Methods Population: 34 men: 23 complete (C4-C8) tetraplegia & 11 healthy controls. median age:25yrs (treatment) & 27yrs (control), 289 months post-injury, ASIA A-B Treatment: Spirometry immediately before and 5-15min following immersion to shoulder level in water (33.5C-34.5C) and 5-10min after withdrawal from the water. All subjects were studied in upright, seated posture, in & out of the water. Outcome Measures: Spirometric measurements. 1. Outcome Immersion increased the FVC and FEV1 of tetraplegic subjects. FVC and FEV1 decreased in control subjects. Among the subjects with tetraplegia, the lower the preimmersion vital capacity (VC), the greater the percentage of improvement following immersion. No relationship was found between the time elapsed since cervical cord injury or its level and the degree of improvement.

Thomaz et al. 2005; Brazil Downs & Black socre=10 Pre-post N=34

2.

3.

Immersion in shoulder-deep water results in changes in lung function tests in tetraplegic subjects. Bosch and Wells (1991) showed that in comparison to able-bodied and paraplegic subjects, tetraplegic subjects have a significant decrease in residual volume with immersion. In a pre-post trial involving 23 motor complete tetraplegic subjects and 11 healthy controls, Thomaz et al. (2005) concluded that overall, immersion in water appeared to improve breathing mechanics in subjects with tetraplegia. Conclusion: There is level 4 evidence that the use of immersion to shoulder-deep 33-34 Celsius water improves pulmonary function in tetraplegia.

There is limited evidence that immersion to shoulder-deep 33-34 Celsius water may improve pulmonary function, but carry-over effects following immersion has not been evaluated.

8.6 Obstructive Sleep Apnea in SCI Obstructive sleep apnea is a disease characterized by recurrent collapse of the upper airway during sleep leading to nocturnal hypoxemia and sleep fragmentation. Characteristic symptoms include loud snoring, excessive daytime sleepiness, and nocturnal choking. Risk factors for disease include alcohol use, sedatives, obesity, increased age, and male gender. Because of activation of systemic inflammation and the sympathetic nervous system, sleep apnea may be an independent risk factor for the development of cardiovascular disease. In the able-bodied, sleep apnea is relatively common and under-diagnosed. Treatment of obstructive sleep apnea includes lifestyle counseling (i.e., weight loss, avoidance of alcohol). For patients with substantial disease, continuous positive airway pressure (CPAP) therapy is considered to be first-line therapy. This consists of a mask placed on the face attached to an air compressor via plastic tubing. CPAP devices establish a positive pressure in the upper airway preventing its collapse during sleep. Studies of CPAP in people without SCI demonstrate significant benefits in terms of reducing sleepiness and preventing motor vehicle crashes. Other therapies that have been used to treat obstructive sleep apnea include mandibular advancement devices (dental splints) and upper airway surgery.

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8.6.1 Prevalence and Risk Factors Breathing disorders including sleep apnea appear to have a higher prevalence in people after SCI than those without. In general, the studies that examined the prevalence of obstructive sleep apnea were limited by small sample sizes and by an experimental design that lacked an able-bodied control group that could be directly compared to the SCI patients. Both overnight oximetry and full polysomnography were used to diagnose disease. The prevalence rate ranged from 9.1-83% (Short et al. 1992; Burns et al. 2000; Burns et al. 2001; Stockhammer et al. 2002; Berlowitz et al. 2005). Obesity was identified as a risk factor for sleep apnea in most studies. The use of muscle relaxants was identified as a potential risk factor for sleep disordered breathing in some but not all studies (Short et al. 1992; Ayas et al. 2001; Burns et al. 2001 Berlowitz et al. 2005). Table 8.11 Treatment of obstructive sleep apnea
Author Year; Country Score Research Design Total Sample Size Methods Population: 50 people with SCI lesion levels between C3 and C8; M:F 40:10; Age: 48.614.0, range from 20-81 years; Mean 11.4 years post injury (range from 0.5 to 37 years) Treatment: CPAP 1. Outcome 31 out of the 50 tetraplegic patients had a respiratory disturbance index (RDI) of 15 or more (mean 30.5) defined as sleep disordered breathing (SDB). 16 patients accepted a trial of CPAP; of these, 11 continued to use CPAP after a few weeks. Of these 11 patients, 10 patients reported an improvement of symptoms after using long term CPAP therapy. CPAP continually used by 63% of the participants out of 32 (80%) of participants who tried it. Main reasons for not using CPAP were inability to fall sleep, mask discomfort & claustrophobia. Most common side effects were nasal congestion in 12 and mask discomfort in 8. In two patients, CPAP treatment decreased daytime sleepiness, improved sleep and oxygen saturation. One patient improved after losing 33 kg, and reducing alcohol intake and smoking

Stockhammer et al. 2002; Switzerland Downs & Black score=15 Pre-post N=50

2.

Burns et al. 2005; USA Downs & Black score=14 Case Series N=40

Population: 40 men after SCI (37 tetraplegics) 2 BMI: 29.26.6 kg/m ; most of whom were diagnosed with sleep apnea . Treatment: Survey requesting information about long-term treatment outcomes and side effects of sleep apnea treatment in persons with SCI. Population: 3 people after SCI, ages: 47, 54, 56 yrs, C6 incomplete, T2 complete/; Duration of injury: 19, 6, 37 years. All 3 patients reported severe daytime sleepiness and sleep complaints Treatment: Continuous positive airway pressure (CPAP) via a nasal mask

1. 2. 3. 1.

Biering-Srensen et al. 1995; England Downs & Black score=8 Case Series N=3

2.

Discussion Obstructive sleep apnea is very common in patients with SCI; obesity appears to be a consistent risk factor. There are few studies that have assessed the impact of sleep apnea therapy in patients with SCI. In a three person case series, Biering-Sorensen demonstrated successful therapy with CPAP in two patients, and with weight loss in the third. No randomized controlled trials of CPAP have been reported. One study (Burns et al. 2000) demonstrated a low acceptance rate of CPAP (2 of 8 patients) given a trial of therapy. However, two larger studies demonstrated greater rates; Burns et al. (2005) demonstrated a long-term acceptance rate of CPAP of 63% (20/32) in patients offered CPAP therapy, and another (Stockhammer et al. 2002) 8-22

a long-term rate of 69% (11/16 who accepted a trial). Patients who continued to use CPAP in general reported beneficial effects. No reports concerning the treatment of SCI patients with sleep apnea with a dental appliance or upper airway surgery were identified. There is a paucity of studies that have examined the impact of therapy on health and quality of life outcomes; this should be a focus of future investigations. Conclusion There is level 4 evidence to support therapies to treat obstructive sleep apnea in people with SCI. Patients with SCI have a high prevalence of obstructive sleep apnea, and therapy may improve quality of life and other outcomes. Therefore, we recommend vigilance for suggestive signs and symptoms (e.g., snoring, obesity, witnessed apneas, daytime sleepiness) and further testing in patients with suggestive symptoms/signs (with overnight oximetry or polysomnography).

8.7 Secretion Removal People with spinal cord injury are at risk for retention of secretions because of an increased prevalence of pneumonia compounded by lower expiratory flows during cough. Increased prevalence of respiratory infections, although decreased during the rehabilitation phase of recovery, is still higher in people with SCI compared to age-matched healthy people. Reduction in expiratory flows during cough is related to the higher levels of SCI. Of considerable surprise, several devices that have been shown to be effective in people with other chronic respiratory conditions have not been evaluated in people with spinal cord injury. Table 8.12 Secretion Removal
Author Year; Country Score Research Design Total Sample Size Kang et al. 2006; Korea Downs & Black score=17 Prospective Controlled Trial N=40 Methods Population: 40 traumatic CSCI Treatment: Compared four types of cough 1. unassisted peak cough flow 2. inspiratory assist cough flow 3. abdominal thrust cough flow 4. inspiratory assist & abdominal thrust cough flow. Outcome Measures: Spirometry, Maximum Inspiratory Pressure (MIP), Maximum Expiratory Pressure (MEP). Population: 11 people with complete SCI (C4 & below), Age group 1: 3811.4 yrs, group 2: 36.77.2 yrs, average time since injury: 12.3 (grp.1), 18yrs (grp.2) Treatment: Assisted coughing by: 1. manual assist or 2. functional electrical stimulation (FES) Outcome Measures: Maximum Expiratory Pressure (MEP). 1. 2. Outcome MIP more so than MEP showed stronger relationships with peak exp flow during cough maneuvers. All three assisted techniques (2,3, & 4) showed higher peak expiratory flows. The combined assist (4) showed significantly higher values than the inspiratory or abdominal thrust assist. (Group 1) MEP generated from spontaneous coughing, manual assist and FES was 27.36.4, 8318.7 and 6022.8 cm H2O, respectively. (Group 1) In all patients in the study, the MEP w/ abdominal muscle FES as well as w/ manually assisted cough. (Group 2) Portable FES compared to spontaneous cough the mean MEP from 32.3 to 58 cm H2O.

1.

Linder 1993; USA Downs & Black score=15 Prospective Controlled Trial N=11

2.

3.

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Author Year; Country Score Research Design Total Sample Size

Methods Population: 18 SCI patients (C1-T3), 88% were C5 or higher Methods: Surveyed preference for: suctioning or maximal inexsufflation (MI-E). Outcome measure: Not Specified. 1.

Outcome MI-E was less irritating, less painful, less tiring, less uncomfortable (p<0.01 or p<0.001). All were clinically significant changes (except less tiring). 16 of 18 patients preferred MI-E and one preferred suctioning; 1 patient had no preference. When surveyed, average time from MI-E was 146 days and from suctioning was 253 days (p<0.001) Number of respiratory infections decreased from 3 to 2. Number of respiratory infections requiring acute care hospitalization decreased from 2 to 0. MIP increased from -10 to -42 cm H2O. Daily suctioning 10x daily decreased to intermittent suctioning not required daily Airway pressure was 90, 82, and 132 cm H2O during stimulation of electrodes stimulated at T9, L1, or combined, respectively. Stimulation causes trunk motion but this was tolerated without pain or discomfort. Maximal stimulation gastric pressure to 76.011.7 in controls and 29.93.7 cmH2O in SCI subjects (p=0.002). The cumulative thickness of the four abdominal muscles was 34% smaller in the people with SCI than in control subjects and correlated positively with changes in gastric pressure induced by stimulation.

Garstang et al. 2000; USA Downs & Black score=11 Pre-post N=18

2. 3. Population: 26 yr old M C3-C4 Treatment: Threshold IMT and Positive expiratory pressure value (Peripep) for one year Outcome Measures: Frequency of suction, Maximum Inspiratory Pressure (MIP), number of respiratory infection. 1. 2. 3. 4. 1.

Ehrlich et al. 1999; Canada Downs & Black score=7 Case Series N=1

DiMarco et al. 2006; USA Downs & Black score=7 Pre-post N=1

Population: 52 y/o male, incomplete C5C6, 7 yrs ago; ASIA C Treatment: Electrical stimulation via epidural electrodes in T9, T11 and L1 spinal cord regions Outcome Measures: Airway pressure Population: 16 subjects: (8 SCI, 8 matched controls), complete tetraplegia, C4-C7, mean age SCI: 393.1yrs; controls: 381.8yrs Treatment: Magnetic stimulation of abdominal muscles. Outcome Measures: Gastric pressure.

2. 1.

Estenne et al. 2000; Belgium Downs & Black score=5 Pre-post N=16

2.

Discussion Very few studies have examined the effectiveness of secretion removal techniques in people with SCI even though respiratory complications are a primary cause of morbidity and mortality in this population. Studies performed to date are limited by a survey (Garstang et al. 2000) or case study design (Ehrlich et al. 1999) or lack of documentation of valid measurement technique of standard pulmonary function (Kang et al. 2006). Limited evidence supports the postulate that improving inspiratory muscle strength (Ehrlich et al. 1999; Kang et al. 2006) in addition to expiratory muscle force (Estenne et al. 2000) are important to maximize expiratory flows during cough. Inspiratory muscle training (Ehrlich et al. 1999) and electrical stimulation of the expiratory muscles (Linder 1993; Estenne et al. 2000; DiMarco et al. 2006) are two potential therapies that can maximize the force produced by the inspiratory and expiratory muscles, respectively, in order to increase expiratory flows during cough. RCTs examining the effectiveness of these techniques in people after SCI have not yet been performed. Other issues that require further study in SCI is to examine the effectiveness of hand-held

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devices that facilitate airway clearance, such as those that apply continuous (Peripep) or oscillating positive expiratory pressure (Flutter). Of equal concern is to evaluate the comfort and preference of airway clearance techniques that are readily adhered to and performed by people with SCI. Some evidence supports the effectiveness of these positive expiratory pressure devices and other secretion removal techniques such as autogenic drainage in people with cystic fibrosis and other chronic respiratory diseases; however, the evidence to date is somewhat equivocal (Hess 2001; Reid & Chung 2004). Conclusion Secretion removal techniques are common practice in people with spinal cord injury and yet only level 4 evidence supports the use of some airway clearance techniques to facilitate secretion removal in this population. No evidence supports the selective use of the best airway clearance technique nor are criteria available to indicate when to implement the various airway clearance techniques. Urgent evaluation is required to determine the most efficient and effective techniques that are comfortable and readily adhered to for people with SCI in order facilitate airway clearance, to improve their quality of life, and decrease health care costs. There is limited evidence that suggests that improving inspiratory and expiratory muscle force is important to maximize expiratory flow during cough. Cough effectiveness can be enhanced by a variety of methods including manual assistance by a caregiver and/or electrical stimulation triggered by the person with SCI. Hand-held expiratory pressure devices may enhance secretion removal in people with SCI.

8.8 Summary Pulmonary function alteration and respiratory complications continue to be a major cause of morbidity and mortality in patients with SCI. There are currently no widely accepted clinical practice guidelines for the long term respiratory management of the SCI patient. Much of the SCI-respiratory literature focuses on the acute care of the SCI patient. However, given that long-term survival rates following SCI injury have increased in recent years a greater understanding of the effects of chronic SCI on the respiratory system is necessary. Moreover, identifying interventions that can improve (or minimize the decline in) pulmonary function and reduce respiratory complications are of great importance. Despite this need there are also no widely accepted clinical practice guidelines available for the respiratory management of the SCI patient following hospital discharge. This is largely due to the fact that there have been relatively few well designed studies that point to effective management strategies. Interpretation of the available literature is difficult because many studies have a least one, and more often multiple methodological or research design concerns. Specific major concerns include an overall lack of RCTs; patient sample sizes are often small with little or no consideration for statistical power; lack of appropriate control or placebo groups; and inadequate characterization of the SCI. In addition, most studies do not take into account gender, time since injury, smoking history and other respiratory complications. As such, the amount and quality of the literature can be considered modest at best and the ability to generalize is limited. 8-25

Despite the above caveats and research design shortcomings, some conclusions can be cautiously drawn regarding commonly used respiratory intervention strategies. (i) Exercise Training. The evidence that the respiratory system is positively influenced by exercise training is not strong. There is some evidence that rigorous training can improve respiratory muscle strength, endurance and efficiency in SCI. There have been no reports of negative consequences of exercise training. Exercise training should be encouraged for maintenance of general cardio-respiratory health in people with SCI. (ii) Respiratory Muscle Training. Specific training of the respiratory muscles in SCI is not well supported by the available research. Well designed studies are lacking but there is some evidence to show that respiratory muscle training can improve respiratory muscle strength and endurance. From the available literature on other subject groups (healthy, lung disease) it appears that training of the respiratory muscle may improve ventilation, decrease dyspnea and improve daily respiratory function. Consistent improvement in respiratory function following respiratory muscle training has not been demonstrated in people with SCI. (iii) Pharmaceutical Interventions. Restrictive ventilatory impairment is common in SCI and is dependent on lesion level and degree of completeness. Obstructive ventilatory impairment is present with cervical injury. There is some evidence to show that use of bronchodilators can elicit a positive response in pulmonary function. Bronchodilators can be recommended for shortterm use in patients with obstructive impairment. The long-term effects are unknown. There is limited evidence to support the use of anabolic steroids for improvement in pulmonary function. (iv) Assistive Devices. Ventilatory weaning in SCI is important but there is no consensus on the ideal weaning protocol. There is some evidence that progressive ventilator free breathing is more effective than intermittent mandatory ventilation in cervical SCI. There is insufficient research to advocate the long-term use of abdominal binding or vibration to improve indices of pulmonary function. (v) Obstructive Sleep Apnea. There is a higher prevalence of sleep apnea in SCI relative to able-bodied individuals. Treatment options include CPAP and weight loss but there is limited research evidence to suggest positive long-term benefits. Anecdotal and patient reports suggest that therapy for sleep apnea is beneficial. (vi) Secretion Removal. Retention of secretions is common in SCI because of a diminished capacity for cough generation. Elimination of secretions is commonplace in clinical practice and is generally considered an integral part of maintaining respiratory health in SCI. There are several commonly used secretion removal techniques but there is no consensus on their effectiveness.

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Linn WS, Adkins RH, Gong H. Jr., Waters RL. Pulmonary function in chronic spinal cord injury: A cross-sectional survey of 222 southern California adult outpatients. Arch. Phys. Med. Rehabil. 2000;81:757-763. Loveridge B, Badour M, Dubo H. Ventilatory muscle endurance training in quadriplegia: effects on breathing pattern. Paraplegia. 1989;27:329-339. McCool FD, Pichurko BM, Slutsky AS, Sarkarati M, Rossier A, Brown R. Changes in lung volume and rib cage configuration with abdominal binding in quadriplegia. J Appl Physiol 1986;60:1198-202. Onders RP, Dimarco AF, Ignagni AR, Aiyar H, Mortimer JT. Mapping the phrenic nerve motor point: the key to a successful laparoscopic diaphragm pacing system in the first human series. Surgery 2004;136:819-26. Peterson W, Charlifue W, Gerhart A, Whiteneck G. Two methods of weaning persons with quadriplegia from mechanical ventilators. Paraplegia 1994;32:98-103. Reid WD, Geddes EL, Brooks D, OBrien K, Crowe J. Inspiratory muscle training in chronic obstructive pulmonary disease. Special Series on Skeletal Muscle Training. Physiotherapy Canada 56(3):128-142, 2004 Reid, W.D., Chung, F. Clinical Management Notes and Case Histories in Cardiopulmonary Physical Therapy. Thorofare, NJ: SLACK Publishers; 2004. Ribot-Ciscar E, Butler JE, Thomas CK. Facilitation of triceps brachii muscle contraction by tendon vibration after chronic cervical spinal cord injury. J Appl Physiol 94:2358-2367, 2003 Ross J, White M. Removal of the tracheostomy tube in the aspirating spinal cord-injured patient. Spinal Cord. 2003;41:636-42. Rutchik A, Weissman AR, Almenoff PL, Spungen AM, Bauman WA, Grimm DR. Resistive IMT in subjects with chronic spinal cord injury. Arch. Phys. Med. Rehabil. 1998;79:293-297. Schilero GJ, Grimm D, Spungen AM, Lenner R, Lesser M. Bronchodilator responses to metaproterenol sulfate among subjects with spinal cord injury. J Rehabil Res Dev. 2004; 41:59-64. Short DJ, Stradling JR, Williams SJ. Prevalence of sleep apnoea in patients over 40 years of age with spinal cord lesions. J Neurol Neurosurg Psychiatry. 1992 Nov;55(11):1032-6. Silva AC, Neder JA, Chiurciu MV, da Cunha Pasqualin D, da Silva RCQ, Fernandez AC, Lauro FAA, de Mello MT, Tufik S. Effect of aerobic training on ventilatory muscle endurance of spinal cord injured men. Spinal Cord. 1998;86:240-245,. Singas E, Grimm DR, Almenoff PL, Lesser M. Inhibition of airway hyperreactivity by oxybutynin chloride in subjects with cervical spinal cord injury. Spinal Cord. 1999;37:279-83. Singas E, Lesser M, Spungen AM, Bauman WA, Almenoff PL. Airway hyperresponsiveness to methacholine in subjects with spinal cord injury. Chest. 1996;110:911-5. Spungen AM, Dicpinigaitis PV, Almenoff PL, Bauman WA. Pulmonary obstruction in individuals with cervical spinal cord lesions unmasked by bronchodilator administration. Paraplegia. 1993;31:404-7. Spungen AM, Grimm DR, Lesser M, Bauman WA, Almenoff PL. Self-reported prevalence of pulmonary symptoms in subjects with spinal cord injury. Spinal Cord. 1997;35:652-657, Spungen AM, Grimm DR, Strakhan M, Pizzolato PM, Bauman WA. Treatment with an anabolic agent is associated with improvement in respiratory function in persons with tetraplegia: a pilot study. Mt Sinai J Med. 1999;66:201-5. Stockhammer E, Tobon A, Michel F, Eser P, Scheuler W, Bauer W, Baumberger M, Muller W, Kakebeeke TH, Knecht H, Zach GA. Characteristics of sleep apnea syndrome in tetraplegic patients. Spinal Cord. 2002 Jun;40(6):286-94. Sutbeyaz ST, Koseoglu BF, Gokkay NKO. The combined effects of controlled breathing techniques and ventilatory and upper extremity muscle exercise on cardiopulmonary responses in patients with spinal cord injury. Int. J. Rehabil. Res. 2005;28:273-276.

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Thomaz S, Beraldo P, Mateus S, Horan T, Leal JC. Effects of partial isothermic immersion on the spirometry parameters of tetraplegic patients. Chest. 2005;128:184-9. Uijl SG, Houtman S, Folgering HT, Hopman MT. Training of the respiratory muscles in individuals with tetraplegia. Spinal Cord. 1999;37:575-9.

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CHAPTER NINE
Bone Health Following Spinal Cord Injury
Maureen C Ashe, PhD, PT B Cathy Craven, MD FRCPC Andrei Krassioukov, MD, PhD Janice J Eng, BSc (PT/OT), PhD

Key Points Fragility fractures, especially around the knee, are very common in people with SCI. Ideally, bone loss intervention should be introduced early following SCI as a large portion of bone is loss during the first year. Oral Tiludronate and Clodronate prevent a decrease in BMD of the hip and knee region with no adverse effects on bone mineralization in men with paraplegia. Oral Etidronate prevents a decrease in BMD of the hip and knee region in people with incomplete paraplegia or tetraplegia. Pamidronate 30 mg IV or 60 mg IV 4x/year is not effective for the prevention of BMD loss at the hip and knee region early after SCI people with motor complete paraplegia or tetraplegia. Alendronate 10 mg daily and Calcium 500 mg orally 3x/day is effective for the maintenance of BMD of the wrist, hip and knee region for men with paraplegia. Short term (6 weeks) therapeutic ultrasound is not effective for preventing bone loss after a SCI. FES-cycling does not improve or maintain bone at the tibial midshaft in the acute phase. Electrical stimulation can maintain or increase BMD over the stimulated areas. Six months of FES cycle ergometry may increase lower extremity BMD over areas stimulated. There is inconclusive evidence for Reciprocating Gait Orthosis (RGO), long leg braces, passive standing or self-reported physical activity as a treatment for low bone mass. Early assessment and monitoring of bone mass after SCI are essential to identify low bone mass and risk for fragility fractures. Prevention with oral bisphosphonates (Tiludronate, Clodronate and Etidronate) may slow the loss of BMD early after SCI, but there is limited evidence that treatment with oral bisphosphonates maintains bone mass late after SCI. There is a lack of definitive evidence supporting nonpharmacological interventions for either prevention or treatment of bone loss after a SCI.

Table of Contents
9.1 Introduction .......................................................................................................................9-1 9.2 Fracture risk following a SCI ...........................................................................................9-1 9.3 Bone Outcome Measures .................................................................................................9-2 9.4 Pharmacologic Therapy: Bisphosphonates ...................................................................9-3 9.4.1 Pharmacologic Therapy: Prevention (within 12 months of injury).......................................9-3 9.4.2 Pharmacologic Therapy: Treatment .................................................................................9-5 9.5 Non-Pharmacologic Therapy: Rehabilitation Modalities ..............................................9-6 9.5.1 Non-Pharmacologic Therapy: Prevention (within 12 months of injury) .............................9-7 9.5.2 Non-Pharmacologic Therapy: Treatment .........................................................................9-8 9.5.2.1 Electrical stimulation .....................................................................................................9-9 9.5.2.2 FES Cycle Ergometry .................................................................................................9-10 9.5.2.3 Standing ........................................................................................................................9-11 9.6 General Discussion ...........................................................................................................9-12 References ...............................................................................................................................9-16

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Ashe MC, Craven C, Krassioukov A, Eng JJ (2006). Bone Health Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 9.1-9.18. www.icord.org/scire

Bone Health Following Spinal Cord Injury

9.1 Introduction Preserving and maintaining bone mass after a spinal cord injury (SCI) is crucial to decrease the risk of fragility fractures that results from bone loss. The pathophysiology of this loss is such that within the first few days following a spinal cord injury there is an increase in excreted calcium (known as hypercalciuria) that is 2-4 times that of individuals who are confined to prolonged bedrest but without a SCI (Bauman & Spungen 2001) and reflects excessive bone resorption. Longitudinal studies also highlight a higher rate of hypercalcemia (excessive calcium in the blood) for people after a SCI that leads to rapid bone mineral loss in the first 4-6 months that slows for the remaining first year post injury (Hancock et al. 1980; Frey-Rindova et al. 2000). Early studies also suggest that bone mineral density (BMD) stabilizes by 1-2 years after SCI (Griffiths et al. 1976; Hancock et al. 1980; Garland et al.1992) at 25-50% below that of ablebodied peers in the hip and knee region. More recent investigations support a continual loss of bone mass with time since injury (Demirel et al. 1998; Bauman et al. 1999) and suggest that a steady-state of lower extremity bone mineral homeostasis is not reached. The immediate and excessive loss of bone mass post SCI is believed to result mostly from a decrease in mechanical loading as a result of reduced or complete loss of muscle function and/or weight-bearing activities. Neural, vascular, hormonal and nutritional changes may also negatively impact bone but the relative contributions of these factors is not known. Aging and inactivity accentuate bone loss resulting in site-specific decrease in bone mineral content (trabecular>cortical bone). Specifically, the decreased systemic calcium and vitamin D (with subsequent increase in parathyroid hormone) that results from SCI can be accentuated by inadequate dietary calcium intake, decreased sunlight exposure and the potential for hyperparathyroidism (Bauman et al. 1995). Further evidence suggests that women with a complete SCI experience bone loss around the hip and knee during menopause that is greater than age-matched able-bodied women (Garland et al. 2001). These factors all contribute to the increased risk for low-trauma or fragility fractures in people who sustain a SCI. 9.2 Fracture Risk following a SCI There is overwhelming evidence that supports the importance of addressing bone health issues early after a SCI. A high incidence of lower extremity fragility fractures (1-46%) exist in people who sustain a SCI (Table 9.1); the majority of fragility fractures occur following transfers or activities that involve minimal or no trauma (Ragnarsson & Sell, 1981). The distal femur and proximal tibia are most at risk, consistent with site-specific decreases in bone mineral density around the knee such that fractures of the distal femur are referred to as the paraplegic fracture (Comarr et al. 1962). There are many notable risk factors for fragility fracture after SCI. There is a greater risk for women compared with men (Vestergaard et al. 1998; Garland et al. 2004), also with increasing age and longer time since injury. Further, paraplegics have more fractures compared with tetraplegics and those with complete injuries have greater bone loss compared with incomplete injuries (Garland et al. 2004). In the general population, individuals with a prior history of fragility fracture or a maternal history of fracture have a greater risk for future fracture, and these risk factors should also be considered in people with SCI.

9-1

Table 9.1 Fracture Incidence and risk factors for Fragility fractures after SCI
First Author /Year Comarr et al. 1962 Ragnarsson & Sell 1981 Freehafer 1995 Frisbie 1997 Vestergaard et al. 1998 McKinley et al. 1999 Lazo et al. 2001 Nelson et al. 2003 Zehnder et al. 2004 41 45 100 0.4-30 yrs <1 yr 1-9 yrs 10-19 yrs 20-29 yrs 26-52 2-43 yrs 2%/yr 1%/yr 1%/yr 3%/yr 5%/yr N 1,363 578 133 120 438 17-77 12-62 20-79 20-39 40-59 60-79 10-80 1-39 40-59 >60 27-83 >10 months 2112 yrs > 1 yr <1.1% 1-54 yrs 33% 15% 31% 46% 21% 2% 9% 34% Women >Men; Family history of fractures Women >Men; Time since injury Time since injury; tibia BMD Age Age Time to 1st Fracture Fracture incidence 6% 4% Risk Factors A complete injury > risk than incomplete injury.

Women >Men; Family history of fractures; Time since SCI > 3 years

Garland et al. 2004

28

Fracture BMD threshold < 0.86 gm/cm2; breakpoint BMD at 0.49 gm/cm2; Women >Men Age; low BMI; Completeness of injury post SCI

Fragility fractures, especially around the knee, are very common in people with SCI. 9.3 Bone Outcome Measures Evaluation of bone occurs in many ways depending on the tools used for investigation. Common methods of bone evaluation include urine and blood (serum) analyses yielding biochemical markers to quantify rates of bone turnover. The most commonly used biochemical markers of bone turnover include osteocalcin, n-telopeptide and hydroxyproline. Areal bone mineral density is quantified non-invasively with imaging technologies such as dual energy X-ray absorptiometry (DXA) and previously with dual energy photon absorptiometry (DPA). Dual energy X-ray absorptiometry is considered by the World Health Organisation as the gold or criterion standard to diagnose osteoporosis and is the most widely used assessment technique for osteoporosis. DXA can measure BMD for the spine, hip or the limbs at relatively low cost and minimal risks to the patient. Volumetric bone mineral density is assessed using peripheral quantitative computed tomography (pQCT). Peripheral quantitative computed tomography (pQCT) is a safe and precise technique to differentiate cortical from trabecular bone and assess both bone geometry and volumetric density. Histomorphometry are measurements from bone biopsies and analyzed at the tissue and cellular level to provide an in-depth understanding of bone. There are two types of bone histomorphometry, dynamic and static. Dynamic histomorphometry involves using substances

9-2

such as tetracycline to measure tissue growth. Static histomorphometry involves determining the size and types of cells; measurements include length, area or cell counts. Static histomorphometry involves embedding bone in a resin then sanding the specimen down until it is very thin (<150 microns) and the images are viewed under microscope at various magnifications. Although bone histomorphometry is considered an important tool, it is not always feasible because it requires taking surgically removed bone specimens from willing participants. In this section, prevention and treatment interventions for bone health after a SCI are discussed. As bone loss is greatest immediately following a SCI, pharmacological and non-pharmacological interventions are classified as either prevention (the participants are less than 1 year post SCI) or treatment (study involved participants who are > 1 year after the injury). The intent is to address two distinct clinical questions: 1.What is the best way to prevent acute regional declines in bone mineral density?; and 2. What are the best treatments for low bone mass of the hip and knee region for people with longstanding SCI? 9.4 Pharmacologic Therapy: Bisphosphonates Within weeks after SCI, there is a marked increase in bone resorption (taking bone away) with a decrease in bone formation (adding new bone) and this is responsible for the significant loss in BMD. Bisphosphonates are a group of medications that are used to prevent declines in bone mass or treat low BMD; they act to slow down excessive bone resorption. Etidronate (Didrocal), Alendronate (Fosamax) and Risedronate (Actonel) are oral bisphosphonates, which are currently approved for the treatment of postmenopausal osteoporosis in Canada (Brown et al. 2002). Clodronate (Benefos or Ostac) is available intravenously (IV) and orally for the treatment of osteoporosis. Tiludronate (Skelid) is available in oral form in the United States. Giving calcium and vitamin D at the same time as bisphosphonate therapy has the potential for greater efficacy for bisphosphonates. Concurrent supplementation with calcium and vitamin D have been important additions to bisphosphonate therapy for other medical conditions (such as postmenopausal osteoporosis) (Brown et al. 2002). 9.4.1 Pharmacologic Therapy: Prevention (within 12 months of injury) Table 9.2 Prevention Studies using Pharmacology for Bone Health after a Spinal Cord Injury.
Author Year; Country Score Research Design Total Sample Size Methods Population: 14 men and women, ages 2161, motor complete para/ tetraplegia. Treatment: Pamidronate for 12 months. Participants randomized to 1. 60mg IV or placebo(saline) at 1, 2, 3, 6, 9, 12-mos. post SCI (N=6). 2. Placebo (N=5). Outcome measures: BMD by DXA, bone turnover markers. Population: 21 men and women, ages 1554 years, complete paraplegia. Treatment: Clodronate for 3.5 months. Participants randomized to 1. 400mg per day (N=7); 2.1,600 per day (N=7); or 3. Placebo (N=7). Outcome measures: BMD dual photon absorptiometry (DPA), histomorphometry 1. 2. Outcome There was no significant between group differences in BMD decline at 1 year. The treatment group had significantly lower 24-hr urinary calcium at 1month vs. placebo group (P<0.05) and there were no significant changes in markers of bone formation over the 12 month study. No reported adverse effects on bone mineralization with intervention. in serum and urine markers in the Placebo group ( bone turnover). Effective for acute prevention of declining bone mass and a maintenance of BMC of the femur and tibia in the treatment groups.

Bauman et al. 2005; USA PEDro=10 RCT N=14

1. 2. 3.

Minaire et al. 1981; France PEDro=10 RCT N=21

9-3

Author Year; Country Score Research Design Total Sample Size Chappard et al. 1995; France PEDro=9 RCT N=20

Methods Population: 20 men and women, ages 1650, injuries between C5-T12. Treatment: Tiludronate for 3 months. Participants randomized to 1. 400 mg/day (N=7); 2. 200 mg/day (N=7); or 3. Placebo (N=6). Outcome measures: histomorphometry. Population: 13 men and women, ages 2257, injuries between C5-T12, ASIA: A or D. Treatment: Etidronate for 30 weeks. Participants randomized to 1.800mg daily (N=6) or 2. Conventional rehab and calcium 1000mg/day (N=7). Outcome measures: DXA and adverse event rate. Population: 21 men and women, ages 1554, complete paraplegia. Treatment: Clodronate for 100 days. . Participants randomized to 1.400mg per day (N=7); 2. 1,600 per day (N=7); or 3. Placebo (N=7). Outcome measures: DXA, histomorphometry, biochemical bone turnover markers. Population: 24 men and women, ages 2557, injuries between C5-T12, ASIA: A-D. Treatment: Pamidronate for 6 months. Participants randomized to 1. 30mg IV every 4wks x 6doses (total 180mg/participant) (N=14) or 2. conventional rehab (N=10). Outcome measures: BMD by DXA, urine biochemical bone markers. 1.

Outcome There was an in total bone volume in the treatment group 1(400mg/day) vs. treatment group 2 (200mg/day) and placebo groups. bone resorption indicators in the placebo group vs. the treatment groups. BMD loss at the distal femur was 26% and 22% at the proximal tibia. The rate of decline in BMD was greatest amongst the ASIA A patients. BMD of lower extremity for the Etidronate treated ASIA D patients were preserved. Oral Etidronate was safe and well tolerated by participants. There was a greater in bone removal markers in Placebo group (48%), compared with treatment groups (1727%). BMD was maintained in treatment groups with a in placebo group. Lower bone turnover markers in treatment groups. There was a lower % decline in BMD in treatment vs. control group. The mean overall bone loss was 8.7% in the placebo group but only 2.7% in the treatment group (p=0.02). The average loss of BMD was 3.1% in the ASIA D group and 7.7% in the ASIA A group.

2. 1.

Pearson et al. 1997; Canada PEDro=8 RCT N=13

2. 1.

Minaire et al. 1987; France PEDro=7 RCT N=21

2. 3. 1.

Nance et al. 1999; Canada PEDro=4 RCT N=24

Discussion Evidence for pharmacological prevention of SCI bone loss includes 6 randomized controlled trials (RCT) (n=113 participants) (Table 2). These studies were difficult to interpret as a group due to the variability in selection of the primary outcome measure, relatively short durations of follow-up, small sample sizes, and the lack of stratification based on impairment level. Preventing bone loss immediately following SCI is challenging given the rapid bone resorption especially in ASIA A patients. The majority of studies found bisphosphonates resulted in a reduction of bone loss compared to a control group. The two studies which report that first generation bisphosphonates (Clodronate) can maintain bone were short in duration (3 month intervention) and participants had less severe injury (paraplegia, incomplete SCI) (Minaire et al. 1981, 1987). In two studies (Pearson 1997; Nance 1999), both groups continued to lose bone, except ASIA D participants who had bone density preservation in the lower extremity with bisphosphonates while participants with ASIA A had the greatest decline in both studies. A recent study which used a secondgeneration version of the bisphosphonate, Pamidronate and a longer intervention period found no significant differences between groups for bone loss after 1 year (Baumann 2005).

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Conclusion There is Level 1 evidence that oral Tiludronate and Clodronate prevent a decrease in BMD of the hip and knee region with no adverse effects on bone mineralization in men with paraplegia. There is Level 1 evidence that oral Etidronate prevents a decrease in BMD of the hip and knee region in people with incomplete paraplegia or tetraplegia (ASIA D impairment) who return to walking within 3 months of the SCI. There is Level 1 evidence that Pamidronate 30 mg IV or 60mg IV four times per year is not effective for the prevention of BMD loss at the hip and knee region early after SCI in men and women who have motor complete paraplegia or tetraplegia.

Ideally, bone loss intervention should be introduced early following SCI as a large portion of bone is loss during the first year. Oral Tiludronate and Clodronate prevent a decrease in BMD of the hip and knee region with no adverse effects on bone mineralization in men with paraplegia. Oral Etidronate prevents a decrease in BMD of the hip and knee region in people with incomplete paraplegia or tetraplegia. Pamidronate 30 mg IV or 60 mg IV 4x/year is not effective for the prevention of BMD loss at the hip and knee region early after SCI people with motor complete paraplegia or tetraplegia.

9.4.2 Pharmacologic Therapy: Treatment Table 9.3 Treatment Studies Using Pharmacology for Bone Health after a Spinal Cord Injury
Author Year; Country Score Research Design Total Sample Size Methods Population: 65 men, ages 18-60, complete injuries between T1-L3, ASIA: A, B. Treatment: Alendronate for 6 months. 1.10mg per day plus 500mg calcium per day (N=33) or 2. calcium alone (500mg per day) (N=32). Outcome measures: BMD by DXA and bone turnover markers. 1. Outcome BMD of the tibia in calcium group but remained stable in the Treatment group (group difference, p = 0.017). There was no change in wrist BMD and a significant in lumbar spine BMD in both groups. BMD of the mid-shaft tibia and hip were maintained in the Treatment group and in the calcium group. Biochemical markers of bone absorption were significantly from baseline in the Treatment group. There was a mean in upper extremity BMD that was greater in Treatment vs. calcium group. There were no group differences for BMD of the lumbar spine, lower extremity or whole body BMD and lower extremity T-score.

Zehnder et al. 2004; Switzerland PEDro=7 RCT N=65

2. Population: 19 men (< 50 yrs) and women (< 35 yrs), para/tetraplegia, ASIA: A, B, or C Treatment: Alendronate for 6 months. 1. 10mg and calcium 500mg bid (N=10) and 2. calcium (500mg bid) (N=9). Outcome measures: BMD by DXA 1.

Moran de Brioto et al. 2005; Brazil PEDro=6 RCT N=19

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Discussion Evidence for pharmacological treatment of SCI bone loss includes 2 RCTs (n=84 participants). In both studies, the treatment group experienced improvement in bone health at various sites. However, the extent of improvement was greater in the study by Zehnder et al. (2004) who found an increase in BMD at the spine with maintenance of BMD at the tibia and hip. In contrast, Moran de Brioto et al. (2005) only found an increase in BMD at the wrist. The difference in outcomes could be a result of the younger participants with less severe injuries in the work by Zehnder and coworkers. This review has provided strong support for second generation bisphosphonates for treatment for low bone mass. This review has provided strong support for using first and second generation oral bisphosphonates for prevention and treatment for low bone mass. Despite the benefits of these medications, they are not without their complications. Oral bisphosphonates must be ingested on an empty stomach, with 4-8oz of water, followed by sitting up for one-hour post ingestion prior to taking any other food or medication. Only 1% of the ingested oral bisphosphonate is absorbed in the upper intestine, yet it remains in the body in an inactive form for several months or years thereafter. Oral bisphosphonate therapy can cause side effects; joint pain and stomach upset being the most frequently reported adverse effects. Intravenous formulations of bisphosphonates are available in daily, monthly and quarterly preparations, and have a greater relative potency. Although their common short-term side effects include fever, low serum calcium and transient decrease in white blood cells, IV preparations are attractive due to the flexibility in dosing regimens, assured compliance and the reduced relative risk of an adverse upper gastrointestinal event. Bisphosphonates should be used with caution in pre-menopausal women due to the unknown effects of these medications on the fetus during pregnancy. Patients taking acetylsalicylic acid (ASA), corticosteroids or NSAIDS may require preventative measures because using these medications with bisphosphonates increases the relative risk of upper gastrointestinal side effects. Conclusion There is Level 1 evidence that Alendronate 10 mg daily and Calcium 500mg orally 3x/day is effective for the maintenance of BMD of the wrist, hip and knee region for men with paraplegia.

Alendronate 10 mg daily and Calcium 500 mg orally 3x/day is effective for the maintenance of BMD of the wrist, hip and knee region for men with paraplegia. 9.5 Non-Pharmacologic Therapy: Rehabilitation Modalities Rehabilitation options after a SCI for bone health focus on stimulating muscles and encouraging weight-bearing. Functional electrical stimulation (FES) is an important option to stimulate muscle with the goal of increasing regional BMD and involves the use of surface or implanted electrodes to stimulate standing, ambulation or bicycling (cycle ergometry). The FES-cycle ergometer uses a series of electrodes placed over the hamstrings, quadriceps and gluteal muscles of the legs to simulate a cycling pattern. Weight-bearing activities are also used for bone health after a SCI; these modalities include either passive (tilt-table or standing frame) or active weight-bearing activities with or without assistance from FES. Many FES studies have enrolled participants with both acute and chronic injuries and are therefore difficult to classify as pure prevention or 9-6

treatment interventions. For the purpose of this review, studies that enrolled participants that ranged from the acute phase to > 1 year were included with the treatment literature as the majority of their participants were in the chronic phase. 9.5.1 Non-Pharmacologic Therapy: Prevention (within 12 months of injury) Table 9.4 Prevention Studies Using Rehabilitation Modalities for Bone Health after SCI
Author Year; Country Score Research Design Total Sample Size Methods FES-cycle ergometer Population: 38 men and women, mean 1. age = 33, complete injuries between C5T12, (19 participants, 19 controls). Treatment: FES-cycle ergometer. Progressive training sessions until able to cycle for 30 mins. Then 3x/wk for 6 mos. from this baseline. On the remaining 2days of the week there was passive standing. Control group performed 30 mins. of passive standing 5 days/week. Outcome measures: CT Standing/Walking Population: 19 men, ages 19-59, injuries 1. between C4-T12, ASIA: A-D Treatment: Standing/Walking. Group 1 had 0-5 hrs per week loading exercises with standing frame. Group 2 had 5+hrs of standing exercises per week (standing). Group 3 had 5+hrs of standing and treadmill (walking). Interventions lasted 25 wks. Outcome Measures: vBMD by pQCT Treadmill training Population: 2 men and 3 women, ages 19-40, injuries between C3-C8, ASIA: B and C. no controls. Treatment: Body-weight supported treadmill training. Initial session started at 5mins and was gradually to 10-15mins in all but 1 participant during 48 sessions of 2x/wk-training over a period of 6-8 months. Outcome measures: BMD by DXA and CT. Ultrasound Population: 15 men, ages 17-40, injuries between C5-T10, ASIA: A-B, (within group design) Treatment: Pulsed therapeutic ultrasound. Applied to both calcanei for each participant for 20 min/day, 5x/wk over a consecutive 6-wk period. Right and left calcaneus within each participant was randomized. Outcome measures: BMD by DXA and quantitative ultrasound (QUS). 1. 2. 3. Outcome

Eser et al. 2003; Switzerland Downs & Black score=14 Prospective Controlled Trial N=38

Both groups had a 0-10% in tibial cortical BMD. There was no difference between groups for BMD after the intervention.

de Bruin et al. 1999; Switzerland PEDro=6 RCT N=19

Marked in trabecular BMD at the left tibia for the immobilized group but minimal in trabecular BMD in Group 2 and 3.

Giangregorio et al. 2005; Canada Downs & Black score=13 Pre-post N=5

in BMD for all participants at almost all lower limb sites after training, ranging from -1.2 to -26.7%. Lumbar spine BMD changes ranged from 0.2 to -7.4%. No consistent changes in bone geometry at distal femur and proximal tibia. Did not alter the expected pattern of change in bone biochemical markers over time.

1.

For specified dose, no significant effect of QUS for any skeletal measurement parameter (p>0.05).

Warden et al. 2001; Australia PEDro=11 RCT N=15

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Discussion Evidence for non-pharmacological prevention of SCI bone loss includes 4 investigations (n=77 participants). This includes 2 RCTs (34 participants), 1 non-randomized controlled trial (38 participants) and 1 pre-post studies (5 participants) (Table 4). As with pharmacology prevention studies, there were difficulties with interpretation because of low numbers of participants and variability with the primary outcome measures. For each of the four different modalities there is only one study available and there was variability for the primary outcome of interest. Only the therapeutic ultrasound study by Warden and coworkers found no significant improvement in bone health after a 6 week intervention. Although prospective observational data (Frey-Rindova et al. 2000) highlight the loss of bone in the early phase (first 6-months post SCI), there was no significant influence of self-reported physical activity level. Overall, the evidence suggests that rehab modalities were not successful in reducing bone loss in the acute phase after SCI. Conclusion For NON-PHARMACOLOGICAL PREVENTION of bone loss after a SCI: There is Level 1 evidence from one RCT that short-term (6 weeks) ultrasound is not effective for treating bone loss after a SCI. There is Level 2 evidence that FES-cycling did not improve or maintain bone at the tibial midshaft in the acute phase. There is Level 4 evidence that walking and standing in the acute phase did not differ from immobilization for bone loss at the tibia.

Short term (6 weeks) therapeutic ultrasound is not effective for preventing bone loss after a SCI. FES-cycling does not improve or maintain bone at the tibial midshaft in the acute phase.

9.5.2 Non-Pharmacologic Therapy: Treatment In this section, non-pharmacological rehabilitation treatment modalities are divided into 4 subsections: Patterned electrical stimulation (PES), functional electrical stimulation (FES) cycle ergometry, standing and walking (Tables 5-7). Both PES and FES use cyclical patterns of electrical stimulation that simulate muscular activity. However, FES is directed towards the attainment of purposeful tasks such as cycling or walking. PES, on the other hand, is focused on producing muscle contractions (isometric, isotonic). In some applications, PES techniques are used as a training stimulus to prepare muscles for a subsequent FES training condition.

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9.5.2.1 Electrical Stimulation Table 9.5 Treatment Studies Using Electrical Stimulation for Bone Health after SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: 14 men and women, ages 2342, complete and incomplete injuries between C5-T6, 14 able-bodied controls. Treatment: PES. Quadriceps training was conducted 5 days/wk for 24 wks. Participants trained for 1hr/day or until fatigue. Right quadriceps were stimulated with no resistance (but against gravity) while the left quadriceps were stimulated against a resistance. Outcome measures: BMD by DXA Population: 12 men and women, ages 1963, para/tetraplegia, complete/incomplete, no controls (only 9 participants had BMD) Treatment: PES. Each participant trained for a total of 36 sessions (3x/wk for 12wks) using a progressive intensity protocol for PES stimulated knee extension. This progression was continued to a maximum 15 kg load. Outcome measures: BMD by DXA Population: 10 men and women, ages 2745, injuries either C6 or T2, no controls Treatment: PES. Stimulated the legs for 30 min, 3x/wk for 12 mos. followed by 1x/wk for 6 mos. Outcome measures: BMD by DXA, biochemical markers. 1. Outcome At baseline BMD from the experimental group was lower at the distal femur, proximal tibia and midtibia ( range: 25.8% to 44.4%) than able-bodied controls. BMD with training (p<0.05) for both sides of SCI participants, but the type of training had no effect (resistance vs. no resistance). There was a significant in the BMD of the distal femur and proximal tibia, but not in the mid-tibia. Tibial BMD was not significantly changed after PES protocol (p>0.05), but BMD was better than predicted values.

Blanger et al. 2000; Canada PEDro=11 Prospective Controlled Trial N=28

2.

1.

Rodgers et al. 1991; USA Downs & Black score=10 Pre-post N=12

1.

Mohr et al. 1997; Denmark Downs & Black score= 9 Pre-post N=10

2. 3.

After 12 mos. of training, there was a significant 10% in proximal tibia BMD (p< 0.05) but no change at the lumbar spine or femoral neck. After 6 mos. of reduced training, BMD for the proximal tibia returned to baseline. Blood and urine markers were within normal limits at baseline and there was no significant change with PES.

Discussion Although there were no randomized controlled trials that assessed the effect of patterned electrical stimulation, Blanger et al. (2000) produced impressive results with a level 2, nonrandomized trial which used 1 limb as the treatment and the other as the control limb. Following training, the BMD recovered 30% of bone loss compared with able-bodied values. Stimulation effects only occur over the areas of stimulation and return to baseline within months once stimulation is stopped (Mohr et al. 1997). Conclusion There is Level 2 evidence that electrical stimulation either increased or maintained BMD over the stimulated areas.

Electrical stimulation can maintain or increase BMD over the stimulated areas.

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9.5.2.2 FES Cycle Ergometry Table 9.6 Treatment Studies Using FES Cycle Ergometry for Bone Health after SCI
Author Year; Country Score Research Design Total Sample Size

Methods
Population: 15 men, ages 23-37, complete, C6-T8. 15 able-bodied controls Treatment: FES-cycle ergometer. Participants performed FES-cycling exercises with minimal resistance for 30 minutes/day, 5 days/week for 6 months. Follow-up 6 months after intervention. Outcome measures: BMD by DXA 1. 2.

Outcome At baseline, participants BMD at the femoral neck, distal femur and proximal tibia was lower than controls. After 6 months, BMD of the distal femur and proximal tibia significantly (p<0.05) and BMD of the calcaneus (p>0.05) showed a trend toward increasing. BMD in the distal femur, proximal tibia, and heel significantly after 6 mos. without intervention (p<0.05). The BMD of the femoral neck progressively throughout the treatment (p>0.05). The BMD of the proximal femurs were below normal before commencing exercise intervention (compared with matched able-bodied individuals). After 7 months of exercise training there was no significant difference in BMD for any of the sites of the proximal femurs compared to normal values. At baseline, SCI participants were not significantly different from agedmatched able-bodied ambulatory men for lumbar-spine BMD. However, BMD was significantly lower for participants at the hip (p<0.025) for bilat trochanters, Wards triangles, and femoral necks. Only the L2-L4 values demonstrated any positive training effects (p=0.056). Further training (Phase 3b) did not demonstrate further increase in BMD at any site. No significant change in lumbar spine and femoral shaft and/or distal tibia trabecular BMD after the intervention.

Chen et al. 2005; Taiwan Downs & Black score= 9 Pre-post N=30

Leeds et al. 1989; USA Downs & Black score=12 Pre-post N=6

BeDell et al. 1996; USA Downs & Black score=10 Pre-post N=12

Pacy et al. 1988; UK Downs & Black score=10 Pre-post N=4

Hangartner et al. 1994; USA Downs & Black score= 9 Pre-post N=15

Population: 6 men, ages 18-27, tetraplegia, no controls. Treatment: FES+ FES-cycle ergometer. 1month quads strengthening exercise, followed by 6-mos cycle ergometry (CE). Knee extension sessions were 45 lifts/leg 3x/week for 1month. CE sessions were 3X/wk up to 30 mins for 6 mos. Outcome measures: BMD by DXA Population: 12 men, ages 23-46, complete injuries between C5-T12, no controls. Treatment: FES+ FES-cycle ergometer. Participants participated in a 3-phase training program of FES-CE. Phase 1: quads strengthening. Phase 2: FES-CE progression until 30 min continuously. Phase 3a: 24x 30-mins continuous exercise sessions performed 3x/wk. Phase 3b: An extra 24x 30-min sessions adding simultaneous arm ergometry (8 participants only). Outcome measure: BMD by DXA Population: 4 men, ages 20-35, paraplegia, no controls Treatment: FES+ FES-cycle ergometer. Part 1 was quads strengthening with load ranging from 1.4-11.4 kg bilateral for 15 mins for 5x/wk (10 wks). Part 2 was CE at 50 rpm with resistance (0-18.75 W). Performed for 15 mins, 5x/wk (32 wks). Outcome measures: BMD by DXA Population: 15 men and women, ages 1746, complete and incomplete injury between C5-T10, no controls. Treatment: FES+ FES-cycle ergometer. Either 1. FES knee extension exercises (n=3) or 2. FES cycling (n=9) or 3. both (n=3). Sessions were 3x/week for 12 wks except Group 3 had 24 weeks. Outcome measures: CT

1.

2.

1.

2.

1.

1.

Participants in the exercise groups continued to lose bone at the distal and proximal end of the tibia, but it was less than expected from the regression lines.

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Discussion For FES-Cycling there are mixed results for bone parameters. One study found an 11-13% increase in BMD at the proximal tibia or distal femur while there was no significant withinparticipant BMD change in 3 pre-post studies. The FES-cycling study which reported a positive effect on bone parameters used a protocol that was 3 sessions/week for at least 6 months in duration, increased bone parameters were over areas directly affected by stimulated muscles (e.g. quads, distal femur and proximal tibia), and FES-cycling intervention needed to be maintained or bone gains were lost. FES shows promise as an effective treatment; however the limited availability of cycle ergometry for home or longitudinal use may limit its generalizibility if the therapy cannot be sustained outside a clinical trial scenario. Conclusion There is Level 4 evidence that 6 months of FES cycle ergometry increased regional lower extremity BMD over areas stimulated amongst paraplegics.

Six months of FES cycle ergometry may increase lower extremity BMD over areas stimulated.

9.5.2.3 Standing Table 9.7 Treatment Studies Using Standing or Walking for Bone Health after SCI
Author Year; Country Score Research Design Total Sample Size Methods Standing (n=4 studies) Population: 6 men, ages 36-65, complete and incomplete, C5-T12, no controls. Treatment: Passive standing frame. Increased gradually until able to "stand" 30 mins 3x/day. Progressed to 45 mins 2x/day then participants completed 45 mins of standing 2x/day for 5 mos. Outcome measures: BMD and fracture risk by DPA Population: 16 men and women, mean age=29, complete injuries, T4-T11, no controls. Treatment: Standing and ambulation. 32 sessions then participants continued ambulation for 8 more weeks. Outcome measures: BMD by DPA Population: 8 men and women, ages 1956, incomplete tetraplegia, no controls. Treatment: Tilt-table weight-bearing and strengthening exercises. Each tilt table session lasted at least 20mins 1x/day, and 0 the tilt table angle attained was 45 . Two groups: 1) early (within 6 mos of SCI) and 2) late group (12-18 mos post SCI). Outcome Measures: urinary calcium excretion Outcome

1.

Kunkel et al. 1993; USA Downs & Black score=12 Pre-post N=6

There was no significant change in fracture risk as measured with BMD for femoral neck or lumbar spine with "standing".

1.

Needham-Shropshire et al. 1997; USA Downs & Black score=10 Pre-post N=16

There were no significant changes in BMD in the femoral neck, Ward's triangle, or the trochanter.

1.

Kaplan et al. 1981; USA Downs & Black score= 8 Pre-post N=8

2.

Significant improvement (p<0.01) in calcium excretion, urinary calcium, and calcium balance for the early group. The late group had a significant improvement for urinary calcium, and calcium balance.

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Author Year; Country Score Research Design Total Sample Size

Methods Walking (n=2 studies) Population: Bone assessment with 2 men and 2 women, ages 16-42, paraplegia. no controls. Treatment: Reciprocal gait orthosis. No protocol provided. Quantitative computed tomography repeated every 6 mos from the 1st referral, orthotic fitting and training, to independent and regulator ambulation (mean=5 mo). The RGO was used daily on average for 3 hrs. Outcome measures: BMD by QCT Population: For bone assessment there were 6 men and 1 woman, ages 26-33, injuries between T2-T10. no controls. Treatment: RGO-II hybrid orthosis. Completed the protocol within 3-14 mos (2hr sessions 2x/wk). Outcome measures: BMD by DPA

Outcome

1.

Three of 4 participants increased or maintained femoral neck BMD but no change in lumbar spine.

Ogilvie et al. 1993; England Downs & Black score= 8 Pre-post N=4

1.

Thoumie et al. 1995; France Downs & Black score= 8 Pre-post N=7

2.

At baseline, participants (compared with age-matched Z-score) had no significant change in L-spine BMD but a in femoral neck BMD. After the training program (16 mos), no consistent changes at the femoral neck BMD among participants (4 participants BMD, 1 participant BMD and no change in 2 participants).

Discussion There is inconclusive evidence for Reciprocating Gait Orthosis (RGO), long leg braces or passive standing as a treatment for bone loss. One cross-sectional study (Goemaere et al. 1994) used a self-report physical activity measure to highlight the potential for standing to reduce bone loss at the femoral shaft; patients with long leg braces had a significantly higher trochanter and total BMD compared with standing frame or standing wheelchair. In contrast, another cross-sectional investigation of bone outcomes and self-report physical activity measures found no effect of activity on lower extremity bone parameters (Jones et al. 2002). Conclusion There is inconclusive evidence for Reciprocating Gait Orthosis (RGO), long leg braces, passive standing or self-reported physical activity as a treatment for low bone mass. There is inconclusive evidence for Reciprocating Gait Orthosis (RGO), long leg braces, passive standing or self-reported physical activity as a treatment for low bone mass.

9.6 General Discussion The risk for fragility fractures after a SCI has been established and low bone mass is an important factor to be considered. In 2002, the Canadian Medical Association published clinical practice guidelines for prevention and treatment of bone health (Brown et al. 2002). Currently, these guidelines do not specifically address persons with spinal cord injury, but they do provide a resource for osteoporosis diagnosis, prevention and treatment. Hopefully future guidelines will provide recommendations for people who have paralysis such as after a stroke, SCI, multiple

9-12

sclerosis or other neurological impairments that lead to reduced weight-bearing, muscle activity and physical activity levels. In the past 40 years there have been a number of interventions (both medications and rehabilitation modalities) aimed to maintain or retard bone loss after SCI yet, consistent methodological oversights have emerged including: small sample sizes and broad inclusion criteria that do not always account for gender, time since injury or impairment differences between participants. The pharmacological interventions (either prevention or treatment interventions) discussed here report stronger methodologies all were RCTs with PEDro scores ranging from 6-10 indicating moderate to high quality. In contrast, the studies employing rehab modalities had low numbers of participants and only 2 of the 17 studies were RCTs. These factors contribute to difficulties drawing generalisible conclusions regarding the impact of rehab interventions on bone parameters. Nonetheless, despite the lack of evidence to establish the effectiveness of these rehab modalities on bone parameters, it does not negate these treatments as beneficial to other body systems. For example, FES-cycling may have small effects on bone, but this modality has been shown to have large effects on cardiovascular health (Jacobs & Nash 2004). There are a few key points to consider when interpreting the results from interventions designed to maintain and/or improve bone parameters after a SCI. These include biological differences in bone development and maintenance between men and women, the natural loss of bone with aging and the type of primary outcome measure used. Age-related changes affect both women and men but the pattern of change is different because estrogen plays such a dominant role in bone remodeling. Consequently in women, the loss of estrogen at the menopause initiates a rapid loss of bone that eventually slows but continues throughout life. Men do not experience the rapid phase of bone loss with aging rather, only the slower phase of bone loss is observed. Therefore, keeping in mind that bone is lost over time, a study that reports no significant difference in BMD between two time periods 6 months apart may be interpreted as positive because of the expected loss. Due to the nature of different primary outcomes (BMD by DPA, DXA or pQCT, urine or blood markers) it can be difficult to determine the level of evidence. When measuring parameters such as urine or blood biomarkers, studies of short duration may yield significant results. However, using imaging, cortical bone remodeling can take at least 6 months in order to observe changes within participants over time. Consequently, investigations that did not maintain an intervention for at least 6-months may not show changes, but, the results cannot be interpreted as negative. Importantly all primary outcomes for bone health after a SCI are surrogate measures, that is, there has yet to be a study published in this area that investigates the effect of an intervention (either pharmacological or non-pharmacological) on reducing fractures. Generally, these types of studies are too costly due to the large number of participants that would need to be enrolled and followed for a long time period. Consequently, the clinical significance of the interventions based on fractures for this population remains to be determined. Conclusion There is a significant risk for lower extremity fragility fractures after a SCI; the risk increases with gender, type and time since injury. Early assessment and ongoing monitoring of bone health is an essential element of SCI care. There is Level 1 evidence for the prevention and treatment of bone loss using medications, however, nonpharmacological evidence for preventing bone loss and treating bone health is limited by small studies, different treatment protocols, participant groups that are too heterogeneous, relatively short treatment sessions given the time required to detect

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improvements in bone parameters and variability with imaging technologies and measured regions of interest.

Early assessment and monitoring of bone mass after SCI are essential to identify low bone mass and risk for fragility fractures. Prevention with oral bisphosphonates (Tiludronate, Clodronate and Etidronate) may slow the loss of BMD early after SCI, but there is limited evidence that treatment with oral bisphosphonates maintains bone mass late after SCI. There is a lack of definitive evidence supporting non-pharmacological interventions for either prevention or treatment of bone loss after a SCI. 9.7 Summary There is Level 1 evidence that oral Tiludronate and Clodronate prevent a decrease in BMD of the hip and knee region with no adverse effects on bone mineralization in men with paraplegia. There is Level 1 evidence that oral Etidronate prevents a decrease in BMD of the hip and knee region in people with incomplete paraplegia or tetraplegia (ASIA D impairment) who return to walking within 3 months of the SCI. There is Level 1 evidence that Pamidronate 30 mg IV or 60mg IV four times per year is not effective for the prevention of BMD loss at the hip and knee region early after SCI in men and women who have motor complete paraplegia or tetraplegia. There is Level 1 evidence that Alendronate 10 mg daily and Calcium 500mg orally 3x/day is effective for the maintenance of BMD of the wrist, hip and knee region for men with paraplegia. For NON-PHARMACOLOGICAL PREVENTION of bone loss after a SCI: There is Level 1 evidence from one RCT that short-term (6 weeks) ultrasound is not effective for treating bone loss after a SCI. There is Level 2 evidence that FES-cycling did not improve or maintain bone at the tibial midshaft in the acute phase. There is Level 4 evidence that walking and standing in the acute phase did not differ from immobilization for bone loss at the tibia. There is Level 2 evidence that electrical stimulation either increased or maintained BMD over the stimulated areas. There is Level 4 evidence that 6 months of FES cycle ergometry increased regional lower extremity BMD over areas stimulated amongst paraplegics. There is inconclusive evidence for Reciprocating Gait Orthosis (RGO), long leg braces, passive standing or self-reported physical activity as a treatment for low bone mass.

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There is a significant risk for lower extremity fragility fractures after a SCI; the risk increases with gender, type and time since injury. Early assessment and ongoing monitoring of bone health is an essential element of SCI care. There is Level 1 evidence for the prevention and treatment of bone loss using medications, however, nonpharmacological evidence for preventing bone loss and treating bone health is limited by small studies, different treatment protocols, participant groups that are too heterogeneous, relatively short treatment sessions given the time required to detect improvements in bone parameters and variability with imaging technologies and measured regions of interest.

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References Bauman WA, Spungen AM, Wang J, Pierson RN Jr, Schwartz E. Continuous loss of bone during chronic immobilization: a monozygotic twin study. Osteoporos Int 1999;10:123-7. Bauman WA, Spungen AM. Body Composition in Aging: Adverse Changes in Able-Bodied Persons and in Those with Spinal Cord Injury. Top Spinal Cord Inj Rehabil 2001;6:22-36. Bauman WA, Wecht JM, Kirshblum S, Spungen AM, Morrison N, Cirnigliaro C, et al. Effect of pamidronate administration on bone in patients with acute spinal cord injury. J Rehabil Res Dev 2005;42:305-313. Bauman WA, Zhong YG, Schwartz E. Vitamin D deficiency in veterans with chronic spinal cord injury. Metabolism 1995;44:1612-6. BeDell KK, Scremin AM, Perell KL, Kunkel CF. Effects of functional electrical stimulation-induced lower extremity cycling on bone density of spinal cord-injured patients. Am J Phys Med Rehabil 1996;75:29-34. Belanger M, Stein RB, Wheeler GD, Gordon T, Leduc B. Electrical stimulation: can it increase muscle strength and reverse osteopenia in spinal cord injured individuals? Arch Phys Med Rehabil 2000;8:1090-1098. Bloomfield SA, Mysiw WJ, Jackson RD. Bone mass and endocrine adaptations to training in spinal cord injured individuals. Bone 1996;19:61-68. Brown JP, Josse RG; Scientific Advisory Council of the Osteoporosis Society of Canada. 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMAJ 2002;12;167(10 Suppl):S1-34. Chappard D, Minaire P, Privat C, Berard E, Mendoza-Sarmiento J, Tournebise H, et al. Effects of tiludronate on bone loss in paraplegic patients. J Bone Miner Res 1995;10:112-118. Chen B, Mechanick JI, Nierman DM, Stein A. Combined calcitriol-pamidronate therapy for bone hyperresorption in spinal cord injury. J Spinal Cord Med 2001;24:235-240. Chen SC, Lai CH, Chan WP, Huang MH, Tsai HW, Chen JJ. Increases in bone mineral density after functional electrical stimulation cycling exercises in spinal cord injured patients. Disabil Rehabil 2005;27:1337-1341. Comarr AE, Hutchinson RH, Bors E. Extremity fractures of patients with spinal cord injuries. Am J Surg 1962;103:732-739. de Bruin ED, Frey-Rindova P, Herzog RE, Dietz V, Dambacher MA, Stussi E. Changes of tibia bone properties after spinal cord injury: effects of early intervention. Arch Phys Med Rehabil 1999;80:214-220. Demirel G, Yilmaz H, Paker N, Onel S. Osteoporosis after spinal cord injury. Spinal Cord 1998;36:822-5. Eser P, de Bruin ED, Telley I, Lechner HE, Knecht H, Stussi E. Effect of electrical stimulationinduced cycling on bone mineral density in spinal cord-injured patients. Eur J Clin Invest 2003;33:412-419. Freehafer AA. Limb fractures in patients with spinal cord injury. Arch Phys Med Rehabil 1995;76:823-827. Frey-Rindova P, de Bruin ED, Stussi E, Dambacher MA, Dietz V. Bone mineral density in upper and lower extremities during 12 months after spinal cord injury measured by peripheral quantitative computed tomography. Spinal Cord 2000;38:26-32. Frisbie JH. Fractures after myelopathy: the risk quantified. J Spinal Cord Med 1997;20:66-69. Garland DE, Adkins RH, Kushwaha V, Stewart C. Risk factors for osteoporosis at the knee in the spinal cord injury population. J Spinal Cord Med 2004;27:202-206. Garland DE, Adkins RH, Stewart CA, Ashford R, Vigil D. Regional Osteoporosis in Women Who Have a Complete Spinal Cord Injury. J Bone Joint Surg Am 2001; 83:1195-1200. Garland DE, Stewart CA, Adkins RH, Hu SS, Rosen C, Liotta FJ, Weinstein DA. Osteoporosis after spinal cord injury. J Orthop Res 1992;10:371-8. 9-16

Giangregorio LM, Hicks AL, Webber CE, Phillips SM, Craven BC, Bugaresti JM, et al. Body weight supported treadmill training in acute spinal cord injury: impact on muscle and bone. Spinal Cord 2005;43:649-657. Goemaere S, Van Laere M, De Neve P, Kaufman JM. Bone mineral status in paraplegic patients who do or do not perform standing. Osteoporos Int 1994;4:138-143. Griffiths HJ, Bushueff B, Zimmerman RE. Investigation of the loss of bone mineral in patients with spinal cord injury. Paraplegia 1976;14:207-12. Hancock DA, Reed GW, Atkinson PJ. Bone and soft tissue changes in paraplegic patients. Paraplegia 1979;17:267-71. Hangartner TN, Rodgers MM, Glaser RM, Barre PS. Tibial bone density loss in spinal cord injured patients: effects of FES exercise. J Rehabil Res Dev 1994;31:50-61. Jacobs PL, Nash MS. Exercise recommendations for individuals with spinal cord injury. Sports Med 2004;34:727-51. Jones LM, Legge M, Goulding A. Intensive exercise may preserve bone mass of the upper limbs in spinal cord injured males but does not retard demineralization of the lower body. Spinal Cord 2002;40:230-235. Kaplan PE, Roden W, Gilbert E, Richards L, Goldschmidt JW. Reduction of hypercalciuria in tetraplegia after weight-bearing and strengthening exercises. Paraplegia 1981;19:289-293. Kunkel CF, Scremin AM, Eisenberg B, Garcia JF, Roberts S, Martinez S. Effect of "standing" on spasticity, contracture, and osteoporosis in paralyzed males. Arch Phys Med Rehabil 1993;74:73-78. Lazo MG, Shirazi P, Sam M, Giobbie-Hurder A, Blacconiere MJ, Muppidi M. Osteoporosis and risk of fracture in men with spinal cord injury. Spinal Cord 2001;39:208-214. Leeds EM, Klose J, Ganz W, Serafini A, Green BA. Bone mineral density after bicycle ergometry training. Archives of Physical Medicine and Rehabilitation 1990;71:207-9. McKinley WO, Jackson AB, Cardenas DD, DeVivo MJ. Long-term medical complications after traumatic spinal cord injury: a regional model systems analysis. Arch Phys Med Rehabil 1999;80:1402-1410. Minaire P, Berard E, Meunier PJ, Edouard C, Goedert G, Pilonchery G. Effects of disodium dichloromethylene diphosphonate on bone loss in paraplegic patients. J Clin Invest 1981;68:1086-1092. Minaire P, Depassio J, Berard E, Meunier PJ, Edouard C, Pilonchery G, et al. Effects of clodronate on immobilization bone loss. Bone 1987;8 Suppl 1:S63-8. Mohr T, Podenphant J, Biering-Sorensen F, Galbo H, Thamsborg G, Kjaer M. Increased bone mineral density after prolonged electrically induced cycle training of paralyzed limbs in spinal cord injured man. Calcif Tissue Int 1997;61:22-25. Moran de Brito CM, Battistella LR, Saito ET, Sakamoto H. Effect of alendronate on bone mineral density in spinal cord injury patients: a pilot study. Spinal Cord 2005;43:341-348. Nance PW, Schryvers O, Leslie W, Ludwig S, Krahn J, Uebelhart D. Intravenous pamidronate attenuates bone density loss after acute spinal cord injury. Arch Phys Med Rehabil 1999;80:243-251. Needham-Shropshire BM, Broton JG, Klose KJ, Lebwohl N, Guest RS, Jacobs PL. Evaluation of a training program for persons with SCI paraplegia using the Parastep 1 ambulation system: part 3. Lack of effect on bone mineral density. Arch Phys Med Rehabil 1997;78:799-803. Nelson A, Ahmed S, Harrow J, Fitzgerald S, Sanchez-Anguiano A, Gavin-Dreschnack D. Fallrelated fractures in persons with spinal cord impairment: a descriptive analysis. SCI Nurs 2003;20:30-37. Ogilvie C, Bowker P, Rowley DI. The physiological benefits of paraplegic orthotically aided walking. Paraplegia 1993;31:111-115. Pacy PJ, Hesp R, Halliday DA, Katz D, Cameron G, Reeve J. Muscle and bone in paraplegic patients, and the effect of functional electrical stimulation. Clin Sci (Lond) 1988;75:481-487. 9-17

Pearson EG, Nance PW, Leslie WD, Ludwig S. Cyclical etidronate: its effect on bone density in patients with acute spinal cord injury. Arch Phys Med Rehabil 1997;78:269-272. Ragnarsson KT, Sell GH. Lower extremity fractures after spinal cord injury: a retrospective study. Arch Phys Med Rehabil 1981;62:418-423. Rodgers MM, Glaser RM, Figoni SF, Hooker SP, Ezenwa BN, Collins SR, et al. Musculoskeletal responses of spinal cord injured individuals to functional stimulation-induced knee extension exercise training. J Rehabil Res Dev 1991;28:19-26. Thoumie P, Le Claire G, Beillot J, Dassonville J, Chevalier T, Perrouin-Verbe B, et al. Restoration of functional gait in paraplegic patients with the RGO-II hybrid orthosis. A multicenter controlled study. II: Physiological evaluation. Paraplegia 1995;33:654-659. Vestergaard P, Krogh K, Rejnmark L, Mosekilde L. Fracture rates and risk factors for fractures in patients with spinal cord injury. Spinal Cord 1998;36:790-796. Warden SJ, Bennell KL, Matthews B, Brown DJ, McMeeken JM, Wark JD. Efficacy of lowintensity pulsed ultrasound in the prevention of osteoporosis following spinal cord injury. Bone 2001;29:431-436. Zehnder Y, Luthi M, Michel D, Knecht H, Perrelet R, Neto I, et al. Long-term changes in bone metabolism, bone mineral density, quantitative ultrasound parameters, and fracture incidence after spinal cord injury: a cross-sectional observational study in 100 paraplegic men. Osteoporos Int 2004;15:180-189. Zehnder Y, Risi S, Michel D, Knecht H, Perrelet R, Kraenzlin M, et al. Prevention of bone loss in paraplegics over 2 years with alendronate. J Bone Miner Res 2004;19:1067-1074.

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CHAPTER TEN
Depression Following Spinal Cord Injury
Steven Orenczuk, PsyD Jim Slivinski, MA Robert W Teasell, MD FRCPC

Key Points Depression is a common consequence of SCI. Despite methodological challenges, our understanding of post-SCI depression, treatment, and associated psychological conditions is growing. Cognitive behavioural interventions provided in a group setting appear helpful in reducing post-SCI depression and related difficulties. The benefits of drug treatment for post-SCI depression are largely extrapolated from studies in non-SCI populations. Programs to encourage regular exercise, reduce stress, and improve or maintain health appear to have benefits in reducing reports of depressive symptoms in persons with SCI.

Table of Contents
10.1 Introduction ..................................................................................................................10-1 10.2 Prevalence of Depression Post-SCI ...........................................................................10-2 10.3 Interventions for Treatment of Depression following SCI........................................10-4 10.3.1 Cognitive Behavioural Therapy...................................................................................10-4 10.4 Pharmacotherapy for Treatment of Depression in SCI ..........................................10-10 10.5 Other Treatments for Depression following SCI .....................................................10-11 10.6 Summary.....................................................................................................................10-16 References............................................................................................................................10-17

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Orenczuk S, Slivinski J, Teasell RW (2006). Depression Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 10.1-10.19. www.icord.org/scire

Depression Following Spinal Cord Injury

10.1 Introduction Practitioners providing clinical rehabilitation services to individuals who have suffered catastrophic injuries and illnesses focus much interest on the issue of psychological adjustment. This chapter summarizes evidence garnered from SCI research that investigates the treatment of post-SCI depression and other psychosocial factors potentially affecting successful recovery. Though as yet quite limited, these findings can assist in developing a foundation for evidencebased practice, and hopefully lead to improved and more consistent care. It should be emphasized however that evidence-based practice constitutes more than the routine use of treatments supported by the best research evidence available. Such practice also necessitates that the practitioner employ his or her clinical judgment in determining the applicability of such research conclusions to the treatment provided each patient (APA 2005). Concerns regarding depression are commonly reported by SCI survivors, staff, or their families. Indeed, Elliott and Umlauf (1995) report that depression is the most frequently researched psychological issue in individuals who have sustained a SCI. Given the innumerable modifications necessitated following a SCI, an individual will likely encounter repeated strains upon their available coping resources. The occurrence of depression is not a surprising outcome of such challenges (Kemp et al. 2004) and some early investigators have described it as an inevitable outcome (e.g. Hohmann 1975). Of added concern, rates of suicide average approximately 3 to 5 times that reported in the general population (e.g. DeVivo et al. 1989; Charlifue & Gerhart 1991; Hartkopp et al. 1998) and stand in contrast to the reductions achieved in other preventable causes of death following SCI (e.g. septicemia, respiratory illness, diseases of the urinary system) (Soden et al. 2000). The term depressed mood refers to a state of dysphoria that occurs routinely and is a normal process (Elliott & Frank 1996). In contrast, a diagnosable depressive syndrome refers to a constellation of observable affective, cognitive and neurovegetative symptoms of sufficient frequency and severity to negatively impact upon an individuals functioning. The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR 2000) is a frequently cited classification system for establishing diagnoses of various depressive and other mental disorders. For example, a diagnosis of Major Depressive Disorder in an adult requires at least a two-week period of five or more symptoms, with at least one either depressed mood or a loss of interest or pleasure in almost all activities. Further, symptoms may include weight changes, changes in sleep, psychomotor agitation or retardation, fatigue, feelings of worthlessness or guilt, indecisiveness or decreased concentration, and/or thoughts of death or suicide. Symptoms together must result in an impairment in functioning (social, occupational or other) and are not due to the direct physiological effects of a substance or medical condition. Identifying depression is often more difficult than might be anticipated. Even rehabilitation staff have been shown to overestimate it in inpatient populations (Cushman & Dijkers 1990) while underestimating patients reported coping ability and mental health (Siosteen et al. 2005). Similarly, the life satisfaction and well-being of persons in the community with complete tetraplegic injuries (including those who required ventilator support) was also shown to be underestimated by health care professionals (Bach & Tilton 1994).

10-1

Various methodological issues have served to constrain the study of depression in the SCI population (Elliott & Frank 1996). The use of ambiguous definitions and the unclear or inconsistent use of diagnostic criteria are two of many such challenges. Others issues include a lack of theoretical models, selection biases, and limited longitudinal studies. How best should the occurrence of depression be viewed in the process of adjustment to SCI? Anecdotal models of adjustment have incorporated the clinical lore that depression was to be universally anticipated soon after injury (Elliott & Kennedy 2004), and demonstrating the individuals rational acceptance of the permanence of the injury and associated losses (Frank et al. 1985). Taken further, those individuals who do not evidence depression were often considered to be in denial and potentially vulnerable to a more precarious adjustment (e.g. Siller 1969). Accordingly, it had been also proposed that depression be induced to encourage appropriate grieving (Nemiah 1957). Indeed both the universality and the benefits of depression in the adjustment process have since come into question by investigative findings (e.g. Howell et al. 1981; Judd et al. 1986). Given the many negative outcomes associated with depression post injury (e.g. longer hospitalization, decreased longevity, increased rates of suicide, reduced health, daily functioning, limited community participation) it is likely best viewed as a secondary complication or sequelae rather than an adaptive process facilitating overall emotional adjustment (Consortium for Spinal Cord Medicine 1998). Contrary to expectations, Kemp et al. (2004) note that depression is not simply a necessary consequence of sustaining a spinal cord injury not all who sustain a spinal cord injury become depressed. Tirch et al. (1999) used several self-report depression scales in a study of 11 pairs of monozygotic twins where one of the pair had sustained a SCI. The SCI and non-SCI cotwins did not differ significantly in their self-reports, lending additional support to the view that SCI does not inevitably lead to increased depression. Further, there is little relationship between depression and the level of SCI or the completeness of the lesion (Kemp et al. 2004). As an example, Hall et al. (1999) sampled 82 individuals with C1-4 quadriplegia between 14 and 24 years post injury, and these individuals reported their self-esteem and quality of life to be high with 95% feeling they were glad to be alive. In reality, it appears more likely that depression post-SCI is a function of difficulties coping with the multiple environmental, social and health related problems that follow. If depression is not inevitable following SCI, then it is noteworthy that depression is related to modifiable factors that play a role in its development and maintenance (Kemp et al. 2004). Elliott and Shewchuk (2000) note that an individuals primary concerns soon after injury (i.e. restorative and curative therapies) tend to change over time, with those with SCI becoming increasingly interested in addressing social and interpersonal barriers as well as age-related health issues. In a summary of the extant adjustment literature, Elliott and Rivera (2002) review a model determining psychological well being and physical health post-SCI. The components include demographics, injury characteristics, preinjury behaviours and psychopathology, personality factors, social/environmental factors and styles of appraisals. The authors highlight how the consequences of physical disability exist within a larger context and that changes in public and health policies can dramatically impact post-injury quality of life. 10.2 Prevalence of Depression Post-SCI Estimates of the prevalence of depression are affected by the nature of the measures used, how depression is defined, and when symptoms are assessed post injury. The common research practice of employing self-report measures is both convenient and cost-effective.

10-2

However, the resulting prevalence rates may reflect subjective anxiety and overall distress rather than symptoms specific to depression, per se. In clinical practice, self-report measures may serve to alert the clinician to the need for additional evaluation. Depression rates post-SCI range from 16-30%, with up to 25% of men and 47% of women (Consortium for SCI Practice Guideline 1998). Krause et al. (2000) suggest a rate of depression of 42% overall with a 21% probable rate of major depression indicative of a 4-fold increase of depressive disorders among individuals with SCI compared with samples of nondisabled individuals. In an Italian sample averaging 6 years post-SCI, Scivoletto et al. (1997) found 16% reported significant symptoms of depression and 13% of anxiety. In a 6-year follow-up study of 233 Albertans with SCI, 28.9% were treated for depression following their traumatic spinal cord injuries, with approximately 59% of these individuals beginning treatment during their initial hospitalization (both acute and rehabilitation admissions). An additional 10% of people were treated during the remainder of the first year. This exceeded depression treatment rates reported in able-bodied controls (approximately 11%) (Dryden et al. 2004), with those at highest risk reporting permanent neurological deficit, a preinjury history of depression, or substance abuse (Dryden et al. 2005). Kennedy and Rogers (2000) reported that anxiety, depression and hopelessness gradually increased beginning at week 30 post injury and continued until discharge from rehabilitation (week 48). At that point 60% of SCI clients scored above a clinical cut-off for depression (i.e. Beck Depression Inventory). It has been questioned whether, despite its reported prevalence, efforts to improve the detection and treatment of depression in individuals with SCI have improved (Bombardier et al. 2004). In an editorial comment, Faber (2005) expressed concern that given possible underestimates, about half of all persons hospitalized for traumatic SCI may benefit from treatment for depression. Similarly, while a substantial percentage of their SCI clinic sample reported symptoms suggestive of major depression, Kemp and Krause (1999) found that none were receiving treatment (psychotherapy or medications). Bombardier et al. (2004) surveyed over 800 SCI survivors at one-year post injury. Using the Patient Health Questionnaire 9, a self-report screening measure, 11.4% met criteria for DSMIV major depressive disorder. Interestingly, the results supported an inclusive approach to diagnose MDD, one that suggests somatic symptoms such as appetite changes, sleep disturbance, and poor energy should be included in identifying MDD in those with SCI. As noted, concerns regarding depression post-SCI are frequently cited in the literature. Data obtained in earlier studies has also suggested that in newly injured persons who met a criteria for major and minor depression, many may remit within 3 months of onset (Kishi et al. 1994) and that the frequency of reported problems decreases over the first year (Richards 1986). Conclusion While not universal, for many persons with spinal cord injury, depression can be a complication that poses a significant impediment to their functioning and adaptation. Identifying depression can be difficult, but is most likely to develop during the initial year post injury. Self-report measures should be viewed as screening tools to alert the clinician to arrange a more thorough evaluation. Depression is a common consequence of SCI.

10-3

10.3 Interventions for Treatment of Depression following SCI The American Psychological Association (APA 2005) states that evidence-based practice involves the integration of the best of existing research with clinical expertise and the reality of the patients needs and wishes. However both the exigencies of the SCI population and practical concerns limit the nature of SCI research topics and designs. Specific to the issue of depression, Elliott and Kennedy (2004) have questioned whether the current glaring lack of intervention data reflects a lack of interest by consumers, researchers and funding agencies to examine the effects of various interventions for depression in those with SCI. Difficulties inherent in conducting intervention studies are numerous (King & Kennedy, 1999). The SCI population can be varied. Most sites do not have access to a large number of patients, thus obtaining treatment and appropriate control groups becomes difficult and would likely require the participation of multiple sites. Also, ethical concerns over providing the best possible care to all SCI patients are obvious, so that withholding aspects of treatment in order to establish control conditions is not acceptable. Current research strategies frequently use selfreport screening measures (e.g. Beck Depression Inventory, Zung Depression Inventory, Patient Health Questionnaire-9, Center for Epidemiological Studies Depression Scale), and while they offer many benefits (e.g. low cost, quick, easy to complete), they require further evaluation to support a diagnosis of depression. Typical SCI interventions to encourage adjustment are often multi-faceted, thereby posing difficulties in identifying which combination of components can offer optimal care for any particular patient. Further, psychosocial interventions cannot be independent of other aspects of care (e.g. medical, rehabilitation). In addition, many pre-morbid psychological and historical influences are very difficult to determine. As many SCI studies lack one or several aspects of gold standard research, the generalizability of the findings may be limited. Despite these challenges, researchers have made invaluable clinical contributions using smaller groups, non-randomized control groups, or controls chosen from historical data. In summarizing the limited research currently available however, Elliott and Kennedy (2004) suggest we have many untested assumptions regarding the available treatments for depression among persons with SCI. Conclusion Despite methodological challenges, our understanding of post-SCI depression, treatment, and associated psychological conditions is growing.

10.3.1 Cognitive Behavioural Therapy In the SCI population, the application of cognitive behavioural therapy (CBT) approaches to aid in the management of anxiety and depression is described as a prudent choice given its demonstrated effectiveness in a wide range of disorders (Craig et al. 1997). CBT strategies can include addressing irrational or negative thoughts, increasing opportunities for participating in rewarding activities, and instruction in relaxation, among others. Within this context, issues of assertiveness, social skills and discussions of sexuality have also at times been included to address the unique concerns of SCI individuals. Employing a group setting to provide CBT can also be a cost effective opportunity for peer support, practice of social skills and the opportunity for gaining additional viewpoints. Several authors have described the effects of group CBT

10-4

interventions for individuals following SCI to reduce psychological distress and/or provide immunization against future difficulties. Table 10.1 CBT Group Interventions
Author Year; Country Score Research Design Total Sample Size Methods Population: 27 treatment gr, 31 controls. Intervention: 10 week program. Small groups (4-5 per group), for 1.5 hours per week. Major aim was to provide cognitive and behavioural skills to cope with the psychological and social difficulties encountered upon entering the community. Cognitive behavioural therapy included muscle relaxation, visualization techniques, self-hypnosis and cognitive restructuring, social skills and assertiveness training, and sexuality sessions. Outcome Measures: State-Trait Anxiety Scale (STAIC); Beck Depression Inventory (BDI) scale. 1. Outcome No significant differences were noted across time for anxiety but there were significant differences noted for depression overall, (p<0.05). Both the treatment and the control groups appeared to be less depressed 1 and 2 yrs after injury. For individuals who scored high on the depression scale before therapy, (9 from each group) there were significant differences after treatment. (p<.01) with the control group reporting higher levels of depressive mood. Depressive mood scores showed significant differences across time (p<0.01) with scores 1 and 2 years post injury were significantly lower than pretreatment scores (p<0.01). Those that scored high on the anxiety scale (n=19 in total), there were significant differences in scores overall across time (p<0.1) with anxiety scores decreasing over time.

2. 3.

Craig et al. 1998a; Australia Downs & Black score=21 Prospective Controlled Trial (Continuation of Craig et al. 1997) Initial N=69; Final N=58

4.

5.

King & Kennedy 1999; UK Downs & Black score=20 Pre-post Initial N=38; Final N=38

Population: Ages:16 65; new injured Intervention: Consisted of 60-75 minute session run twice a week in small groups of 6 to 9 people. Sessions included a mixture of didactic presentations, practical exercises and time allocated for open group discussions. Following components made up the program: appraisal training, cognitive behavioural coping skills training, and strategies for choosing an adaptive match between appraisal and coping skills, and obtaining and maintaining social support. Outcome Measures: Functional Independence Measure, Social Support Questionnaire, Beck Depression Inventory, State Anxiety Inventory, COPE (for coping).

Kennedy et al. 2003; UK Downs & Black score=19 Pre-post Initial N=85; Final N=85

Population: Ages 16-65 years, newly injured traumatic SCI. Intervention: consisted of 7, 60-75 minutes sessions that ran twice a week in small groups of 6-9 participants. Session topics were: normalizing stress, appraisal

Pre-intervention comparisons of groups: 1. On the coping scale two items (religion and humor) showed significant differences, Religion (intervention group mean score was higher, p<0.05). 2. Humor (control group mean higher, p<0.05). There were no preintervention differences between the groups on range of injury, social support, FIM scores, coping, depression or anxiety. Post-intervention comparison of groups: 1. Depression and Anxiety: Across time there were significant decrease in the depression scores (p<0.05) but not for anxiety (p=ns). 2. Coping: No significant differences between the groups or across time. Pre-intervention comparisons of groups: 1. Intervention group was older more likely to have a complete injury and to have been injured longer than the control group (p<0.01).

10-5

Author Year; Country Score Research Design Total Sample Size

Methods skills, problem solving, examination of thoughts feeling and behavior, awareness of negative assumptions, and choosing appropriate ways both to cope and to increase social supports. Outcome Measures: State Anxiety Inventory, Beck Depression Inventory, Coping Strategies Scale, Self Perception Scale, and Functional Independence Measure. Measures were taken before and immediately after the intervention, and at a 6wk follow-up with the intervention group, and every 6 weeks with the historic control group. 2.

Outcome Intervention group tended to use active and religious coping strategies (p<0.05). 3. Intervention group tended to use drugs/alcohol less frequently (adjusted for unequal variance p<0.05). Post-intervention comparison of groups: 1. Overall the intervention was successful in decreasing both depression and anxiety. 2. Mood: depression scores decreased for the intervention group following the intervention (p=0.001). 3. Anxiety: decreased for the intervention group following the intervention (p=0.001). 4. Coping: alcohol use was significantly lower for the intervention group, (p=0.003). 5. Self perception scale: intervention group only-ideal self scores had significantly greater scores than either how they would see themselves without injury (p<0.05) or as I am on all items (p<0.001). Percentages are reported for each area measured. 1. Re-admission: More control were readmitted following discharge (X=3.93, P<0.05). 2. Drug usage: Controls were found to have higher self-reported drug usage than the treatment group (cases) (X=4.12, P<0.05). 3. Relationships and Social discrimination: No significant differences were noted between the two groups in relation to the types of relationship each person developed. 4. Self-reports of adjustment: Treatment groups said they had a higher number of persons who felt they had adjusted well compared to the controls. (X=12.0, P<0.01). 1. No pre-treatment differences between the treatment and the control groups on LCB (t=0.686). 2. No significant differences were found between groups overall for locus of control as a result of treatment (F1.67 = 0.928). 3. No significant differences occurred across time for LCB (F3.201 = 2.07). 4. No significant interactions present between group and time (F3.201 = 0.199). 5. A repeated measure MANOVA was

Craig et al. 1999; Australia Downs & Black score=18 Case Control (Continuation of Craig et al. 1997) Initial N=58; Final N=58

Population: Gender: m=57, f=12, age: 1673yrs, SCI (new injured), 68%-71% complete injury. Intervention: 10 weeks in small groups. Each session lasted from 1.5 to 2 hours replacing normal rehab therapy. Patients underwent cognitive behaviour therapy (CBT) attempts to change behaviour and feeling associated with the problem and considered maladaptive. Main aim of the program was to provide cognitive and behavioural skills to cope with the psychological and social difficulties encountered upon entering the community (as described above). Outcome measures: Re-admissions, drug usage, relationships, social discrimination, self-reports of adjustment Population: Gender: m=57, f=12, age: 1673yrs, SCI (new injured), 68%-71% complete injury. Intervention: 10 week program. Small groups (4-5 per group), for 1.5 hours per week. Major aim was to provide cognitive and behavioural skills to cope with the psychological and social difficulties encountered upon entering the community. Cognitive behavioural therapy included muscle relaxation, visualization techniques, self-hypnosis and cognitive restructuring,

Craig et al. 1998b; Australia Downs & Black score=17 Prospective Controlled Trial (longitudinal) (Continuation of Craig et al. 1997) Initial N=69; Final N=58

10-6

Author Year; Country Score Research Design Total Sample Size

Methods social skills and assertiveness training, and sexuality sessions. Outcome Measures: Locus of Control of Behaviour Scale (LCB), and the Beck Depression Inventory (BDI) scale.

Outcome completed on participants (n=26) who scored higher than 33 on the LCB. 6. Significant differences were noted between the two groups (F1.23 = 4.94, p<0.05). 7. Across time there was a significant reduction in LCB scores across time. (F1.69 = 7.33, p<0.05). 8. Post hoc Scheffe tests indicated posttreatment scores to be lower than pretreatment scores (p<0.01). 9. A significant association was found between depressive mood and locus of control post-therapy, 1 year later and 2 years later. 10. For the control group locus of control was mildly associated with depressive mood and for the treatment groups locus of control was not significantly associated with depressive mood at anytime. 1. Significantly greater self-esteem for treatment group (t=3.18, df=67, p<0.01). Taking this into account, no significant differences between the groups were found immediately after injury or 1 year later. 2. No significant initial differences were found between the groups on anxiety F(1,67) =.47) and depression F(1,67)=.24 when comparing pre, post and 1-year scores. 3. BDI scores were significantly lower for both conditions one year after injury F (2,124) = 4.34, p=0.014. 4. Neither anxiety nor self-esteem scores improved significantly over the year. 5. Those who scored higher than 14 on the depressive mood scale were analyzed using repeated measures ANOVA. 22 persons (from both groups) were looked at. Significant differences were noted between the groups (F1, 20) =7.41, p<0.01). 6. Significant differences were also noted across time for the BDI scores. F (2, 40) =7.1, p<.01. Post hoc tests showed that the treatment group had significantly greater levels of improvement across time (p<0.05).

Craig et al. 1997; Australia Downs & Black score=15 Prospective Controlled Trial N=69

Population: Gender: m=57, f=12; age: 1673yrs; SCI (new injured); 68%-71% complete injury. Intervention: 10 week program. Small groups (4-5 per group), for 1.5 hours per week Provided cognitive and behavioural skills to cope with the psychological and social difficulties encountered upon entering the community. Cognitive behavioural therapy included muscle relaxation, visualization techniques, selfhypnosis and cognitive restructuring, social skills and assertiveness training, and sexuality sessions. Outcome Measures: State-Trait anxiety Inventory (STAIC); Beck Depression Inventory (BDI) scale, Rosenberg SelfEsteem scale.

Discussion In Australia, Craig et al. reported several investigations (1997, 1998a, 1998b, 1999) employing a 10 week CBT based group treatment format involving newly injured SCI rehabilitation inpatients with permanent injuries. They developed a CBT based treatment protocol implemented by a

10-7

psychologist and an occupational therapist. Treatment groups consisted of 4-5 individuals and sessions approximated 1.5 to 2 hours weekly. A matched control group of SCI patients received traditional rehabilitation services. Measures of depression, anxiety and self-esteem were completed when individuals were no longer immobilized in bed, after conclusion of therapy (3 months post-injury) and at one year post injury. Prior to treatment, the treatment group reported greater self-esteem than did controls, but did not differ on other outcome measures. Anxiety did not change over time. Both treatment and control groups reported fewer symptoms of depression at 12 months post injury. Taking into account pretreatment group differences in selfesteem, there was no significant improvement over time for either group. Given that neither group had high levels of depressive mood before treatment, a further analysis of those with elevated scores on depression revealed that the mean score for the treatment group (n= 10) showed improvement after treatment and further gains one year later. Controls (n = 12) who were moderately to severely depressed initially remained at these levels over the year. Patients with initially high levels of anxiety (in either condition) showed symptom decreases over the year, with a trend for those in the treatment group to improve more so than did those in the control group. CBT did not significantly impact upon self-esteem in individuals with recent onset SCI. The authors conclude that clinicians servicing SCI rehabilitation wards should evaluate individuals soon after admission to identify those with high levels of depression and/or anxiety and then recommend CBT. Further, not all persons with SCI are depressed, anxious or low in self-esteem, and may not require intervention. In a follow-up report, Craig et al. (1998a) surveyed a subset of the SCI CBT treatment group participants and SCI controls (noted above) at 24 months post injury. Group differences were not significant for measures of depression and anxiety. At 1 and 2 years post injury, subjects were less depressed but levels of anxiety were essentially unchanged. For those subjects with elevated depressive symptoms prior to treatment, levels of depression over the long term were lower for the treatment than the control group. Differences over time were also noted, with the short-term improvements in the depressive symptoms of the treatment group maintained over the two-year period. In contrast, controls did not show improvement in the short term and were only slightly improved after 1 to 2 years. Interestingly, the authors report that none of the treatment group had sought further treatment for depression between the 12 and 24-month period. Both groups became less anxious over time. The small number of subjects precluded identification of significance, but an inspection of the data revealed that the treatment group lowered their elevated anxiety scores to within the normal range at two years, while the control subjects scores averaged approximately one standard deviation above general population norms. The authors conclude that not all individuals with recent onset SCI require specialized psychological intervention. For those with elevated levels of reported depression and anxiety, these symptoms hypothetically could return to normal levels in the absence of intervention. However, such improvements could require a protracted period and result in both increased health costs and a diminished quality of life. This study further suggests the merits of screening and ongoing benefits of an intervention program. In a related study, Craig et al. (1998b) used the Locus of Control Behaviour Scale (LCB) to assess subjects perceptions that circumstances were within or beyond their control. No treatment differences were found when comparing SCI CBT group participants and controls over a two-year post injury period. Both groups averaged scores in the range suggestive of a more internal rather than external orientation. When subjects with scores suggestive of an external locus of control scores were identified (9 treatment subjects and 16 controls), the treatment group showed a significant reduction in externality over time while controls did not. The finding supports the conclusion that CBT was effective for those in the treatment group who perceived living with a SCI (and related concerns) to be out of their control. Associations of 10-8

locus of control scores and depressive mood (Beck Depression Inventory) almost all reached significance for the control group when assessed pre treatment, post treatment, and at one and two year intervals. In contrast, no associations were evident between LCB scores and reports of depressive symptoms in SCI treatment subjects, even for those who were external in their perceptions prior to participation in the CBT group. The authors speculated that CBT positively interfered in the determination of depressive mood. While there may be a substantial group at risk for developing psychological difficulties following spinal cord injury, the majority did not show problematic levels of externality and helplessness. As such, the authors concluded that CBT for all SCI survivors is costly and unnecessary. Craig et al. (1999) continued a long term (2 years post injury) assessment of persons with SCI who previously participated in a non-randomized longitudinal controlled trial of CBT during their inpatient admission to a rehabilitation ward (1991-1992). These responses were compared with those of control subjects who received only traditional rehabilitation services during their hospital stay. Treatment subjects indicated 15% fewer hospital readmissions, 25% less drug use and much more often reported a positive adjustment than did controls. Of concern, approximately 40% of controls frequently used drugs. Forty three percent of controls reported that they had not adjusted well, while only one treatment subject held a similar view. Neither group reported the occurrence of suicide over the two years. Self-reports of adjustment were negatively correlated with Beck Depression Scale scores. The groups did not differ in the frequency of relationship breakups, with the majority of those married at the time of injury remaining so at two years. Further, about half who were unmarried had formed new relationships. The findings again are seen as suggesting benefits of CBT group treatment in encouraging positive adjustment following SCI. Two studies conducted at the National Spinal Cord Injuries Centre (NSCIC) in the UK investigated group Coping Effectiveness Training (CET). CET includes CBT, didactic, and practical elements. The first (King & Kennedy 1999) was a pilot study of CET, and the second (Kennedy et al. 2003) continued the work with additional subjects and measures. Both studies used matched historic controls from the NSCIC database, although there did remain some significant pre-intervention differences between groups. Results suggest that their intervention package produced a number of positive changes, including less depression and anxiety, less use of alcohol, and more positive self-perception. Participants said that they found the sharing of views and experiences and reviews of real life scenarios to be most valuable aspects of the group. In summary, this series of studies has demonstrated the long term benefits of CBT group programming on various aspects of adjustment. Receiving CBT during the initial rehabilitation phase has been reported to reduce depressive mood, helplessness, anxiety, and is associated with fewer hospital readmissions, less drug use and greater self-reported adjustment. Conclusion A variety of logistical and ethical factors limit the study of depression in SCI samples. Attempts to treat depressive symptoms using multifaceted packages that incorporate cognitive behavioural skills appear encouraging in reducing the incidence of depression, anxiety and encourage positive adjustment post-SCI, particularly for individuals who exhibit substantial emotional distress in the acute phase of rehabilitation. The use of a group format appears to offer a cost-effective method of intervention.

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There is level 2 evidence from 6 non-RCT studies to support the use of small group CBT based treatment packages to decrease depression symptoms following SCI. (Note that 4 of these studies were based on the same groups and intervention.) Cognitive behavioural interventions provided in a group setting appear helpful in reducing post-SCI depression and related difficulties.

10.4 Pharmacotherapy for Treatment of Depression in SCI Several case series studies have reported positive results using pharmacotherapy for depression in SCI individuals (e.g. Kim et al. 1977 (amitriptyline); Fullerton et al. 1981; Judd et al. 1986 (mianserin and nomifensine); Judd et al. 1989 (tetracyclic and tricyclic)). Overall, support for pharmacological treatment of depression in individuals with SCI is largely an extrapolation from the extant literature concerning use in the general population and comparative trials of medications and cognitive behavioural interventions are sorely needed (Elliott & Kennedy 2004). Table 10.2 Combined Individual Psychotherapy and Pharmacotherapy for Treatment of Depression in SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m = 32; f = 11, Age: 20-74 yrs, time since injury: 5-37 years, 28 treated for depression, 15 acted as quasicontrols. Intervention: 6 months of individual treatment. 2 components-psychotherapy and medication were offered to all. Therapy began once a week for the first 2 months then was reduced to twice a month. All were prescribed an antidepressant based upon their needs and physicians decision. Treatment fidelity: average number of therapy session completed was 14 out of 17 (range from 6 to 17). Outcome Measures: Health and mood questionnaire (OAHMQ) Hamilton Depression rating scale Community activities checklist Life satisfaction scale (11 item Likert scale looking at satisfaction with family life, health, economics, and community safety). 1. Outcome Depression Outcomes: A decrease was observed in depression scores from 0-24wks in the treatment group (F (2,26)=51.2, p<0.001). Paired t-tests indicated a 24% decline in depression scores from 0-8wks (time 1=15.7, time 2=11.9, t(27)=6.77, p<0.001) and from 8-24wks (6.7) (t(27)=5.26, p<0.001). 8 subjects continued to score in the range for major depression. If cases with variable treatment adherence were eliminated 100% of participants treated no longer had scores in the range of major depression. Community activities: There was a significant increase in community activities from 0-24wks of treatment (F (2, 26) = 15.7, p<0.001). T-tests showed a 40% increase in activities from 0-8wks (time 1=11.1, time 2=15.5, t (27) =3.73, p<0.001). A further increase was noted between 8 and 24 weeks (time 2=15.5, time 3=22.3, t (27)=4.55, p<0.001). The correlation between the change in # of depressive symptoms and the change in the # of community activities was high (-0.81, p<0.001). Life satisfaction: While a significant overall effect was observed for life satisfaction scores (F(2,26)=14.0,

2.

3.

Kemp et al. 2004; USA Downs & Black score=20 Pre-post Initial N=43; Final N=28

4.

5. 6.

7.

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome p<0.001), significant differences in life satisfaction were noted only between 8 and 24 weeks (time 2=23.5, time 3=28.4, t(27)=5.20, p<0.001). Non-treatment group: Scores on the depression measure did not change significantly over time.

8.

Discussion Kemp et al. (2004) used a pre-post treatment design to assure access to services and avoid ethical concerns that might arise in a randomized trial. A total of 43 community living adult SCI survivors were identified as depressed using the Older Adult Health and Mood Questionnaire and confirmed by clinical interview. Citing distance problems, 15 subjects subsequently declined participation but served as a quasi-control group. The 28 remaining subjects began a combined 6-month trial of antidepressant medications and individual cognitive behavioural psychotherapy. The participants were somewhat older but did not differ from non-participants in terms of level of injury, gender, or race/ethnicity. Medications employed included SSRI and tricyclic antidepressants. Psychotherapy included education regarding the signs, symptoms and consequences of depression, cognitive restructuring and encouraging greater community involvement (average of 14 sessions). During the treatment trial, four subjects discontinued their medications, one discontinued psychotherapy and three developed medical complications. After eliminating these eight results, all of the remaining 20 subjects improved, no longer meeting criteria scores for major depression (12 appeared mildly depressed and eight appeared non-depressed). Their participation in community activities doubled over the 24 weeks, while life satisfaction showed improvement, primarily during the final 16 weeks of the program. The average depression score for non-treated subjects did not change significantly over a 24-month follow-up period and suggests that untreated depression can become a chronic disorder. Conclusion Evidence of the benefits of pharmacotherapy alone and in combination with individual psychotherapy in the treatment of depression in individuals with SCI is encouraging, although support is largely from investigations in other populations. There is level 4 evidence from a single non-RCT study indicating the effectiveness of psychotherapy combined with pharmacotherapy for treatment of depression in SCI. The benefits of drug treatment for post-SCI depression are largely extrapolated from studies in non-SCI populations.

10.5 Other Treatments for Depression following SCI Strategies to encourage health, reduce secondary complications and consequently support positive emotional adjustment following SCI have emerged as a source of increasing research interest. As examples, the following studies review the impact of access to medical care,

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wellness education, regular exercise and massage upon various measures of physical health and emotional well-being. Table 10.3 Other Treatments for Depression following SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: both, Age: 19-65yrs, Time since injury: 1-24yrs. Treatment: Experimental group participated in a progressive exercise training program twice weekly for 9 mths on alternative days 90-120 mins starting with warm up, upper extremity stretching, and 15 to 30 min of aerobic training. As the rate of perceived exertion decreased, workload was increased. Some resistance training took place. Outcome Measures: Changes in cardiovascular function, muscle strength & quality of life. 1. Outcome Quality of life components: Exercisers reported less stress, fewer depressive symptoms, and greater satisfaction with their physical functioning than the controls. (p=0.06). Exercisers reported less pain (p<0.01) and a better Q of L (p<0.05). Performance on the 3-stage arm crank protocol was different paraplegics and tetraplegics. (p<0.05). No changes in HR and BP between groups or after 9 months of training. Arm crank protocol was different between tetraplegia and paraplegia. Training induced increases occurred in all subjects in the experimental group. No significant differences in heart rate response over the 9 mths. Significant group x lesion x time interactions were found in stages 2 (F(3.48)=4.64), p=0.006 and stage 3 (F(3.48)=3.55, p=0.02), indicating the tetraplegics had the greatest decrease in heart rate. Changes in muscle strength: Experimental group showed changes in muscle strength over the 9 mth period. The control group did not show any significant changes. Interaction effect on STAI scores F(1, 18) = 14.51, p<.01. Massage group had significantly lower anxiety scores immediately after treatment on the first (t[9] = 5.05, p<.01) and the last (t[9] = 4.93, p<.01) sessions. CES-D scores obtained on first day vs. last day assessment by group. Repeated measures ANOVA showed a group by day interaction effect F(1, 18) = 5.05, p<.05). t-tests revealed greater decrease in CES-D depression scores for the massage therapy group (t[9] = 2.30, p<.05). Path A (treatment-exercise to outcome) (R2=0.19, p<0.05), and path B (exercise and perceived pain) (R2=0.28, p<0.01) and stress (R2=0.23, p<0.01) were significant. Path C (mediator-outcome) revealed that depression was predicted by stress (=0.49, p=0.02) but not by

2. 3. 4.

Hicks et al. 2003; Canada PEDro=8 RCT Initial N=43; Final N=32

5. 6.

7.

Diego et al. 2002; USA PEDro=8 RCT N=20

Population: Gender: m = 15, F= 5, Age: average 39 years, Tetraplegia, Time since injury: minimum 1 year. Treatment/Controls: One group received a 40 min massage 2 x per week for 5 weeks by a massage therapist while the other was taught an exercise routine that they performed 2 x per week for 5 wks on their own. Outcome Measures: State Anxiety Inventory (STAI), Center for Epidemiological Studies Depression Scale (CES-D), Manual muscle test, Modified Barthel Index, range of motion. Population: Gender m = 5, f = 16; Age: 19-65 years, Years post injury 1-24yrs. Treatment/Controls: A nine-month program of twice-weekly small group exercise sessions of 60-90 minutes duration incorporating stretching, arm ergometry, and resistance exercise under the supervision of volunteers at a university

1. 2.

3.

4.

1.

Latimer et al. 2004; Canada PEDro=6 RCT Initial N=34; Final N=21

2.

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Author Year; Country Score Research Design Total Sample Size

Methods health promotion centre. Control subjects were instructed to continue with their normal activities and were requested to refrain from starting a regular exercise routine during the length of the study. Monthly health information sessions were discontinued due to poor attendance. Outcome Measures: Pain perception (two items from the Short Form 36-Item Health Survey - SF-36 scale); Perceived stress scale (14 items-Likert scale), CES-D scale (score out of 60). Population: Gender: m = 23; f = 11; complete/incomplete; Age: average 38.6 yrs; tiem since injury: average 10.4 yrs Intervention: Those in the exercise group participated in 5 min of stretching, 15 to 30 min of aerobic arm ergometry exercise and 45 to 60 min of resistance exercise. These subjects trained twice weekly in small groups. Participants in the nonexercise group were asked to continue their usual activities but they were asked not to exercise regularly. Outcome Measures: Pain perception (two items from the Short Form 36-Item Health Survey - SF-36 scale); Symptom self efficacy and perceived control (2 core items from the Beliefs Scale a modified version of the Arthritis Beliefs Scale); Perceived Stress Scale (14 items-Likert scale).

Outcome perceived pain (=0.29, p=2.25).

1.

2.

Ginis et al. 2003; Canada PEDro=6 RCT Initial N=34; Final N=34

3.

4.

Zemper et al. 2003; USA PEDro=4 RCT Initial N=67; Final N=43

Population: 43 SCI, M=30 F = 13, mean age 47 range 22-80, 28% single, 23% married, 8% divorced, average 14 years post injury, range 1-49 years, 42% paraplegia, 39% tetraplegia, 3% ambulatory. Participants recruited from an outpatient clinic or Center for Independent living. Intervention group was more educated and had fewer retirees despite random assignment. Intervention: A series of six 4 hr workshop sessions held over a 3 month period, promoting health and wellness. Sessions included lifestyle management, physical activity, nutrition, preventing secondary conditions, individual coaching

1.

2.

Changes in potential mediators: Stress and Pain--ANCOVA showed that after 3 mths of training the exp group showed less stress than controls (F(1,27)=6.98,p=0.01) and less pain (F(1,27)=4.99, p=0.03). Changes in QofL, Physical self concept and depression: After 3 months differences appeared between the 2 groups for QofL (F(1,27)=8.47, p=0.007); satisfaction with physical function (F(1,27)=20.17, p<0.01); satisfaction with physical appearance (F(1,27)=8.47, p=0.007); depression (F(1,27)=6.16, p=0.02). Stress and pain (mediators of QofL): Once baseline pain and stress values were controlled for, the 3 month scores for pain was (R2=.15, p<0.01) and for stress was (R2=0.12,p<0.01). These were significant predictors of baseline adjusted 3 month QofL. Stress and pain as mediators of depression: Changes in pain but not stress explained significant variance in baseline adjusted depression scores (R2=0.19 & 0.04). Adjusted pain scores showed variance in the adjusted 3 month depression scores (R2=0.19, <0.01). The intervention group showed statistically significant improvement after intervention in several areas as compared to the control group: Abilities for Health Practices (SAHP): (p<0.05). Health Promoting Lifestyle (HPLP-II): (p<0.001). Nutrition (HPLPII subscale): improvement in nutritional awareness and behaviour (p <0.05) Stress (HPLP-II subscale): Increased use of stress management techniques and decreases in perceived stress (p =.001). Secondary Conditions (SCS): fewer and less serious secondary conditions (p<0.001) Depression was less though

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Author Year; Country Score Research Design Total Sample Size

Methods sessions, follow-up phone calls during the 4 months following the workshops. Controls participated in pre/post assessment but received no intervention Outcome Measures: Health Promoting Lifestyle Profile II, Secondary Conditions Scale, Self-rated Abilities for Health Practices scale (SAHP), Perceived Stress Scale, Physical activities with disabilities (PADS), Arm crank ergometer testing, neurologic exam, Body Mass Index (BMI). Population: Gender: mixed group-with more males, time since injury: mean 18.44yrs. Intervention: Follow-up after initial rehabilitation was completed addressing the secondary conditions post-SCI as well as the primary effects of their spinal cord injury. The focus is wellness, health promotion, and illness prevention through a continuum of coordinated care. Outcome Measures: The Secondary Surveillance Instrument (SCSI) and the Check Your Health Questionnaire (CHY) (rating the absence of depression.

Outcome did not reach significance. Physical Activity (self-reported on various scales of the HPLP-II): Increased reported physical activity and improved physical fitness (p = 0.001). However there was no improvement in either measured Physical Activity (PADS) or physical fitness measures. An overall difference between the two groups was found (F3,343 = 6.211; p=0.0004). Medical Follow-up group reported a significantly higher subjective rating than did the No-F/U group on 3 variables: Health (p=0.0068), Independence (p=0.005), Absence of depression (p<0.0001). (Fishers protected least significant diff. test). A MANOVA showed a main effect on education on health, independence and absence of depression (F15,900 =2.063, p=0.0098). Further analysis showed that as education increased subjects reported greater health, and independence and lower depression.

3.

4.

1. 2.

Dunn et al. 2000; USA Downs & Black score=17 Non-RCT Initial N=371; Final N=371

3.

Discussion Dunn et al. (2000) reported that veterans approaching 20 years post-SCI with access to medical follow-up through a specialty comprehensive outpatient program reported better health, independence, and less depression than a demographically similar (civilian) group without access to follow-up care. Neither group reported depression with sufficient frequency to earn it a top ten ranking from a list of 40 possible complications. However, those without access to medical follow-up who did endorse depression considered it of sufficient intensity to rank it among the ten most severe problems. While the types of secondary complications were similar, these were less frequent and less severe in those receiving health care. Noting a variety of methodological concerns that limit conclusions and generalizability, the authors reported that their findings were consistent with those in other studies (involving SCI and other patient groups). Zemper et al. (2003) examined a holistic wellness program for SCI patients. The intervention in this RCT study involved six group workshop sessions focused upon lifestyle management (including sexual health and stress management), physical activity, nutrition, and preventing secondary complications. It also included individual coaching sessions and follow-up phone calls. Assessments were completed at three times: prior to the series, two weeks following completion and four months later. Results of this study pointed to improvements in awareness and behavior in areas of health practices, nutrition, and stress. Also secondary conditions were fewer and less serious. Reports of depression intensity decreased but did not reach

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significance. Self-reports indicated improvements in physical activity, while more objective tests showed no improvement in physical fitness. In a series of Canadian studies, Ginis et al. (2003), Hicks et al. (2003) and Latimer et al. (2004) reported RCT investigations of sedentary community dwelling SCI adult volunteers who participated in 3, and later 9 month trials of twice weekly, 60-90 minute sessions of stretching, aerobic arm ergometry and resistance exercises or a wait control condition who were asked to continue usual activities and refrain from beginning an exercise program. Among other findings, Exercisers reported less stress, fewer depressive symptoms and greater satisfaction with physical functioning than did controls. While the average frequency of depressive symptoms in the intervention group did not vary substantively over the 9 months (and remained below clinically significant levels), depressive symptoms in the control group increased and the average exceeded levels considered at risk for clinical depression. The authors suggested the benefits of exercise as offering a prophylactic or stabilizing effect on pain perhaps reducing the propensity for flare-ups, and the potential benefits of targeting sources of recurrent pain (i.e. shoulder pain). Consistent with the Chronic Pain Process Model, a series of regression analyses the nine-month data revealed that changes in perceived pain mediated changes in stress, and the change in stress mediated a change in reported depression. It was recommended that clinicians prescribe exercise as a therapeutic modality for improving and maintaining well-being among people with SCI. With a university clinic group of 20 outpatients with quadriplegic injuries, Diego et al. (2002) compared the effects of a 5-week massage therapy program to those of an independently performed exercise routine conducted over a similar period. Subjects were stratified according to range of motion and then assigned to either of the two treatment groups. While both groups averaged pretreatment depression scores approaching the clinically depressed range, only the massage therapy group showed a decrease in reported post treatment depression symptoms. The massage therapy group also reported lower anxiety immediately after treatment on the first and last days of the protocol. The authors suggested that the significant gains in upper limb muscle strength and wrist range of motion demonstrated by the massage therapy group may have contributed to their reported reduction in subjective distress. Conclusion Access to medical follow-up for individuals with SCI can lead to reports of better health, independence, less depression and fewer secondary complications. Wellness education can assist in encouraging improved health practices and reducing the frequency and seriousness of secondary conditions, including reported depression. Regular physical exercise may contribute to a reduction of pain, stress, and depression as well as potentially offering a prophylactic effect on sources of recurrent pain and in preventing a decline in quality of life following SCI. Massage may aid in decreasing depression and anxiety in SCI individuals, with gains in physical strength potentially contributing to a reported decrease in distress. There is level 2 evidence from 1 RCT and 1 non-RCT that a wellness and health promotion program can decrease depression symptoms. There is level 1 evidence from 3 RCTs that exercise based programs can contribute to reduced depression symptoms. There is level 1 evidence that massage therapy can reduce depression symptoms. 10-15

Programs to encourage regular exercise, reduce stress, and improve or maintain health appear to have benefits in reducing reports of depressive symptoms in persons with SCI.

10.6 Summary This chapter has summarized research highlighting several promising approaches to the management of post-SCI depression. The research has also provided some evidence for these approaches being effective for related therapeutic targets such as anxiety and self-esteem. When leavened with clinical judgment, this research offers preliminary empirical support to guide the practitioner in employing evidenced-based therapeutic strategies. Future investigations, particularly those employing more stringent research designs, will continue to expand the options and confidence of clinical efforts to assist those individuals who have sustained spinal cord injuries. The reader is encouraged to also consider the following topic reviews of depression and SCI (Consortium for Spinal Cord Medicine 1998; Elliott & Frank 1996; Elliott & Kennedy 2004) and also, more generally, a recent state of the science review of SCI rehabilitation (Sipski & Richards 2006). There is level 2 evidence from 6 non-RCT studies to support the use of small group CBT based treatment packages to decrease depression symptoms following SCI. There is level 4 evidence from a single non-RCT study indicating the effectiveness of psychotherapy combined with pharmacotherapy for treatment of depression in SCI. There is level 2 evidence from 1 RCT and 1 non-RCT that a wellness and health promotion program can decrease depression symptoms. There is level 1 evidence from 3 RCTs that exercise based programs can contribute to reduced depression symptoms. There is level 1 evidence that massage therapy can reduce depression symptoms.

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References
American Psychological Association. Policy statement on evidence-based practice in psychology. American Psychological Association Representatives Meeting, August 2005, http://www.apa.org/practice/ebpreport.pdf Bach JR, Tilton MC. Life satisfaction and well-being measures in ventilator assisted individuals with traumatic tetraplegia. Arch Phys Med Rehabil 1994 Jun;75(6):626-632. Bombardier CH, Richards JS, Krause JS, Tulsky D, Tate DG. Symptoms of major depression in people with spinal cord injury: implications for screening. Arch Phys Med Rehabil 2004 11//;85(11):1749-1756. Charlifue SW, Gerhart KA. Behavioral and demographic predictors of suicide after traumatic spinal cord injury. Arch Phys Med Rehabil 1991 Jun;72(7):488-492. Consortium for Spinal Cord Medicine. (1998). Depression following spinal cord injury: A clinical practice guideline for primary care physicians. Washington, DC: Paralyzed Veterans of America. Craig A, Hancock K, Chang E, Dickson H. The effectiveness of group psychological intervention in enhancing perceptions of control following spinal cord injury. Aust N Z J Psychiatry 1998 Feb;32(1):112-118. Craig A, Hancock K, Dickson H. Improving the long-term adjustment of spinal cord injured persons. Spinal Cord 1999 May;37(5):345-350. Craig AR, Hancock K, Chang E, Dickson H. Immunizing against depression and anxiety after spinal cord injury. Arch Phys Med Rehabil 1998 Apr;79(4):375-377. Craig AR, Hancock K, Dickson H, Chang E. Long-term psychological outcomes in spinal cord injured persons: results of a controlled trial using cognitive behavior therapy. Arch Phys Med Rehabil 1997 Jan;78(1):33-38. Cushman LA, Dijkers MP. Depressed mood in spinal cord injured patients: staff perceptions and patient realities. Arch Phys Med Rehabil 1990 Mar;71(3):191-196. DeVivo MJ, Black KJ, Richards JS, Stover SL. Suicide following spinal cord injury. Paraplegia 1991 Nov;29(9):620-627. Diego MA, Field T, Hernandez-Reif M, Hart S, Brucker B, Field T, et al. Spinal cord patients benefit from massage therapy. Int J Neurosci 2002 02//;112(2):133-142. Dryden DM, Saunders LD, Rowe BH, May LA, Yiannakoulias N, Svenson LW, et al. Depression following traumatic spinal cord injury. Neuroepidemiology 2005;25(2):55-61. Dryden DM, Saunders LD, Rowe BH, May LA, Yiannakoulias N, Svenson LW, et al. Utilization of health services following spinal cord injury: a 6-year follow-up study. Spinal Cord 2004 Sep;42(9):513-525. Dunn M, Love L, Ravesloot C. Subjective health in spinal cord injury after outpatient healthcare follow-up. Spinal Cord 2000 02//;38(2):84-91. Elliott TR, Frank RG. Depression following spinal cord injury. Arch Phys Med Rehabil 1996 Aug;77(8):816-823. Elliott TR, Kennedy P. Treatment of depression following spinal cord injury: An evidence-based review. Rehabil Psychol 2004; 49:134-9. Elliott TR, Rivera P. Spinal cord injury. In Nezu A. (Ed); Maguth C. (Ed); Geller P. (Ed) (2003). Handbook of psychology: Health psychology, Vol. 9. (pp. 415-435). xx, 668 pp. Hoboken, NJ, US: John Wiley & Sons, Inc. Elliott TR, Umlauf, Robert L. Measurement of personality and psychopathology following acquired physical disability. [References]. [Book; Edited Book] Cushman, Laura A (Ed); Scherer, Marcia J (Ed). (1995). Psychological assessment in medical rehabilitation. (pp. 325-358). xv, 471 pp. Washington, DC, US: American Psychological Association. Faber RA. Depression and Spinal Cord Injury. Neuroepidemiology 2005; 25:53-54. Fullerton DT, Harvey RF, Klein MH, Howell T. Psychiatric disorders in patients with spinal cord injuries. Arch Gen Psychiatry 1981 Dec; 38(12):1369-1371. Ginis KAM, Latimer AE, McKechnie K, Ditor DS, McCartney N, Hicks AL, et al. Using exercise to enhance subjective well-being among people with spinal cord injury: the mediating influences of stress and pain. Rehabil Psychol 2003 Aug;48(3):157-164.

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Hall KM, Knudsen ST, Wright J, Charlifue SW, Graves DE, Werner P. Follow-up study of individuals with high tetraplegia (C1-C4) 14 to 24 years postinjury. Arch Phys Med Rehabil 1999 Nov;80(11):1507-1513. Hartkopp A, Bronnum-Hansen H, Seidenschnur AM, Biering-Sorensen F. Suicide in a spinal cord injured population: its relation to functional status. Arch Phys Med Rehabil 1998 Nov;79(11):13561361. Hartkopp A, Bronnum-Hansen H, Seidenschnur AM, Biering-Sorensen F. Survival and cause of death after traumatic spinal cord injury. A long-term epidemiological survey from Denmark. Spinal Cord 1997 Feb;35(2):76-85. Hicks AL, Martin KA, Ditor DS, Latimer AE, Craven C, Bugaresti J, et al. Long-term exercise training in persons with spinal cord injury: effects on strength, arm ergometry performance and psychological well-being. Spinal Cord 2003 Jan; 41(1): 34-43. Hohmann GW. Psychological aspects of treatment and rehabilitation of the spinal cord injured person. Clin Orthop Relat Res 1975 Oct;(112)(112):81-88. Howell T, Fullerton DT, Harvey RF, Klein M. Depression in spinal cord injured patients. Paraplegia 1981; 19(5): 284-288. Judd FK, Burrows GD, Brown DJ. Depression following acute spinal cord injury. Paraplegia 1986 Nov-Dec; 24(6): 358-363. Judd FK, Stone J, Webber JE, Brown DJ, Burrows GD. Depression following spinal cord injury. A prospective in-patient study. Br J Psychiatry 1989 May; 154:668-671. Kemp BJ, Kahan JS, Krause JS, Adkins RH, Nava G. Treatment of major depression in individuals with spinal cord injury. J Spinal Cord Med 2004; 27(1): 22-28. Kemp BJ, Krause JS. Depression and life satisfaction among people ageing with post-polio and spinal cord injury. Disability and Rehabilitation 1999 21 5/6: 241-249. Kennedy P, Duff J, Evans M, Beedie A. Coping effectiveness training reduces depression and anxiety following traumatic spinal cord injuries. Br J Clin Psychol 2003 Mar;42(Pt 1):41-52. Kennedy P, Rogers B. Anxiety and Depression After Spinal Cord Injury: A longitudinal analysis. Arch Phys Med Rehabil 2000 July 81; 932-937. Kim SP, Davis SW, Sell GH. Amitriptyline in severely depressed spinal cord-injured patients: rapidity of response. Arch Phys Med Rehabil 1977 Apr;58(4):157-161. King C, Kennedy P. Coping effectiveness training for people with spinal cord injury: preliminary results of a controlled trial. Br J Clin Psychol 1999 Mar;38 ( Pt 1)(Pt 1):5-14. Kishi Y, Robinson RG, Forrester AW. Prospective longitudinal study of depression following spinal cord injury. J Neuropsychiatry Clin Neurosci 1994 Summer;6(3):237-244. Krause JS, Kemp B, Coker J. Depression after spinal cord injury: relation to gender, ethnicity, aging, and socioeconomic indicators. Arch Phys Med Rehabil 2000 Aug;81(8):1099-1109. Krause JS. Adjustment after spinal cord injury: a 9-year longitudinal study. Arch Phys Med Rehabil 1997 Jun;78(6):651-657. Krause JS. Aging after spinal cord injury: an exploratory study. Spinal Cord 2000 Feb;38(2):77-83. Latimer AE, Martin Ginis KA, Hicks AL, McCartney N. An examination of the mechanisms of exerciseinduced change in psychological well-being among people with spinal cord injury. Journal of Rehabilitation Research & Development 2004; 41(5): 643-651. Nemiah JC. The psychiatrist and rehabilitation. Arch Phys Med Rehabil 1957 38:143-147. Richards JS. Psychologic adjustment to spinal cord injury during first postdischarge year. Arch Phys Med Rehabil 1986 Jun;67(6):362-365. Scivoletto G, Petrelli A, DiLucente L, Castellano V. Psychological Investigation of spinal cord patients. Spinal Cord 1997 Aug; 35(8): 516-520. Siller J. Psychological situation of the disabled with spinal cord injuries. Rehabil Lit 1969 Oct;30(10):290-296. Siosteen A, Kreuter M, Lampic C, Persson LO. Patient-staff agreement in the perception of spinal cord lesioned patients' problems, emotional well-being, and coping pattern. Spinal Cord 2005 Mar;43(3):179-186. Sipski ML, Richards JS. Spinal cord injury rehabilitation: state of the science. Am J Phys Med Rehabil 2006 Apr;85(4):310-342. Soden RJ, Walsh J, Middleton JW, Craven ML, Rutkowski SB, Yeo JD. Causes of death after spinal cord injury. Spinal Cord 2000 Oct;38(10):604-610.

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Tirch D, Radnitz CL, Bauman WA. Depression and spinal cord injury: a monozygotic twin study. J Spinal Cord Med 1999 Winter;22(4):284-286. Zemper ED, Tate DG, Roller S, Forchheimer M, Chiodo A, Nelson VS, et al. Assessment of a holistic wellness program for persons with spinal cord injury. Am J Phys Med Rehabil 2003 Dec;82(12):957-68; quiz 969-71.

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CHAPTER ELEVEN
Sexual Health Following Spinal Cord Injury
Stacy Elliott, MD Kate McBride, RN, BSN, CRRN Sally Breen, RN, BSN, CRRN Caroline Abramson, MA

Key Points Phosphodiesterase Type 5 Inhibitors (PDE5i) can be used safely and effectively for treatment of erection dysfunction (ED) in men with SCI and are recommended as first line treatment for ED after SCI. Intracavernosal (penile injectable) medications (ICI) are very effective for the treatment of ED in men with SCI and may be used with some precautions. Topical agents are not effective for treatment of erection dysfunction in men with SCI. Intraurethral preparations are not effective for treatment of erection dysfunction in men with SCI. Vacuum devices and penile rings may be used for treatment of erection dysfunction in men with SCI. Penile prostheses, while the last resort, are effective for treatment of erection dysfunction in men with SCI. The use of PDE5i for treatment of ED in men with SCI is effective, safe and popular, followed by the more invasive but highly effective method of intracavernosal injection. The use of mechanical devices is effective but less popular, and surgical options should be reserved for cases where other ED treatments fail. The least invasive sperm retrieval method should be tried first (i.e. vibrostimulation in the clinic setting to monitor for autonomic dysreflexia) followed with the more invasive electroejaculation (in clinic or operating room settings). Vibrostimulation is most successful in men with SCI above T10. Vibratory stimulus may result in better sperm quality. Antegrade samples appear to have better sperm motility than that found in retrograde samples. Bladder management with clean intermittent catheterization may improve semen quality over indwelling catheterization, reflex voiding or straining. SCI sperm quality may be improved by processing in able-bodied seminal plasma. Men with SCI can have realistic expectations of becoming a biological father. Depending on semen quality and female factors, a progression from intravaginal insemination to assisted techniques such as intrauterine insemination, in vitro fertilization (IVF) to IVF plus intracytoplasmic sperm injection (ICSI) is recommended. Sildenafil may partially reverse subjective sexual arousal difficulties in women with SCI; however, larger scale studies are required to solidify this conclusion. Continent urinary diversion in women with tetraplegia results in improved self-image, quality of life, and enables greater sexual satisfaction. No conclusive evidence exists to suggest that a comprehensive gynecologic service improves womens health behaviors.

Table of Contents
11.1 Introduction ..................................................................................................................11-1 11.2 Sexual Functioning in Men after Spinal Cord Injury.................................................11-1 11.2.1 Male Erectile Response and Enhancement................................................................11-1 11.2.1.1 Phosphodiesterase Type 5 Inhibitors (PDE5i) and Other Oral Agents ....................11-2 11.2.1.2 Intracavernosal (penile injectable) Medications or ICI .............................................11-5 11.2.1.3 Topical Agents .........................................................................................................11-7 11.2.1.4 Intraurethral Preparations ........................................................................................11-8 11.2.1.5 Mechanical Methods - Vacuum Devices and Penile Rings......................................11-8 11.2.1.6 Surgical Penile Implants ........................................................................................11-10 11.2.1.7 Behavioral Management ........................................................................................11-11 11.2.1.8 Summary: Treatment for ED ..................................................................................11-11 11.3 Ejaculation and Orgasm............................................................................................11-12 11.4 Male Fertility ...............................................................................................................11-13 11.4.1 Sperm Retrieval ........................................................................................................11-13 11.4.2 Sperm Quality ...........................................................................................................11-19 11.4.3 Pregnancy.................................................................................................................11-23 11.5 Sexual and Reproductive Health in Women with Spinal Cord Injury....................11-26 11.5.1 Sexual Response......................................................................................................11-26 11.5.2 Gynecological Health ................................................................................................11-26 11.5.3 Fertility/Contraception ...............................................................................................11-27 11.5.4 Obstetrical Health .....................................................................................................11-27 11.5.5 Menopause ...............................................................................................................11-27 11.6 Sexual Adjustment.....................................................................................................11-29 11.6.1 Sexual Behaviour......................................................................................................11-29 11.6.2 Sexual Satisfaction ...................................................................................................11-30 11.7 Summary.....................................................................................................................11-32 References............................................................................................................................11-34

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Elliott S, McBride K, Breen S, Abramson C (2006). Sexual Health Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 11.1-11.40. www.icord.org/scire

Sexual Health Following Spinal Cord Injury

11.1 Introduction Spinal Cord Injury (SCI) significantly changes motor, sensory and autonomic function affecting many areas of a persons life including sexual functioning. Sexuality is an integral part of being human. While changes to sexual function usually refer to changes in arousal (erection in men, vaginal lubrication and accommodation in women), ejaculation in men, and orgasm in men and women, sexuality is also inclusive of the psychological and physiological effects of loss of motor and sensory function, bladder and bowel control and alterations to body image and sexual self esteem. Furthermore, in men with SCI, fertility is affected not only by altered erection and ejaculatory function, but also by changes to semen quality. The impact of an SCI on sexual functioning depends on the location and severity of the injury. In 2004, Anderson surveyed 681 participants (approximately 25% were female) asking what gain of function was most important to their quality of life. For the majority of paraplegics, regaining sexual function was rated the highest priority. Quadriplegics identified regaining sexual function as the second highest priority preceded only by regaining hand and arm function. In contrast to the priority given to sexuality by people with SCI, the medical and research community has not done a body of sufficient research that would result in evidence-based information to guide clinical sexual health practice (Biering-Sorensen & Sonksen 2001; Deforge et al. 2005). Several authors have highlighted the lack of attention given to this area and the resulting dissatisfaction within the SCI community (Tepper 1992; Tepper et al. 2001; Anderson 2004; Kennedy 2006). Current sexual health clinical practice has limitations since it is primarily based on results from case reports and observational studies with some areas (such as erection dysfunction in men with SCI) having a larger body of evidence. This review attempts to summarize the literature and to provide some recommendations for sexual and reproductive clinical practice based on the evidenced-based literature. In areas where evidence is lacking, recommendations based on case reports, opinions and observational studies are also indicated. The clinician can therefore weigh the recommendations separately. 11.2 Sexual Functioning in Men after Spinal Cord Injury 11.2.1 Male Erectile Response and Enhancement In general, the majority of men can attain an erection after SCI either though the psychogenic (via T11 L2 pathways) or reflexogenic pathways (S2- S4 reflex), depending on the level and completeness of injury. However, these erections are often not reliable or adequate for sexual intercourse since there may be difficulties with maintenance of the erection (Alexander et al. 1993; Courtois et al. 1993). Treatments in the area of erectile dysfunction (ED) for men with SCI have advanced in the last several years with the ability to take phosphodiesterase type 5 inhibitors (PDE5i) in the form of a pill. However, other methods are still being utilized when the pill is not effective or affordable. There is stronger evidence for treatment of erectile dysfunction than other areas of sexuality and SCI, primarily due to the advent of the PDE5i and their effectiveness in this population.

11-1

Therapies for erectile dysfunction (ED) include: 1. Oral medications which indirectly relax the penile smooth muscle and enhance an erection attained from sexual stimulation, such as the oral phosphodiesterase V inhibitors [PDE5i] Viagra, Levitra and Cialis 2. Injectable medications which directly relax the penile smooth muscle creating an erection (prostaglandin E1 penile injections [compounded or Caverject] and other injectable combinations of papaverine and phentolamine) 3. Topical agents for penile smooth muscle relaxation (prostaglandin, minoxidil and nitroglycerine) 4. Intraurethral preparation of prostaglandin E1 (MUSE) 5. Mechanical methods such as vacuum devices and penile rings 6. Surgical penile implants 7. Behavioral methods (perineal muscle training). All methods except penile implants are clinically reversible. The use of implantable sacral stimulators to assist an erection via stimulation of S2 and S3 anterior roots has not been well explored due to its limited use in those with complete injuries (Brindley et al. 1989). 11.2.1.1 Phosphodiesterase Type 5 Inhibitors (PDE5i) and Other Oral Agents Erection is initiated by smooth muscle relaxation of the corpora cavernosa (erectile bodies) of the penis, which is dependant on the nitric oxide- cyclic quanosine monophoshpate [cGMP] pathway. The PDE5i are selective inhibitors of type 5 (cGMP specific) phosphodiesterase, which in turn allows for cGMP to not be broken down as quickly, prolonging and enhancing the erectile response. Apomorphine is a dopamine-receptor agonist important in the control of sexual functioning whereas 4 aminopyridine is a K+ channel blocking agent noted for increasing neurotransmitter release at neuroneuronal sites. Table 11.1 Effects of Phosphodiesterase Type 5 Inhibitors (PDE5i) and Other Oral Agents
Author Year; Country Score Research Design Total Sample Size Methods Population: 418 men, treatment n= 207, placebo n=211, age range: 18-80 yrs. Treatment: Randomized to 12 wks of vardenafil (10mg for the first 4 wks) or placebo. 1 tablet 1 hr before each attempt at intercourse, not more than 1/day. At wks 4 and 8, dose maintained or titrated or 1step (to 5 or 20 mg). Outcome Measures: efficacy and tolerability of vardenafil, Erectile Function Domain Scores (from International Index of Erectile Function), Sexual Encounter Profile. Population: 27 men, treatment n=12, placebo n=14, mean age: 32-34 yr, injury level: T6-L5, ASIA: A-D but must have partial reflexogenic erection to vibrostimulation. Treatment: Randomized to receive 50mg of sildenafil or placebo not more than 1/day, approx 1 hr before sexual activity. 1. Outcome EF domain scores in the vardenafil group improved (22.0 from 11.6) compared to the placebo group (13.5 from 12.1) (p<0.001). Over 12 weeks of treatment, mean per-patient penetration (76% vs 41%), maintenance (55% vs 22%), and ejaculation success rates (19% vs 10%) on vardenafil were significantly greater vs the placebo group (p<0.001 for all measures). 75% on sildenafil & 7% on placebo reported that treatment improved erections (p=0.0043). Significant satisfaction improvement with sex life reported by sildenafil group (p=0.012). Mean # of grade 3-4 erections was 1.8/wk for sildenafil group, 0.4/wk

Giuliano et al. 2006; USA PEDro=9 RCT N=418

2.

1. 2. 3.

Derry et al. 1998; UK PEDro=9 RCT Initial N=27 Final N=26

11-2

Author Year; Country Score Research Design Total Sample Size

Methods Outcome Measures: efficacy and safety of sildenafil, sexual function questionnaire. Population: age range 21-49yrs, ASIA A: 14, B: 3, C: 5, D: 5, level of injury: T6-L5. Treatment: Single dose sildenafil 50mg or matching placebo (part I) in random order followed by at least a 3 day washout period before cross-over treatment (part II) for 28 days. Outcome Measures: efficacy and safety of sildenafil, duration & rigidity of erections, self-report diary data. Population: 30 men, age range: 21-60 yrs, 6-12 months post-injury. Treatment: Randomized to sildenafil (4 doses 50mg) or tadalafil (4 doses 10 mg). To attempt intercourse on 4 separate occasions: within 4h of 1st tablet, 12h of 2nd tablet, 24h of 3rd and 24-36h after 4th tablet. Cross-over after 2 wk wash-out. Outcome Measures: safety, time/duration effectiveness, Sexual Encounter Profile. Population: 178 men, average age: 38 yrs, 53% complete SCI. Treatment: 25, 50, or 100mg of sildenafil or placebo 1hr pre-sexual activity for 6 weeks followed by a 2-week washout before cross-over. Outcome Measures: efficacy and safety of oral sildenafil, International Index of Erectile Function (IIEF), event log data. Population: 26 men, incomplete SCI, 19 tetratplegic, 10 paraplegic, mean age: 40.6 yrs, level: C4-T12. Treatment: Fampridine-SR or placebo 12.5mg for first week, 17.5 mg for 7 days, 1 week washout before cross-over. Outcome Measures: safety and efficacy of oral Fampridine-SR, patient satisfaction, quality of life, sensory & motor scores, Ashworth. Population: 178 men, SCI, age range: 1963 yrs, mean age: 38 years. Treatment: Sildenafil upward and downward titration with variable dose of 25mg 1hr pre-sexual activity to a maximum of 100mg. Doses adjusted by 25mg/wk during 6-wk period. Randomized to 6-wk flexible dosing, 2 wk washout, then 6-wk placebo or vice versa. Outcome Measures: efficacy of Sildenafil citrate, IIEF (Q13,14), Medical Outcomes Survey, SF-12, Psychological General Well-Being Index .

Outcome for placebo patients (p=0.0761). 1. 2. 3. Part I: 65% had erections (defined as >60% rigidity) on sildenafil, 8% with placebo. Part II: 75% on sildenafil & 7% on placebo reported improved erections (p<0.005). Sexual Satisfaction: the sildenafil group were more satisfied with their sex lives (p=.001). Tadalafil allowed normal sexual functioning up to 24hr post dosing compared to sildenafil (p<0.01).

Maytom et al. 1999; UK PEDro=8 RCT N=27

1.

Del Popolo et al. 2004; Italy PEDro=7 RCT N=30

1. 2.

Giuliano et al. 1999; UK PEDro=7 RCT (cross-over) N=178

3. 1. 2.

Potter et al. 1998; USA PEDro=7 RCT Initial N=29 Final N=26

IIEF: 83% reported improved erections with sildenafil vs. 12% on placebo (p<0.0001). Ability to achieve & maintain erection, satisfaction of sexual intercourse, & satisfaction of sexual relationship with partner significantly improved with sildenafil over placebo (p<0.0001). Ejaculation and orgasm frequency improved in sildenafil group over placebo (p=0.0012). No significant results related to sexual function. 5 fampridine-SR patients reported erection improvement; however 4 placebo patients also reported erection improvement.

1. 2. 3.

Hultling et al. 2000; Australia PEDro=6 RCT (cross-over) N=178

in overall satisfaction with sex life (49% over baseline). Sexual relationship with partner (d 34% over baseline) with Viagra. Impact of erectile problems assessing emotional distress improved 23% above baseline.

11-3

Discussion Just under 1000 men have been investigated in seven RCTs and two non-RCT studies with the use of oral agents for ED in men with SCI. The evidence supports the use of PDE5i as the first line of treatment in men with ED secondary to SCI. Random effects pooled estimate of efficacy of Viagra was 79%, with the ranges appearing to be anywhere from 75% - 85% (Sanchez Ramos et al. 2001; DeForge et al. 2004a, 2004b). In addition, significant increases in satisfaction with sexual life (49% over baseline) and sexual relationship with partner (34%) is noted with the use of sildenafil (Hultling 2000). The one study on vardenafil that has been done (Guiliano et al. 2006) was a large placebo controlled randomized multi-centered trial of men with SCI (n=418) showed 76% ( vs. 41% with placebo) had erections firm enough for penetration, and 59% felt these erections lasted for satisfactory intercourse (vs. 22% with placebo). One small comparative study of sildenafil and tadalafil use (Del Popolo et al. 2004) in men with SCI was found that tadalafil allowed the majority of men to achieve normal sexual functioning up to 24 hours post dosing compared to sildenafil. Of interest, two patients with low motor neuron incomplete lesions, did not respond to sildenafil but did respond to tadalafil, but other than that, the advantage of tadalafil over sildenafil in terms of duration of action was not influenced by degree or level of lesions in SCI men. Headache (10% - 15%) and flushing (6 10%) were noted to be the most common side effect for men with SCI using the PDE5i, followed by dyspepsia, nasal congestion, dizziness and visual disturbances. Two non-RCT studies trialed other oral medications for men with SCI are mentioned here to point out their relative ineffectiveness as compared to the PDE5i. Apomorphine, relatively successful in men without SCI, was used for 22 men with SCI and was noted to have an overall low rate of response for erectile dysfunction; several side effects (headache, nausea, tiredness) were noted in 41% (Strebel et al. 2004). Potter et al. (1998) looked at 26 men with incomplete SCI in an exploratory trial of fampridine-SR. Although the Global Assessment of Patient Satisfaction statistically improved, only five patients (19%) on fampridine-SR had stronger, more frequent and more sustainable penile erections, however, four patients on placebo also reported improved erections. Conclusion There is level 1 evidence (from 7 RCTs) that supports the use of PDE5i as a safe and effective treatment for erection dysfunction in men with SCI. Phosphodiesterase Type 5 Inhibitors (PDE5i) can be used safely and effectively for treatment of erection dysfunction (ED) in men with SCI and are recommended as first line treatment for ED after SCI.

11-4

11.2.1.2 Intracavernosal (Penile Injectable) Medications or ICI Table 11.2 Effects of Intracavernosal (Penile Injectable) Medications or ICI
Author Year; Country Score Research Design Total Sample Size Renganathan et al. 1997; India PEDro=4 RCT N=28 Methods Population: 28 men, age range: 16-60 yrs. Treatment: Randomized to transdermal nitro-glycerine or Intracavernous injection of papaverine, two week washout, crossover. Outcome Measures: effectiveness of transdermal nitroglycerin vs. intracavernous injection of papaverine. Population: 101 men, SCI, 65 paraplegia, 36 tetraplegia, age range: 20- 51 yrs, lesion level: C4-L4. Treatment: intracavernosal injection (ICI) of papavarine hydrochloride. Outcome Measures: erectile rigidity, duration of erection. 1. 2. 3. 1. 2. 3. 4. Population: 37 men, mean age: 43.7 years, age range: 24-72, level: C3-L4. Treatment: intracavernosal injection (ICI) of papaverine & prostaglandin E1 (PGE1). Dosage was titrated until satisfactory erection obtained. Outcome Measures: safety & efficacy of intracavernosal injection therapy, satisfaction. 1. 2. 3. 4. 5. Outcome Erectile index of papaverine significantly higher than that of nitroglycerine. 93% who received papaverine had a complete response vs. 61% who received nitroglycerine (P=0.004). 32% of patients had complications with papaverine vs 21% with nitorglycerine. Satisfactory erection sufficient for penetration was possible in 98 patients. 78 subjects had good erection within 10 minutes, 13 within 20 minutes, 7 within 30 minutes. Older patients required higher dose. Erections lasted from< 1 hour to >4 hours. 28 patients (76%) responded to injection. 21% ejaculated during >50 % of sexual encounters. At 3 months: 77% were moderately or extremely satisfied with therapy; 85% rated their intracavernosal injection -produced erections as good or excellent. 60% on intracavernosal injection reported almost always or always being able to have successful intercourse. SCI patients required lower doses, used injections less frequently, had longer lasting, better quality erections than patients with vascular based impotence. Minor complications occurred frequently in both groups. Rigid erections in 45 patients (90%). 53% of participants dropped out of program, usually after 1stinjection or during titration period. Main complication was prolonged erection necessitating aspiration and epinephrine injection.

Kapoor et al. 1993; India Downs & Black score=17 Post-test N=101

Zaslau et al. 1999; USA Downs & Black score: 15 Pre-post N=37

Lloyd & Richards 1989; USA Downs & Black score=12 Pre-post N=40

Population: 40 SCI (116 vascular based impotence), mean age: 34.7 yrs, complete: 26, incomplete: 14. Treatment: injection of intracavernous phentolamine and papaverine. Outcome Measures: complications, dosage, quality of erection. Population: 58 men, age range: 19-68yrs, 44 complete, 14 incomplete, 19 cervical, 32 thoracic, 17 lumbar, (53%) dropped out. Treatment: 7.5mg papaverine, titrated to dosage that produced adequate erection, evaluated every week during titration period, then every 2 months. Outcome Measures: erectile rigidity, complications.

1.

2.

1. 2. 3.

Bodner et al. 1992; USA Downs & Black score=12 Post-test N=58

11-5

Author Year; Country Score Research Design Total Sample Size Sidi et al. 1987; USA Downs & Black score=11 Post-test N=66

Methods Population: 66 males, age range: 18-61. Treatment: intracavernsoa injection of papaverine hydrochloride & phentolamine mesylate (n=22), papaverine hydrochloride alone (n=44). Outcome Measures: erection quality. Population: 22 men, age range: 18-52. Treatment: 20-30mg papaverine. Outcome Measures: effectiveness of papaverine. 1. 2. 3. 4. 1. 2. 3.

Outcome 52 patients had functional erections. In response to plain papaverine 20/30 responded with functional erections. 4 patients had sustained erections that had to be drained. 71% continued to use method. 20/22 were able to achieve an erection with complete rigidity with a mean duration of 4.1 hrs. 20 patients who were successful at intercourse were offered training in self injection, but only 10 accepted. 7/22 lasting >5 hrs controlled with ethilefrine and aspiration of corpus.

Beretta et al. 1986; Italy Downs & Black score=7 Post-test N=22

Discussion There is only one RCT study (Renaganathan et al. 1997) in this area and it is a comparative one looking at two forms of administration, intracavernosal papaverine and transdermal nitroglycerine. Patients who received papaverine were statistically more likely to have a complete response (erection) than those patients who received nitroglycerine. There are other non-RCTs of clinical importance since they underscore that intracavernosal (penile injectable) medications (ICI) are more efficacious and provide a firmer erection than PDE5i and that there is a dose response to the efficacy of ICI. The most common side effects of ICI are transient, such as pain and swelling at the injection site. The more serious side effect of priapism (or prolonged erection) can be treated with irrigation (blood removal) of cavernosal bodies with alpha-adrenergic drugs (Sidi et al. 1987). One series of 58 patients using papaverine or papaverine/phentolamine combinations demonstrated 90% rigidity (Bodner et al. 1992). Sustained erections were treated with aspiration and injection of a dilute epinephrine solution. Lowered frequency of injections and lowered doses of medications reduced the risk of subtle plaque development, a complication of scarring of the tunica albuginia. In general, lower doses of ICI were required in neurogenic patients, but a combination of SCI and another comorbidity (diabetes, hypertension) decreased the efficacy of injections (Sidi et al. 1987; Zaslau et al. 1999). Complication rates of ICI have been reported in the 15-31% range (Lloyd & Richards 1989; Dietzen & Lloyd 1992) with the caveat that accumulated experience of clinicians and dosage adjustments reduce this substantially. Prior to the availability of PDE5i, ICI had a high acceptance rate (70%) in the SCI population (Sidi et al. 1987; Watanabe et al. 1996). Conclusion There is level 2 evidence that supports the use of ICI as treatment for erection dysfunction in men with SCI. Intracavernosal (penile injectable) medications (ICI) are very effective for the treatment of ED in men with SCI and may be used with some precautions.

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11.2.1.3 Topical Agents Table 11.3 Effects of Topical Agents

Author Year; Country Score Research Design Total Sample Size Kim et al. 1995; USA Downs & Black score=15 Prospective Controlled Trial N=20 Methods Population: 13 SCI, 7 non-SCI, age range: 19-73 yrs, range of duration ED: 0.6-27 yrs. Treatment: papaverine gel or placebo gel, dose range: 133-500mg. Outcome Measures: safety and efficacy of topical papaverine gel. Outcome For SCI patients (n=12) 1. 3 patients with papaverine gel had full erections, but full erections also occurred with placebo gel.

Chancellor et al. 1994; USA Downs & Black score=11 Post-test N=18

Population: 18 males, age range: 19-65 yrs, level: C7-L3, 15 thoracic. Treatment: minoxidil spray, papaverine injection, or vacuum constriction device (VCD). Outcome Measures: erectile response.

1.

2. 3. 4.

5. Population: 15 men, age range: 20-38 yrs, Level: T2-L5. Treatment: Prostaglandin E1 and 2% Minoxidil solution. Outcome Measures: erectile response. 1. 2. 3. Population: 17 men, age range: 19-51 yrs, level: C2-L4, 13 complete, 4 incomplete. Treatment: Transiderm-Nitro plaster (10mg/24hrs), which contains 50mg glyceryli nitras. Outcome Measures: erectile response. 1.

Beretta et al. 1993; Italy Downs & Black score=10 Post-test N=15

Papaverine injections median rigidity 77% (range 30-100%). Rigidity was significantly less with minoxidil (p<0.05). Vacuum constriction device changed rigidity a median of 57% (range 30-80%). No difference between vacuum constriction device and papaverine. Patient subjective rating scale was significantly lower for minoxidil than vacuum constriction device or papaverine (p<0.05). Physicians subjective ratings were significantly lower for minoxidil than other treatments (p<0.05). 4 patients had complete responses, 5 had partial, 6 had no response. 9 patients with complete/partial response continued to use minoxidil at home for 1 month. 26.6% obtained an erectile response sufficient for vaginal penetration. 5 patients had complete responses (full rigidity), 7 had partial responses (some rigidity &/or increase in penile circumference), & 5 had no response (no noticeable erection). Erection duration (complete response): 20-45 min. 5 (29%) had erections sufficient for vaginal penetration.

Sonksen et al. 1992; Denmark Downs & Black score=9 Post-test N=17

2. 4.

Discussion There are no RCT studies in this area. Topical agents such as minoxidil, PGE1, papaverine and nitroglycerin, although generally safe and act as vasodilators, were not found to be effective beyond 25 40%, most likely due to their inability to be absorbed well through the tunica albuginia. One study found topical minoxidil spray to have no effect. The move to use of topical agents does not seem to be progressive in the SCI population likely due to the efficacy of PDE5i and ICI.

11-7

Conclusion There is level 2 evidence that shows that the use of topical agents is not effective as treatment for erection dysfunction in men with SCI. Topical agents are not effective for treatment of erection dysfunction in men with SCI. 11.2.1.4 Intraurethral Preparations Table 11.4 Effects Intraurethral Preparations
Author Year; Country Score Research Design Total Sample Size Bodner et al. 1999; USA Downs & Black score=12 Post-test N=15 Methods Population: 15 men age range: 30-70 yrs, 7 tetraplegia, 8 paraplegia. Treatment: intraurethral alprostadil (1251000g); MUSE (application system for medicated transurethral system for delivery of alprostadil to the male urethra). Outcome Measures: efficacy of intraurethral prostaglandin E1. 1. 2. Outcome 12 achieved grade 1-3 erections, 3 achieved grade 4 erections. All could achieve grade 5 erections with intracavernosal injections therapy. The three that achieved gr.4 erections all tried MUSE at home and were dissatisfied.

Discussion There are no RCT studies in this area. In a series of 15 SCI, Bodner et al. (1999) found that the use of intraurethral alprostadil (PGE1) was ineffective in sustaining adequate erections and without the penile ring to sustain any increases in penile circumference (tumescence), patients experienced hypotension from the medication. Based on the evidence to date, such studies do not seem worth pursuing. Conclusion There is level 4 evidence that suggests that the use of intraurethral preparations is not effective as treatment for erection dysfunction in men with SCI. Intraurethral preparations are not effective for the treatment of erection dysfunction in men with SCI. 11.2.1.5 Mechanical Methods - Vacuum Devices and Penile Rings Table 11.5 Effects of Vacuum Devices and Penile Rings
Author Year; Country Score Research Design Total Sample Size Heller et al. 1992; Israel Downs & Black score=14 Pre-post N=30 Methods Population: 30 men, 10 paraplegia, 7 paraparesis, 7 hemiplegia, 2 quadriplegia, 2 multiple sclerosis, 2 autonomic neuropathy. Treatment: pilot trial of vacuum tumescence constriction therapy (VTCT). Outcome Measures: device usage, 1. 2. 3. Outcome 17 (57%) of 30 patients bought vacuum tumescence constriction therapy device. 83% very satisfied at follow-up. 53% using device at follow-up.

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Author Year; Country Score Research Design Total Sample Size

Methods frequency of coitus. Population: 20 SCI males age range: 2165 yrs, level: C4-L2. Intervention: each patient was custom fitted for the synergist erection system. Outcome Measures: efficacy of the synergist erection system. Population: 20 men, SCI, age range: 2050 yrs, 13 complete, 7 incomplete. Treatment: use vacuum erection device (VED). Outcome Measures: safety and efficacy of vacuum erection device, patient & partner satisfaction.

Outcome

1. 2.

Zasler & Katz 1989; USA Downs & Black score=13 Post-test N=20

1. 2. 3. 4.

Denil et al. 1996; USA Downs & Black score=12 Post-test N=20

Chancellor et al. 1994; USA Downs & Black score=11 Post-test N=18

Population: 18 males, age range: 19-65 yrs, level: C7-L3, 15 thoracic. Treatment: minoxidil spray, papaverine injection, or vacuum constriction device (VCD). Outcome Measures: erectile response.

1. 2. 3.

4.

Snap gauge assessment correlated with subjective reports of erectile capability (r=0.92, p<0.001). n=15 men and n=14 women rated the quality of coitus as very good to excellent compared to previous best since injury (r=0.78 p<0.001). At 3 months, 93% of the men and 83% of the women reported rigidity sufficient for vaginal penetration. At 6 months, 14 couples were regularly using device at least 1/wk. At 6 months, 41% of the men and 45% of the women were satisfied with the device. 60% of men and 42% of women indicated an improvement of the sexual relationship. Vacuum constriction device changed rigidity a median range of 57% range (30-80%). No difference between vacuum constriction device and papaverine. Patient subjective rating scale was significantly lower for minoxidil than vacuum constriction device or papaverine (p<0.05). Physicians subjective ratings were significantly lower for minoxidil than other treatments (p<0.05).

Discussion There are no RCT studies in this area, but level 4 pre-post studies noted that the vacuum device is an acceptable alternative for ED therapy in men with SCI who may not tolerate other methods and whose hand function can warrant its use (unless a partner applies it). Premature loss of rigidity, petechiae and penile skin edema were unwanted side effects. The maximum vacuum pressure should not exceed 250 mmHg (to prevent petechiae and ecchymosis) and the penile ring placed at the base of the penis to trap blood does not remain for more than 30 45 minutes. An alternative vacuum device (Synergist) is a vacuum device within a silicone sheath that remains on the penis that can be used for longer periods of time due to the absence of constricting bands and a much lower vacuum pressure (8 20 mmHg), and which the majority of patients found satisfying. Denil et al. (1996) reported on 20 couples where 93% of men with SCI and 83% of their female partners reported sufficient penile rigidity for intercourse obtained by the use of a vacuum device after 3 months, but by 6 months less than half the couples were satisfied with the device. Most side effects were temporary and minor. Conclusion There is level 4 evidence that supports the use of vacuum devices and penile rings as treatment for erection dysfunction in men with SCI.

11-9

Vacuum devices and penile rings may be used for treatment of erection dysfunction in men with SCI.

11.2.1.6 Surgical Penile Implants Table 11.6 Effects of Surgical Penile Implants
Author Year; Country Score Research Design Total Sample Size Methods Population: 63 men, SCI. Treatment: penile implantation of semirigid device or Mentor inflatable prosthesis. Outcome Measures: penile implantation functionality. 1. Outcome 53 patients with a semi-rigid implant, 44 currently have functional prosthesis (83% overall success rate). 10 patients received inflatable penile prostheses: 4 were lost, 2 had successful reimplantation. Overall complication rate in the 63 patients=33% (lost prosthesis). After reimplantation, 52/63 patients had functional device, resulting in 82% ultimate success rate. 31 patients have intercourse regularly and pleased with decision to have device. 4 patients dissatisfied, all had semirigid implant.

Collins & Hackler 1988; USA Downs & Black score=7 Post-test N=63

2. 3. 4.

Green & Sloan 1986; USA Downs & Black score=10 Observational N=40

Population: 40 men, age range: 21-60 yrs, ASIA A: 31, B-D: 9. Treatment: penile prosthesis. Outcome Measures: sexual questionnaire.

1. 2.

Discussion There are no RCT studies in this area. In a systematic review of male erectile dysfunction following SCI, Deforge et al. (2006) examined 5 case-series reports on the use of penile prosthesis in men with SCI and found that there was a high level of satisfaction amongst the users and that they were helpful for condom drainage placement. The negatives were that those men who were explanted were no longer candidates for other treatment options due to the extent of the penile damage. Penile implantation is reserved now only for failure of the reversible ED therapies or for those men who find reversible alternatives unacceptable. However, implantable devices have improved in design and a reduced infection rate has been noted over the last 5 10 years. Conclusion There is level 4 evidence that suggests that penile prostheses should not be used as treatment for erection dysfunction (ED) in men with SCI unless there is a failure of all other ED treatments. Penile prostheses, while the last resort, are effective for treatment of erection dysfunction in men with SCI.

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11.2.1.7 Behavioral Management Table 11.7 Effects of Behavioral Management

Author Year; Country Score Research Design Total Sample Size Courtois et al. 2001; Canada Downs & Black score=10 Pre-post N=10/8 Methods Population: 10 men, age range: 25-52 yrs. Treatment: Perineal training combined with biofeedback and home exercises. Outcome Measures: tumescence (penile circumference) 1. 2. Outcome Perineal training resulted in significant differences in tumescence. After treatments were stopped there was a in penile circumference that was statistically significant from the treatment .

This study (n=10) is worth mentioning since it focuses on the relatively successful use of perineal muscle training exercises to improve penile rigidity in those men with some capacity for voluntary pelvic floor contraction. The approach of maximizing the physiological potential before introducing pharmacological or mechanical intervention is an approach often forgotten in rehabilitation (Elliott 2003). Conclusion There is level 4 evidence that suggests that perineal training may result in improvement in erectile function in men with SCI who have some voluntary pelvic floor muscle contraction. Perineal training may enhance erectile function in men with SCI who have some voluntary pelvic floor muscle contraction.

11.2.1.8 Summary: Treatment for ED There is a wide discrepancy and little standardization, except in the area of PDE5i, between various research designs and how outcome measures are attained in the area of treatment of ED in men with SCI. Little in the way of RCT studies have been done, mainly due to the lack of financial incentive to do large trials in this population on ED therapies that will not have a large market (except PDE5i use). That said, to the individual with SCI, the differences between the efficacy, practicality and safety of each method is very relevant. In summary, the effectiveness of all 3 of the PDE5i in the SCI population is generally excellent (about 80% success). The longer acting tadalafil may be advantageous in those men where Viagra failed or for those wishing for more spontaneous activity (longer action of up to 2436 hours versus 1-4 with Viagra and Levitra). In general, PDE5i works best on those with upper motor neuron lesions (UMN) versus those with lower motor neuron lesions (LMN) whose nitric oxide release at the nerve end terminal may not be as consistent. Effectiveness of sildenafil in men with LMN is about 50% (Del Popolo et al. 2004). Short term side effects are approximately the same as with ablebodied (headache and flushing between 10 15%, dyspepsia about 5% and visual disturbances noted in higher doses), but caution should be used in differentiating the side effects of the PDE5i with those seen with autonomic dysreflexia (AD) - especially the presence of headache so as not to ignore the symptoms of AD. The use of PDE5i is contraindicated in men taking nitrates, and should be used with a caution in men with

11-11

symptomatic hypotension due to its mildly hypotensive effect. Long term side effects have not been evaluated in the SCI population. At the present time, there is not enough evidence to suggest either sublingual Apomorphine or oral fampridine-SR are useful in the SCI population for the treatment of ED. Injectable medications have better efficacy (90%) than PDE5i, but are more invasive, and have a higher risk of short term side effects, especially prolonged erection in the SCI population (Deforge et al. 2004a). Careful teaching and titration dosing can virtually eliminate this problem. PGE1, papaverine and phentolamine all require refrigeration; PGE1 is the least stable at room temperature (Deforge et al. 2004b). Prolonged use of papaverine is more likely to cause cavernosal fibrosis due to its low ph of 3-4, and therefore is more commonly used in conjunction with other medications (commonly papaverine, phentolamine or atropine). All injection medications can cause subcutaneous hematomas, cavernosal or tunica fibrosis (usually small and reversible with time) or mild edema. The use of intraurethral prostaglandin (MUSE) and topical preparations have not been that successful and are rarely used. Penile implant surgery is reserved now for those men with failed or unacceptable reversible methods (ICI, Oral therapy or vacuum device), although some men with difficulties with external drainage devices may find penile implants helpful. Conclusion Oral PDE5i are the first line treatment for ED in men with SCI, with the more invasive but successful use of ICI being used most often in men who do not respond to the oral medications. Mechanical devices such as vacuum devices and rings are effective but not as popular. Surgical prostheses are reserved for refractory cases. The use of PDE5i for treatment of ED in men with SCI is effective, safe and popular, followed by the more invasive but highly effective method of intracavernosal injection. The use of mechanical devices is effective but less popular, and surgical options should be reserved for cases where other ED treatments fail.

11.3 Ejaculation and Orgasm Very little has been written about ejaculation and orgasmic sexual satisfaction outside of the fertility literature. There is one recent study that has explored the responses of men with SCI and their partners to these changes (Sipski et al. 2006). There are no RCT studies in this area, as expected. All reports of ejaculation and orgasm in the non-fertility literature are self-reports from surveys, with only one recent study (Sipski et al. 2006) performing laboratory evaluation. However, orgasm is not defined and only self described by subjects as either similar or different compared to their pre-injury experience. Neurophysiologically, orgasm is not defined. Orgasm may be cerebrally, body or genitally generated, and is an area of much needed research. A study by Phelps et al. (1983) reported orgasmic self-report of 42% in 50 male SCI veterans with various levels and completeness of SCI. Alexander et al. (1993) showed in their series that the majority of 38 men with SCI could not ejaculate, with the exception of incomplete paraplegics of whom 75% could ejaculate in some fashion. They reported that 50% of the quadriplegics and 25% of paraplegics with complete injuries reported they could have some sort of orgasm, and of those that could, 38% of quadriplegics and 67% of paraplegics reported it was not accompanied by ejaculation. For the men with incomplete injuries, 66% of the quadriplegics

11-12

said they could have orgasm (of which 50% said it was accompanied by ejaculation) and 75% of the paraplegics reported they could have some kind of orgasm that was always accompanied by ejaculation. There was a significant correlation between the ability to have an orgasm and ejaculation, as was the ability to ejaculate and having an erection firm enough for penetration. Similarly, a recent laboratory study of 45 men with SCI and 6 able-bodied controls (Sipski et al. 2006) demonstrated that 78.9% of the men with incomplete injuries and 28.0% of those with complete injuries achieved orgasm in the laboratory setting (historically, these men reported post-injury orgasmic ability to be 84.2% and 50% respectively). Independent significant predictors of orgasm in the laboratory were completeness of injury and prior history of orgasm post-injury. Those men with lower motor neuron lesions affecting the sacral segments (n=4) had no historic or laboratory experience with orgasm. They also reported that although orgasm and ejaculation were likely to occur together there was a disconnect between the presence of orgasm and the presence of ejaculation. 11.4 Male Fertility Male fertility after SCI is affected by the functional difficulties of erection and ejaculation. Few men with SCI are able to ejaculate and require medical assistance to obtain sperm. This sperm is then used for intravaginal, intrauterine or other assisted reproductive technology (ART). Although most of the male fertility studies describe issues of retrieval, sperm quality, reproductive technology, pregnancy and live births within a single study, the tabled studies have been sorted into the topics of sperm retrieval, sperm quality and pregnancy based on the primary focus of the paper, although overlap does occur. 11.4.1 Sperm Retrieval The two methods of sperm retrieval most commonly used are vibrostimulation (VS) and electroejaculation (EE). VS is a specialized vibrator placed on the penis to induce reflex ejaculation, whereas EE uses a rectal probe to deliver electrical current to the periprostatic nerves, eliciting seminal emission. Semen can only be attained by EE in the first months after injury since spinal shock renders VS ineffectual. Table 11.8 Sperm Retrieval
Author Year; Country Score Research Design Total Sample Size Methods Population: 34 couples (males were SCI), 21-37 yrs (females), 28-46 yrs (males), paraplegia, tetraplegia, C6-L1. Treatment: The male partner was randomly assigned to single transrectal electroejaculation or multiple (baseline, 1month, 3- month) transrectal electroejaculation before intracytoplasmic sperm injection (ICSI). Outcome Measures: sperm concentration, morphology, and motility. 1. Outcome Electroejaculation was successful in 32 of 34 cases. The rate of normal sperm morphology was not different between groups. The mean sperm concentration and rate of total sperm motility increased at 1- and 3-month in multi-transrectal electroejaculation group. A fertilization rate of 63.6% was observed and the pregnancy rate per patient was significantly higher (p<0.001) in multi-transrectal electroejaculation group.

Giulini et al. 2004; Italy PEDro=5 RCT N=34

2.

3.

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Author Year; Country Score Research Design Total Sample Size

Methods Population: 24-44 yrs, n=9, C4-C9, n=10, T4-T12/L1, 1-24 yrs post-injury, 12 complete and 7 incomplete. Treatment: sperm was extracted through vibrator application or electroejaculation followed by assisted reproductive treatments (intrauterine insemination, gamete intrafallopian transfer, in vitro fertilization and embryo transfer, intracytoplasmic sperm injection). Outcome Measures: seminal parameters, pregnancy rates (intrauterine insemination, gamete intrafallopian transfer, intracytoplasmic sperm injection). Population: mean age=28.5 yrs, age range=19-49 yrs, 8 complete, 9 incomplete, 17 tetraplegic, C4-L2, 22 paraplegic, T1L2. Treatment: Retrospective analysis of vibratory stimulation, electroejaculation or subcutaneous physostigmine (at least 2 sessions). Outcome Measures: conception, sperm count, motility Population: SCI males with erectile dysfunction, age range=18-44 yrs, 0.6-39 yrs post-injury, C2-L1. Treatment: Vibrator (multicept ApS) and Relax (Nordic Light) vibrators. Different amplitudes were tested. Outcome Measures: ejaculation responses. Population: n=33 couples, age range=2344 yrs, 37 cervical, 41 thoracic. Treatment: Retrospective review of electrical stimulation followed by cervical self-insemination, intrauterine insemination, in vitro fertilization, or gamete intrafallopian transfer. Outcome Measures: sperm quality, pregnancy rates. 1. 2.

Outcome 14/19 achieved at least 1 pregnancy Methods used: Intrauterine insemination 12% (11/92), gamete Intrafallopian transfer 38.9% (8/18), intracytoplasmic sperm injection 19.2% (5/21). In patients with incomplete lesions vibratory stimulation was more commonly useful (4/7) 53%. Complete lesions required more advanced procedures to achieve pregnancy, (7/12) 58% required electroejaculation. 30/39 patients produced an ejaculation. Greater success rate with tetraplegic (96%), then T1-T10 (73%), then T11L2 (42%). Vibratory stimulation had better sperm quality collected. Among 10 couples who wanted children, 3 pregnancies resulted & 2 births of healthy children. Similar ejaculation responses when using frequencies of 80-100Hz and an amplitude of 1mm. At 100Hz and a 2.5mm amplitude there were higher ejaculation rates (p<0.0001) than an amplitude of 1mm. Ejaculation occurred in 58/66 men (88%). Vibratory stimulation achieved ejaculation in 20/37 cervical patients, 14/26 at or above T10 and 0/15 below T10. Pregnancy rates: 17/27 achieved pregnancy (10 with vibratory stim, 7 with electroejaculation). 5/8 achieved self-home insemination with PVS. 17/27 couples were successful at conception (5 self-insemination, 5 intrauterine insemination and 7 assisted reproductive techniques). 20 live births in 14 couples. Post-implant, all patients achieved external emission of semen, volume between 1-5ml in 4 patients, only a drop or two drops in 3 patients (but good quantities obtained later). 5 pregnancies (2 live births) in the partners of 4 patients. Implants functioned for years without deterioration in performance.

Taylor et al. 1999; Australia Downs & Black score=13 Post-test N=19

3. 4.

1. 2. 3. 4. 1. 2. 3. 1.

Le Chapelain et al. 1998; France Downs & Black score=13 Case Series N=44

Sonksen et al. 1994; Denmark Downs & Black score=13 Post-test N=66

2. 3. 4.

Nehra et al. 1996; USA Downs & Black score=12 Case Series N=78

Brindley et al. 1989; UK Downs & Black score=12 Post-test N=8

Population: 7 SCI, 1 primary anorgasmia, age range=27-37 yrs, C5-T9, 5 complete, 2-15 yrs post-injury. Treatment: Implantation of radio-linked hypogastric plexus stimulator device. Outcome Measures: seminal emission and erection (with use of implant).

5. 1.

2.

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Author Year; Country Score Research Design Total Sample Size Halstead et al. 1987; USA Downs & Black score=12 Post-test N=12

Methods Population: age range=23-38 yrs, C5-C6, n=4, T3-T12, n=7, L1, n=1, 8 para, 4 quad, 0.5-18 yrs post-injury, ASIA A, n=7, B, n=1, C, n=3, D, n=1. Treatment: rectal probe electroejaculation on 38 occasions. Outcome Measures: ejaculation response and sperm quality. Population: mean age=36.2 yrs, > 2 yrs post-injury, C4-T11. Treatment: Electroejaculation was performed with the Seager Model 14 electroejaculation unit. A total of 99 electroejaculation trials were administered 4-8 weeks apart according to a random schedule. Each trial consisted of continuous or interrupted current delivery. Outcome Measures: semen quality. 1.

Outcome Anterograde ejaculation occurred in 9 patients with improvement in % motility and total live sperm count on repeated stimulations in 5 patients. Significant retrograde ejaculation occurred in 1 patient. Sperm acceptable for artificial insemination from 4 patients. For anterograde ejaculation, interrupted current produced greater semen volume (2 vs .9 ml), total sperm count (130 vs 79 million) and # motile sperm (34 vs 25 million) compared to continuous current delivery. In retrograde fractions, total sperm count was higher for continuous (113.6 million) than for interrupted delivery (29 million). Retrograde sperm motility was lower than anterograde sperm motility regardless of the method used. > 10 million sperm obtained in 71% of subjects (n=34). Age and interval since injury had no effect on outcome. Higher success in thoracic paraplegics (90% ejaculated successfully) and in those using intermittent catheterization for bladder management compared to cervical or lumbar patients (successful ejaculation in 60% and 50%, respectively). Indwelling urethral catheters and high pressure reflex voiding had a negative impact on EE results. Initial PSC application successful in 5/20 patients. 3 patients successful in subsequent tests. 12 not successful. Only successful if T12-L2 myelomeres intact.

2. 3. 1.

Brackett et al. 2002; USA Downs & Black score=11 Post-test N=12

2.

3. Population: mean age=31yrs, age range=20-53 yrs, cervical=15, thoracic=29, lumbar=4, 4mo-34 yrs post-injury, 56% complete, 44% incomplete. Treatment: rectal probe electroejaculation (EE). Outcome Measures: sperm quality. 1. 2. 3.

Ohl et al. 1989; USA Downs & Black score=11 Post-test N=48

4. Population: T6-L4, >6months post-injury, paraplegia. Treatment: physostigmine (PSC) followed by intraspinal injection of neostigmine (ISN) (0.25-0.5mg) or PSC (2mg physostigmine sulfate injected 30min after 40mg Nbuthylhyocine) several weeks later. Outcome Measures: ejaculation. Population: all male, C1-C5 to L1-L2, n=35 female partners, age range=21-42 yrs. Treatment: Sperm was extracted through vibrator application, drug application (Nifidepine 10-30mg), electroejaculation or sperm aspiration from the vas deferens. Sperm was then introduced by insemination or IVF. Outcome Measures: live births. 1. 2.

Chapelle et al. 1983; France Downs & Black score=11 Post-test N=20

1. 2.

Dahlberg et al. 1995; Finland Downs & Black score=10 Post-test N=63

Fertility rates: of 35 males seeking pregnancy, 29 could produce viable sperm. Live births: n=24 children from 18/35 couples). Miscarriages: n=4.

11-15

Author Year; Country Score Research Design Total Sample Size

Methods Population: 10 couples, N=10 SCI men, age range=27-37 yrs, C6-T12, 9 incomplete & 1 complete, 9 paraplegics & 1 tetraplegics, 4-20 years post-injury. Treatment: If semen sample from electroejaculation (EE) was of fair quality, then 3 cycles of intrauterine insemination (IUI) prior to intracytoplasmic sperm injection treatment (ICSI). If semen samples were poor, ICSI was suggested. If no sperm from EE, surgical retrieval of sperm was performed. Outcome Measures: pregnancy rates. Population: 28 couples, 28 males, age range=24-43 yrs, 1-22 yrs post-injury, C2L4; 28 females, mean age=29 yrs, age range=19-39 yrs. Treatment: Males with SCI: vibratory stimulation or electroejaculation. Female partners: assisted reproductive techniques (vaginal self-insemination at home, intrauterine insemination, in vitro fertilization with or without intracytoplasmic sperm injection). Outcome Measures: ejaculation rates, seminal parameters, pregnancy rates. Population: n=12 SCI, n=2 non-SCI (diabetes), mean age=34.6 yrs, age range=25-46 yrs, C5-T10. Treatment: electrical stimulator (up to 35V, 900mA, 50Hz). Outcome Measures: fertility rates, seminal parameters, pregnancy rates. Population: m=27, n=9 couples, 10 Cervical, 16 Thoracic, 1 Lumbar. Treatment: electrical stimulation (12-18V, 400-600mA for 30 second bursts) followed by intrauterine insemination or IVF. Outcome Measures: seminal parameters, ejaculation rates, cycle function, pregnancy rates. Population: mean age=29.5 yrs, age range=19-61years, cervical=15 (9 complete, 6 incomplete) & thoracic=22 (20 complete, 2 incomplete), 3mo-23yrs postinjury. Treatment: 10mg nifedipine for autonomic dysreflexia, 40mg butylbromure hyoscine subcutaneously, 2-4mg physostigmine subcutaneously 30 mins later and masturbation by female partner. Outcome Measures: ejaculation responses, pregnancies. 1.

Outcome 7 clinical pregnancies achieved, 2 of which ended with spontaneous abortion. 1 couple accomplished pregnancy by ICSI with cryopreserved sperm from vasal aspiration. The fertilization and pregnancy rates of ICSI cycles using sperm from men with SCI were comparable to men without SCI. One couple attained pregnancy by using donor sperm. The cumulative successful pregnancy rate per couple was 80%. 28/28 men were able to ejaculate, 22 by vibratory stimulation (all with lesion above T10), 6 by electroejaculation. 4/16 achieved pregnancy and had healthy babies. This was achieved by home vibratory stimulation and self insemination within two years. All couples who had children had significantly higher median motile sperm per ejaculate (105 million vs. 10 million, p=0.01) Overall 9/28 couples (32%) achieved 10 pregnancies with a delivery of 9 healthy babies. Seminal parameters: volume obtained: a few drops to 5.5ml, % of progressive motility: 0-60%, and sperm concentration: 0-260 million/ml. 1 pregnancy recorded (father:T10 paraplegia, 8 yrs post-injury, 54million/ml, 30% motility) resulted in a singleton with no genetic abnormalities. Ejaculation rates: 43/112 were antegrade ejaculations (38%), 24/112 were retrograde ejaculations, 45/112 were both antegrade and retrograde ejaculations (40%) and 2/112 were not able to ejaculate (2%) Pregnancy rate: 3/9 couples achieved pregnancy, 2 or which resulted in live births and both were twins. 54% of cases resulted in antegrade ejaculation. 46 samples showed mean normal count but low motility rate (28%). Fresh unwashed sperm artificial insemination performed in 6 couples with 3 successful pregnancies.

Shieh et al. 2003; Taiwan Downs & Black score=10 Post-test N=10

2.

3. 4. 1. 2.

Sonksen et al. 1997; Denmark Downs & Black score=10 Case Series N=28

3.

4. 1.

Lucas et al. 1991; UK Downs & Black score=9 Post-test N=14

2.

1.

Kolettis et al. 2002; USA Downs & Black score=8 Post-test N=27

2.

1. 2. 3.

Leduc et al. 1992; Canada Downs & Black score=8 Post-test N=37

11-16

Author Year; Country Score Research Design Total Sample Size

Methods Population: 102 men, mean age: 25.6 yrs, cervical-sacral lesions, >T11 (n=58), thoracolumbar lesions (n=36), sacral (n=8), mean 6.1yrs post-injury. Treatment: simple vibrator applied to the penis for ejaculatory response. 15 patients who wanted to conceive a child received instruction in home use of vibrator. Outcome Measures: ejaculation frequency, sperm quality. Population: N=81 males with SCI, mostly complete. Treatment: application of a vibrator of 80 Hz and 2.5mm amplitude to the lower surface of the glans penis, electroejaculation (EE). Outcome Measures: semen retrieval. 1. 2. 3.

Outcome Penile vibrators triggered ejaculation in 72 patients (70.5%). 11 other patients showed 'weak' ejaculation with poor contractions of perineal muscles. Stimulation ranged from 30sec-20min. Of 15 'home-use' patients, in sperm concentration and steep in abnormal spermatozoa over 3 months. 6 couples had homologous artificial insemination, 3 pregnancies resulted. Required duration <20min (usually <3min) in 48/81 SCI men. It failed in 19/81 who lacked reflex hip flexion on scratching soles of feet and in 14 others. It failed in 11/12 men with injuries <6 months duration. From 21/34 men for whom the vibrator failed, semen cold be obtained by electroejaculation (EE). 11 pregnancies reported. 9 healthy children born. 52/121 became pregnant, 39 by IUI alone. All patients undergoing IVF had higher cycle fecundity than did those undergoing IUI (p<0.001). The rates of spontaneous abortion and multiple gestations were 23% and 12%, respectively. Vibrostimulation in supranuclear lesions was successful in 133 patients, and in 5 more after physostigmine injection. EE was successful in all 7 infranuclear lesions and in 4 supranuclear patients failing with vibrostimulation. 8 more supranuclear patients responded to EE and physostigmine. Surgical retrieval was applied in 27 patients. In 109 patients who wanted children, 73 pregnancies in 46 couples, leading to 54 births and 16 abortions. Semen obtained from 21 of 24 men with a lesion at T8 or above, and from 4 of 11 men with lesions below T10. 8 pregnancies from 6 couples.

Beretta et al. 1989; Italy Downs & Black score=8 Post-test N=102

4. 1. 2.

Brindley 1984; England Downs & Black score=8 Post-test N=81

3. 4.

Ohl et al. 2001; USA Downs & Black score=7 Post-test N=121

Lochner-Ernst et al. 1997; Germany Downs & Black score=7 Post-test N=219

Population: 121 couples (87 involved an SCI patient). Treatment: electroejaculation followed by intrauterine insemination (IUI) was the route of sperm delivery. If not successful after 3-6 cycles of IUI, GIFT (gamete intrafallopian transfer) or IVF procedures were recommended. Outcome Measures: pregnancy success and pregnancy outcomes. Population: all male, 51 tetraplegics & 161 paraplegics, mean 11.9 yrs post-injury. Treatment: supranuclear patients were treated by vibrostimulation. When this failed, further treatment was applied: physostigmine medication and vibrostimulation, electroejaculation, physostigmine with electroejaculation (EE), surgical approaches. Infranuclear patients were treated by EE. Outcome Measures: semen retrieval and pregnancy success. Population: C4-L5. Treatment: electroejaculation (EE), vibration ejaculation (VE), and subcutaneous physostigmine (SP). Outcome Measures: conception, seminal emission, pregnancies.

1. 2. 3.

1.

2.

3. 4. 1. 2.

Rawicki & Hill 1991; Australia Downs & Black score=4 Post-test N=39

11-17

Discussion Most studies included in this section were not comparative for differences in sperm retrieval technique (surgical and non surgical), but rather focused on cumulative ejaculatory and/or pregnancy success (Dahlberg et al. 1995; Nehra et al. 1996; Brinsden et al. 1997; Chung et al. 1997; Lochner-Ernst et al. 1997; Le-Chapelain et al. 1998). The evidence was often from retrospective chart reviews and prospective clinical trials were rare. The application of a specialized vibrator, with settings of approximately 70100 Hz with 2.5- 3.5 mm amplitude (Brindley 1984; Sonsken et al. 1994; Ohl et al. 1997) on the penis (usually frenulum) produces antegrade, retrograde, and some mixed semen samples. Vibrostimulation worked most reliably in those men with lesions above T10, those men with SCI who had a reflex hip flexion with scratching the soles of the feet and with injuries over 6 months (Brindley 1984; Sonsken et al. 1994; Lochner-Ernst et al. 1997; Sonsken et al. 1997) or in patients with incomplete lesions (Taylor et al. 1999). Vibrostimulation application for 30 sec 20 minutes (most occurring in less than 3 min) resulted in ejaculation between 60 100% (Beretta et al. 1989; Rawicki & Hill 1991; Sonksen et al. 1994; Rutkowski et al. 1995; Chung et al. 1997; Sonksen et al. 1997). Those that failed vibrostimulation could usually have semen obtained by electroejaculation (Taylor et al. 1999), a method successful in lower lesions (Ohl et al. 2001). Since ejaculate was almost always attainable by vibrostimulation or electroejaculation, the need for surgical aspiration was rare but reported (Dahlberg et al. 1995; LochnerErnst et al. 1997; Shieh et al. 2003). Controlling severity of autonomic dysreflexia with nifedipine allowed for better sperm retrieval technique (VerVoort et al. 1988; Lucas et al. 1991; Brackett et al. 2002; Elliott & Krassioukov 2006). Electroejaculation is considered more invasive and painful than penile vibratory stimulation for men with SCI, and patients prefer penile vibratory stimulation if sperm quality was equal between the two techniques (Ohl et al. 1997). The use of physostigmine injections alone or in conjunction with both vibrostimulation and electroejaculation has largely dropped out of use since the mid1990s (Chapelle et al. 1983; Leduc et al. 1992). An implantable hypogastric nerve stimulator (radio-controlled) was also successful in yielding semen with sperm (not necessary all motile), but has not been further developed (Brindley et al.1989). Conclusion There is level 4 evidence that semen retrieval can be assisted by vibrostimulation in men with lesions above T10. There is level 4 evidence that semen retrieval can be assisted by electroejaculation in men who failed vibrostimulation. There is level 4 evidence that surgical aspiration can be used to retrieve sperm if vibrostimulation and electroejaculation are not successful. The least invasive sperm retrieval method should be tried first (i.e. vibrostimulation in the clinic setting to monitor for autonomic dysreflexia) followed with the more invasive electroejaculation (in clinic or operating room settings). Vibrostimulation is most successful in men with SCI above T10.

11-18

11.4.2 Sperm Quality Unfortunately after SCI, semen quality also declines. The literature supports what Deforge et al. (2005) wrote about semen quality after SCI. Semen obtained by EEP in the first 2 3 days after injury was scant, but had normal quality by 6 10 days post injury (Mallidis et al. 1994). After approximately 2 weeks semen quality deteriorates to levels reaching those observed in males with chronic SCI. After 6 months to 1 year there is no relationship between duration of injury and sperm quality (Sarkarati et al. 1987). Semen quality in men with chronic SCI is reported to have decreased motility and viability, although total numbers of sperm tend to remain high (Brackett et al. 1997b). The following studies investigate the sperm quality under a number of conditions including: repeated ejaculations, different bladder management, antegrade versus retrograde ejaculation, vibratory stimulation versus electroejaculation, heat and varying seminal plasma. Table 11.9 Sperm Quality
Author Year; Country Score Research Design Total Sample Size Brackett et al. 1997a; USA Downs & Black score=17 Prospective Controlled Trial N=77 Methods Population: 77 males, 45% cervical, 51% thoracic, 4% lumbar. Treatment: 1) vibration (n=23), 2) electroejaculation (n=44) or 3) underwent both procedures (n=10). Outcome Measures: sperm quality. Population: all males. Treatment: n=5 FertiCare Clinic Vibrator (2.5 mm, 100Hz, for 3 min) or electroejaculation (Seager model 11). Outcome Measures: sperm quality. 1. 2. Outcome motile sperm with vibratory stimulation compared to electroejaculation. No difference in total sperm count.

1.

Ohl et al. 1997; USA Downs & Black score=14 Prospective Controlled Trial N=11

2. 3. Population: all male, mean age=30 yrs, age range=19-59 yrs, n=36, C1-C8, n=19, T1-T9,n=15, T10-L2, mean 6 yrs postinjury. Treatment: Vibroejaculation at 10-50Hz, 3 cycles for 45seconds (n=36) or electroejaculation (n=34). Outcome Measures: seminal parameters, type of catheterization, method of ejaculation. 1.

Rutkowski et al. 1995; Australia Downs & Black score=14 Case Series N=70

2.

3. Population: 7 SCI, 5 fertile age matched donors, age range=27-54 yrs, 5 to 31 yrs post-injury, C4-C7, 5 incomplete, 2 complete. Treatment: electrovibratory stimulation. Outcome Measures: semen quality. 1. 2. 3.

Monga et al. 2001; USA Downs & Black score=13 Prospective Controlled Trial N=12

No difference in antegrade sperm count, but penile vibratory stimulation specimens had greater motility, viability and motile sperm count compared to EE. No difference in sperm functional assessment (mucus or sperm penetration assay). Electroejaculation was more painful and less preferred than penile vibratory stimulation. Neurological level (p<0.0072) and method of bladder management (p<0.0115) were found to be significant variables that influenced 70% of the patients sperm sample quality. As neurological level became more caudal, motile sperm decreased. Use of a catheter greatly increased the number of motile sperm. Intermittent self catheterization was superior to suprapubic catheter or no catheter. The majority of sperm (65%) exhibited degenerative changes and significant axonemal defects. A significant percentage of sperm (65%) demonstrated disappearance of fiber doublets. Incubation of normal sperm with seminal fluid of subjects with SCI

11-19

Author Year; Country Score Research Design Total Sample Size

Methods

Outcome induced a significant (p<0.05) 43% decrease in motility within 15 min. Antegrade specimens collected in 51 trials (84%) and retrograde specimens obtained in all 61 trials (100%). Non-statistically significant trend toward higher sperm counts in the antegrade samples (mean=74.1 million) than in retrograde (40 million). No difference in sperm motility and morphology between antegrade and retrograde specimens. Fructose and zinc were present in all antegrade and retrograde specimens. 21/25 retrograde, 12/21 antegrade ejaculations. Poor sperm mobility in most cases, no motile Spermatozoa in 6/21. No correlation in sperm quality and quantity with method of bladder management, age, level of injury or time after injury. Sperm quality declines after stimulations are repeated more than once a week. Initial stimulation yielded semen in 29 men (91%; 22 had antegrade and 7 retrograde ejaculation). 16 with antegrade ejaculation started 4-6 months of home stimulation which resulted in a rise of semen volume and fructose and acid phosphatase levels in seminal plasma (improved function of the seminal vesicles and prostate). % motile sperm was low (before and after treatment period). 11 men (69%) showed normal or nearly normal penetration tests after the period of regular stimulation. Sperm was obtained from 9/12 SCI patients and 12/14 non-SCI patients having a vasectomy. SCI aspirated sperm had greater motility (54.4%) and viability (74.1%) compared to ejaculated sperm (14.1%) motility and viability (26.1%) (p<0.0001). Controls showed no difference between aspirated and ejaculated sperm. At 5 minutes, seminal plasma from SCI males reduced motility of sperm from control. Seminal plasma from controls improved motility of sperm from SCI males. At 60 minutes the values were not different from each other.

Chen et al. 1999; USA Downs & Black score=13 Post-test N=14

Population: all male, age range=25-41 yrs, 8 cervical, 6 thoracic, Frankel A (n=8), B (n=4), and C (n=2). Hip flexion reflex in 13 (93%) and spasticity in 12 (86%). Treatment: antegrade sample obtained using Ling vibrator. Bladder catheterized for collection of any retrograde ejaculate. Vibratory stimulation at clinic every 2-4 wk. Outcome Measures: sperm quality.

1. 2.

3. 4.

Wang et al. 1992; Taiwan Downs & Black score=13 Post-test N=25

Siosteen et al. 1990; Sweden Downs & Black score=13 Post-test N=32

Population: age range=19-43 yrs, C5-T12 all complete. Treatment: Pharmacologic: meperidine and diazepam; Device: Electroejaculation using Seger model 12 (max 60 stimulations). Bladder was emptied and then 20ml of Hams F-10 solution was instilled. Outcome Measures: seminal parameters, sperm motility, sperm quality and quantity, ejaculation rate. Population: all males, age range=18-40 yrs, C4-L1, 5 incomplete, 27 complete, 23 tetraplegics, 9 paraplegics. Treatment: vibrator stimulation (29/32 subjects with hip flexion reflex) or electrostimulation (3 subjects), 4-6 months of 'at-home' treatment, 1X/week stimulation. Outcome Measures: semen quality.

1. 2. 3.

4. 1. 2.

3. 4. Population: 12 males, age range=29-40 yrs, C4-L1, mean 14.6 yrs post-injury, 14 able-bodies controls, all had vasectomy and biological children. Treatment: 1) sperm retrieved by electrical stimulator or vibratory stimulation for SCI patients, 2) sperm retrieval before exposure to the seminal and prostatic fluids during vasectomy surgery in controls and vas aspiration surgery in SCI. Outcome Measures: sperm quality. Population: 12 SCI, age range=18-42 yrs, 3-28 yrs post-injury, thoracic injuries, n=14 age matched controls. Treatment: vibratory stimulation (SCI) or masturbation (controls). Effect of SCI seminal plasma was tested on control sperm and vice versa. 1. 2.

Brackett et al. 2000; USA Downs & Black score=12 Prospective Controlled Trial N=26

3. 1. 2. 3.

Brackett et al. 1996; USA Downs & Black score=12 Prospective Controlled Trial N=26

11-20

Author Year; Country Score Research Design Total Sample Size

Methods Outcomes Measures: seminal parameters. Population: 135 complete SCI subjects, n=13 age matched controls, age range 1847 yrs. Treatment: 0.2mg physostigmine. Outcome Measures: ejaculation rates and procreation, level of injured metamers, testical volume. Population: age range=23-38 yrs, C5-C6, n=4, T3-T12, n=7, L1, n=1, 8 para, 4 quad, 0.5-18 yrs post-injury, ASIA A, n=7, B, n=1, C, n=3, D, n=1. Treatment: rectal probe electroejaculation on 38 occasions. Outcome Measures: ejaculation response and sperm quality. Population: all male, age range=16-36 yrs, 14 cervical (3 complete, 11 incomplete), 13 thoracic T1-T9 (all complete), 7 T10-L3 (3 complete, 4 incomplete). Treatment: vibratory stimulation and/or electrostimulation. Outcome Measures: ejaculation response. Population: all male, mean age=28 yrs, age range=22-36 yrs. Treatment: electroejaculation using CGS Electroejaculator with progressively increasing sine wave current at 20 Hz over 4 consecutive days. Outcome Measures: semen quality. Population: 10 SCI males, mean age=33.1 yrs, 11.4 yrs post-injury, C4-C5, n=5, T5-T6, n=4, T12, n=1, 9 age matched non-SCI males. Treatment: electroejaculator (Seager model 14, 1-10Volts) or laboratory stimulation. Specimens stored at room temperature (23C) or body temperature (37C). Outcome Measures: fertility rates. Population: n=18 SCI, n=22 non-SCI, 2 cervical, 15 thoracic, 1 lumbar, 33 of 40 were in a relationship with a female. Treatment: Retrospective review of electrical stimulator with rectal stimulation followed by intrauterine insemination (126 cycles in n=33) or in vitro fertilization (n=7 total 14 cycles). Outcome Measures: fertility rates, seminal parameters, ejaculatory rates, cycle function, pregnancy rates.

Outcome

1. 2.

Chapelle et al. 1988; France Downs & Black score=12 Prospective Controlled Trial N=148

75/135 patients ejaculated after pharmacologic intervention. Only 3/75 who could ejaculate had lesions T12-L2 lesions (p<0.001) and testicle volume was significantly lower in patients with injured T12 segments.

1.

Halstead et al. 1987; USA Downs & Black score=12 Post-test N=12

2. 3. 1.

Anterograde ejaculation occurred in 9 patients with improvement in % motility and total live sperm count on repeated stimulations in 5 patients. Significant retrograde ejaculation occurred in 1 patient. Sperm acceptable for artificial insemination from 4 patients. Semen obtained during first 6 months after injury was not of a quality consistent with successful fertilization, owing to poor motility. Semen quality and motility were better in patients who had been injured for more than 6 months. Repeated electro-ejaculation did not improve the quality of semen. Mean sperm motility increased 23% on days 2 and 3; however, sperm concentration and volume decreased. In 3 of 7 patients sperm motility still remained low. Major gains in sperm motility and viability were achieved by day 2 with some improvements in day 3 for three patients. Heat did not affect rate of degradation in motility in control specimens, but body temperature reduced sperm motility in SCI specimens compared to room temperature.

Sarkarati et al. 1987; USA Downs & Black score=12 Post-test N=34

2. 3. 1. 2. 3.

Mallidis et al. 2000; Australia/USA Downs & Black score=11 Post-test N=9

1.

Brackett et al. 1997b; USA Downs & Black score=10 Prospective Controlled Trial N=19

1.

Matthews et al. 1996; USA Downs & Black score=10 Case Control N=40

2.

3.

Motile sperm were obtained in 95% of men. Semen quality improved with subsequent rectal probe ejaculation in 23/35 men. Antegrade ejaculations produced greater percentage sperm motility in 59% of procedures in which both types of ejaculation were obtained in a patient. However, total motile sperm in retrograde samples exceeded

11-21

Author Year; Country Score Research Design Total Sample Size

Methods

Outcome antegrade in 57% of the cases. Pregnancy rate: 15/33 couples achieved pregnancy (45%), of which, 10/15 were achieved through intrauterine insemination. Pregnancies leading to live birth were recorded in 5/7 couples undergoing IVF.

4.

5.

Discussion Results varied, however, in general, sperm parameters found in antegrade and retrograde samples were approximately the same except for decreased motility in non-alkalinized retrograde samples and one study which showed antegrade samples were better in motility and viability than retrograde samples (Ohl et al. 1997). There is some evidence to suggest that vibratory stimulus seems to produce more viable samples than electroejaculation in terms of motility and volume (Ohl et al. 1997; Le Chapelain et al. 1998). Semen quality appeared to improve with repeated ejaculations in some series (Matthews et al. 1996; Giulini et al. 2004), and not in others (Sarkarati et al. 1987). It has been suggested that parameters improve with consecutive days of electroejaculation (Mallidis et al. 2000). Once weekly vibrator stimulation resulted in an increase of semen volume and of fructose and acid phosphatase levels in the seminal plasma (suggesting improved function of the seminal vesicles and prostate) (Siosteen et al. 1990), whereas other investigators found that too frequent ejaculation caused semen quality to deteriorate (Wang et al. 1992). The chance of improved semen parameters came with consistency of ejaculations over a regulated time period. Poor sperm motility may be due in part to the seminal plasma secondary to disturbed nervous systems and anejaculation (Brackett et al. 2000), and there may be testicular functional or anatomical anomalies (Chapelle et al. 1988; Elliott et al. 2000; Monga et al. 2001). Once ejaculated, sperm motility in men with SCI declines rapidly, and storing at body temperature (in a 37C incubator) may exacerbate this (Brackett et al. 1997b). Bladder management also seems to affect sperm quality, with clean intermittent catheterization improving semen quality over indwelling catheterization, reflex voiding or straining (Ohl et al. 1989; Rutkowski et al. 1995). Conclusion There is level 4 evidence that vibratory stimulus appear to result in better sperm motility than electrostimulation. There is level 4 evidence that sperm obtained by antegrade samples appear to have better motility than retrograde samples. There is level 4 evidence that bladder management with clean intermittent catheterization may improve semen quality over indwelling catheterization, reflex voiding or straining. There is level 4 evidence that SCI sperm quality can be improved by placing sperm from SCI in able-bodied seminal plasma, and that aspirated sperm from the vas deferens had better motility than that ejaculated, demonstrating the etiology of poor semen quality may lie within the seminal constitutes in men with SCI. These techniques have not been studied clinically with respect to pregnancy rates.

11-22

Vibratory stimulus may result in better sperm quality. Antegrade samples appear to have better sperm motility than that found in retrograde samples. Bladder management with clean intermittent catheterization may improve semen quality over indwelling catheterization, reflex voiding or straining. SCI sperm quality may be improved by processing in able-bodied seminal plasma.

11.4.3 Pregnancy Unfortunately, after SCI, semen quality declines necessitating assistive reproductive technologies to compensate for the alterations (Elliott 2003). Pregnancy rates are lower than the general population but have been much improved since the advent of in vitro fertilization (IVF) and intracytoplasmic injection (ICSI). Table 11.10 Pregnancy
Author Year; Country Score Research Design Total Sample Size Methods Population: 84 SCI, 49 couples, age range=19-45 yrs, cervical (34.5%), thoracic (59.5%), lumbar (5.9%), ASIA level: n=63 A, n=15 B n=5 C, n=1 D, 4 mos-34yrs postinjury. Treatment: electroejaculation followed by intrauterine insemination for 3 trials (10million sperm/cc). If this did not result in fertilization, intracytoplasmic sperm injection and IVF. Outcome Measures: volume, sperm count, motility, morphology, total motile sperm count, conception. Population: all male, tetraplegic SCI with partners. Treatment: electrical stimulation or vibratory stimulation followed by 1) intrauterine insemination of partner 24 hour after Luteinizing Hormone surge (n=5), 2) 50 mg clomiphene citrate & hCG, followed by insemination after 32-34 hours (n=5), or 3) same as #2, except 38-40 hour delay (n=10). Outcome Measures: fertility rates, seminal parameters. Population: all male with female partners, age range=24-47 yrs, female: age range=21-43 yrs, C5-L1, 1-27 yrs postinjury. Treatment: trans-rectal electroejaculation with in-vitro fertilization. 71 IVF cycles were used. Outcome Measures: pregnancies, fertilization rate, motile sperm count. 1. 2. Outcome Ejaculation occurred in 98.6% of patients, with sperm in 88% of patients and enough viable sperm in 54.8%. Antegrade semen parameters had better sperm count, morphology and motility than retrograde samples (p>0.001). No significant improvements were seen in seminal parameters after repeated ejaculations. 69.2% overall pregnancy rate/couple. 33% (5/15) after intrauterine insemination, 70% (14/20) after IVF 26 live births (n=12 singletons, n=5 twins, n=1 triplets) and 4 abortions. No pregnancies with protocol 1 or 2. 6/10 patients became pregnant with protocol 3, which has the longest delay between drug administration and insemination.

Heruti et al. 2001; Israel Downs & Black score=19 Post-test N=84

3. 4. 5. 1.

Pryor et al. 2001; USA Downs & Black score=15 Prospective Controlled Trial N=11

1. 2. 3.

Brinsden et al. 1997; UK Downs & Black score=15 Post-test N=35

Pregnancy rates: 18 total (14 were fresh embryo transfers, 4 were frozen embryo transfers). Pregnancy rate per treatment cycle was 21.2% (18/35). Overall clinical pregnancy rate per stimulated IVF treatment was 25.4% (18/71).

11-23

Author Year; Country Score Research Design Total Sample Size

Methods Population: all male, 24 with SCI, n=3 with retroperitoneal dissection, age range=2448 yrs, 3-25 yrs post-injury. Treatment: electrostimulation and nifidepine (10mg) for prophylaxis of autonomic dysreflexia. Outcome Measures: ejaculation rates, pregnancy rates, seminal parameters. Population: mean age=38.9 yrs, 10 SCI, 7 non-SCI related anejaculation. Treatment: electroejaculation and intracytoplasmic sperm injection and results compared to 620 ICSI cycles for non-SCI severe male factor infertility with normal ejaculation. Outcome Measures: pregnancy rate. Population: 12 couples, 12 male SCI, 12 female partners, age range= 27-38 yrs, C4L3, 4-33 yrs post-injury. Treatment: vibratory stimulation and, if necessary, physostigmine and/or electroejaculation followed by IVF. Outcome Measures: seminal parameters, pregnancy rates. Population: age range=30-35 yrs, C4-C7, 6-18 yrs post-injury, 6 tetraplegics. Treatment: vibratory stimulation (using 4,200rpm for 5-45min, with 5 min breaks every 5 min) followed by intrauterine inseminations. Outcome Measures: pregnancy rates. Population: age range=22-43 yrs, C5-T12, 12 complete, 6 incomplete, 2-22 yrs postinjury, ASIA A, n=12, ASIA B-D, n=6. Treatment: rectal probe electroejaculation (RPE). Outcome Measures: sperm quality. 1.

Outcome 7 pregnancies in 13 couples with a total of 56 IUI, 2 spontaneous abortions, 4 live births, 1 ongoing twin pregnancy.

Chung et al. 1997; USA Downs & Black score=14 Post-test N=27

1. 2.

Schatte et al. 2000; USA Downs & Black score=13 Post-test N=17

ICSI resulted in a median fertilization of 60%, 15% pregnancies per cycle and 29% pregnancies per couple. Pregnancy rates were lower for the anejaculation group compared to the severe male factor group.

1.

Hultling et al. 1994; Sweden Downs & Black score=13 Post-test N=12

Pregnancy rates: 7 pregnancies in 6 couples, 3 spontaneous abortions, 2 live births, 2 ongoing pregnancies.

1. 2.

Pryor et al. 1995; USA Downs & Black score=11 Post-test N=6

Pregnancies occurred in 5/6 of the partners. 2 partners delivered healthy boys, 1 partner miscarried at 9 wks. One couple has completed second vibratory stimulation without conception and will try again. After fertility testing, 6/18 men proceeded to use RPE in effort to conceive. Sperm obtained in 16/18 cases. Ejaculate total sperm count=306 million (good), but motility (22%) was poor. Adequate sperm retrieval after processing yielded normal sperm penetration assay in 4/16 (25%) cases in which sperm was obtained. Live births in 2/6 couples attempting conception. Pregnancy rate: 16/25 pregnancies occurred leading to 11 deliveries. n=9 singletons, n=2 sets of twins. n=4 miscarriages during the first or second trimester (1 case of intrauterine death in week 31 of gestation). Pregnancy occurred in all groups of patients in the ASIA scale A-D from injuries from C2-L2.

1.

2. 3.

Buch & Zorn 1993; USA Downs & Black score=11 Post-test N=18

4. Population: all male SCI with female partner, males: mean age=25-51 yrs, female partners: mean age=21-38 yrs, C2L3, 3-33 yrs post-injury. Treatment: vibratory or electrical stimulation followed by IVF. Outcome Measures: conception. 1. 2.

Hultling et al. 1997; Sweden Downs & Black score=10 Post-test N=25

3.

11-24

Author Year; Country Score Research Design Total Sample Size

Methods 4.

Outcome Clinical pregnancy rate was 31% and the cumulative pregnancy rates up to four cycles were 56%.

Discussion Pregnancy rates were dependant on obtaining motile sperm and were improved consistently with higher levels of reproductive assisted technology. The following order indicates progressively improved fertility rates as assisted reproductive technology (ART) advanced: at home (intercourse or vaginal insemination) intrauterine insemination in vitro fertilization (IVF) IVF + intracytoplasmic sperm injection (ICSI).

Reports varied in their description of pregnancy rates, using either pregnancy rate per couple or pregnancy rate per insemination method. In general, reported as per couple, there was considerable improvement in rates over the last 20 years due to better technology (Brinsden et al. 1997; Schatte et al. 2000). In assessing many authors, there appeared to be an average 30 50% pregnancy rate and a 40% live birth rate (Beretta et al. 1989; Hultling et al. 1994; Dahlberg et al. 1995; Chung et al. 1997; Hultling et al. 1997; Heruti et al. 2001; Sheih et al. 2003; Giulini et al. 2004). Cumulative pregnancy rates could go as high as 80% (Sheih et al. 2003). The number of attempts varied greatly, with pregnancy unlikely to occur after 5 attempts of any method (recognizing that some couples advanced on the continuum of increasing ART). Cycle fecundity rate (chance of pregnancy per cycle) for intrauterine insemination is <15%, whereas for IVF/ICSI it is between 25 40%. In one study it was felt that delayed timing of intrauterine insemination resulted in significantly improved pregnancy rates in female partners of quadriplegic men (Pryor et al. 2001). While fresh semen samples were preferred, cryopreserved semen samples were used successfully for IVF technology. Cryopreservation of embryos to be replaced at a later date is also useful (Buch & Zorn 1993). Multiple gestations were more frequent with IVF/ICSI. Testicular aspiration is rarely used since it commits the man and his partner to IVF /ICSI procedures. Substantial heterogeneity of the data has provided estimates of the feasibility of and effort required to pursue biological fatherhood after SCI. This cumulative evidence and substantial clinical experience suggest starting with proper assessment of the physical health and risk factors for the man (i.e. autonomic dysreflexia), as well as fertility history and blood work for the female partner. Assessment of sperm retrieval methods follows with evaluation of the resultant semen samples retrieved. Female intervention is determined by her fertility factors and by the quality of semen available. The least invasive and least expensive insemination options are pursued after weighing invasiveness and risk of sperm retrieval and semen quality. Men with SCI stand a good chance (>50%) of becoming biological fathers with access to specialized clinics and care.

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Conclusion There is level 4 evidence that men with SCI have a good chance (>50%) of becoming biological fathers with access to specialized care utilizing reproductive assisted technology. Men with SCI can have realistic expectations of becoming a biological father. Depending on semen quality and female factors, a progression from intravaginal insemination to assisted techniques such as intrauterine insemination, in vitro fertilization (IVF) to IVF plus intracytoplasmic sperm injection (ICSI) is recommended.

11.5 Sexual and Reproductive Health in Women with Spinal Cord Injury For many years the sexual and reproductive health of women with SCI was not studied. Although few intervention trials exist on this topic, there are observational studies of clinical importance, as they provide information as well as serve to highlight the major sexual and reproductive health issues that exist for women with SCI. 11.5.1 Sexual Response While it is true that women with SCI have clinically significant impairment in arousal and orgasm, women with complete SCI have been self-reporting orgasm that seemed physiologically impossible (Richards et al. 1997). Recent laboratory work using functional magnetic resonance imaging has documented the presence of vaginal-cervical perceptual awareness and orgasm in women with complete SCI (Whipple & Komisaruk 2002; Komisaruk et al. 2004). The vagus nerves are thought to be a spinal cord bypass pathway that facilitates those responses (Komisaruk et al. 2004). Preservation of T11 L2 sensory dermatomes is associated with psychogenically mediated genital vasocongestion and lubrication (Sipski et al. 1997; Sipski et al. 2001). Furthermore, women with LMN injuries affecting S2 S5 were less likely to achieve orgasm compared with women who had other levels and degrees of SCI (Sipski et al. 2001). Women with SCI are less likely to achieve orgasm than able-bodied women, and time to orgasm is significantly increased compared to able-bodied controls (Sipski et al. 2001). Some studies found similar cardiovascular responses in women with SCI compared to able-bodied controls (Sipski et al. 1995; Sipski et al. 1996), while a different study found a greater increase in heart rate and BP for the control group (Whipple et al. 1996) during orgasmic responses. 11.5.2 Gynecological Health There are conflicting reports on the occurrence of dysmenorrhea post-injury. Jackson and Wadley (1999) and Comarr (1966) found a decrease and absence, respectively, whereas Axel (1982) found the majority of women had no change in menstrual discomfort. Other gynecological problems reported by women with SCI include increase incidence of urinary tract infections and vaginal yeast infections (Jackson & Wadley 1999). One qualitative study found a common pattern of diarrhea frequently occurring in conjunction with menstruation, leading to bowel accidents during transfers, and in turn to bladder and vaginal infections (Pentland et al. 2002). In terms of health promotion behaviour of women with SCI, women were found to be less likely to have routine mammograms and annual Papanicolaou smears (Nosek 1996; Jackson &

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Wadley 1999) than women without disabilities; however, they had a similar practice of breast self-exam (Jackson & Wadley 1999). 11.5.3 Fertility/Contraception Amenorrhea may occur immediately following injury, lasting 4-5 months on average (Jackson & Wadley 1999; Axel 1982). It is commonly believed that despite this initial delay in menstruation following traumatic SCI, fertility in women is unaffected. However, as DeForge et al. (2005) point out, there are no controlled studies comparing fertility rates with non-SCI cohorts and thus, there may be unknown effects of SCI on the rate of miscarriages and live births in couples trying to conceive. Jackson and Wadley (1999) found 70.3% of sexually active women use some form of contraception after injury and that fewer women used the birth control pill compared to before the injury. 11.5.4 Obstetrical Health Women with SCI are able to conceive, carry and deliver a baby; however, there is an increased frequency of complications during pregnancy, labour and delivery (Baker & Cardenas 1996; Jackson & Wadley 1999). Bladder problems, spasticity, pressure sores, autonomic dysreflexia, and problems with mobility can pose a threat to the pregnant woman with SCI (Baker et al. 1992; Jackson & Wadley 1999). Obstetric outcomes include higher rates of Caesarian-sections and increased incidence of low birth-weight babies (Jackson & Wadley 1999). Fewer women practice breastfeeding post-SCI (Jackson & Wadley 1999). Breastfeeding was thought to be compromised in women with SCI above T7; however, a recent report of 3 cases of women with tetraplegia suggests that, with psychogenic and pharmacologic induction of the let-down reflex, long-term breastfeeding may be possible (Cowley 2005). 11.5.5 Menopause Little has been published on womens experience of menopause post-SCI. In their observational study, Dannels and Charlifue (2004) report presence of typical perimenopausal symptoms in women with SCI but at a lower rate compared to the general population. The authors surmise several explanations for this difference, including the possibility of the symptoms mimicking those related to SCI, or a lack of communication about perimenopause between providers and women with SCI (Dannels & Charlifue 2004). Jackson and Wadley (1999) also found a lower frequency of menopausal symptoms post-injury, but higher than those women who had undergone menopause pre-injury. The aforementioned studies illuminate the unique experiences of women after SCI in terms of their sexual and reproductive health. Numerous clinical questions remain unanswered however, leaving women with SCI frustrated and angry about the lack of information and support for the particular needs of women with SCI and gynecological health (Pentland et al. 2002). This lack of information combined with the fact that obtaining access to gynecological and obstetric care is a challenge for many women with SCI (Nosek et al. 1996) raises the question of whether women with SCI are receiving adequate sexual and reproductive health care (Jackson & Wadley 1999). The following two studies evaluate interventions in the field of sexual and reproductive health for women with SCI.

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Table 11.11 Sexual and Reproductive Health in Women with Spinal Cord Injury
Author Year; Country Score Research Design Total Sample Size Methods Population: age range: 25-45 yrs, 19 females, 13 complete, 6 incomplete, length of injury range=15-457mos. Treatment: random assignment to sildenafil (50mg) or placebo on day 1 and the alternate medication on day 2. One hour after drug, subjects underwent two 12-minute periods of audiovisual stimulation, followed by two 12-minute periods of audiovisual plus manual clitoral stimulation, each separated by 6-minute baseline periods. The identical protocol was administered on the subsequent day with the alternate medication. Outcome Measures: subjective arousal, vaginal pulse amplitude. 1. Outcome Significant increases in subjective arousal were observed with both drug (p<0.01) and sexual stimulation conditions (p<0.001). Borderline significant (p<0.07) effect of drug administration on vaginal pulse amplitude, an objective measure of vaginal arousal, was noted. Findings suggest that sildenafil may partially reverse sex dysfunction in women with SCI.

2.

Sipski et al. 2000; USA PEDro=9 RCT N=19

3.

Discussion Sipski et al. (2000) evaluated the use of sildenafil (Viagra) 50 mg in women with SCI and reported promising increases in subjective arousal especially when combined with manual and visual stimulation. The results of this study support the need for larger scale studies of sildenafil to augment sexual arousal in women with SCI. Table 15.12 Sexual and Reproductive Health in Women with Spinal Cord Injury
Author Year; Country Score Research Design Total Sample Size Schopp et al. 2002; USA Downs & Black score=13 Pre-post N=28 Methods Population: age range=17-59 yrs. Treatment: attended a womens health clinic, completed pre and post surveys at baseline, 3 months and 12 months. Outcome Measures: survey, breast self exam (BSE), willingness to receive a mammogram. 1. 2. Outcome Trend towards increased frequency of BSE 3 months after initial participation in the clinic (p=0.11). Increased willingness to receive a mammogram between baseline and 12 months (p=0.125).

Discussion Schopp et al. (2002) investigated the effect of comprehensive gynecologic services on the health behaviour of women with SCI. The authors note a trend towards desired behavioural improvement in one outcome measured, namely, increased willingness to receive a mammogram. The other outcome measure (adoption of healthpromoting behaviours) was not shown to change. Conclusion There is level 1 evidence (from 1 RCT) that supports the use of sildenafil in women with SCI to partially reverse subjective sexual arousal difficulties.

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There is level 4 evidence that suggests that comprehensive gynecologic services may not affect womens health behaviours. Sildenafil may partially reverse subjective sexual arousal difficulties in women with SCI; however, larger scale studies are required to solidify this conclusion. Limited evidence exists that participation in a specialized womens health clinic may lead to an increase in preventative gynecologic health care behaviours.

11.6 Sexual Adjustment There is a growing body of SCI literature on aspects of sexuality beyond genital sexual functioning and fertility. A large scale (350 respondents over 4 European countries) crosssectional questionnaire identified sexual activity as the area of greatest unmet need for persons with SCI (Kennedy 2006). This is even more disconcerting given the importance placed on sexuality by men and women with SCI (Anderson 2004). Sexual rehabilitation is recognized as an important component of the overall rehabilitation program for patients with SCI; however, retrospective studies identify a gap between services desired by patients and the services actually provided (White et al. 1993; McAlonan 1996; Tepper 1999). As far back as 1982, Schuler compared five sexual rehab programs for persons with SCI, and urged clinicians to evaluate the sexual rehab services provided (Schuler 1982) Few intervention trials exist in this area, but a number of observational studies offer insight into post-injury sexual adjustment in terms of sexual behaviour and sexual satisfaction, as to what factors are perceived as contributing to or hindering sexual satisfaction. A summary of these findings follows. 11.6.1 Sexual Behaviour Frequency of sexual activity and desire for sexual activity decrease after injury in both men and women (Alexander 1993; White et al. 1993; Jackson & Wadley 1999; Fisher et al. 2002). Fisher et al. (2002) showed a significant increase in sexual activity between inpatient rehab discharge and their 6 month survey. For women, longer duration of injury and lower level of injury (not extent of injury) were significant positive predictors of sexual intercourse (Jackson & Wadley 1999). For men, level and extent of injury have not been found to affect frequency of sexual activity (Alexander 1993). The preferred type of sexual activity for men and women changes after injury. Preferred activities for women are kissing, hugging and touching, instead of penis-vagina intercourse (Sipski & Alexander 1993) and for men, oral sex, kissing and hugging (Alexander et al. 1993). Males reported engaging in masturbation significantly more often than females whereas females indicated being involved in intimate touching more often than males (Mona et al. 2000). Males used condoms during penile-vaginal intercourse more often than females and more females used condoms during oral sex compared to males (Mona et al. 2000). Both women and men remain interested in sexual activity after SCI but level of desire decreases (Charlifue et al. 1992; Alexander et al. 1993) 11-29

11.6.2 Sexual Satisfaction Sexual satisfaction is reportedly lower in both men and women after SCI (Alexander et al. 1993; Fisher et al. 2002; Reitz et al. 2004; Kennedy et al. 2006; Sharma et al. 2006). In an exploratory study of comparing African-American men and women with SCI, authors found that the women reported greater satisfaction with their sex lives than the men (Krause et al. 2004). A comparison study of women with and without SCI, found that married women with SCI are as sexually satisfied as their able-bodied counterparts (Black et al. 1998). In a study involving women with SCI of East Indian culture, the women reported lack of sexual satisfaction more often than the men (Sharma et al. 2006).
Positive or Negative Impact () (+) () () () () () (+) () () (+) () (+) (+) () (+) (+) (+) () (+) (+) (+) (+) women both both women Women, both Both Women women women women Both Both, women Women Both, men Women Both/men Men, women women Men, women

Table 11.13 Sexual Satisfaction

Issues perceived to affect sexual satisfaction and/or sexual adjustment Age (<18 years or >30 years old) Time since injury Severity of injury Bladder management problems (incontinence/UTIs) Spasticity Fecal incontinence Autonomic dysreflexia Sexual self esteem Altered body image Altered genital sensation Sexual desire Lack of a partner Quality of intimate relationship/relationship satisfaction Repertoire of sexual behaviour Partner as caregiver Perceived partner satisfaction Partners understanding of his partners sexual needs Level of social and vocational activity; outgoing personality; acceptance of the disability** Inadequate vaginal lubrication Ability to move Mental well-being Sexual education and counseling Peer support Reported in men/women or both women Studies supporting Kreuter et al. 1994; Westgren et al. 1997; Ferreiro-Velasco et al. 2005 Black et al. 1998; Tepper et al. 2001 Mona et al. 2000 White et al. 1993; Richards et al. 1997; Jackson & Wadley 1999; Benevento & Sipski 2002; Blok & Holstege 1999 Jackson & Wadley 1999 Charlifue et al. 1992; White et al. 1993; Richards et al. 1997 Charlifue et al. 1992; Jackson & Wadley 1999 Mona et al. 2000 Richards et al. 1997; Elkland & Lawrie 2004; Reitz et al. 2004 Richards et al. 1997 Phelps et al. 2001; Reitz et al. 2004 Jackson & Wadley, 1999 Jackson & Wadley 1999; Phelps et al. 2001; Reitz et al. 2004 Richards et al. 1997; Phelps et al. 2001 Kreuter et al. 1996; Black et al. 1998; Pentland et al. 2002 Phelps et al. 2001; Ekland & Lawrie 2004 Kreuter et al. 1996 Kreuter 2000 Charlifue et al. 1992; Jackson & Wadley 1999 Reitz et al. 2004 Reitz et al. 2004 White et al. 1993; Westgren et al. 1997 Richards et al. 1997; Fisher et

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Issues perceived to affect sexual satisfaction and/or sexual adjustment

Positive or Negative Impact

Reported in men/women or both

Studies supporting

al. 2002; Pentland et al. 2002; Ekland & Lawrie 2004 **correlates positively with partner availability thereby indirectly related to sexual satisfaction

Despite the importance of sexual adjustment to overall quality of life, there have been few studies addressing this topic and few investigating the effectiveness of interventions on sexual satisfaction and adjustment to SCI. Studies do support the need for health care providers to address the area of sexuality during the inpatient rehabilitation period and beyond (Fisher et al. 2002). For women with SCI, qualitative studies reveal a desire for sexuality information to be received from their peers with SCI (Richards et al. 1997; Fisher et al. 2002; Pentland et al. 2002; Ekland & Lawrie 2004). The following studies included evaluation of specific interventions on the sexual satisfaction and adjustment of women with SCI. Table 11.14 Sexual Parameters Outcome of Continent Urinary Diversion with a Catheterizable mbilical Stoma in Women with Tetraplegia
Author Year; Country Score Research Design Total Sample Size Methods Population: 3 females, SCI, age range=32-33 yrs, level of injury: C5-C7, length of injury: 5-15 yrs. Treatment: catheterizable umbilical stoma. Outcome Measures: pelvic pain, urinary tract infections, frequency of sexual intercourse, body image. Outcome 1. Both sexually active women report a subjective improvement in the quality and enjoyment of their sexuality. 2. Body image an overall satisfaction with urologic management improved in all three patients. 3. All three women were able to empty their neo-bladder using a 14F clear plastic catheter.

Moreno et al. 1995; USA Downs & Black score=13 Pre-post N=3

Moreno et al. (1995) included sexual parameters in their report of outcome of continent urinary diversion with a catheterizable umbilical stoma in women with tetraplegia (n=3). They found that sexual satisfaction improved in the 2 women who were sexually active and body image improved in all 3 women. Table 11.15 Common Points from Discussions with Women with SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: ~70 females, SCI. Treatment: informal discussion of predecided topics surrounding sexual rehabilitation. Outcome Measures: qualitative reports based on sexual rehabilitation. 1. 2. 3. 4. Outcome Majority admitted that sex and sexual rehabilitation was not a primary concern during initial rehabilitation. All expressed dissatisfaction with amount and quality of the information received during initial rehabilitation. Patients expect clinicians to initiate discussion about sex and sexuality. Women recounted difficulties in adjusting to their "new" bodies and most felt that they had become less attractive since suffering SCI. The vast majority felt that they first

Forsythe & Horsewell 2006; UK Downs & Black score= 5 Observational N=~70

5.

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome became aware of their sexual problems when they returned home so post-rehabilitation counseling would be helpful. The opportunity to talk to other women who had learned to cope with living with SCI was regarded by all as being extremely useful. There was an anxiety about the lack of knowledge and information about the effects of SCI on other aspects of their physiology.

6.

7.

Forsythe and Horsewell (2006) identified common points from their discussions with women with SCI (all of whom were expected to attend a course dealing with topics of sexuality and fertility). Women desired more information during the initial rehabilitation phase and continued opportunity for sexual counseling post-rehabilitation. They indicated sexual counseling should be initiated by the personnel of the clinic not by the individual patient. They also regarded peer counseling as extremely useful in their sexual adjustment. Women expressed anxiety about the lack of information about gynecological and obstetric issues. Conclusion There is level 4 evidence to suggest that a catheterizable umbilical stoma in women with tetraplegia may improve sexual satisfaction and body image. There is level 5 evidence to suggest that a comprehensive gynecologic service may improve womens health behaviours. Continent urinary diversion in women with tetraplegia may result in improved self-image, quality of life, and enables greater sexual satisfaction. There is level 5 evidence to suggest that a comprehensive gynecologic service may improve womens health behaviors.

11.7 Summary There is level 1 evidence (from 7 RCTs) that supports the use of PDE5i as a safe and effective treatment for erection dysfunction in men with SCI. There is level 2 evidence that supports the use of ICI as treatment for erection dysfunction in men with SCI. There is no evidence to support the use of topical agents as treatment for erection dysfunction in men with SCI.

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There is no evidence that supports the use of intraurethral preparations as treatment for erection dysfunction in men with SCI. There is level 4 evidence that supports the use of vacuum devices and penile rings as treatment for erection dysfunction in men with SCI. There is no evidence to support the use of penile prostheses as treatment for erection dysfunction (ED) in men with SCI unless there is a failure of all other ED treatments. Oral PDE5i are the first line treatment for ED in men with SCI, with the more invasive but successful use of ICI being used most often in men who do not respond to the oral medications. Mechanical devices such as vacuum devices and rings are effective but not as popular. Surgical prostheses are reserved for refractory cases. There is level 4 evidence that semen retrieval can be assisted by vibrostimulation in men with lesions above T10. There is level 4 evidence that semen retrieval can be assisted by electroejaculation in men who failed vibrostimulation There is level 4 evidence that surgical aspiration can be used to retrieve sperm if vibrostimulation and electroejaculation are not successful. There is level 4 evidence that vibratory stimulus appear to result in better sperm motility than electrostimulation. There is level 4 evidence that sperm obtained by antegrade samples appear to have better motility than retrograde samples. There is level 4 evidence that bladder management with clean intermittent catheterization improving semen quality over indwelling catheterization, reflex voiding or straining. There is level 4 evidence that SCI sperm quality can be improved by placing sperm from SCI in able-bodied seminal plasma, and that aspirated sperm from the vas deferens had better motility than that ejaculated, demonstrating the etiology of poor semen quality may lie within the seminal constitutes in men with SCI. These techniques have not been studied clinically with respect to pregnancy rates. There is level 4 evidence that men with SCI have a good chance (> 50%) of becoming biological fathers with access to specialized care utilizing reproductive assisted technology. There is level 1 evidence (from 1 RCT) that supports the use of sildenafil in women with SCI to partially reverse subjective sexual arousal difficulties. There is level 4 evidence that suggests that comprehensive gynecologic services may not affect womens health behaviours. There is early evidence to suggest that a catheterizable umbilical stoma in women with tetraplegia may improve sexual satisfaction and body image. There is no conclusive evidence to suggest that a comprehensive gynecologic service improves womens health behaviour.

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Kim ED, el-Rashidy R, McVary KT. Papaverine topical gel for treatment of erectile dysfunction. J Urol 1995;153:361-365. Kolettis PN, Lambert MC, Hammond KR, Kretzer PA, Steinkampf MP, Lloyd LK. Fertility outcomes after electroejaculation in men with spinal cord injury. Fertil Steril 2002;78:429431. Komisaruk BR, Whipple B, Crawford A, Liu WC, Kalnin A, Mosier K. Brain activation during vaginocervical self-stimulation and orgasm in women with complete spinal cord injury: FMRI evidence of mediation by the vagus nerves. Brain Res 2004;1024:77-88. Krause JS, Broderick LE, Broyles J. Subjective well-being among african-americans with spinal cord injury: An exploratory study between men and women. NeuroRehabilitation 2004; 19:81-89. Kreuter M, Sullivan M, Siosteen A. Sexual adjustment after spinal cord injury-comparison of partner experiences in pre- and postinjury relationships. Paraplegia 1994;32:759-770. Kreuter M, Sullivan M, Siosteen A. Sexual adjustment and quality of relationship in spinal paraplegia: A controlled study. Arch Phys Med Rehabil 1996;77:541-548. Kreuter M. Spinal cord injury and partner relationships. Spinal Cord 2000;38:2-6. Le Chapelain L, Nguyen Van Tam P, Dehail P, Berjon JJ, Barat M, Mazaux JM, et al. Ejaculatory stimulation, quality of semen and reproductive aspects in spinal cord injured men. Spinal Cord 1998;36:132-136. Leduc BE, Roy D, Poulin O. The use of physostigmine in men with spinal cord injury with ejaculatory dysfunction. Can J Rehabil 1992;5:231-235. Lloyd LK, Richards JS. Intracavernous pharmacotherapy for management of erectile dysfunction in spinal cord injury. Paraplegia 1989;27:457-464. Lochner-Ernst D, Mandalka B, Kramer G, Stohrer M. Conservative and surgical semen retrieval in patients with spinal cord injury. Spinal Cord 1997;35:463-468. Lucas MG, Hargreave TB, Edmond P, Creasey GH, McParland M, Seager SW. Sperm retrieval by electro-ejaculation. Preliminary experience in patients with secondary anejaculation. Br J Urol 1991;67:191-194. Mallidis C, Lim TC, Hill ST, Skinner DJ, Brown DJ, Johnston WI, et al. Collection of semen from men in acute phase of spinal cord injury. Lancet 1994;343:1072-1073. Mallidis C, Lim TC, Hill ST, Skinner DJ, Brown DJ, Johnston WI, et al. Necrospermia and chronic spinal cord injury. Fertil Steril 2000;74:221-227. Matthews GJ, Gardner TA, Eid JF. In vitro fertilization improves pregnancy rates for sperm obtained by rectal probe ejaculation. J Urol 1996;155:1934-1937. Maytom MC, Derry FA, Dinsmore WW, Glass CA, Smith MD, Orr M, et al. A two-part pilot study of sildenafil (VIAGRA) in men with erectile dysfunction caused by spinal cord injury. Spinal Cord 1999;37:110-116. McAlonan S. Improving sexual rehabilitation services: The patient's perspective. Am J Occup Ther 1996;50:826-834. Mona LR, Krause JS, Norris FH, Cameron RP, Kalichman SC, Lesondak LM. Sexual expression following spinal cord injury. NeuroRehabilitation 2000;15:121-131. Monga M, Dunn K, Rajasekaran M. Characterization of ultrastructural and metabolic abnormalities in semen from men with spinal cord injury. J Spinal Cord Med 2001;24:41-46. Moreno JG, Chancellor MB, Karasick S, King S, Abdill CK, Rivas DA. Improved quality of life and sexuality with continent urinary diversion in quadriplegic women with umbilical stoma. Arch Phys Med Rehabil 1995;76:758-762. Nehra A, Werner MA, Bastuba M, Title C, Oates RD. Vibratory stimulation and rectal probe electroejaculation as therapy for patients with spinal cord injury: semen parameters and pregnancy rates. J Urol 1996;155:554-559.

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CHAPTER TWELVE
Neurogenic Bowel Following Spinal Cord Injury
Geri Claxton, RN Caroline Abramson, MA

Key Points There is limited evidence that supports a multifaceted program for managing a neurogenic bowel. Electrical stimulation of the abdominal wall muscles can improve bowel management for individuals with tetraplegia. Functional magnetic stimulation may reduce colonic transit time in individuals with SCI. Pulsed water irrigation may remove stool in individuals with SCI. Often more than one procedure is necessary for individuals that are unable to develop an effective bowel routine. There is a need for further research to examine the optimal level of dietary intake in spinal cord injured patients. Cisapride, prucalopride, and metoclopramide may be used for the treatment of chronic constipation in persons with SCI. There is sufficient evidence to support including polyethylene glycol-based (PGB) suppositories (10 mg. bisacodyl) in bowel management programs, especially for persons with an upper motor neuron SCI. Colostomy is a safe and effective treatment for severe, chronic gastrointestinal problems and perianal pressure ulcers in persons with SCI, and greatly improves their quality of life.

Table of Contents
12.1 Introduction ..................................................................................................................12-1 12.2 Function........................................................................................................................12-2 12.2.1 Bowel Function ...........................................................................................................12-2 12.2.2 Anorectal function .......................................................................................................12-2 12.3 Management .................................................................................................................12-3 12.3.1 Multifaceted Programs ................................................................................................12-3 12.3.2 Stimulation ..................................................................................................................12-4 12.3.3 Pulsed water irrigation ................................................................................................12-6 12.3.4 Dietary Fibre ...............................................................................................................12-7 12.3.5 Use of Pharmacological Agents..................................................................................12-8 12.3.6 Use of Suppositories.................................................................................................12-11 12.3.7 Colostomy .................................................................................................................12-12 12.4 Summary.....................................................................................................................12-14 References............................................................................................................................12-16

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material.

Claxton G, Abramson C (2006). Neurogenic Bowel Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 12.1-12.17. www.icord.org/scire

Neurogenic Bowel Following Spinal Cord Injury

12.1 Introduction Neurogenic bowel is defined as a bowel that does not function normally after a spinal cord injury, as messages to and from the spinal cord are interrupted. It has the potential to disrupt almost every aspect of life. The effects of neurogenic bowel on quality of life of spinal cord injury patients are significant. One report found that 27 41 % of patients with neurogenic bowel report chronic gastrointestinal problems that alter lifestyle and may require treatment (Correa & Rotter 2000). Fear of bowel accidents is a frequent event for people with SCI that causes individuals to not participate in social and other outside activities (Correa & Rotter 2000). Severe constipation often follows spinal cord injury. Chronic constipation in patients with spinal cord injury has a significant impact on quality of life (Longo et al. 1995). The prevalence of chronic gastrointestinal (GI) symptoms increases with time after injury, suggesting that these problems are acquired and potentially preventable (Rajendran et al.1992). Clinical experience indicates that an effective and successful bowel program consists of the predictable, regular and thorough evacuation of the bowels without the occurrence of incontinence and prevention of complications. It takes into consideration diet and nutritional factors, use of medications when necessary and a well-developed, appropriate program that is consistent with the neurologic condition and needs of the patient with SCI. It is important to emphasize that each person with SCI is unique and that individual bowel programs need to be client specific. Clinical experience indicates that the procedures used and the need for medications will depend greatly on the level of neurologic injury, the extent of impairment and subsequent effect of the injury on bowel function. The effectiveness of a bowel program should be reevaluated and modified as needed. Figure 12.1 Gastrointestinal System

Those with an incomplete injury may retain the sensation of rectal fullness and ability to evacuate bowels so no specific bowel program may be required. A lower lumbar-sacral injury presents with a spastic bowel, also known as an areflexic or lower motor neuron bowel characterized by no reflex activity in the rectum. In these individuals manual removal of the stool from the rectum is required. A higher injury (cervical and thoracic) usually presents with a reflexic bowel, also known as a spastic or upper motor neuron bowel. It is characterized by

12-1

reflex activity in the rectum. Stool evacuation occurs by means of reflex activity caused by a stimulus introduced into the rectum such as an irritant suppository or digital stimulation. Improvement in rehabilitation and medical care has led to increased life span in persons with SCI. As a result of increased life expectancy, chronic problems are becoming more prevalent in this population (Rosito et al. 2002). Colostomy is an option when the extent of bowel dysfunction is severe and other non-surgical methods have failed to produce a desired result. Colostomy is a safe, effective and well-accepted treatment for severe, chronic gastrointestinal problems, and perianal pressure ulcers in persons with SCI, and it greatly improves their quality of life (Stone et al. 1990). 12.2 Function 12.2.1 Bowel Function Bowel function is a major physical and psychological problem for persons with spinal cord injury. Following a spinal cord injury, changes in bowel motility, sphincter control and gross motor dexterity interact to make bowel management a major life-limiting problem. In 2000, Lynch et al. surveyed 1200 persons with SCI and 1200 age and gender-matched controls to describe bowel function. For persons with SCI, their mean Fecal Incontinence Score (FIS) was significantly higher than controls. It was also noted that for persons with complete SCI, their mean FIS was significantly higher than those persons with incomplete SCI. Quality of life was affected by incontinence in 62% of SCI respondents compared with 8% of controls. Fecal urgency and time spent at the toilet were also significantly higher for persons with SCI. A significantly higher percentage (39%) of SCI respondents use laxatives compared to 4% of controls. The decreased ability to discriminate gas and liquid for complete SCI patients also makes the chance for fecal incontinence more likely. 12.2.2 Anorectal function Difficulties with bowel emptying are of concern to most persons with spinal cord injury. For the quadriplegic patient, loss of control over visceral function may be seen as more important than the ability to walk (Frost et al. 1993). Urinary problems in patients with SCI have been extensively studied, and with the advent of intermittent self-catheterization, electrical stimulation of the bladder and advances in diagnostic techniques, considerable improvements have been made in managing lower urinary tract and renal function. In contrast, the management of bowel disorders, and in particular, the intractable constipation that is so common in these patients, has remained essentially unchanged over the past two decades (MacDonagh et al. 1990). Various researchers have shown that electrical stimulation of the somatic nervous system can bring about an alteration in visceral function in humans. Riedy et al. (2000) showed that the impact of short periods of electrical stimulation with perianal electrodes, increased anal pressures. Bowel reflex centres within the sacral spinal cord may be released from descending inhibition after SCI and may be altered with somatic input (Frost et al. 1993). Electrical sacral root stimulation induces defacation in SCI patients and is currently under examination as a new therapy for fecal incontinence. In contrast to electrical stimulation, magnetic stimulation may produce similar results and is noninvasive (Morren et al. 2001). Morren et al. (2001) studied the effects of magnetic sacral root stimulation on anorectal pressure and volume in both fecal incontinence and SCI patients. Sun et al. (1995) investigated the role of spinal reflexes in anorectal function. Their subjects underwent anorectal manometry and electromyography, before and after having a sacral posterior rhizotomy performed by the same neurosurgeon. They found that all subjects lost conscious control of the external anal sphincter, response to intra-abdominal pressure and response to rectal distention. While the use of sacral root

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stimulation, either electrical or magnetic, seems to be producing positive results, further research is required. 12.3 Management Few SCI patients feel normal desire to defecate and most use laxatives, enemas, suppositories or digital stimulation of the rectum and anal canal to initiate defecation. SCI results in severely prolonged colonic transit times both in the acute and chronic phase. However, the type of colorectal dysfunction depends on the level of SCI (Krogh et al. 2000). Colorectal problems often restrict their social activities and influence their quality of life. Colorectal function is not completely understood (Krogh et al. 2000). Krogh et al. (2000) and Nino-Murcia et al. (1990) measured colonic transit time in individuals using ingested radiopaque markers, and abdominal radiographs taken at 24 hour intervals. They found that the mean transit time through the entire colon in SCI patients was significantly longer than normal adults. They also note that better information about colonic transit times and anorectal dynamics could aid in the approach to management of SCI patients with bowel dysfunction. Difficulty with evacuation has been attributed to prolongation of the colonic transit time in individuals with SCI. The Consortium for Spinal Cord Medicine developed guidelines for neurogenic bowel management (Consortium for Spinal Cord Medicine, 1998). The recommendations include: a comprehensive evaluation of bowel function, impairment, and possible problems (completed at the onset of SCI and at least once annually) including a patient history, physical exam, assessment of function (ability of individual/caregiver to perform procedures safely and effectively), bowel program design, assistive techniques/devices, and nutrition. The management of neurogenic bowel complications is reliant on the physician to recognize the common complications and their clinical presentation (Consortium for Spinal Cord Medicine, 1998). Common complications include constipation, fecal impaction and hemorrhoids. The management protocols recommended for constipation are: establishment of a balanced diet, adequate fluid and fibre intake, increased daily activity, and if possible reduction or elimination of medication contributing to constipation. If these recommendations fail, prokinetic medication may be used to promote transit through the gastrointestinal tract. The management protocols recommended for fecal impaction are (in order): manual evacuation, oral stimulants, and oil retention enemas. To minimize the development of hemorrhoids, oral agents (to maintain softformed stool), less straining, and minimal physical trauma during anal stimulation are recommended. Once hemorrhoids have developed, topical anti-inflammatory creams or suppositories are suggested as early treatment. Overall the Consortium for Spinal Cord Medicine recommends further research in all bowel management areas (Consortium for Spinal Cord Medicine, 1998). 12.3.1 Multifaceted Programs There are several factors that may influence bowel function including nutrition, fluid consumption, and routine bowel evacuations. Multifaceted programs incorporate more than one of the factors in an attempt to reduce colonic transit time as well as decrease the incidences of difficult evacuations.

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Table 12.1 Multifaceted Programs after a spinal cord injury

Author Year; Country Score Research Design Total Sample Size Methods Population: age range=19-71yrs 21 complete, 10 incomplete, and 7 medullary cone syndrome and cauda equina; 2/21 tetraplegic and 19/21 paraplegic (complete lesions); length of injury range=5 months16yrs Treatment: Intestinal program administration and 6-month follow-up. Outcome Measures: Difficulty in intestinal evacuation (DIE); colonic transit time; anorectal manometry; recto-colonoscopy; gastrointestinal (GI) symptoms Population: Gender: m=5, f=5; Age: range 20 to 60, mean 33yrs; Level of injury: C3 to L4 Treatment: multifaceted intervention including diet, water intake, and evacuation schedule Outcome Measures: 3 variables were assessed: bowel movement frequency, bowel habit, total and segmental largebowel transit time. 1. 2. 3. Outcome Post SCI DIE was increased (from 2.6% to 26.3%) from pre SCI DIE (recall from memory) The most frequent GI symptom was abdominal distention. With the intestinal program, the incidence of DIE was reduced to 8.8% and manual extraction was reduced from 53% to 37%.

Correa & Rotter 2000; Chile Downs & Black score=13 Pre-post N=38

1. 2.

Badiali et al. 1997; Italy Downs & Black score=13 Pre-post N=10

Bowel frequency was reported to have increased at the end of training. By the end of the study period the gastrointestinal transit time (TGITT) was reduced.

Discussion The two different multifaceted bowel management programs above reduced both the gastrointestinal transit time (Badiali et al. 1997) and the incidences of difficulty in intestinal evacuation (Correa & Rotter 2000). As both studies incorporated several factors into the bowel management programs including diet, fluid consumption, and routine bowel practice it is not possible to determine the key factor. Conclusion There is level 4 evidence (from two pre-post studies) that multifaceted bowel management programs reduce gastrointestinal transit time and incidences of difficult evacuations. There is limited evidence that supports a multifaceted program for managing a neurogenic bowel.

12.3.2 Stimulation The Consortium of Spinal Cord Medicine (1998) acknowledges the use of electrical stimulation as a potential treatment modality but recommends further research. Different types of stimulation that have been tested are functional magnetic stimulation (FMS), abdominal belt with embedded electrodes for electrical stimulation, and a Brindley implanted stimulator. Magnetic stimulation applies Faraday's law which generates magnetic field changes to induce an electric field. This induced electric field can generate sufficient current to stimulate

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nerves. Magnetic stimulation is relatively new compared to standard electrical current stimulation applied by electrodes. Anterior nerve root stimulation (e.g., Brindley implanted stimulator) was originally developed for bladder control but has been also used to treat bowel function. Table 12.2 Electrical stimulation for neurogenic bowel after a spinal cord injury
Author Year; Country Score Research Design Total Sample Size Methods Population: Age range=23-67 years (SCI part A subjects), mean=48 years (part B SCI subjects); 9 tetraplegics, 7 paraplegics; mean length of injury=13 yrs Treatment: An abdominal belt with embedded electrodes was wrapped around at the umbilicus level. Device activation was random, subjects did not know whether the device was activated. Subjects used belt for six bowel care sessions over 2 weeks (the belt was activated for three sessions and deactivated for three sessions). Outcome Measures: time to first stool, time for total bowel care. Population: 13 SCI, 2 controls, level of injury range=C3-L1; length of injury range=11-35 years (protocol 2 only); ASIA classes=7 A, 3 B, 1 C. Treatment: Protocol 1: measured the effects of functional magnetic stimulation (FMS) on rectal pressure by placing the magnetic coil on the transabdominal and lumbosacral regions. Protocol 2: consisted of a 5-week stimulation period to investigate the effects of functional magnetic stimulation on total and segmental colonic transit times. Outcome Measures: rectal pressure and total and segmental transit times Population: 4 SCI, 5 controls, mean age: 42+/-5.8 years; level of injury: C3-C7; ASIA: 3 B, 1 D Treatment: Each subject participated in a 3-day protocol. On the first day subjects received a baseline gastric emptying study. On day 2 there was no change in the eating pattern and the subject did not undergo any intervention. On day 3 subjects received functional magnetic stimulation (FMS) while undergoing a second gastric emptying study. Outcome Measures: Rate of gastric emptying Population: 12 Patients with complete supraconal spinal cord lesions, > 2 years post-injury Treatment: Implanted Brindley-Finetech 1. Outcome Activation of the abdominal belt resulted in a significant reduction in time to first stool and time for total bowel care independent of the level of injury. The time to first stool and time for total bowel care were significantly shortened in the 6 subjects with tetraplegia, but not in the 2 subjects with paraplegia.

Korsten et al. 2004; USA PEDro=6 RCT N=16

2.

1. Rectal pressures increased with sacrolumbar stimulation, and with transabdominal stimulation. 2. With stimulation, the mean colonic transit times decreased from 105.2 to 89.4 hours.

Lin et al. 2001; USA Downs & Black score=12 Pre-post N=15

Lin et al. 2002; USA Downs & Black score=11 Pre-post N=9

1. The gastric emptying time of poststimulation was significantly shorter than the baseline. 2. The percentage of gastric emptying at baseline and with FMS was significantly different over the time course of the measurements.

MacDonagh et al. 1990; UK Downs & Black score=10 Pre-post

1. 2.

6 patients achieved full defecation with implant and manual help no longer required. time taken to complete defecation was

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Author Year; Country Score Research Design Total Sample Size N=12

Methods intradural sacral anterior root stimulator Outcome Measures: full defecation Population: 2 groups: 7 SCI with implanted stimulator; 10 SCI without implant, Age range=20-50 years; C3-T10; time since injury range=1-21 years Treatment: comparing individuals with SCI with a Brindley anterior sacral root stimulator implant to individuals with SCI without the implant Outcome Measures: Oro-caecal and oroanal transit time, fecal water content, and frequency of defecation 3. 1.

Outcome reduced 3.all were free from constipation There was no significant difference between the oro-caecal times for the controls and the SCI group or between the controls and the Brindley stimulator group (p>0.05). Paraplegics in stimulator group had a significant increase in defecation frequency compared to the SCI group. There was a non-significant trend towards a more rapid CTT in the stimulator group compared to the SCI group.

Binnie et al. 1991; UK Downs & Black score=8 Prospective Controlled Trial N=27

2. 3.

Discussion Stimulation has been tested to determine whether or not it affects colonic transit time in individuals with SCI. The use of functional magnetic stimulation decreased the mean colonic transit time (Lin et al. 2002; Lin et al. 2001), as did an overnight abdominal belt (with implanted electrodes) for tetraplegic subjects (Korsten et al. 2004). However, an implanted Brindley stimulator did not reduce oro-caecal time for individuals with SCI (Binnie et al. 1991). Conclusions There is level 1 evidence (from 1 RCT) that electrical stimulation of the abdominal wall muscles can improve bowel management for individuals with tetraplegia. There is level 4 evidence that supports the use of functional magnetic stimulation as a method to reduce colonic transit time in individuals with SCI. There is level 2 evidence that supports the use of sacral anterior root stimulation to reduce severe constipation in complete injuries. Electrical stimulation of the abdominal wall muscles can improve bowel management for individuals with tetraplegia. Functional magnetic stimulation may reduce colonic transit time in individuals with SCI.

12.3.3 Pulsed water irrigation Persons with spinal cord injury require assistance with the regular emptying of their bowels, and this may include the use of medications, suppositories, digital stimulation and/or mini enemas (Consortium of Spinal Cord Medicine, 1998). Clinical experience shows that in spite of their best effort, some persons with SCI, especially with a lower injury, are unable to achieve an effective, productive, regular bowel routine, and must look to other methods to assist in this process. Pulse water irrigation (intermittent rapid pulses of warm water) into the rectum, to break up stool impactions and stimulate peristalsis, is one such technique (Puet et al. 1997).

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Table 12.3 Pulsed water irrigation for neurogenic bowel after spinal cord injury
Author Year; Country Score Research Design Total Sample Size Methods Population: 31 SCI Treatment: Pulsed irrigation evaluation was used in SCI patients. It consists of intermittent, rapid pulses of warm water to break up stool impactions and stimulate peristalsis. Outcome Measures: Efficacy of technique, outpatient use Outcome 1. Successful in removing stool in all but three patients. 2. 11 patients had multiple procedures. 3. 162 procedures were performed on 4 outpatients on a regular basis because they could not develop an effective bowel routine with the standard digital stimulation, suppositories, or mini enemas.

Puet et al. 1997; USA Downs & Black score=12 Case Series N=31

Discussion Pulsed irrigation evacuation is a safe and effective method for individuals with SCI (Puet et al. 1997) who develop impactions or do not have an effective bowel routine. Conclusion There is level 4 evidence (from 1 case series study) that supports using pulsed water irrigation (intermittent rapid pulses) to remove stool in individuals with SCI. Pulsed water irrigation may remove stool in individuals with SCI. Often more than one procedure is necessary for individuals that are unable to develop an effective bowel routine. 12.3.4 Dietary Fibre It is well known that fibre is an important part of any diet. There are different types of fibre, which are beneficial in different ways. Soluble fibres mix with water in the intestine to form a gel-like substance, which acts as a trap to collect certain body wastes and move them out of the body. Insoluble fibres absorb and hold water. They provide bulk that pushes food through the digestive system quickly. Insoluble fibres promote regularity and treat constipation. The Consortium for Spinal Cord Medicine (1998) recommends an initial diet with no less than 15 grams of fibre daily. They do not recommend placing individuals with SCI on high fibre diets (Consortium for Spinal Cord Medicine, 1998). The most common source of dietary fibre is bran. Clinical experience shows that too much fibre can cause problems, such as constipation, for people with spinal cord injuries. Finding the right balance is essential.

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Table 12.4 Dietary fibre for managing neurogenic bowel after a spinal cord injury
Author Year; Country Score Research Design Total Sample Size Methods Population: Age range: 19-53yrs, SCI: C4T12; 1 incomplete and 10 complete; 7 tetraplegics and 4 paraplegics Treatment: In phase 1, subjects ate a normal hospital diet and maintained their bowel routine. In phase 2, fibre intake was increased with the addition of 40g Kelloggs All Bran. Outcome Measures: stool weight, total and segmental transit time, bowel evacuation time and dietary intake 1. 2. Outcome Following the addition of bran, dietary fibre intake significantly increased from 25g/d to 31g/d. Mean colonic transit time increased from 28.2 hours to 42.2 hours (p<.05)

Cameron et al. 1996; Australia Downs & Black score=10 Case Series N=11

Discussion Results of this study suggest that increasing dietary fibre in SCI patients does not have the same effect on bowel function as has been previously demonstrated in individuals with normally functioning bowels. The effect may actually be the opposite of the desired result (Cameron et al. 1996). Therefore, adding more fibre alone does not increase bowel function. Conclusion There is level 4 evidence that indicates high fibre diets may increase colonic transit time. There is a need for further research to examine the optimal level of dietary intake in spinal cord injured patients. 12.3.5 Use of Pharmacological Agents Prokinetic agents are presumed to promote transit through the gastrointestinal tract, thereby decreasing the length of time for stool to pass through the intestines, and increase frequency of stool available for evacuation. Cisapride (the most common), prucalopride and metoclopramide, are three examples used in the following research. The presence of constipation with slow transit in patients with SCI has been well documented (Geders et al. 1995). Often medication is a last resort, when modification of the bowel program by altering diet or increasing fluids does not achieve the required result a decrease in constipation. Its use is often reserved for persons with SCI with severe constipation and where modification of the bowel program has failed. Chronic constipation is a common problem after spinal cord injury affecting up to 80% of such patients (Krogh et al. 2002).

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Table 12.5 Treatment studies using pharmacology for neurogenic bowel after SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: mean age range: SCI - 58.8 years, controls - 63.4 years, 2 paraplegics, 7 quadriplegics Treatment: Cisapride or placebo administered in oral doses. Pts received cisapride or placebo 3 days before ingestion of the radiopque markers. Outcome Measures: total and segmental colonic transit time (CTT), questionnaire on type, frequency, and severity of clinical symptoms before and after cisapride or placebo administration Population: Age range: 19-71yrs, SCI: C4L2; 7 tetraplegics and 7 paraplegics; length of injury range=7months-33yrs Treatment: Subjects were administered cisapride orally (10mg four times a day) for 4d. Gastric emptying or mouth-to-cecum transit time (MCTT) was measured either on the 4th or 5th day after the administration of cisapride or placebo. The control subjects were tested without medication or placebo. Outcome Measures: mouth-to-cecum transit time; gastric emptying Population: mean age: 34.72.49 yrs (placebo), 36.53.91 yrs (1mg group), 44.33.05 yrs (2mg group) Treatment: Pts randomized to double-blind treatment with prucalopride 1mg or placebo, taken 1/day for 4 wks. A 2nd group of pts was randomized to double-blind treatment with prucalopride 2mg or placebo for 4wks. Outcome measures: constipation; urinary habit; constipation severity and symptoms; colonic transit times Population: mean age: 34.1yrs, 9 males, 1 female, age range 20-45yrs; level of injury: C4-T10, all complete; length of injury: mean 8.1yrs, range 1-20 yrs Treatment: Intravenous injection of 10 mg cisapride. After an interval of at least 48 hours the subject was commenced on oral cisapride. Outcome measures: Oro-caecal transit time Population: Age range was from 20 to 55 years, complete SCI, 11 quadriplegic, 9 paraplegic, 8 controls Treatment: subjects ingested a liquid nd meal, then within 2 weeks, ingested 2 liquid meal while metoclopramide was administered intravenously; gastric emptying (GE) was evaluated after each liquid meal Outcome Measures: 1. 2. 3. 4. 1. 2. Outcome Mean total colonic transit time (CTT) was significantly longer in SCI patients than controls. Subjects with a normal CTT demonstrated no benefit to the administration of cisapride. 5 quadriplegic subjects with initial abnormal total CTT improved their left CTT following treatment No adverse side effects of cisapride administration were noted. No delay or improvement in gastric emptying was observed after the administration of cisapride. Mean MCTT in quadriplegic subjects was significantly longer than normal subjects; cisapride resulted in normalization of the quadriplegic subjects MCTT

Geders et al. 1995; USA PEDro=8 RCT N=9

Rajendran et al. 1992; USA PEDro=8 RCT N=14

Krogh et al. 2002; Denmark PEDro=7 RCT N=22

1. Compared with baseline, mean changes in constipation severity increased with placebo, but decreased with prucalopride. 3. Diary data showed an improvement in average weekly frequency of all bowel movements over 4wks within the 2mg group 4. 4 patients (2mg group) reported moderate/severe abdominal pain. 1. The colonic transit time (CTT) was reduced from 185 to 123 hours.

Binnie et al. 1988; UK Downs & Black score=12 Case Series N=10

Segal et al. 1987; USA Downs & Black score=9 Prospective Controlled Trial N=20, Control N=8

1. The mean gastric emptying (GE) half time for a liquid meal decreased in the quadriplegic subjects from 104.8 min to 18.8 min after treatment with metoclopramide. 2. In the paraplegic subjects, a pretreatment mean GE of 111.5 min decreased to 29.1min.

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Author Year; Country Score Research Design Total Sample Size

Methods half time of gastric emptying, gastric emptying patterns in the early (alpha) and later (beta) phases Population: Gender: male; SCI: 12 tetraplegics and 3 paraplegics, length of injury=3-356 months Treatment: After establishing baseline studies, patients with constipation, received one oral cisapride 20mg tablet three times each day for one month. Pts offered drug for two additional months, all measurements were repeated. Outcome Measures: colonic transit study; anorectal manometry; bowel movement per day or week; intestinal transit and pelvic floor studies 1. 2. 3. 4.

Outcome

Longo et al. 1995; USA Downs & Black score =9 Case Series N=15

All patients had three months or more of treatment with cisapride. 6/12 reported that symptoms of constipation improved. 9/12 patients reported that the amount of time needed to accomplish a bowel movement decreased. No patient reported a worsening of constipation.

Discussion In persons with SCI with chronic constipation, cisapride appears to produce subjective improvement in both colonic and anorectal function with alleviation of symptoms (Longo et al. 1995). Their study also found that there an increase in stool frequency and less use of laxatives, as well as an increase in the ease of defecation. A significant reduction in colonic transit time (CTT), from 7.7 days to 5.1 days, was reported (Binnie et al. 1988). Geders et al. (1995) and Rajendran et al. (1992) found that in quadriplegic subjects with initial abnormal transit times, cisapride improved transit times. In conjunction with newer and more sophisticated techniques of CTT measurement, further investigations of cisapride in those with SCI and symptomatic bowel dysfunction is warranted (Geders et al. 1995). Segal et al. (1987) investigated the use of metoclopramide in enhancing gastric emptying in the SCI. They found that impaired gastric emptying is a characteristic of SCI and is correlated with decreased drug absorption. Since constipation in patients with both acute and chronic SCI is considered primarily a consequence of prolonged colonic transit time, stimulating intestinal motility would appear to be a reasonable therapeutic approach. Prucalopride is a novel, highly selective, specific serotonin receptor agonist with enterokinetic properties and facilitates cholinergic and excitatory non-adrenergic non-cholinergic neurotransmission (Krogh et al. 2002). Conclusion Cisapride: There is level 1 evidence (from 2 RCTs) that cisapride significantly reduces the colonic transit time for chronic constipation. Prucalopride: There is level 1 evidence (from 1 RCT) that prucalopride increases stool frequency, improves stool consistency and decreases gastrointestinal transit time. Metoclopramide: There is level 2 evidence (from 1 prospective controlled trial) that intravenous administration of metoclopramide corrects impairments in gastric emptying. Cisapride, prucalopride, and metoclopramide may be used for the treatment of chronic constipation in persons with SCI.

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12.3.6 Use of Suppositories More than 20% of persons with SCI report difficulty with evacuation of their bowels (House et al. 1997). The use of chemical rectal agents (suppositories) is a common, often necessary part, of a successful bowel management program, for a person with spinal cord injury. Bisacodyl (dulcolax) and glycerin are the most common active ingredients in these suppositories. The glycerin suppository is a mild local stimulus and lubricating agent. Bisacodyl (dulcolax) is an irritant that acts directly on the colonic mucosa producing peristalsis throughout the colon. The bisacodyl may also have a vegetable oil, or polyethylene glycol base. The most commonly used laxative suppositories contain 10mg. Bisacodyl powder distributed within a hydrogenated vegetable-oil base (HVB) (House et al. 1997). Table 12.6 Treatment studies using suppositories for neurogenic bowel after SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Age range=26-61, 9 cervical, 6 thoracic, 11 complete, 4 incomplete, length of injury: 3 months to 45 years Treatment: At each regularly scheduled bowel care session, either a 10 mg hydrogenated vegetable-oil base (HVB) or 10 mg polyethylene glycol base (PBG) suppository was inserted. Outcome Measures: time to flatus, flatus to stool flow, defecation period, wait until transfer cystometrogram, intracolonic pressure, colonic motor and myoelectrical activity Population: age range=27-67yrs, C5-L1, 5 tetraplegics, 9 paraplegics, length of injury range=2-38yrs Treatment: pts used bisacodyl suppositories for five bowel programs for baseline data, used Theravac SB for the next five bowel programs, then used bisacodyl for five more bowel programs all while recording similar information in a diary log. Outcome Measures: time of insertion of the rectal medication; time of first evacuation; time required to complete the first evacuation; other interventions used; bowel problems between bowel programs Population: Age range=21-76yrs, C4-T12, 6 tetraplegics, 1 paraplegic, length of injury range=2-25yrs Treatment: Each subject was studied after receiving one week of therapy with one of the following four modalities: 1) two bisacodyl suppositories, 2) two glycerin suppositories, 3) one mineral oil enema and 4) one docusate sodium mini enema (Theravac SB) daily. Outcome Measures: total colonic and segmental colonic transit times Outcome Time to Flatus 1. PGB sig. less time than HVB Flatus to stool flow 2. No sig. differences Defecation Period 3. PGB sig. less time than HVB Overall 4. PGB suppositories significantly decreased bowel care time

House & Stiens 1997; USA PEDro=7 RCT N=15

Dunn & Galka 1994; USA Downs & Black score=12 Case Series N=14

1. For group A the mean evacuation time was significantly reduced with Theravac SB compared to the mean times with the bisacodyl interventions. 2. There was a significant reduction in mean evacuation time with the Theravac SB intervention compared to the mean time with both of the bisacodyl interventions. 3. There was not significant difference in evacuation time between the first and second bisacodyl interventions. 1. The total CTT was significantly reduced with docusate sodium minienemas. 2. There was no significant difference in total CTT between docusate sodium and mineral oil enema, and both produced significantly shorter transit times compared to bisacodyl or glycerin suppositories. 3. Bowel evacuation time was least for docusate sodium mini-enemas. 4. In terms of difficulty with evacuation, docusate sodium scored best in symptom reduction followed by, in

Amir et al. 1998; USA Downs & Black score=9 Cohort N=7

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome descending order of efficacy, mineral oil enema, bisacodyl suppositories and glycerin suppositories.

Discussion The effectiveness of the hydrogenated vegetable oil-based (HVB) bisacodyl suppositories compared to the polyethylene glycol-based (PGB) suppositories has often been examined. The total bowel care time with the polyethylene glycol-based suppository is often significantly less (Dunn & Galka 1994). House and Stiens (1997) compared the effectiveness of hydrogenated vegetable-based, polyethylene glycol-based and docusate glycerin (mini-enema) in subjects with upper motor neuron (UMN) lesions. Results showed a significant decrease in bowel care time using the PGB suppository and the mini-enema as compared with the HVB suppositories. Chemical rectal agents (suppositories) are used commonly by persons with SCI to maintain or enhance a successful bowel management program. Conclusion There is level 1 evidence (from 1 RCT) to support polyethylene glycol-based (PGB) suppositories for bowel management. There is a clinically significant decrease in the amount of nursing time for persons requiring assistance and less time performing bowel care for the independent individual. There is sufficient evidence to support including polyethylene glycol-based (PGB) suppositories (10 mg. bisacodyl) in bowel management programs, especially for persons with an upper motor neuron SCI. 12.3.7 Colostomy Bowel dysfunction is perceived as one of the most important disabilities, causing great anxiety and a source of emotional upset. Of all the medical problems experienced by persons with SCI, many rate the loss or change in bowel habit, to be one of the most significant factors affecting their quality of life. A colostomy is the surgical formation of an artificial anus by connecting the colon to an opening in the abdominal wall. SCI patients, who receive elective colostomy, have usually exhausted medical treatments available to them for bowel management. Colostomy is an option when the extent of bowel dysfunction becomes severe and other non-surgical methods have failed to produce a desired result. Colostomy is also frequently advocated as an adjunct in the treatment of perineal pressure ulcers, in SCI patients. However, colostomy following SCI is not routinely used, and is seen by many as failure of rehabilitation services. There is no general consensus as to when colostomy should be performed in SCI patients because there has been no way to capture the vague gastrointestinal problems that often necessitate colostomy. Colostomy significantly improved the quality of life (QOL) index in patients with SCI (Rosito et al, 2002). Table 12.7 Colostomy after a spinal cord injury 12-12

Author Year; Country Score Research Design Total Sample Size Randell et al. 2001; New Zealand Downs & Black score=17 Case Control N=52

Methods Population: 26 pts w/ colostomy: age: 2287 yr, 10 pts w/ cervical SCI, 16 w/ lumbar/lower thoracic SCI, 26 SCI without colostomy Treatment: Burwood Quality of Life Outcome Measures: Burwood Quality of Life Questionnaire: 5 areas: systemic symptoms, and emotional, social, work and bowel function Population: Age at injury: average 28.9 yrs; level of injury: 10 cervical, 18 thoracic, 3 lumbar; length of injury: mean 17.1 years Treatment: Medical records were reviewed for patients who had a colostomy. Outcome Measures: Results of surgery 1.

Outcome No significant difference (p>0.05) in the 2 groups of pts in regard to their general well being, emotional, social or work functioning.

1. 2. 3. 4.

Branagan et al. 2003; UK Downs & Black score=11 Case Series N=32

Stone et al. 1990; USA Downs & Black score=11 Retrospective Case Series N=7

Rosito et al. 2002; USA Downs & Black score=8 Case Series N=27

Population: Mean age 51.6 years, level of injury C4-T10; length of injury mean 15.7 years Treatment: Medical records were reviewed for patients who had undergone a colostomy Outcome Measures: Efficacy of colostomy. Population: mean age=62.9 years; 26 males, 1 female, level of injury range=C4L3; 17 complete and 10 incomplete injuries; mean length of injury=25.8 years Intervention: completed questionnaire Outcome Measures: Quality of Life questionnaire with 5 domains: physical health, psychosocial adjustment, body image, self-efficacy, and recreation/leisure

1.

2. 1. 2. 3. 4.

5.

The average time spent on bowel care per week decreased from 10.3 hours to 1.9 hours (p<.0001). 18/31 patients felt the colostomy gave them greater independence. 25 patients wished they had been offered a stoma earlier. No patients wanted a stoma reversal. All seven patients who had colostomy performed as an adjunct to the treatment of perianal pressure ulcers successfully healed their ulcers. The amount of time spent on bowel care decreased dramatically in the patients with prolonged bowel care. quality of life (QOL) improved significantly (p<0.0001) after colostomy. all 27 patients were satisfied, 16 very satisfied Colostomy reduced the number of hospitalizations caused by chronic bowel dysfunction by 70.4%. After colostomy, the average amount of time spent on bowel care was reduced from 117.0 min/day to 12.8 min/day (p<0.0001). Significance improvements were recorded in the areas of physical health, psychosocial adjustment, and self-efficacy.

Discussion Colostomy is a safe, effective and well-accepted treatment for severe, chronic gastrointestinal problems and perianal pressure ulcers in persons with SCI. As the research shows, colostomy reliably reduces the number of hours spent on bowel care, greatly simplifies bowel care routine, reduces the number of hospitalizations caused by gastrointestinal problems and improves quality of life (Stone et al. 1990). Colostomy increases independence, ability to travel, elevates the feelings of self-efficacy, and does not negatively affect body image. Colostomy was well received by the patients and either met or exceeded their expectations. It appears that most patients would have preferred to have the colostomy done earlier. The evolution of health care will require physicians to evaluate more critically the impact of surgical interventions, e.g. colostomy, on the patients well-being.

12-13

Conclusions There is level 4 evidence (one level 4 study) that colostomy reduces the number of hours spent on bowel care, greatly simplifies bowel care routines, and reduces the number of hospitalizations caused by gastrointestinal problems. There is level 4 evidence (one level 4 study) that colostomy improves the physical health, psychosocial adjustment and self-efficacy areas within quality of life. Colostomy is a safe and effective treatment for severe, chronic gastrointestinal problems and perianal pressure ulcers in persons with SCI, and greatly improves their quality of life. 12.4 Summary Gastrointestinal (GI) complications are frequent following a SCI and their daily challenges can severely affect the quality of life of an individual. In addition, GI complications can lead to visits to physicians, re-hospitalizations and even death. The evidence suggests that a multi-faceted approach to bowel management is effective and includes consideration of diet, medications, fluid intake, and evacuation schedules. When severe constipation persists and a bowel program cannot be attained, surgical options such as a colostomy or implanted stimulator may be considered. There is level 4 evidence (from two pre-post studies) that multifaceted bowel management programs reduce gastrointestinal transit time and incidences of difficult evacuations. There is level 1 evidence (from 1 RCT) that electrical stimulation of the abdominal wall muscles can improve bowel management for individuals with tetraplegia. There is level 4 evidence that supports the use of functional magnetic stimulation as a method to reduce colonic transit time in individuals with SCI. There is level 2 evidence that supports the use of sacral anterior root stimulation to reduce severe constipation in complete injuries. There is level 4 evidence (from 1 case series study) that supports using pulsed water irrigation (intermittent rapid pulses) to remove stool in individuals with SCI. There is level 4 evidence that indicates high fibre diets may increase colonic transit time. Cisapride: There is level 1 evidence (from 2 RCTs) that cisapride significantly reduces the colonic transit time for chronic constipation. Prucalopride: There is level 1 evidence (from 1 RCT) that prucalopride increases stool frequency, improves stool consistency and decreases gastrointestinal transit time.

Metoclopramide: There is level 2 evidence (from 1 prospective controlled trial) that intravenous administration of metoclopramide corrects impairments in gastric emptying.

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There is level 1 evidence (from 1 RCT) to support polyethylene glycol-based (PGB) suppositories for bowel management. There is a clinically significant decrease in the amount of nursing time for persons requiring assistance and less time performing bowel care for the independent individual. There is level 4 evidence (one level 4 study) that colostomy reduces the number of hours spent on bowel care, greatly simplifies bowel care routines, and reduces the number of hospitalizations caused by gastrointestinal problems. There is level 4 evidence (one level 4 study) that colostomy improves the physical health, psychosocial adjustment and self-efficacy areas within quality of life.

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References Amir I, Sharma R, Bauman WA, Korsten MA. Bowel care for individuals with spinal cord injury: comparison of four approaches. J Spinal Cord Med 1998;21:21-24. Badiali D, Bracci F, Castellano V, Corazziari E, Fuoco U, Habib FI, Scivoletto G. Sequential treatment of chronic constipation in paraplegic subjects. Spinal Cord 1997;35:116-120. Binnie NR, Smith AN, Creasey GH, Edmond P. Constipation associated with chronic spinal cord injury: the effect of pelvic parasympathetic stimulation by the Brindley stimulator. Paraplegia 1991;29:463-469. Binnie NR, Creasey GH, Edmond P, Smith AN. The action of cisapride on the chronic constipation of paraplegia. Paraplegia 1988;26:151-158. Branagan G, Tromans A, Finnis D. Effect of stoma formation on bowel care and quality of life in patients with spinal cord injury. Spinal Cord 2003;41:680-683. Cameron KJ, Nyulasi IB, Collier GR, Brown DJ. Assessment of the effect of increased dietary fibre intake on bowel function in patients with spinal cord injury. Spinal Cord 1996;34:277283. Consortium for Spinal Cord Medicine. Neurogenic bowel management in adults with spinal cord injury. In Clinical practice guidelines. Paralyzed Veterans of America; 1998. Correa GI, Rotter KP. Clinical evaluation and management of neurogenic bowel after spinal cord injury. Spinal Cord 2000;38:301-308. Dunn KL, Galka ML. A comparison of the effectiveness of Therevac SB and bisacodyl suppositories in SCI patients' bowel programs. Rehabil.Nurs 1994;19:334-338. Frost F, Hartwig D, Jaeger R, Leffler E, Wu Y. Electrical stimulation of the sacral dermatomes in spinal cord injury: effect on rectal manometry and bowel emptying. Arch Phys Med Rehabil 1993;74: 696-701. Geders JM, Gaing A, Bauman WA, Korsten MA. The effect of cisapride on segmental colonic transit time in patients with spinal cord injury. Am.J.Gastroenterol 1995;90:285-289. Glick ME, Meshkinpour H, Haldeman S, Hoehler F, Downey N, Bradley WE. Colonic dysfunction in patients with thoracic spinal cord injury. Gastroenterology 1984;86:287-294. Heart Health. The complete healthy shopping check list [pamphlet]. Heart Health. Becel and Heart and Stroke Foundation. House JG, Stiens SA. Pharmacologically initiated defecation for persons with spinal cord injury: effectiveness of three agents. Arch Phys Med Rehabil 1997;78:1062-1065. Keshavarzian A, Barnes WE, Bruninga K, Nemchausky B, Mermall H, Bushnell D. Delayed colonic transit in spinal cord-injured patients measured by indium-111 Amberlite scintigraphy. Am J Gastroenterol 1995;90:1295-1300. Korsten MA, Fajardo NR, Rosman AS, Creasey GH, Spungen AM, Bauman WA. Difficulty with evacuation after spinal cord injury: Colonic motility during sleep and effects of abdominal wall stimulation. JRRD 2004;41:95-99. Krogh K, Jensen MB, Gandrup P, Laurberg S, Nilsson J, Kerstens R, De Pauw M. Efficacy and tolerability of prucalopride in patients with constipation due to spinal cord injury. Scand J Gastroenterol 2002;37:431-436. Krogh K, Mosdal C, Laurberg S. Gastrointestinal and segmental colonic transit times in patients with acute and chronic spinal cord lesions. Spinal Cord 2000;38:615-621. Lin VW, Kim KH, Hsiao I, Brown W. Functional magnetic stimulation facilitates gastric emptying. Arch Phys Med Rehabil 2002;83:806-810. Lin VW, Nino-Murcia M, Frost F, Wolfe V, Hsiao I, Perkash I. Functional magnetic stimulation of the colon in persons with spinal cord injury. Arch Phys Med Rehabil 2001;82:167-173. Longo WE, Woolsey RM, Vernava AM, Virgo KS, McKirgan L, Johnson FE. Cisapride for constipation in spinal cord injured patients: a preliminary report. J Spinal Cord Med 1995;18:240-244. 12-16

Lynch AC, Wong C, Anthony A, Dobbs BR, Frizelle FA. Bowel dysfunction following spinal cord injury: a description of bowel function in a spinal cord-injured population and comparison with age and gender matched controls. Spinal Cord 2000;38:717-723. MacDonagh RP, Sun WM, Smallwood R, Forster D, Read NW. Control of defecation in patients with spinal injuries by stimulation of sacral anterior nerve roots. BMJ 1990;300:1494-1497. Menardo G, Bausano G, Corazziari E, Fazio A, Marangi A, Genta V, Marenco G. Large-bowel transit in paraplegic patients. Dis Colon Rectum 1987;30:924-928. Meshkinpour H, Nowroozi F, Glick ME. Colonic compliance in patients with spinal cord injury. Arch Phys Med Rehabil 1983;64:111-112. Morren GL, Walter S, Hallbook O, Sjodahl R. Effects of magnetic sacral root stimulation on anorectal pressure and volume. Dis Colon Rectum 2001;44:1827-1833. Nino-Murcia M, Stone JM, Chang PJ, Perkash I. Colonic transit in spinal cord-injured patients. Invest Radiol 1990;25:109-112. Puet TA, Jackson H, Amy S. Use of pulsed irrigation evacuation in the management of the neuropathic bowel. Spinal Cord 1997;35:694-699. Rajendran SK, Reiser JR, Bauman W, Zhang RL, Gordon SK, Korsten MA. Gastrointestinal transit after spinal cord injury: effect of cisapride. Am J Gastroenterol 1992;87:1614-1617. Randell N, Lynch AC, Anthony A, Dobbs BR, Roake JA, Frizelle FA. Does a colostomy alter quality of life in patients with spinal cord injury? A controlled study. Spinal Cord 2001;39:279-282. Riedy LW, Chintam R, Walter JS. Use of neuromuscular stimulator to increase anal sphincter pressure. Spinal Cord 2000;38:724-727. Rosito O, Nino-Murcia M, Wolfe VA, Kiratli BJ, Perkash I. The effects of colostomy on the quality of life in patients with spinal cord injury: a retrospective analysis. J Spinal Cord Med 2002;25:174-183. Segal JL, Milne N, Brunnemann SR, Lyons KP. Metoclopramide-induced normalization of impaired gastric emptying in spinal cord injury. Am J Gastroenterol 1987;82:1143-1148. Stone JM, Wolfe VA, Nino-Murcia M, Perkash I. Colostomy as treatment for complications of spinal cord injury. Arch Phys Med Rehabil 1990;71:514-518. Sun WM, MacDonagh R, Forster D, Thomas DG, Smallwood R, Read NW. Anorectal function in patients with complete spinal transection before and after sacral posterior rhizotomy. Gastroenterology 1995;108:990-998.

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CHAPTER THIRTEEN
Bladder Health And Function Following Spinal Cord Injury
Jane TC Hsieh, MSc Dalton L Wolfe, PhD Robert W Teasell, MD FRCPC

Key Points Those able to use intermittent catheterization will likely have fewer short- and longterm urological and renal complications and become catheter free faster but will not necessarily have a greater chance of becoming catheter-free as compared to other methods of bladder management. Early electroacupuncture therapy as adjunctive therapy with other bladder management methods may result in decreased time to achieve desired outcomes. Although both pre-lubricated and hydrophilic catheters have been associated with reduced incidence of UTIs as compared to conventional Poly Vinyl Chloride catheters, less urethral microtrauma with their use may only be seen with pre-lubricated catheters. Oxybutynin administered along with intermittent catheterization may reduce incontinence. Valsalva or Crede maneuver may assist some individuals to void spontaneously but also may produce high intra-vesical pressure, increasing the risk for long-term complications. Penile implants may allow easier use of condom catheters and reduce incontinence. With diligent care and ongoing medical follow-up indwelling suprapubic catheterization may be an effective and satisfactory bladder management choice for some people. Sacral anterior root stimulation (accompanied in most cases by posterior sacral rhizotomy) enhances bladder function and is an effective bladder management technique for some people. Dorsal penile nerve stimulation and direct bladder stimulation may be effective in enhancing bladder function but requires further study. Epidural dorsal spinal cord stimulation and functional electrical stimulation of the lower limbs are not effective in enhancing bladder function. Surgical and prosthetic approaches (with a sphincterotomy and stent respectively) to allow bladder emptying from a previously dysfunctional external sphincter both seem equally effective resulting in enhanced bladder function. Transurethral balloon dilation of the external sphincter may be associated with enhanced bladder function but requires further study. Cutaneous ileal conduit diversion may increase the likelihood of achieving continence but may also be associated with a high incidence of various long-term complications. Propiverine, oxybutynin, tolterodine and trospium chloride are efficacious anticholinergic agents for the treatment of SCI neurogenic bladder.

Oxybutynin co-treatment with Verapamil may enhance the standard formulation of oxybutynin in the treatment of SCI detrussor hyperreflexia. Tolterodine likely results in less dry mouth but is similar in efficacy to oxybutynin in terms of improving neurogenic detrusor overactivity. Tamsulosin is likely to improve urine flow in SCI individuals with bladder neck dysfunction. Mosixylyte is likely able to decrease maximum urethral closure pressure at a dose of 0.75mg/kg in individuals with SCI. Terazosin may be an alternative treatment for bladder neck dysfunction in individuals with SCI. but side effects and drug tolerance should be monitored. Phenoxybenzamine may be useful as an adjunct therapy for reducing residual urine volume in SCI neuropathic bladders maintained by crede or tapping. Six months of alpha 1-blocker therapy in male SCI patients may improve upper tract stasis. Intra-thecal clonidine may be beneficial as an adjunct treatment to detrussor hyperreflexia in SCI. Intrathecal Baclofen may be a beneficial adjunct treatment for bladder dysfunction in SCI. Botox A injections into the detrusor muscle or external sphincter may provide targeted treatment for bladder dysfunction in SCI. Cisapride should not be used for treatment of SCI bladder dysfunction due to lack of efficacy and risk of serious cardiac arrhythmias. Vanillanoid compounds (CAP or RTX) improve function of neurogenic detrusor overactivity of spinal origin. Capsaicin may not be linked to common bladder cancers within 5 years of use, when instilled in the bladders of individuals with SCI . N/OFG is effective for the treatment of neurogenic bladder in SCI. Intranasal DDVAP may decrease the frequency of voids or catheterizations in SCI neurogenic bladder otherwise unresponsive to conventional therapy. UTI educational intervention improves bladder health and a patients perception of the control that they have of their own health behaviours. Out-patient, nursing-mediated, re-education may be cost-effective in reducing the number of UTIs in SCI individuals identified as high risk for UTI.

Adjunct tapping and compression may help to maintain acceptable residual urine volumes in SCI bladder management. The use of portable ultrasound devices is accepted by patients and the number of intermittent catheterizations per day are reduced in patients using these devices. Quadriplegic patients can be successful with clean intermittent catheterizations for many years post-discharge. Quadriplegic patients taught clean intermittent catheterizations may continue to use this technique successfully for many years after discharge. Urostomy as a alternative to insufficient common bladder management methods may lead to long-term renal impairment. External chlorohexidine application or methenamine mandelate with hemiacidrin bladder instillant are separate techniques that are likely to reduce the incidence of UTI. Sterile vs clean catheterization technique is more effective at reducing rate of UTI but is much more costly to maintain. The prevalence of gram-negative bacteriuria is not affect by continual use or nighttime discontinuation of condom drainage. Oral methenamine mandelate in combination with hemiacidrin bladder instillant likely lowers the rate of UTI. Sterile intermittent catheterization is likely to provide successful bladder management with a lower rate of UTI and complications with a maintained continence level after discharge. There is no difference between incidence of bacteriuria in catheterized patients instilled with Kanamycin-Colistin versus Trisdine. Both limited and full microbial investigation result in adequate clinical response to UTI treatment with antibiotics. Urinalysis and urine culture results of SCI patients are not affected by sample refrigeration (up to 24 hours). Norfloxacin may be a reasonable treatment choice for UTI in SCI but subsequent resistance must be monitored. Weekly oral cyclic antibiotic (WOCA) may be beneficial in preventing UTI in SCI patients. Improved clinical and microbiological SCI UTI treatment outcome is achieved after 14 (vs 3) days of treatment with Ciprofloxin. Aminoglycosides have a low success rate in the treatment of SCI UTI.

Ofloxacin, after a 3 day treatment regimen resulted in significant UTI cure rate and bladder cell biofilm eradication rate. Successfully SCI UTI prophylaxis without appreciable side effects is possible with low-dose, long-term ciprofloxacin but not TMP-SMX. Bladder irrigation is ineffective to treat neurogenic bladder bacteriuria. Intermittent neomycin/polymyxin bladder irrigation may be effective in altering the resistance of the offending bladder organism(s) to allow for appropriate antibiotic treatment. Conflicting evidence exists for the effectiveness of cranberry juice or extracts used in the treatment of UTI. Use of cranberry, phosphate or ascorbic acid supplementation is not efficacious in acidifying the urine in SCI. Mandatory post-discharge urological management may improve quality of life in patients with neurogenic bladder secondary to SCI. Higher functioning and work-productive individuals seem to have fewer UTIs per year and this is likely associated with higher global satisfaction. Urostomy may not be a good long-term bladder management method although it may improve quality of life when other methods fail.

Table of Contents
13.1 Introduction ...................................................................................................................13-1 13.2 Bladder Function in SCI - Abbreviations and Definitions .........................................13-2 13.4 Enhancing Bladder Function By Non-pharmacological Means................................13-2 13.4.1 Comparative Studies of Various Methods of Bladder Management ............................13-3 13.4.2 Intermittent Catheterization..........................................................................................13-8 13.4.3 Triggering-Type or Expression Voiding Methods of Bladder Management................13-11 13.4.4 Condom Catheterization ............................................................................................13-13 13.4.5 Indwelling Suprapubic Catheterization for Bladder Management ..............................13-14 13.4.6 Electrical Stimulation to Enhance Bladder Function ..................................................13-16 13.4.7 Surgical and Related Techniques ..............................................................................13-21 13.5 Enhancing Bladder Use with Pharmacological Interventions ................................13-26 13.5.1 Pharmacological Interventions to Treat SCI Bladder Dysfunction .............................13-26 13.5.1.1 Anticholinergics.......................................................................................................13-27 13.5.1.2 Alpha Adrenergic Blockers......................................................................................13-29 13.5.1.3 Alpha Adrenergic Agonists......................................................................................13-32 13.5.1.4 Antispasmodics (Muscle Relaxants) .......................................................................13-33 13.5.1.5 Botulinum Toxin for the Treatment of Bladder Dysfunction in SCI..........................13-34 13.5.1.6 Other Pharmacologic agents ..................................................................................13-36 13.6 Non-pharmacological Interventions for Preventing and Treating UTIs .................13-40 13.6.1 Educational interventions...........................................................................................13-41 13.6.2 Managing Possible Sources of Contaminants ...........................................................13-46 13.6.3 Bladder Management Techniques .............................................................................13-49 13.7 Pharmacological Interventions for Preventing and Treating UTIs .........................13-52 13.7.1 Preventative Pharmacological Interventions..............................................................13-52 13.7.2 Antibiotic Interventions for Treating UTIs ...................................................................13-54 13.7.3 Dietary supplementation Based Interventions for Preventing UTIs ...........................13-60 13.8 Bladder Function and Quality of Life ........................................................................13-62 13.9 Overall Comment ........................................................................................................13-65 13.10 Summary....................................................................................................................13-65 References............................................................................................................................13-71
This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material.

Hsieh JTC, Wolfe DL, Teasell RW (2006). Bladder Health and Function Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 13.1-13.77. www.icord.org/scire

Bladder Health And Function Following Spinal Cord Injury

13.1 Introduction Bladder dysfunction, secondary to spinal cord injury (SCI), is not only disabling medically and physically but also socially (Liguori et al 1997). Normally, a full bladder provides the brain the signal to initiate bladder muscle and sphincter contraction when a person is ready to void. However, disruption of these signals through SCI causes too little, too much and/or uncoordinated contraction and prevents normal voluntary voiding without assistance. In the case of a flaccid bladder, loss of detrusor muscle tone prevents bladder emptying and leads to bladder wall damage from over-filling, urine reflux and/or an increase in infection risk. In the case of a spastic bladder, lack of or insufficient voluntary detrusor muscle and/or bladder sphincter control leads to accidental voiding or incomplete emptying. Alternatively, dysnergia of the sphincter muscles leads to un-coordination of urine outflow which can result in reflux and infection in the kidneys, ureters or bladder. A healthy bladder is possible through a bladder training program, medication and/or surgery. As well, many tests are available to help assess the bladder dysfunction (i.e. cystogram or intravenous pyelogram (IVP), cystometrogram, cystoscopy, renal ultrasound, etc.) and maintain a healthy urinary system (i.e. urinalysis, urine culture and sensitivity, BUN and creatinine, etc.). The most common problem resulting from a dysfunctional bladder, secondary to SCI, is a urinary tract infection (UTI). Bacteria carried in from a catheter or growing in residual urine is the usual cause of an UTI. Prevention, through sterile catheter technique and a complete bladder emptying routine, is the best method to combat UTIs. However, once a UTI has begun, antibiotic treatment is commonly required to remove the offending bacteria. Regardless of type of bladder management, early and accurate detection of UTI is an important aspect of bladder health in individuals with SCI. Many patients become very astute at recognizing early UTI symptoms such as increased voiding urge, blood in the urine, cloudy or smelly urine, increased spasticity in the lower extremities, fevers, chills and possibly painful urination or discomfort in the lower mid-region of the body. However, these symptoms can also be associated to medical problems other than UTI. For objective UTI confirmation, microbial investigation is often required. In the present chapter, the literature has been classified into sections pertaining either to interventions focusing on maintaining or enhancing bladder function or those aimed at preventing or treating UTIs. Within these sections the literature is further classified by nonpharmacological vs. pharmacological interventions. It should be noted that this distinction is somewhat arbitrary in that it is generally recognized that prevention of UTIs is best accomplished by optimizing bladder function including the most appropriate bladder management method.

13-1

13.2 Bladder Function in SCI - Abbreviations and Definitions

(some modified from Regional SCI Center of Delaware Valley, 2001)

Blood Urea Nitrogen (BUN) and Creatinine - Blood tests for urea nitrogen and creatinine. These provide information about kidney function. Cystoscopy - A procedure that provides a view of the inside of the bladder and urethra in great detail using a specialized endoscope (a tube with a small camera) called a cystoscope. This allows the detection of bladder stones or tumours. Alternative name: Cystourethroscopy Intermittent Catheterization (IC) A bladder management program in which the bladder is drained by inserting a catheter into the bladder at certain, typically routine times. Variants of this procedure include Sterile Intermittent Catheterization (SIC) and Clean Intermittent Catheterization (CIC). Intravenous Pyelogram (IVP) A measure of urinary function involving a contrast (iodine) dye in combination with x-rays to obtain an idea of the size, shape, functioning and abnormalities of the kidneys, ureters and bladder. Urinalysis Urine test that provides information about kidney function. Tells if there are any white blood cells, protein, sugar, blood or bacteria in the urine that are not there usually. Also determines Ph. Urine Culture and Sensitivity Urine test which assesses the amount and type of bacterial growth that occurs with an infection. The sensitivity refers to the antibiotic(s) for which the bacteria species may be susceptible. Urodynamics (Cystometrogram) Functional series of tests of the bladder that measures the way the bladder contracts when it fills and empties. Fluid or a gas is inserted slowly through a catheter into the bladder allowing a variety of procedures including among others monitoring the amount of bladder emptying (called post-void urine residual) and the pressure of the sphincters in the bladder neck (called the UPP or Urethral Pressure Profile), bladder storage pressures and whether or not the sphincter pressure creates the problem called bladder-sphincter dyssynergia. Urinary Tract Infection (UTI) An infection in the bladder or ureter. A more detailed and rigorous definition is found in 13.6. 13.4 Enhancing Bladder Function By Non-pharmacological Means In this section, the evidence for treating and maintaining healthy bladder function via nonpharmacological means will be reviewed. First and foremost, a healthy bladder involves careful selection of the most appropriate bladder management technique, with a preference for more conservative approaches that serve to minimize potential long-term complications while maintaining optimal function in a manner most suited to an individuals ability and lifestyle (Weld and Dmochowski, 2000). Often, individuals are fitted initially in the acute phase with an indwelling catheter or managed with a form of IC depending on the practice of the specific SCI unit providing care (Jamil, 2001). After the resolution of spinal shock, careful consideration of the most appropriate method takes place, ideally guided by clinical investigation involving urodynamic assessment (Jamil, 2001) in addition to the factors noted above. During rehabilitation, a complete bladder management program focuses on practice of the selected method and education highlighting the importance of regular and complete bladder emptying. 13-2

The primary purpose of a bladder management program is to ensure that the patient takes control of their voiding process and works towards emptying the bladder with a minimum of accidents (Regional SCI Center of Delaware Valley, 2001). A successful bladder management program will involve a method(s) that allows maximum independence while continuing to be effective at avoiding residual urine in the bladder and infections. The most common approaches to bladder management include intermittent catheterization (IC), reflexive bladder techniques (i.e., manually triggering the bladder reflex to assist emptying), bladder expression (e.g., Valsalva or Crede maneuvers), condom catheterization and indwelling (i.e., urethral or suprapubic) catheterization (Regional SCI Center of Delaware Valley, 2001; Wyndaele et al., 2001; Weld and Dmochowski, 2000). If these methods alone or in combination do not prove adequate, other therapeutic modalities (e.g., acupuncture), assistive devices, electrical stimulation techniques or surgical augmentations may also be employed to assist or replace the bladder management method chosen. In the present section, the literature examining each of these approaches will be grouped by individual treatment. However, in some cases specific treatments may be combined with one another and reported within the subsection deemed as the primary method of bladder management. In other cases treatments are grouped because they are associated with the same anatomical or functional entity (e.g., literature pertaining to surgical sphincterotomy is combined with that relating to use of sphincter stents). 13.4.1 Comparative Studies of Various Methods of Bladder Management As noted above, the most appropiate bladder management method is selected and practiced as part of inpatient rehabilitation. The bladder management techniques presented during rehabilitation will depend on the type of bladder dysfunction (i.e. flaccid, spastic/reflex or sphincter dysnergia), an individuals susceptibility to infection and are best based on urodynamic evaluation (Wyndaele et al., 2001). Prior to discharge, an individuals activities of daily living, psychological factors and potential caregiving needs will further impact the optimum bladder management program. Typically, conservative methods are attempted first including the following: IC, indwelling urethral catheterization or condom catheterization (males only). A slightly less conservative option involves suprapubic catheterization especially in the acute stage, which has some advantages initially in that there is no disturbance to the urethra and may also be favoured in the case of obesity, lower extremity spasticity, lack of hand function or inceased ability to engage in sexual relations (Weld and Dmochowski, 2000; Peatfield et al., 1983). If bladder function permits, spontaneous triggered or expression voiding without the need for an external drainage system may also be an option, although the disadvantages with these approaches have been outlined in a recent review (Wyndaele et al., 2001). This involves tapping on the abdomen or raising the bladder pressure through maneuvers such as Crede or Valsalva to assist voiding. Valsalva is defined as increasing the abdominal pressure by using the diaphragm and/or abdominal musculature, while Crede involves the manual application of suprapubic pressure over the bladder (Greenstein et al., 1992). Often, these approaches are attempted in combination with each other and in particular, these latter maneuvers are sometimes employed to initiate voiding, no matter what the primary method. In this way, these maneuvers act as triggering mechanisms to initiate voiding (Regional SCI Center of Delaware Valley, 2001). For the most part, these approaches are considered in advance of other options involving surgery or stimulator implantation and there are several authors that have compared the relative effectiveness of these various methods of bladder management.

13-3

Table 13.1 Individual Studies Comparing Bladder Management Methods to Optimize Bladder Function
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Cheng et al. 1998; Taiwan PEDro=4 RCT N=60

Population: SCI; Acupuncture vs Control Group; Gender (M/F): 24/8 vs 23/5; Mean Age: 39.412.1 vs 34.311.6 years; 34 above T11, 26 below T11; 25 Frankel A, 35 Frankel B; Post-injury time: 23.712.8 vs 26.112.1 days. Treatment: Electroacupuncture to 4 points (CV3,CV4,UB32 bilateral) + conventional bladder training (n=32) vs control group of conventional bladder training only (n=28). Outcome measures: Time from SCIbladder balanced, urodynamic assessment in n=20 of acupuncture group.

1.

2. 3.

4.

time to achieve bladder balancing for those with upper motor lesions acupuncture vs control, 57.122.5 vs 85.227.4 days (p<0.005). Similar for lower motor neuron lesions, 55.4 22.6 vs 83.4 26.1 days (p<0.01). If it was started within 3 weeks of SCI, bladder balancing was achieved sooner, 46.613.2 vs 65.815.4 days (p<0.005). No significant changes seen in urodynamic assessment associated with 1st acupuncture session but in bladder capacity and voiding pressure seen by time bladder was balanced. Both forms of indwelling catheterization had an increased risk of getting bladder stones and requiring hospitalization for bladder stones over IC and condom drainage with or without sphincterotomy. Relative to IC, hazard ratio was 10.5 for suprapubic catheters and 12.8 for indwelling urethral catheters. Incidence density ratio (like odds ratio) was 40.7 for developing bladder stones for indwelling catheters relative to IC. Condom incidence density ratio was 7.5 relative to IC. % Annual risk for stone formation: Condom & Sphincterotomy 0%; IC 0.2%; Expression voiding with or without condom 0.5%; Indwelling catheter 4% (first stone), 16% (subsequent stone). Complication rates for those managed by IC, voiding spontaneously, suprapubic and urethral catheterization were 27.2%, 32.4%, 44.4% and 53.5% respectively. Frequency of those managed by IC, voiding spontaneously, suprapubic and urethral catheterization was 92, 74, 36 and 114 respectively. Urethral catheter users had the highest rates for epididymitis, pyelonephritis, upper tract stone, bladder stone, urethral strictures and periurethral abscess. Suprapubic catheter users had the

Ord et al. 2003; England Downs & Black score=15 Case Series N=457

Population: SCI with > 6 months followup; 88% males; Mean Age: 29-40 years for various groups; Average injury level: T3 T9 for various groups; complete, incomplete; Median follow-up: 48 107 months for various groups. Treatment: Assessment of various bladder management methods (i.e., sphincterotomy, condom, IC, indwelling urethral catheter, suprapubic catheter, + combinations of each). Outcome measures: Bladder stone formation rate.

1.

2. 3.

4.

Weld & Dmochowski 2000; USA Downs & Black score=15 Case Series N=316

Population: SCI; 313 males, 3 females; Mean Age: 33.9-41.0 years for various groups; 269 suprasacral, 47 sacral; 45 complete, 271 incomplete; Mean follow-up: 17.8-19.3 years for various groups. Treatment: Assessment of various bladder management methods (i.e., IC, voiding spontaneously, indwelling urethral catheter, suprapubic catheter). Outcome measures: Urological complication rate (epididymitis, pyelonephritis, upper tract stone, bladder stone, urethral strictures, periurethral abscess, vesicoureteral reflux, abnormal upper tracts).

1.

2.

3.

4.

13-4

Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

highest rates for vesicoureteral reflux and abnormal upper tracts. Population: SCI; 36 males, 14 females ; Age: 3815 (18 to 58) yrs; ASIA: A-D; 7 tetraplegia, 43 paraplegia; time since injury: 12480 (10-210) days; Rehabilitation LoS: 13050 (40 to 190) days; Follow-up: 248 (5 to 40) months;. Treatment: Follow-up of those with various bladder management methods. Outcome measures: Bladder management method, compliance. 1. 2. At admission 86% used indwelling catheter and by discharge IC was used by 74%. At follow-up, of 38 people using IC, 52% reverted back to indwelling catheter by 24 months, 42% continued with IC. Tetraplegics had lower compliance with IC than paraplegics (p<0.05) majority of tetraplegics (80%) reverted to indwelling catheter vs only 40% of paraplegics. More females (60% vs 50%) reverted to indwelling catheters but this was not significant. More with complete injuries reverted to indwelling catheters (68% vs 31%, p<0.01). Main reasons for changing method = dependence on care givers, severe spasticity, incontinence and inconvenience (females). No difference between the methods in proportion of people catheter free. Of those becoming catheter free, those using IC became catheter free significantly faster (p<0.01). Most urological complications (including UTIs) were most frequent with use of indwelling Foley catheters.

3.

Yavuzer et al. 2000; Turkey Downs & Black score=11 Case Series N=50

4. 5. 6.

Wyndaele et al. 1985; Belgium Downs & Black score=7 Case Series N=115

Population: Traumatic and non-traumatic SCI; 92 males, 23 females; Mean age=34 (males), 42 (females); Paraplegia, Tetraplegia. Treatment: Voiding by subrapubic catheter, indwelling Foley catheter, IC or indwelling Foley and IC combined during spinal shock. Outcome measures: % patients being catheter-free, UTIs and various urological complications. Population: SCI; all above T11; time since injury> 5 years. Treatment: Assessment of urological/renal complication rate associated with suprapubic cystostomy drainage of >=5 year vs condom or Foley catheter drainage. Outcome measures: Intravenous urography (IVU) and cystourethrogram (CUG) evaluated at >= 5 years post-injury.

1. 2. 3.

1.

Hackler 1982; USA Downs & Black score=7 Case Series N=31

2.

Renal complication rate is greater after 8 years of suprapubic cystostomy (SPC) than for those with 20 years use of condom or to a lesser extent Foley catheter drainage. Percentages reported for various complications: Normal - 39% with suprapubic vs 51% Foley and 66% condom; Caliectasis (calculi) - 50% with SPC vs 24% Foley and 23% condom; Hydronephrosis - 10% with SPC vs 19% Foley and 10% condom.

Discussion Several authors have examined the frequency of a variety of urological and renal complications associated with various forms of chronic bladder management (Ord et al., 2003; Weld and 13-5

Dmochowski, 2000; Hackler, 1982). These authors have all employed retrospective chart reviews to examine complication rates associated with long-term follow-up data. In general, these authors concur that the greatest number of complication occur with long-term use of indwelling suprapubic and urethral catheters. In particular, of these investigations, Weld and Dmochowski (2000) employed a large sample (N=357) and examined the greatest range of complications. These authors noted that long-term urethral catheterization was associated with the largest overall number of complications, with long-term suprapubic cathetrization ranked next. Depending on the specific complication, one of these two methods was associated with the highest incidence. Urethral catheter users had the highest rates for epididymitis, pyelonephritis, upper tract stones, bladder stones, urethral strictures and periurethral abscess. Suprapubic catheter users had the highest rates for vesicoureteral reflux and abnormal upper tracts. It should be noted that these authors did not account for changing bladder management methods, preferring to simplify the analysis by classifying the results by the most predominate bladder management method. Ord et al. (2003), on the other hand, also examined a relatively large dataset (n=467) but examined all the combinations of changing methods. However, these authors limited their analysis to the effect of various bladder management techniques on the risk of bladder stone formation. Similar to Weld and Dmochowski (2000), these authors also found a slightly greater incidence of bladder stones for indwelling urethral catheters as compared to suprapubic catheters with each much greater than for IC. Ord et al. (2003) reported, hazard ratios relative to IC of 10.5 for suprapubic catheters and 12.8 for indwelling urethral catheters. In contrast, Hackler (1982) reported comparisons between long-term complication rates among those with condom (Texas), urethral (Foley) and suprapubic catheterization and found markedly higher rates for those managed with suprapubic catheters even though the follow-up period for these patients was only 5 years as compared to 20 years for those managed with the other 2 methods. However, these findings reflected a much smaller series of patients (N=31) and the comparisons were made from patients from different time periods reflecting different generations of care. As opposed to later and chronic use, Wyndaele et al., (1985) employed a retrospective case series design to examine the effect that various bladder management approaches used during the period of spinal shock had on outcomes as assessed at 8 months. They evaluated those individuals using IC, indwelling urethral (Foley) catheter, combination of indwelling urethral (Foley) with IC and subrapubic catheter alone or with IC in a case series of 115 patients. Only 6 individuals used a suprapubic catheter alone or with IC so this was likely too small a number from which to draw meaningful conclusions. As with investigations of long-term usage, those individuals able to use IC as their primary method during earlier acute and post-acute care (i.e., prior to the resolution of spinal shock) had the in fewest complications number of complications as assessed at 8 months. In addition, Wyndaele et al. (1985) noted that those using IC became catheter-free faster although there were no differences in the proportion of those becoming catheter-free in comparison to those using the other bladder management methods. It should be noted that even though there are differences in rates between bladder approaches supportive of the clinical preference of intermittent catheterization or use of triggered spontaneous voiding, it is not always possible to use these methods. Spontaneous voiding may not be possible given the state of bladder function and intermittent catheterization is limited in those with impaired hand function. Yavuzer et al., (2000) employed a case series (N=50) and reported the compliance of those employing various bladder methods at discharge from inpatient rehabilitation. At admission 86% of their patients used indwelling catheters and by discharge intermittent catheterization was used by 74%. However, at follow-up (mean time = 24 13-6

months) 52% of those individuals employing intermittent catheterization at discharge had reverted back to indwelling catheters with only 42% continuing with intermittent catheterization. The majority of those with tetraplegia (80%) reverted to indwelling catheters as compared to only 40% of those with paraplegia, presumably due to limitations with hand function. In addition, having a complete injury and being female also was associated with a greater likelihood of reverting to indwelling catheters. The primary reasons indicated for changing methods were a greater dependence on care-givers than originally thought, presence of severe spasticity, incontinence and inconvenience with intermittent catheterization (females only). It should be noted that some assistive devices that may enhance compliance with intermittent catheterization for those with impaired hand function do exist, although these are likely not in widespread use. For example, Adler and Kirshblum (2002) reported a series of 9 individuals with C5-C7 SCI, originally unable to perform intermittent catheterization, having success and expressing satisfaction with a device to help performance of intermittent catheterization. Other trials have been conducted which examine approaches that may prove effective as adjunctive therapies. For example, Cheng et al. (1998) conducted a RCT (N=60) investigating the effectiveness of electroacupuncture administered in combination with the bladder management of choice as compared to those not receiving electroacupuncture. Their primary outcome measure was the time to achieve bladder balancing which was defined as the time when 1) the patient could easily pass adequate urine at low pressure, 2) residual urine of approximately 100 ml or less and 3) absent UTIs. Although employing a randomized, controlled design, some limitations of the design (i.e., lack of blinding, concealed allocation or intent to treat) constrained the level of evidence assigned to this trial (i.e., Level 2). Regardless, those receiving electroacupuncture had a reduced time to achieve bladder balancing for both those with upper motor lesions (p<0.005) and lower motor neuron lesions (p<0.01). In addition, if electroacupuncture was started within 3 weeks of SCI, bladder balancing was achieved sooner than those in which started after 3 weeks (p<0.005). Conclusion There is Level 4 evidence that indwelling urethral catheterization, employed acutely, has abated is associated with a higher rate of acute urological complications than intermittent catheterization. There is Level 4 evidence that prolonged indwelling catheterization, whether suprapubic or urethral, may result in a higher long-term rate of urological and renal complications than IC, condom catheterization or triggered spontaneous voiding. There is Level 4 evidence that intermittent catheterization, whether performed acutely or chronically, has the lowest complication rate. Chronic use of a spontaneous triggered voiding method has comparable long-term complication rates to intermittent catheterization. There is Level 4 evidence that acute use of intermittent catheterization is associated with reduced time to become catheter-free in comparison with indwelling urethral or suprapubic catheterization. There is likely no difference among these methods for the likelihood with which one will become catheter-free.

13-7

There is Level 4 evidence that those who use intermittent catheterization at discharge from rehabilitation may have difficulty continuing with particular difficulty for those with tetraplegia and complete injuries. To a lesser degree females also have more difficulty than males in maintaining compliance with IC procedures. There is Level 2 evidence that early treatment with electroacupuncture may shorten the time that it takes for urine to pass at low pressure with minimal residual volume, no matter the primary method of bladder management. Those able to use intermittent catheterization will likely have fewer short- and long-term urological and renal complications and become catheter free faster but will not necessarily have a greater chance of becoming catheter-free as compared to other methods of bladder management. Early electroacupuncture therapy as adjunctive therapy with other bladder management methods may result in decreased time to achieve desired outcomes.

13.4.2 Intermittent Catheterization As noted above, intermittent catheterization is a preferred method of bladder management which if able to be performed, is associated with a reduced number of complications and faster time to achieve spontaneous voiding (if this becomes possible). The present section outlines those studies focusing on specific aspects of intermittent catheterization, providing information about catheter selection (Waller et al.,1997; De Ridder et al.,2005; Giannantoni et al.,2001) and potential adjunctive therapies (Vaidyananthan et al.,1998) as well as a study examining bladderrelated quality of life of those using IC vs able-bodied controls (Oh et al.,2005). Table 13.2 Individual Studies Examining Use of Intermittent Catheterization to Enhance Bladder Function
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Giannantoni et al. 2001; Italy PEDro=9 RCT N=18

Population: SCI; Mean Age: 38.216.4 years; C5-Cauda Equina; AIS A-D; Postinjury time: 18-60 days. Treatment: Assessment of Instacath nonhydrophilic pre-lubricated catheter vs conventional uncoated PVC Nelaton catheter for IC (crossover design). Outcome measures: symptomatic UTI, incidence of urethral complications (ultrasound, CUG), urinalysis, visual analog scale of patient satisfaction. Collected at the start and end of 7 week study period.

1.

2.

3. 4. 5.

Lower incidence of UTIs (p=0.03) and asymptomatic bacteriuria (p=0.0244) of those using pre-lubricated catheters vs PVC. More epithelial cells found on conventional vs pre-lubricated catheter (p=0.01) indicative of possible microtrauma. 2 people had urethral bleeding with conventional catheter, 0 with prelubricated. Pre-lubricated catheters had significantly higher satisfaction scores for 4 of 5 items on the scale. 3 subjects requiring assistance with the conventional catheter became independent with the pre-lubricated

13-8

Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

6.

catheter (order effect unreported) No subject had impaired renal function of upper & lower tract abnormalities with either catheter. Lo-Fric catheter had significantly reduced friction (55%) as compared to Easicath (p<0.001). Nurses reported fewer # of times catheters had stickings with Lo-Fric catheter as compared to Easicath (3 vs 42). There was no significant difference in the incidence of UTIs with either catheter (2 vs 3). Mean catheterization time was similar for both catheters. Lo-Fric catheter had >10x higher osmolality as compared to Easicath Lower incidence of UTIs of those using SpeediCath hydrophilic vs PVC (p=0.02). No difference in number of bleeding episodes or occurrence of hematuria, leukocyturia and bacteriuria between 2 catheters. More individuals expressed greater satisfaction with various aspects of the hydrophilic catheter, although these differences were not significant. 54% dropout rate (slightly moreso in hydrophilic group) partially due to the fact that many subjects no longer needed to catheterize when bladder function was retained within the 1 year period. All scores for the non-SCI subjects were significantly higher than those with SCI, indicative of QoL. Within the SCI group, older patients (>50) had significantly lower scores for energy and vitality (p=0.003). Those with non-cervical injury had higher physical functioning scores than those with cervical injury (p<0.001). Those able to perform selfcatheterization had higher physical functioning scores than those unable (p<0.0001). There were no differences due to gender, education level or income within the SCI group.

Waller et al. 1997; Sweden PEDro=7 RCT N=14

Population: SCI treated at SCI Unit; Median Age: 30 (22-62) years; 5 paraplegia, 8 tetraplegia; 8 complete, 6 incomplete; Post-injury time: 5 days 5 months. Treatment: Assessment of Lo-Fric vs EasiCath hydrophilic catheters for IC. Outcome measures: Friction force on removal, # of times catheter stuck, UTIs, osmolality.

1. 2.

3. 4. 5.

De Ridder et al. 2005; Belgium, Spain PEDro=5 RCT N=123

Population: SCI using hydrophilic vs PVC catheter; Mean Age: 37.514.6 vs 36.714.6 years; AIS A-D. Treatment: SpeediCath hydrophilic catheters vs conventional uncoated PVC catheter for IC. Outcome measures: Occurrence of symptomatic UTIs, hematuria, strictures, convenience of use, satisfaction with catheter collected over a 12 month period.

1. 2.

3.

4.

Oh et al. 2005; South Korea Downs & Black score=18 Post Trial with Control (Inadequate Control) N=282

Population: SCI vs healthy controls; 81 males, 51 females ; Age: 41.81.4 yrs; 81.8% tetraplegia, 18.2% paraplegia; time since injury: 67.88.6 months. Treatment: Assessment of health-related quality of life of those using IC vs matched healthy controls. Outcome measures: SF-36, demographics collected at outpatient appointment or post-rehabilitation hospital visit.

1. 2. 3.

4.

Vaidyananthan et al. 1998; England

Population: SCI; Age=22-69; Level=C6T12; Time post-injury=6-38 years.

No group results reported. 1. All subjects showed continence with

13-9

Author Year; Country Score Research Design Total Sample Size Downs & Black score=10 Pre-post N=7

Methods

Outcome

Treatment: IC 5-6 times a day alone first then with intra-vesical instillation of oxybutynin (5 mg in 30 ml) 1-3 times a day for 14 to 30 months in individuals originally managed by condom catheterization. Outcome measures: Customized scales of urinary continence, sexuality, quality of life and monitoring of side effects.

2. 3. 4.

IC and much moreso with oxybutynin added. 6/7 subjects reported sexuality with IC and all subjects had even much higher ratings with oxybutynin added. Mixed results with quality of life with IC but consistently quality of life when added oxybutynin. UTIs with IC and oxybutynin.

Discussion There are several trials which have investigated the effects of varying the properties of catheters used for intermittent catheterization (De Ridder et al., 2005; Giannantoni et al., 2001; Waller et al., 1997). For example, Giannantoni et al. (2001) employed a double-blind, crossover RCT design (N=18) to examine the difference between a pre-lubricated nonhydrophillic Instantcath catheter as compared to a conventional polyvinyl chloride (PVC) silicon-coated Nelaton catheter with respect to the occurrence of UTIs and urethral trauma. The subjects were randomized to 1 of 2 groups which tried each catheter for a period of 7 weeks in an A-B, B-A design. Both incidence of UTIs and presence of asymptomatic bacteriuria was reduced for the pre-lubricated catheter vs the conventional PVC catheter. Perhaps most interesting, 3 subjects requiring assistance with the conventional catheter became independent with the pre-lubricated catheter, although it was not reported if these individuals were in the group using the conventional catheter initially or lastly. The existence of an order effect (or not) for any of the measures was not reported. In terms of general satisfaction with use, subjects rated the pre-lubricated catheter significantly higher than the conventional catheter with respect to comfort, ease of inserting and extracting, and handling. A similar finding of reduced incidence of UTIs was reported by De Ridder et al. (2005), but in this case the comparison was between a hydrophilic catheter as compared to the conventional PVC catheter, with the hydrophilic catheter associated with fewer infections. This multi-centre investigation also employed a RCT design (N=123) but had several methodological problems that likely constrained the potential utility of the results. Most significant was a high drop-out rate (54%) with slightly more individuals not completing the study from the hydrophilic catheter group. A probable cause for many of these drop-outs was the lengthy treatment period of 1 year during which many individuals were likely to improve bladder function such that intermittent catheterization was no longer required. There were no other significant differences noted between the two groups including the number of bleeding episodes or occurrence of hematuria, leukocyturia and bacteriuria. More individuals expressed greater satisfaction with various aspects of the hydrophilic catheter, although these differences were also not significant. A third investigation examining catheter properties was designed to examine the effect of osmolality on two different hydrophilic catheters. Waller et al. (1997) demonstrated significantly reduced friction with one catheter vs the other and nurses also reported significantly fewer times this catheter had stickings. These differences did not translate into clinically significant results, however, as there was no significant difference in the incidence of UTIs with either catheter. However, the friction difference was explained by the authors as consistent with a greater than 10-fold higher osmolality for the catheter with lower friction. 13-10

Another investigation employed a different method to enhance bladder function by an adjunctive therapy to intermittent catheterization. Vaidyananthan et al. (1998) reported a pre-post trial (N=7) for which individuals originally managed by condom catheterization were switched to intermittent catheterization for a period of time, followed by another period when an intra-vesical instillation of oxybutynin was administered as well. Although no group statistical results were reported, all subjects showed improved continence with intermittent catheterization and even moreso when oxybutynin was added. Quality of life scores were mixed with intermittent catheterization alone but showed a definite improvement when oxybutynin was added. This may have been partly due to a reduced incidence of UTIs with the combination of intermittent catheterization and intra-vesical oxybutynin. Quality of life assessments associated with intermittent catheterization were also reported by Oh et al. (2005). These authors conducted interviews with the SF-36 in 132 individuals with SCI who performed clean intermittent catheterization and compared the results with 150 able-bodied controls of similar gender and age distribution. Generally, all scores for the non-SCI subjects were significantly higher than those with SCI indicative of reduced health-related quality of life for those with SCI. Within the SCI group, those able to perform self-catheterization had higher physical functioning scores than those unable (p<0.0001). These results are not surprising and the role of intermittent catheterization in these differences is likely relatively minor given the potential for other physical limitations within the SCI group. Conclusion There is Level 1 evidence based on 1 RCT that pre-lubricated hydrophilic catheters are associated with fewer UTIs and reduced incidence of urethral bleeding and microtrauma as compared to conventional Poly Vinyl Chloride catheters. There is Level 2 evidence based on 1 RCT that fewer UTIs, but not necessarily urethral bleeding may result with the use of hydrophilic catheters as compared to conventional PVC catheters. There is Level 4 evidence that those with neurogenic bladder due to SCI and managed with IC may have a lower health-related quality of life on most domains assessed by the SF-36. There is Level 4 evidence that incontinence may be reduced with intermittent catheterization and even moreso when oxybutynin is administered as well. Although both pre-lubricated and hydrophilic catheters have been associated with reduced incidence of UTIs as compared to conventional Poly Vinyl Chloride catheters, less urethral microtrauma with their use may only be seen with pre-lubricated catheters. Oxybutynin administered along with intermittent catheterization may reduce incontinence. 13.4.3 Triggering-Type or Expression Voiding Methods of Bladder Management Individuals with SCI undergoing inpatient rehabilitation are taught various maneuvers in order to initiate or attempt spontaneous voiding, termed expression voiding as well as to provide a

13-11

trigger to initiate voiding via catheters (Regional SCI Center of Delaware Valley, 2001; Wyndaele et al., 2001). As noted previously, these involve methods to increase intra-abdominal pressure so as to facilitate voiding. The recent literature addressing these techniques is sparse and only 1 study is included in the present review. Table 13.3 Individual Studies Describing Triggering-Type Bladder Management Methods
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Greenstein et al. 1992; USA Downs & Black score=8 Case Series N=5

Population: SCI; 5 males; Age: 29-58yrs; Paraplegic; Incomplete, Complete; Time since injury=2.5-34yrs. Treatment: Voiding by Valsalva or Crede maneuver. Outcome measures: Bladder pressure (urodynamics), bladder and renal complications.

No group results reported. 1. The Valsalva procedure enabled bladder emptying in 4 and the Crede procedure in 1 people. 2. 1 of 5 people using these methods long-term developed a significant complication (increasing difficulty voiding, several UTIs with bilateral hydronephrosis) associated with bilateral grade 3 reflux. 3. 1 other had grade 2 vesicoureteral reflux. 4. 3 had symptomatic UTIs and 1 had an asymptomatic UTI.

Discussion Greenstein et al. (1992) documented the use of Valsalva and Crede maneuvers to initiate spontaneous voiding in a small case series of 5 males with paraplegia. This study was intended to examine the potential for long-term complications in those who employed these techniques over an extended period of time. It was noted via urodynamic studies that a bladder pressure during voiding ranged from 95 to 160 cm of H2O. In 2 individuals vesicoureteral reflux was demonstrated, with one of these more serious (Grade 3) and this individual had impaired renal function and hydronephrosis. The authors suggested that long-term monitoring for these individuals is advisable and intermittent catheterization should replace these methods in the event of urological complications. Conclusion There is Level 4 evidence that triggering mechanisms such as the Valsalva or Crede maneuvers may assist some individuals with neurogenic bladder to void spontaneously but these are also associated with high intra-vesical pressures which could conceivably lead to renal complications.

Valsalva or Crede maneuver may assist some individuals to void spontaneously but also may produce high intra-vesical pressure, increasing the risk for long-term complications.

13-12

13.4.4 Condom Catheterization A viable option for bladder management in males is condom catheterization. As noted above, condom catheterization is associated with relatively fewer complications than indwelling methods but more than IC (Ord et al., 2003; Hackler, 1982). One issue with condom catheterization is the difficulty by which they may be applied, especially in the event of impaired hand function. Also, slippage of the condom can result in leaks. The paper reviewed below describes the use of penile implants, in part as a means to circumvent these issues. Table 13.4 Individual Studies Describing Issues Associated with Condom Catheterization
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Perkash 1992; USA Downs & Black score=7 Case Series N=79

Population: SCI; Mean age: 41.9 (20-74) years; 38 tetraplegia, 37 paraplegia, 4 cauda equina; all above T11; 61 complete, 18 incomplete; Mean time since injury: 8.24 (1-21) years. Treatment: Follow-up of individuals implanted with a penile implant allowing condom placement or sexual penetration. Outcome measures: Failures, complications, Quality of Life Satisfaction survey.

1. 2. 3.

4. 5. 6.

Penile implants in place mean of 7.08 years. Overall failure rate was 8% with an infection complication rate of < 2%. Prior to implant, 77% of people lost condoms and had accidents with urine leakage > 2 x week, while only 19% reported this after. Prior to implant, 18% of people had indwelling catheters, while none had indwelling catheters after. 68% of patients expressed satisfaction with sexual intercourse. All felt it was easier to keep themselves clean and dry.

Discussion Perkash et al. (1992) conducted a retrospective analysis of 79 male patients with penile implants in place over a mean time of 7.08 years. A primary reason for obtaining a penile implant in these patients, among others, was to provide a stable penile shaft to hold a condom for external urinary drainage. Prior to implant, 77% of these individuals reported having lost a condom or having an accident with urine leakage greater than twice per week. After implant, these issues were greatly improved with only 19% reporting these problems. In addition, penile implantation allowed some to switch to a more effective and safer bladder management method. Prior to implant, 18% of people had indwelling catheters, while none had indwelling catheters after. All reported improved continence, feeling it was easier to keep themselves clean and dry. Conclusion There is Level 4 evidence that penile implants may allow easier use of condom catheters, thereby reducing incontinence.

Penile implants may allow easier use of condom catheters and reduce incontinence.

13-13

13.4.5 Indwelling Suprapubic Catheterization for Bladder Management Suprapubic catheterization, first described in SCI by Cook and Smith (1976), is a preferred choice for effective bladder management in some circumstances. Although typically IC is the first choice in the acute setting during spinal shock, suprapubic catheterization is considered if there is a special concern over the potential for urethral damage with IC or indwelling urethral catheterization, the former being especially time-consuming for medical staff. Later, in chronic situations, suprapubic catheterization may also be favoured by individuals with SCI in the case of obesity, lower extremity spasticity, lack of hand function or because of perceived inceased ability to engage in sexual relations (Weld and Dmochowski, 2000; Peatfield et al., 1983). However, several have reported a high incidence of complication rates with long-term use, typically due to the inevitable incidence of accompanying bacteriuria (Jamil, 2001; Hackler, 1982). Others have noted that for the right individual and with special care and proper monitoring, suprapubic catheterization is an effective and well-tolerated method of management (Sheriff et al., 1998; MacDiarmid et al., 1995). Table 13.5 Individual Studies Describing Outcomes Associated with Suprapubic Catheterization
Author Year; Country Score Research Design Total Sample Size Methods Outcome

MacDiarmid et al. 1995; USA Downs & Black score=15 Case Series N=44

Population: Traumatic SCI with indwelling suprapubic catheter for > 1 year; 31 males, 13 females ; Age: 36 (13 79) years; paraplegia, tetraplegia; complete, incomplete; time since injury: 69 (15 151) months. Treatment: Assessment of urological/renal complication rate associated with suprapubic cystostomy drainage. Outcome measures: Urological and renal complication rate. Population: SCI; 80 male , 77 female; Age: 17-71 years; Time post-procedure: 24 (3-68 months). Treatment: Long-term follow-up of those managed by subrapubic catheter. Outcome measures: Indication, stable serum creatine levels, ultrasonography and satisfaction survey

1.

Percentages reported for various complications:0% renal deterioration, 0% vesicoureteral reflux, 0% bladder cancer, 11% incontinence, 100% asymptomatic bacteriuria, UTIs with +ive cultures 43% uncomplicated and 9% complicated, 5% hematuria, 7% renal calcul, 41% bladder calculi, 36% blocked cystostomy tubes.

1.

2. 3.

Sheriff et al. 1998; England Downs & Black score=8 Observational N=185

4. 5.

Primary indications for insertion included failed IC due to poor hand function, persistent incontinence, recurrent UTIs or bulbar strictures. In patients using suprapubic catheter for > 2 years - no apparent decline in renal function. Overall complaint rate -30%. Most common was recurrent catheter block (18%), persistent urinary leakage (8%) and a recurrent symptomatic UTI rate of 4%. 48% of patients had bladder calculi requiring intervention. Satisfaction survey indicated that for a variety of questions (e.g., impact on life, pleasure with the switch, would you do it again, etc.) 70-90% of those responding answered favourably. 15/41 had died, 2 due to renal causes; 10 year survival rate 68%, 15 year

Peatfield et al. 1983; England

Population: SCI; 15 Paraplegia, 25 Tetraplegia.

1.

13-14

Author Year; Country Score Research Design Total Sample Size Downs & Black score=11 Case Series N=41

Methods

Outcome

Treatment: Long-term follow-up (minimum of 8 years) of those managed originally by subrapubic catheter as reported in 1976. Outcome measures: Mortality, renal function.

2. 3.

4.

63%. 22 of 23 surviving, evaluable patients had normal blood urea levels. IVP Results: 15 Normal, 3 bilateral pelvic/ureter dilation, 2 kidney stones, 3 non-functioning kidneys (all with indwelling urethral catheters). Current drainage system in Para (P) vs Tetra (T) as follows: Dead - 9 T, 6 P; Condom - 2 T, 12 P; Catheter - 3 T, 6P; Ileal conduit - 1 T, 1 P

Discussion The specific concerns regarding suprapubic catheter use centre on the potential for urological complications with long-term use. Several investigators have attempted to address these concerns by performing retrospective reviews of the patients within their practice (Sheriff et al., 1998; MacDiarmid et al., 1995). In particular, Sheriff et al. (1998) and MacDiarmid et al. (1995) conducted reviews focused on evaluation of long-term suprapubic catheter users. MacDiarmid et al. (1995) conducted a case series investigation of the 44 patients treated with a suprapubic catheter for at least 1 year out of the total of 688 patients seen by their spinal unit during the study period. They reported relatively low incidences for various complications (i.e., 0% renal deterioration, 0% vesicoureteral reflux, 0% bladder cancer, 11% incontinence, 100% asymptomatic bacteriuria, UTIs with +ive cultures 43% uncomplicated and 9% complicated, 5% hematuria, 7% renal calcul, 41% bladder calculi, 36% blocked cystostomy tubes) which they ascribed to strict adherence to the catheter protocol with regular follow-up and close surveillance with a dedicated medical and nursing team and informed primary care practitioners. Similarly, Sheriff et al. (1998) reported their experience with 185 patients having undergone long-term use of suprapubic catheterization, representing 23% of all new patients referred to their unit. Primary indications for insertion included failed IC due to poor hand function, persistent incontinence, recurrent UTIs or bulbar strictures. In addition, suprapubic catheters were placed to replace urethral catheters or by patient request. In all patients using suprapubic catheter for > 2 years there was no apparent decline in renal function as indicated by stable serum creatine levels and ultrasonography. There was a significant incidence of complaints associated with suprapubic catheterization (i.e., 30%). Most common was recurrent catheter block (18%), persistent urinary leakage (8%) and a recurrent symptomatic UTI rate of 4%. 48% of patients had bladder calculi requiring intervention. In spite of this, and perhaps more importantly, a satisfaction survey indicated that for a variety of questions indicating satisfaction with the catheter (e.g., impact on life, pleasure with the switch, would you do it again, etc.) 7090% of those responding answered favourably. In contrast, Peatfield et al. (1983) also conducted a long-term follow-up investigation (minimum of 8 years), however these authors examined the long-term outcomes of those managed soon after injury by subrapubic catheter as reported initially in a prior study (Smith et al., 1976). They focused on mortality and assessing renal function. In their original series of 41 patients 15 had died, 2 due to renal causes; resulting in a 10 year survival rate of 68% and a 15 year survival rate of 63%. Of 23 surviving patients, 22 were evaluable and had normal blood urea levels. IVP 13-15

results demonstrated low morbidity with the majority having normal kidney function and those with current kidney or urological problems (i.e., stones, non-functioning, dilation of pelvis or ureter) being currently managed with indwelling urethral catheterization. Although no control data was provided, the authors purported that these rates represented low mortality and morbidity rates indicating successful early intervention with suprapubic catheterization, stating it may even well become the treatment of choice in all spinal injury units (Peatfield et al., 1983). However, there were so many intervening variables unaccounted for in such an analysis and little information is provided about other potential treatments used by the subjects that such a conclusion is somewhat tenuous as has been borne out by more recent practice (Wyndaele et al., 2001). Conclusion There is Level 4 evidence that despite a significant incidence of urological and renal complications associated with acute and chronic indwelling suprapubic catheterization, this is still a reasonable choice for bladder management for some people.

With diligent care and ongoing medical follow-up indwelling suprapubic catheterization may be an effective and satisfactory bladder management choice for some people.

13.4.6 Electrical Stimulation to Enhance Bladder Function Although electrostimulation to induce voiding has been studied since the 1950s it was not until the development of the Brindley anterior sacral nerve root stimulator, and subsequent implantation of the first device in a human in1978 that widespread clinical applications have been available (Egon et al., 1998; Brindley et al., 1982). Although there are several configuarations, Creasey et al. (2001) described a system as consisting of an implanted internal stimulator-receiver which is controlled and powered via telemetered radio transmission by an external controller-transmitter. Cables and electrodes are also implanted which are held in contact with sacral nerves (i.e., often S2-S4). This system allows programmable stimulation patterns and permits control of both bowel and bladder function. Often dorsal sacral rhizotomy is performed at the same time as stimulator implantation (Vastenholt et al., 2003; Creasey et al., 2001; Egon et al., 1998). Various investigators have examined other forms of stimulation (e.g., direct bladder stimulation) employing stimulators intended for other purposes such as enhancing muscle functions for improving movement, spasticity or muscle strength. In addition, multifunctional stimulators may be configured so as to provide similar stimulation patterns to similar targets as the bladder-specific stimulators. For example, Johnston et al. (2005) reported a case series (n=3) of the results associated with a multi-functional stimulator serving functions of enhancing standing and stepping ability and bowel and bladder management. This article was not included in the review outlined below as the stimulator function was only configured for bladder function in 2 of the subjects and only fully explored in 1 of these, thereby falling short of the criteria of n3.

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Table 13.6 Individual Studies Describing Use of Bladder Stimulation to Enhance Bladder Function
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Kirkham et al. 2001; England Downs & Black score=15 Pre-post N=14

Population: SCI; 14 males; C6 L1; Complete, incomplete; > 1 year post-injury. Treatment: Different patterns of dorsal penile nerve stimulation (continuous or conditional which was a one minute burst triggered by a rise in detrusor pressure of 10 cm H2O) assessed during urodynamic evaluation. Outcome measures: Urodynamic parameters (bladder capacity, bladder compliance). Collected prior and during/following stimulation.

1. 2. 3.

4.

Both continuous and conditional stimulation increased bladder capacity. Continuous stimulation increased bladder compliance. Of 6 subjects in which both stimulation methods were tested, 4 showed bladder capacity with the conditional vs continuous method but the difference was not significant. The authors suggest the conditional neuromodulation method would be effective for use in an implanted device. At 3 months, 19/21 were successful in voiding more than 200 ml of urine on demand, while 17/21 achieved residual volumes of less than 50 ml. These results were maintained at 12 months and were compared to 4/23 and 3/23 respectively prior to implantation (p<0.001). Median voided volume (p<0.001) and residual volume (p<0.001as compared to baseline. By 12 months 18/23 people used the system as their primary bladder management method. median # of UTIs/person/year from 3 to 2 at 12 months. # of people using anticholinergics (17 2 at 12 months). # of people experiencing autonomic dysreflexia (8 2 at 12 months). Most people were satisfied with device. Also helped with bowel management. 15 of 17 time spend on bowel management. Median time was halved (p<0.001). Bladder capacity from 242 120 (40 to 600) to 567 51 (300 to 600) ml for males and from 118 80 (50 to 600) to 560 43 (400 to 600) ml for females. 56 of 65 surviving males and 26 of 28 females were all continent. All but 1 female was incontinent prior. 5 patients required an anticholinergic for continence. 58 males and 25 females used the stimulator for bladder emptying with a

Creasey et al. 2002; USA Downs & Black score=14 Pre-post N=23

Population: Complete, suprasacral (C4T12) SCI; 16 males, 7 females; Median Age: 40 (14-67) years; Median time since injury: 7 (3-26) years. Treatment: Implantation of externally controlled neuroprosthesis for stimulating the sacral nerves and posterior sacral rhizotomy. Outcome measures: Voided and residual volumes, catheter use, UTIs, anticholinergic use, autonomic dysreflexia, incontinence, satisfaction. Collected at baseline, 3 months and 12 months postimplantation.

1.

2. 3. 4. 5. 6. 7. 8.

Egon et al. 1998; France Downs & Black score=11 Case Series N=96

Population: SCI; 68 males, 28 females; Mean Age: 34.3 (males) 31.4 (females) years; 41 tetraplegia, 55 paraplegia; Time post-injury to implantation: 6.9 (males) & 6.1 (females) years; Time implantation to follow-up: 5.4 (males) & 5.8 (females) years. Treatment: 6 month follow-up of those implanted with Finetech-Brindley sacral anterior root stimulator and in most cases posterior sacral rhizotomy. Outcome measures: Urodynamic

1.

2.

3.

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

assessment prior and at follow-up as noted above.

4. 5.

6. Population: SCI; 31 males, 2 females; Mean Age: 40 (24-66) years; 21 tetraplegia, 12 paraplegia (C4-T10); 11 motor incomplete; Mean time since injury: 83.6 (7-378) months. Treatment: Implantation of epidural dorsal spinal cord stimulator at T1 (tetraplegia) or T11-T12 (paraplegia) intended primarily for spasticity relief. Outcome measures: Urodynamic parameters. Collected prior and 3 months to 1 year post-implantation. Population: SCI; 32 males, 5 females; Mean Age: 43 (23-63) years; 14 tetraplegia, 23 paraplegia; Time post-injury to implantation: 87 (11-471) months; Time implantation to follow-up: 86 (16-159) months. Treatment: Long-term follow-up of those implanted with sacral anterior root stimulator. Outcome measures: Qualiveen questionnaire for Quality of Life and impact of urinary problems, plus questions about effectiveness, side effects, advantages. 1.

residual volume of < 50 ml. UTIs . 4 reported at least 1 UTI after, 35 prior. Some reported spasticity which was transitory, pre-existing autonomic dysreflexia in 22 with bladder filling ceased. 2 stimulators became infected, 5 stimulators failed, 3 had cable failures. For the most part, 17 of 23 evaluable patients had no change in urodynamic values and mean urodynamic parameters showed no change (p>0.05). 6 of these subjects had changes in lower urinary tract function but these changes were not systematic.

Katz et al. 1991; USA Downs & Black score=11 Case Series N=33

2.

1.

2. 3. 4. 5. 6. 7. 8. 9.

Vastenholt et al. 2003; Netherlands Downs & Black score=7 Case Series N=37

32 of 37 still use the stimulator complete continence for 57% during day and 70% at night. 73% reported an improvement in continence. UTIs decreased with stimulator with majority saying they had >3/year before and 0-2/year after. Overall, patient expectations for micturition were met in 62% and partially met in 32%. Top 3 advantages UTI 68%, social life 54%, continence 54%. 30% noted no disadvantage. Impact of urinary problems on quality of life with the stimulator. quality of life as compared to a reference group reported previously with various methods of management. External technical failures = 1/17 years for cable breaks and 1/38 years for transmitter defects. Internal technical failures = 1/66 useryears.

Robinson et al. 1988; England Downs & Black score=5 Pre-post N=22

Population: SCI; 20 males, 2 females; Mean Age: 30 (20-46) years; 7 tetraplegia, 15 paraplegia; generally complete; > 1 year post-injury. Treatment: Implantation of Brindley anterior sacral root stimulator. Outcome measures: Urodynamics, intravenous urography, continence. Collected prior and following implantation.

No group results reported. 1. 16/22 using implant (11 continent, 5 incontinent). 2. Of 5 incontinent, 4 had hyperreflexia and these were unable to use stimulator with sufficient frequency. 3. 2 had hydronephrosis, both eventually undergoing sphincterotomy. 4. 6 were able to sustain an erection.

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

5. Population: SCI; 15 males; Mean Age: 47 (22-70) years; C5-T12; incomplete, complete; Time post-injury: 4 months 16 years. Treatment: 4 to 8 weeks of quadriceps muscle reconditioning by surface electrical stimulation (FES) bilaterally intended for strength and spasticity. Outcome measures: Urodynamic assessment, strength (force transducer), spasticity (pendulum test). Collected prior and following stimulation program.

Dyssynergia was noted as the main complication (n=6).

Wheeler et al. 1986; USA Downs & Black score=5 Pre-post N=15

No group results reported. 1. In general, slightly more individuals had enhanced bladder function with treatment than those with no change or reduced bladder function. 2. 7 people had bladder capacity with pressure that or stayed the same. 3. 6 people had bladder capacity with pressure that or stayed the same, however 2 of these results were confounded by resolution of spinal shock. 4. Changes in bladder function were correlated with changes in strength and spasticity. No group results reported. 1. 17 of 29 became continent, 10 others became socially dry without need for pads and urinals. 2. 26 gained perfect bladder sensation. 25 achieved satisfactory bladder contractions. 3. 28 had residual urine below 50 cc. 4. At one year, patients reported effect.

Madersbacher et al. 1982; Austria Downs & Black score=5 Case Series N=29

Population: SCI; 26 males, 3 females; Mean Age: 18-60 years; C5-S1; incomplete; Mean time post-injury to stimulation: 3 months (14 days to 8 months). Treatment: Impulses packages applied to a saline filled bladder. Minimum of ~ 50 stimulations for up to 90 minutes daily until maximal improvement is attained. Outcome measures: Urodynamic assessment, incontinence assessed with urilos-meter. Collected prior and at unspecified follow-up time.

Discussion Sacral anterior root stimulation is the most well studied method of producing bladdar voiding via electrical stimulation techniques. Vastenholt et al. (2003), Creasey et al. (2001), Egon et al. (1998) and Robinson et al. (1988) all employed Level 4 type studies consisting of case series, pre-post or post-test study designs of externally controlled sacral anterior root stimulators. Most importantly, in each of these studies the vast majority of subjects became continent and were able to successfully void with these devices, whereas this was typically not the case for most participants with whatever bladder management method was used prior to implantation. These findings appear to persist with perhaps a slight drop-off in success in that both Vastenholt et al. (2003) and Egon et al. (1998) reported continence rates of 73% and 88% for those using the stimulators an average of 7 and ~5.5 years respectively. Several of these investigators reported a significant decrease in UTIs (Vastenholt et al., 2003; Creasey et al., 2001; Egon et al., 1998) and autonomic dysreflexia (Creasey et al., 2001; Egon et al., 1998) among participants, even after long-term use. Several investigators performed satisfaction surveys and reported that most participants remained satisfied with the device, even after many years. In particular, Vastenholt et al. (2003) conducted a Qualiveen questionnaire for assessing the bladder health-related quality of life and impact of urinary problems. Overall, the top 3 advantages noted by stiulator users was a reduction in UTIs (68% reporting), improved social life (54%) and improved 13-19

continence (54%). It was also noted that the impact of urinary problems on quality of life decreased with the stimulator. There was an increased quality of life with stimulation users as compared to a reference group which had been reported previously consisting of those with SCI using various other methods of bladder management. These investigators also reported the incidence of external technical failures as 1 per 17 years for cable breaks and 1 per 38 years for transmitter defects. Internal technical failures were reported as 1 per 66 user-years. Other investigators have employed various other forms of stimulation in an effort to elicit similar benefits to the neurogenic bladder as those seen with anterior sacral root stimulation. For example, Kirkham et al. (2001) delivered two patterns of dorsal penile nerve stimulation (i.e., continuous vs one minute bursts triggered by a rise in detrusor pressure of 10 cm H2O) for this purpose. They assessed the effects of these forms of stimulation in14 individuals with SCI urodynamic evaluation before and after stimulation sessions. Both continuous and conditional stimulation increased bladder capacity whereas only continuous stimulation increased bladder compliance. Of 6 subjects in which both stimulation methods were tested, 4 showed increased bladder capacity with the conditional method vs the continuous method but the difference was not significant. Given these findings, the authors suggested that the conditional neuromodulation method would be effective for ongoing use in an implanted device which stimulates this nerve. A novel approach, which differs from the others reported here involving ongoing stimulation, was reported by Madersbacher et al. (1982). In this study, the stimulation, in the form of impulse packages applied to a saline filled bladder, was not delivered each time the subject wished to void. Rather, there was a defined treatment period (although variable for each subject) afterwhich the treatment effect persisted although by one year most subjects had reported a definite waning of the benefits. The treatment involved a minimum of 50 stimulations for up to 90 minutes daily until maximal improvement was attained. Unlike other studies presented here, this was conducted on those more relatively recently injured with mean time post-injury to stimulation being 3 months (range 14 days to 8 months). With this approach17 of 29 became continent and 10 others became socially dry without need for pads and urinals. In addition, 28 had post-void residual urine levels below 50 cc. This study involved a case series design but would have been much more powerful with the inclusion of a control group, given the potential for natural bladder recovery in individuals with more recent injuries. All of the approaches noted thus far have involved stimulation of neurons or other structures with direct connections to the urinary system. Other investigators have attempted stimulation of systems with less direct connection to the urinary system. For example, Katz et al. (1991) tested the effect of epidural dorsal spinal cord stimulation at T1 (for those with tetraplegia) or T11-T12 (for those with paraplegia) intended primarily for spasticity relief and Wheeler et al. (1986) investigated the effect of 4 to 8 weeks of quadriceps muscle reconditioning by surface electrical stimulation (FES) bilaterally intended primarily for strength and spasticity. In each case, these techniques had marginal effects on bladder function at best, however, in the latter experiment it was noted that some subjects did achieve beneficial changes in bladder function and that these tended to be most noticeable in the same subjects that showed positive improvements in strength and spasticity. Conclusion There is Level 4 evidence that ongoing use of sacral anterior root stimulation (accompanied in most cases by posterior sacral rhizotomy) results in reduced

13-20

incontinence for the majority of those implanted. This is associated with increased bladder capacity and reduced post-void residual volume. There is Level 4 evidence that sacral anterior root stimulation (accompanied in most cases by posterior sacral rhizotomy) may be associated with reducing UTIs and autonomic dysreflexia. There is Level 4 evidence that other forms of neuroanatomically-related stimulation (e.g., dorsal penile nerve stimulation or direct bladder stimulation) may have similar effects to sacral stimulation but require further study. There is Level 4 evidence that epidural dorsal spinal cord stimulation originally intended for reducing muscle spasticity may have little effect on bladder function. There is Level 4 evidence that a program of functional electrical stimulation exercise involving the quadriceps muscle originally intended for enhancing muscle function and reducing muscle spasticity has only marginal (if any) effects on bladder function.

Sacral anterior root stimulation (accompanied in most cases by posterior sacral rhizotomy) enhances bladder function and is an effective bladder management technique for some people. Dorsal penile nerve stimulation and direct bladder stimulation may be effective in enhancing bladder function but requires further study. Epidural dorsal spinal cord stimulation and functional electrical stimulation of the lower limbs are not effective in enhancing bladder function. 13.4.7 Surgical and Related Techniques There are several surgical options available for enhancing bladder function with most authors suggesting that conservative approaches should be exhausted first (Pazooki et al., 2006; Kato et al., 2002; Juma et al., 1995). Most common are those approaches associated with the external sphincter. Transtherurethral sphincterotomy and related procedures such as insertion of sphinteric stents or balloon dilation of the external urinary sphincter provide a means to overcome persistent dysynergia (Chancellor et al., 1999; Juma et al., 1995; Chancellor et al., 1993b; Chancellor et al., 1993c). Often these are performed when IC is not an option because of lack of manual dexterity or other reasons (Chancellor et al., 1999; Juma et al., 1995). Ileal conduit diversion, another surgical approach more commonly performed in females, is often performed for these same reasons of lack of manual dexterity or ease of care and convenience (Pazooki et al., 2006; Chartier-Kastler et al., 2002). This technique aims to establish lowpressure urinary drainage by diverting urine prior to entering the bladder and connecting the ureters to an external urinary collection system via a catheter passed through the ileal lumen.This procedure is sometimes conducted along with removal of the bladder as well (Chartier-Kastler et al., 2002; Kato et al., 2002). Another approach has been reported by Chancellor et al. (1993) involving bladder augmentation using the stomach in SCI patients with impaired renal function. This particular article did not meet the criteria for inclusion in the present review as it involved a case series of N<3.

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Table 13.7 Individual Studies Describing Surgical Methods to Enhance Bladder Function
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Chancellor et al. 1999; USA PEDro=5 RCT N=57

Population: SCI; 26 sphincterotomy vs 31 stent; 57 males; Mean Age: 34.59.9 vs 39.111.8 years; 70% cervical, 30% thoracic; Mean time post-injury: 8.76.6 vs 8.05.3 years. Treatment: Sphincterotomy vs placement of a sphincteric stent (UroLume prosthesis). Outcome measures: Urodynamic parameters (maximum detrusor pressure, bladder capacity, post-void residual urine volume), length of hospitalization. Collected pre-operatively and 3, 6, 12 and 24 months post-op.

1.

2. 3.

4.

5.

6. Population: SCI; 25 males; Mean Age: 32.8 (19-50) years; 23 tetraplegia, 2 paraplegia; Mean time post-injury: 7.2 (215) years. Treatment: Insertion of a sphincteric stent (UroLome prosthesis). Outcome measures: Urodynamic parameters (voiding pressure, bladder capacity, post-void residual urine volume) and various complications. Collected preoperatively and 3, 6, 12 months post-op. 1. 2. 3. 4.

Significant in detrusor pressure (p<0.05) relative to baseline with both treatments and no difference between sphincterotomy and stent at any time. No significant change in bladder capacity with either treatment at any time. Significant in post-void residual volume (p<0.05) at some time points but not others no difference between treatments. The need for catheterization, initially required in 50% of the sphincterotomy group and 71% of the stent group, was reduced to just 3, 4, 1, & 1 and 1, 0, 1 & 2 individuals respectively at each follow-up period. There was little difference in subjective assessment of impact of bladder function on quality of life or in the incidence of complications between the treatment groups. Those in the stent group spent less time in the hospital for the procedure. Significant in voiding pressure (p<0.001) relative to baseline at all follow-up times. No significant change in bladder capacity (p=0.57) at any follow-up time. Significant in post-void residual volume (p<0.01) at all follow-up times. Positive urine cultures (i.e., UTI) occurred in 22 of 25 patients prior to surgery but only in 9, 11 and 4 of the patients at 3, 6 and 12 months respectively. Subjective autonomic dysreflexia improved in all 19 who had previously complained of this. Pre-existing hydronephrosis in 5 patients resolved in 4. Of all 17 patients previously managed by indwelling Foley catheter, 15 now used condom catheters and 2 voided on their own. Significant in voiding pressure (p=0.008) relative to baseline at all follow-up times. No change in bladder capacity (p=0.30) at any follow-up time. Significant in post-void residual volume (p<0.05) at all follow-up times.

Chancellor et al. 1993c; USA Downs & Black score=15 Pre-post N=25

5. 6. Population: 16 SCI, 1 MS; 17 males; Mean Age: 34.7 (20-58) years; 13 tetraplegia, 4 paraplegia; Mean time postinjury: 13 (3-20) years. Treatment: Transurethral balloon dilation of external urinary sphincter. Outcome measures: Urodynamic parameters (voiding pressure, bladder capacity, post-void residual urine volume), cystoscopy, UTIs, autonomic dysreflexia and monitoring of renal and erectile 1.

Chancellor et al. 1993b; USA Downs & Black score=15 Pre-post N=17

2. 3. 4.

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

function. Collected prior and 3, 6, 12 months post procedure.

5.

6. 7. 8. 9.

+ive urine cultures (i.e., UTI) in 15/17 prior to surgery but only in 5, 8 and 4 of the patients at 3, 6 and 12 months respectively. Subjective autonomic dysreflexia improved in all 9 who had previously complained of this. Pre-existing hydronephrosis in 2 resolved. 3 had subjectively improved erectile function. Post-procedural complications included bleeding (1), development of new obstructions (2), stricture (1).

Juma et al. 1995; USA Downs & Black score=6 Case Series N=63

Population: SCI; Mean Age: 53 (23-76) years; 32 cervical, 25 thoracic, 6 lumbar; 32 complete, 32 incomplete; Mean time since injury: 27 (3-50) years; Mean followup since last sphincterotomy: 11 (2-30) years; Mean # of sphincterotomies: 1.74 (1-4). Treatment: Follow-up evaluation of those having sphincterotomy. Outcome measures: Complicatons since sphincterotomy as determined by following: urinalysis, urine culture (UTI), urea, creatine levels, IVP, renal ultrasound, urodynamics, cystoscopy and voiding cystorethrogram (as indicated). Collected at follow-up at mean of 11 (2-30) years since last sphincterotomy.

No statistical comparisons reported 1. 25/63 had upper tract pathology (12 renal calculi, 11 renal scarring, 1 atrophic kidney, 1 renal cyst). 19 of these were deemed significant. 2. Risk of significant upper tract complications in presence or absence of bacteria was 38% and 13% respectively. 3. 30/63 had lower tract complications (5 bladder calculi, 10 recurrent UTI, 3 urethral diverticula, 6 urethral stricture or bladder neck stenosis and 6 recurrent epididymitis). 4. Risk for lower tract complications with in leak point pressure; 50% for those with leak point pressure of > 70 cm H2O; reduced to 25% when leak point pressure of < 30 cm H2O. 5. Mean post-void residual remained high (496 ml). No statistical comparisons reported 1. Initial surgery was successful. All patients became continent after initially being incontinent prior to surgery. 2. Of 17 with pre-op hydronephrenosis, 10 showed a or disappearance. 3. 12 patients developed one or more complications during follow-up. 4 early complications and 13 late complications. 4. Most prevalent long-term complications were pyocystitis (4), pyelonephritis (4) and urethral leak (2). 5. Satisfaction survey indicated none regretted surgery (9.12.8 out of 10). No statistical comparisons reported 1. 3 subjects died (constrictive ileus,

Chartier-Kastler et al. 2002; France Downs & Black score=14 Case Series N=33

Population: SCI (21), MS (4), CP (3), Myelitis (3), Other (2); 14 males, 19 females; Mean Age: 40.615.2 years; 32 cervical, 25 thoracic, 14 C1-T10, 6 T11-L1, 1 below L2; complete, incomplete; Mean follow-up: 48 (12-240) months. Treatment: Follow-up evaluation of those having cutaneous ileal conduit (ileoureterostomy) diversion. Outcome measures: IVU, serum creatinine, cystoscopy, urine cultures and UTIs, visual analog patient satisfaction. Collected at follow-up as indicated above.

Kato et al. 2002; Japan Downs & Black score=11

Population: SCI; 13 males, 3 females; Mean Age: 4615.2 (19-70) years;

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Author Year; Country Score Research Design Total Sample Size Case Series N=16

Methods

Outcome

tetraplegia; Mean follow-up: 8.7 (2-17) years. Treatment: Follow-up evaluation of those having ileal conduit formation. Outcome measures: IVU, serum creatinine, cystoscopy, urine cultures and UTIs, visual analog patient satisfaction. Collected at follow-up as indicated above.

2. 3. 4. 5.

unknown, septicemia associated with UTIs) during the follow-up period. 7/16 patients had calculus formation in the upper urinary tract. 8 subjects of 13 in whom a bladder was initially preserved sustained a procyst. 5 experienced calculus formation in the upper urinary tract, 3 of these having severe UTIs as a result. Most patients were more satisfied with procedure than previous management method upon survey a few months after operation (no long-term follow-up on this issue).

Discussion A common surgical method of treating bladder outlet obstruction or detrusor-sphincter dyssynergia is transurethral sphincterotomy. Juma et al. (1995) reported a case series of N=63 individuals who had received 1 or more sphincterotomies with a mean follow-up time of 11 (range 2-30) years. This study was directed at describing the risk for long-term complications following this procedure. Although more than half of these individuals had normal upper tract imaging studies a significant proportion had complications - with 25/63 having some upper tract pathology (i.e., 12 renal calculi, 11 renal scarring, 1 atrophic kidney, 1 renal cyst). Nineteen of these were deemed significant. Risk of significant upper tract complications in presence or absence of bacteria was 38% and 13% respectively. 30/63 had lower tract complications (5 bladder calculi, 10 recurrent UTI, 3 urethral diverticula, 6 urethral stricture or bladder neck stenosis and 6 recurrent epididymitis). The authors noted that the most reliable urodynamic measure for predicting potential complications following sphincterotomy appeared to be an increase in leak point pressure. Complication rates of 50% were noted for those with leak point pressure of > 70 cm H2O, whereas rates were reduced to 25% when leak point pressure was < 30 cm H2O. One alternative to sphinterotomy is placement of a stent passing through the external sphincter thereby ensuring an open passage. Chancellor and colleagues have conducted several studies examining this approach (Chancellor et al., 1999, 1993c). In an initial study these investigators conducted a pre-post trial of 25 individuals focusing on urodynamic parameters as outcome measures collected pre-operatively and 3, 6 and 12 months post-operatively (Chancellor et al., 1993c). Significant reductions in voiding pressure (p<0.001) relative to baseline at all follow-up times were noted wheras no significant changes were seen in bladder capacity (p=0.57) at any follow-up time. In addition, significant decreases were seen in post-void residual urine volumes (p<0.01) at all follow-up times. Positive urine cultures (i.e., UTI) occurred in 22 of 25 patients prior to surgery but only in 9, 11 and 4 of the patients at 3, 6 and 12 months respectively. Subjective autonomic dysreflexia improved in all 19 who had previously complained of this. Subsequently, this research group conducted a RCT (N=57) comparing the outcomes associated with sphincterotomy as compared to placement of the stent prosthesis (Chancellor et

13-24

al., 1999). This study was deemed a low quality RCT, largely because blinding and concealed allocation was not possible given the nature of the intervention. Similar measurement procedures and overall findings were noted as reported for the study above (i.e., Chancellor et al., 1993c) with significant decreases in detrusor pressure (p<0.05) relative to baseline with both treatments and no difference between sphincterotomy and stent at any time. In this study, the same time periods of baseline, 3, 6 and 12 months were recorded as well as a urodynamic assessment conducted at 24 months. There were no significant changes reported for bladder capacity with either treatment and significant reductions were seen in post-void residual urine volumes (p<0.05) at some time points but not others no difference between treatments.The need for catheterization, initially required in 50% of the sphincterotomy group (N=26) and 71% of the stent group (N=31), was reduced to just 3, 4, 1, & 1 and 1, 0, 1 & 2 individuals respectively at 3, 6, 12 and 24 months respectively. There was little difference in subjective assessment of impact of bladder function on quality of life or in the incidence of complications between the treatment groups although those in the stent group spent less time in the hospital for the procedure. Chancellor et al. (1993b) also have examined a third procedure with similar rationale as that associated with sphinterotomy. This investigation involved a pre-post trial design (N=17) of transurethral balloon dilation of the external urinary sphincter. Again, similar methods were employed as the studies noted above and findings were also similar. Of all 17 patients previously managed by indwelling Foley catheter, 15 now used condom catheters and 2 voided on their own. Significant decreases were noted in voiding pressure (p=0.008) relative to baseline at all follow-up times (i.e., 3, 6 and 12 months). No changes were seen in bladder capacity (p=0.30) and significant reductions in post-void residual urine volumes (p<0.05) were seen at all follow-up times. Positive urine cultures (i.e., UTI) were noted in 15/17 prior to surgery but only in 5, 8 and 4 of the patients at 3, 6 and 12 months respectively. Subjective autonomic dysreflexia improved in all 9 individuals who had previously complained of this. Ileal conduit diversion is another surgical procedure noted with some frequency in the literature. Chartier-Kastler et al. (2002) and Kato et al. (2002) have reported separate case series (N=33 and N=16 respectively) examining this approach. Some success was reported with the procedure in that Chartier-Kastler et al. (2002) reported all patients became continent after initially being incontinent prior to surgery and Kato et al. (2002) reported most patients were more satisfied with the procedure than their previous management method upon survey a few months after the operation. Both authors also reported several long-term complications. However, it is uncertain if these high complication rates noted (as also indicated for sphinterotomy by Juma et al. (1995)) would be comparable in the event individuals had continued with their previous form of bladder management as often surgical procedures are performed only if other more conservative methods are unsuccessful. Some form of controlled trial is required to address this issue. Conclusion There is Level 2 evidence based on 1 RCT comparative study that both sphincterotomy and implantation of a sphincteric stent resulted in enhanced bladder function, with little need for subsequent catheterization. The only significant difference in these 2 treatments was the reduced initial hospitalization associated with the stent, given the lesser degree of invasiveness.

13-25

There is Level 2 evidence that both sphincterotomy and implantation of a sphincteric stent are associated with reduced detrusor pressure and reduced post-void residual volume but not changes in bladder capacity. There is Level 4 evidence that implantation of a sphincteric stent may result in reduced incidence of UTIs and bladder-related autonomic dysreflexia. There is Level 4 evidence from long-term follow-up of those having a previous sphincterotomy that the incidence of various upper and lower tract urological complications is quite high. There is Level 4 evidence that transurethral balloon dilation of the external sphincter may be associated with enhanced bladder function, notably reduced detrusor pressure and reduced post-void residual volume but not changes in bladder capacity. Most individuals undergoing the procedure were able to discontinue use of indwelling catheters in favour of condom catheterization. There is Level 4 evidence that most individuals undergoing cutaneous ileal conduit (ileoureterostomy) diversion became newly continent and were more satisfied than with their previous bladder management method. Long-term follow-up demonstrated the presence of a high incidence of urological or renal complications.

Surgical and prosthetic approaches (with a sphincterotomy and stent respectively) to allow bladder emptying from a previously dysfunctional external sphincter both seem equally effective resulting in enhanced bladder function. Transurethral balloon dilation of the external sphincter may be associated with enhanced bladder function but requires further study. Cutaneous ileal conduit diversion may increase the likelihood of achieving continence but may also be associated with a high incidence of various long-term complications.

13.5 Enhancing Bladder Use with Pharmacological Interventions The disruption of information transmittal between the brain and the bladder resulting from spinal cord injury causes bladder dysfunctions such as abnormal detrusor muscle tone, urine reflux, accidental voiding or incomplete emptying. There are two general categories of bladder dysfunction: 1) spastic or reflex bladder and flaccid or non-reflex bladder. The former causes involuntary voiding while the latter results in overfilling of the bladder. Dyssynergia occurs when the bladder contracts but the sphincter does not open. The nature of the problem can be assessed with tests such as cystograms or intravenous pyelograms (IVP), cystometrograms, cystoscopy, renal ultrasound, and/or routine laboratory analysis such as urinalysis, urine culture and sensitivity, BUN and creatinine, etc. Pharmacological management is often used to augment one or more non-pharmacological bladder management methods. 13.5.1 Pharmacological Interventions to Treat SCI Bladder Dysfunction As with many organ systems, the genitourinary system is modulated by both the voluntary (somatic) and involuntary (autonomic) nervous system. The striated muscles of the external sphincter are under control of the somatic nervous system while the smooth muscles of the 13-26

detrusor and the internal sphincter are in large part under control of the autonomic nervous system. To complicate matters further, the autonomic nervous system is comprised of both the sympathetic and parasympathetic nervous systems whose actions can be oppositional depending on emotional states. Injuries to the spinal cord can result in damage to parasympathetic nerve supply to the detrusor smooth muscles, the sympathetic nerve supply to the bladder neck smooth muscle and/or somatic nerve supply to the striated muscle of the external urethral sphincter. As a result of heterogenous innervations to the urinary system, alternative treatments are widely varied. Commonly chosen pharmacological agents for the treatment of bladder dysfunction include anticholinergics, alpha adrenergic blockers, alpha adrenergic stimulants, muscle relaxants, botulinum toxin and others. 13.5.1.1 Anticholinergics Of the two general categories of bladder dysfunction, spastic or reflex bladder causes involuntary voiding that can be treated with smooth muscle relaxants that are called anticholinergics. The muscarinic receptros in the detrusor muscle are blocked by anticholinergics to decrease inappropriate bladder contraction. Overactive bladder secondary to a variety of indications is commonly treated with marketed drugs such as Ditropan, Detrol, Levsinex. Table 13.8 Summary Table of Anticholinergics
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Stohrer et al. 1999; Germany PEDro=9 RCT Initial N=124; Final N=113

Population: Gender: m=69, f=44; Age: mean 29-30 yrs Treatment: 15mg of propiverine or placebo were given 3 times a day for 14 days Outcome Measures: Urodynamic parameters, patients clinical symptoms, physicians assessment of efficacy, adverse events and laboratory parameters (haematology, bleeding times, clinical chemistry etc) Population: SCI, MS; Mean Age: 40.5 years; 9 male, 1 female; Mean Post-injury time: 13.7 years. Treatment: Neurogenic detrusor overactivity tx. Double-blind design with tolterodine (T) 2mg twice daily vs placebo (P). Open label: tolterodine self-selected dose (TSSD) vs oxybutynin SSD (OSSD) Outcome measures: Cystometric capacity, catheterization volumes, number of episodes of urinary incontinence per day, degree of mouth dryness per day using visual analog scale (VAS).

Ethans et al. 2004; Canada PEDro=6 RCT (Tolterodine vs placebo) Cohort (Oxybutynin vs tolterodine) N=14

Significant treatment increases: 1. Bladder capacity (p=0.006). 2. Maximal cystometric bladder capacity (p<0.0001). 3. Residual urine i (p=0.01). Significant treatment decreases: 4. Maximal detrusor contractions (p<0.001). 5. Detrusor contraction duration (p<0.03). Improved clinical symptoms: Treatment =63.3%; placebo =22.6%. No significant difference between T vs P groups in: 1. mean cystometric capacity 2. degree of mouth dryness T vs P significantly improved: 3. mean catheterization volume (263 mL vs 188 mL, p<0.001) 4. # incontinence episodes/day (1 vs 2.8, p<0.005) No sig. diff. btwn TSSD vs OSSD in : 1. mean cystometric capacity 2. catheterization volume 3. # incontinence episodes/day TSSD <OSSD for dry mouth (VAS 2.6 vs 4.4, p<0.05). Statistical improvements (p<0.001) in the treatment group vs placebo: 1. increased MCC

Stohrer et al. 1991; Australia PEDro=6

Population: SCI with detrusor hyperreflexia Treatment: trospium chloride (20mg bid,

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Author Year; Country Score Research Design Total Sample Size RCT N=61

Methods

Outcome

OLeary et al. 2003; USA Downs & Black score=23 Pre-post N=10

Bodner et al. 1999; USA Downs & Black score=7 Case Series N=14

3wks) vs placebo Outcome Measures: Pre-/post-treatment max cystometric capacity (MCC); max detrusor pressure (MDP), urinary flow rate and residual urine volumes, adverse events. Population: m=2, f=; Age 35-77; SCI, ASIA:A-D; omplete/incomplete. Treatment: Initial 10 mg of oxybutynin XL daily; increased by 5mg daily until symptoms were controlled or until a max dosage of 30 mg per day. Outcome Measures: Micturation frequency diaries and urodynamics were completed at baseline and repeated at week 12. Tolerability info was also collected. Population: m=10, f=4; age 19-55yrs, SCI, time since injury: 5mths-27yrs Treatment: Oxybutynin chloride alone or combined with verapamil. A few subjects were treated with Verapamil alone Outcome Measures: Not specified

2. decreased MDP No effect in either group on: 1. max flow rate 2. residual urine volume Side effects low and no difference between groups. 1. Urodynamic bladder capacity: mean cystometric bladder capacity volume significantly increased (p=0.008). 2. Mean number of voids / 24 hr period decreased (p=0.003). 3. Residual urine increased (p=0.02). 4. Nocturia decreased but not significant. 5. Incontinence episodes / week: decreased (p=0.03) No statistical results reported: 13 of the 14 improved clinically on oxybutynin and verapmil over oxybutynin alone.

Discussion Propiverine is anticholinergic or antimuscarinic muscle relaxant that works by relaxing the involuntary smooth muscle that is found in the wall of the bladder and was tested specifically in the SCI population. In a double-blind, placebo-controlled, randomized, multicentre (N=124 with 113 completers) study, 15mg tid administration of propiverine over 2 weeks yielded significant improvement of SCI detrusor hyperreflexia represented by increased maximal cystometric bladder capacity (Stohrer et al, 1999). A subsequent increase in residual urine volume was considered by the authors to be acceptable with concurrent intermittent catheterization and side effects (primarily dry mouth) considered tolerable. Oxybutynin is another anticholinergic agent used to treat overactive bladder in a variety of indications. OLeary et al 2003, in a small (N=10), before and after trial showed that controlledrelease oxybutynin was efficacious for SCI individuals with detrusor hyperreflexia as reflected by significantly increased bladder volume with decreased mean number of voids per 24 hours. However, post-void residual volumes, nocturia and weekly incontinence episodes did not change significantly. Bodner et al 1999, used standard oxybutynin in combination with verapamil (a calcium channel blocker) to treat detrusor hyperreflexia in SCI individuals and found that 13 of 14 subjects showed clinical signs of improvement with oxybutynin plus varapamil over oxybutynin alone. Although oxybutynin is commonly chosen to treat overactive bladder, it is accompanied by annoying side effects such as dry mouth. A new anticholinergic, tolterodine, that causes less dry mouth has also been shown to be efficacious for the treatment of neurogenic bladder dysfunction. In a RCT (Ethans et al., 2004) tolterodine was significantly better at increasing intermittent catheterization (IC) volumes (p<0.0005) and reducing incontinence (p<0.001) but 13-28

was similar in its effects on cystometric bladder capacity when compared to placebo. As an eligibility criteria, subjects were using oxybutynin and IC prior to a 4-day washout prior to randomization to the tolterodine vs placebo study. This design allowed for an efficacy comparison between oxybutynin and tolterodine where the two drugs were found to be equivocal with respect to IC volumes, degree of incontinence and bladder capacity. Although available in Europe for many years, trospium chloride (an anticholinergic antispasmodic, antimuscarinic medication) was approved in 2004 for use in overactive bladder causing symptoms of frequency, urgency, or urge incontinence. The efficacy of trospium chloride (20mg bid) in SCI with detrusor hyperreflexia was confirmed in a RCT. Specifically, highly significant (p<0.001) responses were recorded in favour of trospium chloride vs placebo for increased bladder capacity and compliance, and decreased bladder pressure with low side effects and no effect on flow rate and residual urine volumes. Conclusion Level 1 evidence supports the use of propiverine to treat detrusor hyperreflexia by significantly improving bladder capacity. Early experience in the form of level 4 evidence (1 before/after trial with N=10 and 1 N=14, case series study) exists to support the potential benefits of controlled-release oxybutynin. Standard oxybutynin may be enhanced by co-verapamil administration, in the treatment of detrusor hyperreflexia in individuals with SCI. Level 1 evidence supports the use of tolterodine vs placebo to significantly increase intermittent catheterization volumes and decrease incontinence in neurogenic detrusor overactivity. There is level 2 evidence that for neurogenic detrusor overactivity, efficacy of tolterodine and oxybutynin is equivocal except that tolterodine results in less dry mouth as confirmed by level 2 evidence. Level 1 evidence supports the use of trospium chloride to increase bladder capacity and compliance, and decrease bladder pressure with very few side effects in SCI individuals with neurogenic bladder. Propiverine, oxybutynin, tolterodine and trospium chloride are efficacious anticholinergic agents for the treatment of SCI neurogenic bladder. Oxybutynin co-treatment with Verapamil may enhance the standard formulation of oxybutynin in the treatment of SCI detrussor hyperreflexia. Tolterodine likely results in less dry mouth but is similar in efficacy to oxybutynin in terms of improving neurogenic detrusor overactivity.

13.5.1.2 Alpha Adrenergic Blockers Alpha adrenergic blockers in general have been used to treat SCI bladder dysfunction. Alpha adrenoreceptor blocker subtypes may also be used to specifically target bladder neck dysfunction, increased bladder outlet resistance, detrusor-sphincter dyssynergia, autonomic hyperreflexia or upper tract stasis. 13-29

Table 13.9 Summary Table of Alpha Adrenergic Blockers

Author Year; Country Score Research Design Total Sample Size Methods Outcome

Abrams et al. 2003; UK PEDro=8 RCT Study 1 Initial N=263 Study 1 Final N=244 Study 2 Initial N=186 Study 2 Final N=134

Population: Age:>18yrs; SCI, Time since injury: 85-103 mths. Treatment: Subjects were randomized to one of three groups; the 0.4 mg tamsulosin, the 0.8mg tamsulosin or the placebo group. Medication or placebo were given once daily (after breakfast). Assessment for the groups was 2 and 4 weeks after treatment Outcome measures: Not specified Population: male; age 18-60 yrs; SCI, complete/incomplete; length of injury: 4mths-7yrs. Treatment: .25, .50, .75 or placebo on different days separated by 4 to 7 days. according to the balance incomplete block design (3 treatments/patient). Outcome Measures: Maximum urethral closure pressure (trapezoidal rule used on tracings); pre/post arterial blood pressure and heart rate; pharmacodynamic analysis.

Costa et al. 1993; France PEDro=8 RCT N=20

Perkash 1995; USA Downs & Black score=10 Pre-post N=28

Chancellor et al. 1993; USA Downs & Black score=12 Case Series Study 1:n=15 Study 2: n=9

Population: Age: 20-74; SCI; Frankel: A, C-D. Treatment: Terazosin to voiding Outcome Measures: subjective assessment and voiding pressure (urodynamics) Population: m=15; age: 18-45yrs; SCI Treatment: Once Detrusor External Sphincter Dyssynergia (DESD) without obstruction of the bladder neck or prostate was documented, therapy with terazosin (5mg daily) was initiated. Outcome Measures: Not specified

Al-Ali et al. 1999; Iraq Downs & Black score=12 Case Series Initial N=46; Final N=41

Population: Age: 13-49yrs; SCI, complete/incomplete Treatment: Phenoxybenzamine 10mg daily increased to 10 mg/twice daily and then 10 mg/3 x daily for 3 wks to 6 mos. Outcome measures: Not specified

No significant change-maximal urethal closure pressure. 2. Significant patient micturition diary change 1) incontinence episode frequency and pad change freq: 0.04 mg (p=0.009); 2) mean void volume : 0.08mg (p=0.003); 3) some QoL, bladder storage /emptying symptoms of autonomic dysrelfexia 3. 71% Improved (44% slightly; 27% much improved) 1. No side effects reported. 2. Treatment effects at 10 mins. (p=0.0106) 3. Decrease in diastolic blood pressure of 17.8%, 14%, 5.2% after .75 mg, .50 mg, .25 mg. Significant heart rate increases at 5, 10*, 15, 20, 30, 60 minutes (p= 0.0016*) *=max For .50 & .75 mg/kg, significant difference at 20 min (p<0.02) but not at 15 min (p=0.0598). 4. Urethral closure pressure dose related max of 47.6% reduction at 10 min after .75mg/kg 1. Improved voiding-no difference. 2. Occasional autonomic dysreflexia in 39% of patients 3. Decreased voiding pressure in 42%, no change in37%, increased pressure in 21% . 1. No significant differences in DESD voiding pressure after 4-12 weeks initial terazosin treatment (p=.48) 2. Voiding pressure was reduced (p<0.001) after subsquent external sphincterotomy or sphinceter sting placement. Out of 9 subjects who experienced persistent voiding symptoms after sphincterotomy following initial terazosin treatment, subsequent terazosin treatment improved voiding in patients with only bladder neck obstruction while the other 4 who did not improve had obstruction only at the external sphincter. No statistically significant results reported. 1. Improved max urethral closure pressure in 19 patients with reflex bladders. 2. Non-responders=22 (9=areflexive bladders; 13=reflex bladders)

1.

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

Linsenmeyer et al. 2002; USA Downs & Black score=14 Case Series Study 1: n=10 Study 2: n=7

Population: Study 1: gender m=10; age: mean=28yrs; SCI; ASIA A&B. Study 2: gender m=7 Treatment: Study 1: impact of alpha blockers on upper tract stasis. Study 2: the impact of alpha blockers on urodynamic parameters in those with and without resolution of stasis. Outcome Measures: Urodynamic paramters: mean changes in opening pressure, maximum detruor voiding pressure and duration uninhibited contraction.

1. 2. 3. 4.

Pre-treatment: 6 subjects taking prazosin, 4 taking terazosin. Three month treatment with alpha blockers resolves upper tract stasis (p<0.0003). Study 2: Uninhibited bladder contraction duration decreased with alpha-blocker usage (p<0.001). Mean arterial pressure during uninhibited contraction significantly decreased during alpha-blocker treatment (p<0.01).

Discussion An alpha1 adrenoreceptor antagonist that has been used to treat SCI bladder neck dysfunction is Tamsulosin. Tamsulosin was found to cause smooth muscles in the bladder neck to relax and improve urine flow rate. A large scale (N=263) RCT conducted by Abrams et al., (2003), provides evidence for increased micturition frequency and improvement in urinary leakage parameters for individuals with SCI. Moxisylyte is an alpha adrenoreceptor blocker used commonly in the treatment of Raynauds disease where narrowing of the blood vessels in the hands causes numbness and pain in the fingers. Costa et al., (1993) in an N=20 RCT investigated the off-label use of moxisylyte in the treatment of SCI bladder neck dysfunction. With its smooth muscle relaxant property, the decrease in urethral closure pressure was found to be dose related and significant when compared to placebo, with the maximum reduction of 47.6% occurring at 10 minutes after 0.75mg/kg in individuals with SCI. Terazosin is often used to treat hypertension. However, this alpha-adrenergic blocker is also useful in treating bladder neck dysfunction by relaxing the bladder neck muscles and easing the urination process. Perkash (1995) reported that although 82% of patients (N=28), with absent detrusor sphincter dyssynergia, perceived improvement in voiding, only 42% registered meaningful objective decreases in maximum urodynamic voiding pressure. Side effects, tolerance and required subsequent urodynamic monitoring may be deterrents to the wide-spread adoption of Terazosin as a alternative treatment for bladder neck dysfunction in SCI individuals. The specificity of Terazosin action on the bladder neck, exclusive of the external sphincter, was demonstrated by Chancellor et al. (1994) in a subgroup of SCI patients who had persistent voiding difficulty after previous sphinterotomy subsequent to failed initial terazosin treatment. In contrast to the alpha adrenoreceptor blockers discussed above, phenoxybenzamine is one that is not efficacious for bladder neck dysfunction. Phenoxybenzamine is an antihypertensive usually chosen to treat autonomic symptoms of pheochromocytomas, such as high blood pressure or excess sweating. Al-Ali et al. (1999) undertook to utilize the autonomic effects of phenoxybenzamine to treat bladder dysfunction which is in part under autonomic control. Treatment with phenoxybenzamine (N=46 with 41 completers), resulted in a reduction of bladder outlet resistance, detrusor-sphincter dyssynergia or autonomic hyperreflexia in some subjects while no benefits were recorded for areflexive bladders. Phenoxybenzamine can be beneficial as 13-31

an adjunct treatment for neuropathic bladder following SCI, when tapping or crede is unable to achieve satisfactory residual urine volumes of < 100 mL. The lack of efficacy in those with bladder neck dysfunction was specifically noted in this study. Since statistically significant results were not reported in this study, further appropriately sized RCTs would be helpful in providing sufficient evidence for the use of phenoxybenzamine in the treatment of SCI neuropathic bladder. The pyeloureteral smooth muscle responsible for ureteral peristalsis and movement of the urine from the kidneys to the bladder via the ureters is also a potential site of action for certain alpha 1receptor antagonist therapy. Linsenmeyer et al. (2002), in a small (N=10) retrospective chart review found that in men with upper tract (i.e. kidneys and ureters) stasis secondary to SCI at or above T6, 6 months of alpha1-blocker therapy provided improvement in upper tract stasis in 80% of subjects, who used reflex voiding to manage their bladder as measured by significant decreases of the duration of uninhibited contractions. Firm conclusions about effectiveness and the optimum duration of treatment can only be validated with further RCT trials. Conclusion Level 1 evidence supports the use of Tamsulosin to improve bladder neck relaxation and subsequent urine flow in SCI individuals. Level 1 evidence suggests that moxisylyte decreases maximum urethral closure pressure by 47.6% at 10 minutes after an optimum dose of 0.75mg/kg in individuals with SCI. Level 4 evidence (two non-RCT, N=28 & 9), supports Terazosin as an alternative treatment for bladder neck dysfunction in SCI individuals provided that side effects and drug tolerance are monitored. Level 4 evidence derived from a single, case series study involving 46 subjects (41 completers) indicates a potential for phenoxybenzamine as an adjunct treatment for neuropathic bladder following SCI, when tapping or crede is insufficient to achieve residual urine volume of <100mL. Level 4 evidence from 1 small retrospective chart review suggests that 6 months of alpha 1-blocker therapy may improve upper tract stasis secondary to SCI in men by decreasing the duration of involuntary contractions. Tamsulosin is likely to improve urine flow in SCI individuals with bladder neck dysfunction. Mosixylyte is likely able to decrease maximum urethral closure pressure at a dose of 0.75mg/kg in individuals with SCI. Terazosin may be an alternative treatment for bladder neck dysfunction in individuals with SCI. but side effects and drug tolerance should be monitored. Phenoxybenzamine may be useful as an adjunct therapy for reducing residual urine volume in SCI neuropathic bladders maintained by crede or tapping. Six months of alpha 1-blocker therapy in male SCI patients may improve upper tract stasis. 13.5.1.3 Alpha Adrenergic Agonists Alpha-adrenergic agonists are thought to be of benefit bladder dysfunction by increasing bladder neck and urethral pressure to prevent accidental voiding. One drug in this class,

13-32

clonidine has already been shown to be efficacious in treating general spasticity secondary to SCI (Donovan et al., 1988, Nance et al., 1989, Nance, 1994). Table 13.10 Summary Table of Alpha Adrenergic Agonists
Author Year; Country Score Research Design Total Sample Size Chartier-Kastler et al, 2000; France Downs & Black score=7 Case Series N=9 Methods Outcome

Population: m=6, f=3; Paraplegia; complete/incomplete Treatment: All underwent surgery to have a catheter implanted allowing intrathecal injections of Clonidine. Outcome measures: not specified

No statistical results reported. 1. Six of 9 subjects elected to have permanent pump implantation for the treatment of severe detrussor hyperreflexia 2. No complication or infections reported.

Discussion Chartier-Kastler et al. (2000) specifically used test bolus intrathecal injections of Clonidine (ITC) to investigate its effects over SCI detrussor hyperreflexia that was otherwise resistant to a combination of oral treatment and self-clean intermittent catheterization (SCIC). After the test bolus injection, 6 of 9 subjects elected to have permanent pump implantation for the treatment of severe detrussor hyperreflexia. Further confirmatory study of this proposed alternative treatment is needed as the sample size was small and no objective outcome measures were used. Conclusion Level 4 evidence is available from a single, small (N=9), case series study for the use of intra-thecal clonidine to improve detrussor hyperreflexia in individuals with SCI when a combination of oral treatment and sterile intermittent catheterization are insufficient.

Intra-thecal clonidine may be beneficial as an adjunct treatment to detrussor hyperreflexia in SCI. 13.5.1.4 Antispasmodics (Muscle Relaxants) Baclofen, a derivative of gamma aminobutyric acid (GABA), is used as the pharmacological treatment of choice for spasticity in SCI (Taricco et al., 2006; Kirshblum, 1999) by enhancing inhibitory influences on the spinal stretch reflex via increasing presynaptic inhibition (Kirshblum, 1999). Table 13.11 Summary Table of Antispasmodics
Author Year; Country Score Research Design Total Sample Size Steers et al. 1992; USA PEDro=8 RCT Methods Outcome

Population: m=7, f=3 Age range 24-61yrs: SCI; Time since injury: 1 to 12 years

Post bolus intrathecal 1. Increase in bladder volume at first sensation and bladder compliance at 2

13-33

Author Year; Country Score Research Design Total Sample Size Initial N=10; Final N=9

Methods

Outcome

Treatment: Intrathecal bolus of baclofen or saline at L3 to L4. Outcome measures: Reduction in spasticity, urodynamics.

hrs (p<0.05). 2. Ashworth decrease >2. Pre-post continuous intrathecal baclofen: 1. Increased volume, volume at first sensation, compliance, residual volume: p<0.05 2. Decreased maximum urethral pressure, voiding pressure: p<0.05. 3. Change in bladder symptoms reported at or after 48 hours. 4. Dosages ranged from 94-372 ug (mean 220 ug) and followup ranged from 12-23 months (mean 18).

Discussion Steers et al. (1992), investigated the use of intrathecal baclofen (ITB) specifically for the treatment of genitourinary function in 10 SCI patients with severe spasticity. Compared with placebo, involuntary bladder contraction induced incontinence was eliminated and 1 patient was able to convert from indwelling urethral catheterization to intermittent self-catheterization. Bladder capacity was increased by a mean of 72% while detrusor-sphincter dyssynergia was eliminated in 50% of patients. These authors recommend the use of ITB for SCI genitourinary dysfunction when oral pharmacological interventions are insufficient to improve bladder function. Conclusion There is Level 1 evidence that Intrathecal Baclofen may be beneficial for bladder function improvement in individuals with SCI when oral pharmacological interventions are insufficient.

Intrathecal Baclofen may be a beneficial adjunct treatment for bladder dysfunction in SCI.

13.5.1.5 Botulinum Toxin for the Treatment of Bladder Dysfunction in SCI Botulinum toxin (Botox), the most toxic naturally occurring substance, used in minute doses was approved for therapeutic use on eye and facial muscle overactivity in 1989 (i.e. BTX-A). Although the more publicized use of Botox is in the area of cosmetic dermatology, its use in the treatment of spasticity and muscle pain is gaining popularity. As such, BTX-A has been tested for targeted bladder dysfunction treatment in individuals with SCI. The advantage over systemic drug administration is the treatment of discreet portions of the dysfunctional voiding process.

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Table 13.12 Individual Studies of Botulinum Toxin for the Treating of Bladder Dysfunction in SCI
Author Year; Country Score Level Total Sample Size Wheeler et al, 1998; USA Downs & Black=8 Level 4 Case Series N=3 Schurch et al, 2000; Switzerland Downs & Black=20 Level 4 Before and After Initial N=21; Final N=19 Methods Results

Population: males; Age: 26-37 yrs; SCI; Chronic. Treatment: Transperineal botulinum toxin injections Outcome Measures: bladder function as assessed with urodynamics Population: m=14, f=7; Age: 15-59yrs, SCI Treatment: Outpatient botulinum-A toxin injection under cystoscopic control Outcome Measures: Continence level achieved, dose of anticholinergic medication, reflex volume, max detrusor pressure during voiding, detrusor compliance, max cystometric bladder capacity and patient satisfaction.

No systematic or group effects noted; 1 patient no response, 2 had improved voiding with IC although only one of these continued using this method and eventually had a sphincterotomy. Significant increase in reflux volume, maximum cystometric bladder capacity (p<0.016). 2. Increase in post void residual urine volume. 3. Non-significant voiding pressure change. 4. At the 6-wk followup complete continence was restored in 17 of 19 cases in which anticholinergic medication was markedly decreased or withdrawn 5. Eleven patients at 16 & 36 wks followup continued to show bladder function improvement . No statistics provided. 1. 19/21 subjects voiding without catheterization after injection. 2. 14 (67%) reported significant subjective improvement in voiding patterns 3. Postoperative post void residual decreased by 71%. 1.

Phelan et al, 2000; USA Downs & Black score=9 Level 4 Case Series N=21

Population: gender: m=8, f=13; age 3474yrs Treatment: Botuliumn A toxin (80-100 units) injected via cystoscipic collagen needle/cytoscope into the external sphincter at 3, 6, 9 and 12 oclock. Outcome Measures: Able to void without catheterization.

Discussion Schurch and colleagues (2000) undertook to evaluate the efficacy of Botox A injections into the detrusor muscle in men with spinal cord injury to reduce incontinence and increase bladder capacity. Pre-operatively, the subjects had detrusor hyperreflexia and urge incontinence resistant to high-dose oral anticholinergic treatment and emptied their bladders by intermittent self-catheterization. Ninety percent of subjects were catheter free in conjunction with markedly decreased or withdrawn anticholinergic drug administration by the 6-week post-operative follow-up. Although mean post-void residual urine volume significantly increased postoperatively, autonomic dysreflexic (AD) hypertensive crisis were abolished in the 3 patients with a history of AD, and significant increases in cystometric bladder capacity as well as decreases in maximum detrusor voiding pressure were additional reported findings. This group reported that a dose of 300 units of Botox A was required for successful treatment of detrusor overactivity lasting at least 9 months per injection. Wheeler et al, in a 1998 case series of 3 patients, showed preliminary results confirmed by Schurch and colleagues 2 years later. Phelan et al. (2000), undertook to expand the use of botox to include those with voiding dysfunction as a result of neurogenic detrusor-sphincter dyssynergia, pelvic floor spasticity, or acontractile detrusor. After injection into the external sphincter, 95% (18/19) of patients who 13-35

pre-operatively required catheterization were catheter free, and post-void residuals and voiding pressures decreased on average by 71% and 38%, respectively. Sixty-seven percent of subjects reported subjective improvement in voiding patterns. Conclusion Level 4 evidence based on 3 studies supports the use of Botox A injections into the detrusor muscle to provide targeted treatment for detrusor hyperreflexia and urge incontinence resistant to high-dose oral anticholinergic treatments with intermittent selfcatheterization in SCI. Additional level 4 evidence supports Botox A injected into the external sphincter to assist with SCI related voiding dysfunctions including neurogenic detrusor-sphincter dyssynergia, pelvic floor spasticity, or acontractile detrusor.

Botox A injections into the detrusor muscle or external sphincter may provide targeted treatment for bladder dysfunction in SCI.

13.5.1.6 Other Pharmacologic agents Pharmacologic manipulation can also be applied to other parts of the urinary system such as somatic innervation of the lower urinary tract (i.e. pudenal nerve), receptors within the kidney and at the level of neurotransmitter release. Table 13.13 Individual Studies Describing Use of Other Pharmacological Interventions to Treat Bladder Function
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Wyndaele & Van Kerrebroeck 1995; Belgium PEDro=7 RCT N=21

Silva et al. 2005; Portugal PEDro=10 RCT N=28

Population: Gender m=14, f=4; Age:1759yrs, SCI Treatment: Cisapride or placebo/4 wks. Outcome Measures: Max cystometric capacity, first filling sensation volume, void sensation volume, max detrusor pressure, compliance, first involuntary detrusor contraction bladder capacity, and residual urine. Population: SCI neurogenic detrusor overactivity; Age: 38y; 15M, 13F. Treatment: intravesical resiniferatoxin (RTX) vs placebo Outcome measures: max cystometric capacity (MCC) and volume of first involuntary detrusor contraction (FDC), discomfort Visual analog scale (VAS). 1mo & 1wk pre-tx and 1&3mo post-tx cystometries. 3d micturation diary precystometry.

No significant pre/post differences between groups.

RTX (over Placebo) significantly: 1. increased FDC (14395mL to 18493mL; p=0.03) 2. increased MCC(11561mL to 20492mL;p=0.02) 3. decreased urinary frequency (=0.01) 4. decreased incontinence (p=0.03) Similar side effects (VAS) as compared to placebo.

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

deSeze et al. 2004; France PEDro=10 RCT N=39

Population: 18 SCI; 21 MS; m=17, f=22; 21-64y (mean 47y); 14/4 SCI para/tetra, AIS A & B; bladder management method: IC/23, reflex or voluntary voiding/8, suprapubic percussion/2, spontaneous voiding/14. Treatment: 100ml 100nMol/l resiniferatoxin (RTX) in 10% ethanol or 1mmol/l capsaicin (CAP) diluted in glucidic solvent Outcome Measures: Clinical: daily voids/catheterization, leakage episodes with urgency/ leakage delay. Urodynamic: max cystometric capacity [MCC]; max detrusor pressure [DPmax]. Day 30&60=general tolerability; Cystoscopy on day 60.

deSeze et al. 1998; France PEDro=10 RCT N=20

Lazzeri et al. 2003; Italy PEDro=10 RCT N=14

Kim et al. 2003; USA PEDro=8 RCT N=36

Population: MS 12, SCI 8; m=11, f=9; Age 20-66; Duration of illness 1-27y; compl/incompl 6/14; para/tetra 17/3. Treatment: 30mg capsaicin in 100ml 30% ethanol or 100ml 30% ethanol alone Outcome Measures: Clinical: voiding diary. Urodynamic: max cystometric capacity [MCC]; max detrusor pressure [DPmax]. Population: SCI subjects with neurogenic detrusor overactivity; Mean Age: 43.7 8.3 years (treatment) and 41.4 11.9 years (placebo); Gender: 6M, 8F (ratio 3:4 per group); Level of Injury: T4-L2; 10 Traumatic, 4 Non-traumatic (ratio 5:2 per group); Post-injury time: 8.7 3.4 years (treatment) and 7.0 3.5 years (placebo) Treatment: Evaluate the neuropeptide nociceptin/orphanin FQ (N/OFQ) vs placebo (randomized placebo-controlled, double-blind study). Outcome measures: bladder capacity, volume threshold for the appearance of detrusor overactivity (DO), and maximal bladder pressure during involuntary bladder contractions. Population: SCI=20, MS=7, Other=9 with detrusor hyperreflexia (DH) and intractable UTIs despite previous anticholinergic drug use; m=22, f=14; Treatment: Double-blind dose escalation of single instillation of 100 mL intravesical resineferatoxin (RTX 0.005, 0.025, 0.05, 0.10, 0.2, 0.5, or 1.0 microM of RTX; n=4/group) or placebo (n = 8 ).

No significant difference between groups: both resulted in clinical and urodynamical improvement at day 30 2. CAP attained statistical significance for increase in security delay (p<0.01) 3. Trend to greater increase in MCC in CAP group 4. No difference in DP. 5. Persistent clinical improvement 94% vs 60% in favour of RTX but not significant. 6. MCC improvement maintained at 90 days with 86% vs 68% in favour of CAP but not statistically significant. 7. Duration of efficacy similar. 8. Side effects similar between groups except clinically tolerable/brief suprapubic pain sig higher in CAP group (P<0.04). 9. No cystocopic pathological changes on day 60. 30 days after instillation, results favoured capsaicin over placebo: 1. Decrease in 24h voiding freq (p=0.016); 2. Decrease in 24h leakages (p=0.0008). 3. Increase in MCC (p=0.01) 4. Decrease in MDP (p=0.07; not significant). 5. Similar side effects in each group. N/OFQ resulted in sig increase in: 1. capacity (p<0.001; 139 48mL to 240 61mL) 2. DO volume threshold (p<0.01 84 32mL to 201 68mL). N/OFQ resulted in non-sig decrease: 3. in max bladder pressure: 81 25cm H20 to 66 12cm H20. No diff btwn N/OFG and Placebo in: 4. no phasic contractions or autonomic dysreflexia 5. Incomplete patients - no suprapubic or urethral sensation 6. vital signs unchanged. N/OFQ (but not placebo) elicits robust acute inhibitory effect on micturition reflex in patients with neurogenic bladder. 1. VAPS: min. to mild discomfort with values of 2.85 and 2.28 for the 0.5microM and 1.0-microM RTX treatment groups. 2. No statistically significant changes in MCC or incontinence at lower doses. 3. MCC increased by 53% & 48% for the 0.5-microM & 1.0-microM RTX at 3 wks.

1.

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

Outcome measures: A visual analog pain scale (VAPS), bladder diary, mean cystometric bladder capacity (MCC) at wks 1, 3, 6 & 12 posttreatment, adverse events including autonomic dysreflexia (AD) Das et al. 1996; USA Downs & Black score=11 Case Series Initial N=7; Final N=5 Dasgupta et al. 1998; UK Downs & Black score=10 Post Test N=20 Population: Age: 23-52; Mixed group Treatment: Intravesical capsaicin treatment: 100uM, 500uM, 1mM, 2 mM Outcome Measures: Not specified Population: m=9, f=11; Age: 40-70; SCI & MS. Treatment: Intravesical capsaicin Outcome Measures: Histopathological examination of bladder biopsies, urodynamics to assess bladder capacity, cystoscopy in 2 patients Population: m=3, f=4; Age:22-52; SCI Treatment: 10ug/day intranasal DDAVP after urodynamic evaluation. Outcome Measures: Not specified

4.

Incontinence decreased by 51.9% & 52.7% for the 0.5-microM & 1.0microM RTX. 5. No long-term complications. Intravesical RTX is well-tolerated for DH but monitoring for AD required. 1. Symptomatic improvement: 3/5 completers - Mean urodynamic bladder capacity increased (p<0.05) 1. All biopsies were benign. Some reflected chronic inflammation (cystoscopy: 2 males with TM transient inflammatory reaction to treatment). Bladder capacity improvement at 6 weeks. No statistical results reported. 1. Decreased nocturia for 4 patients treated at night (Nocturnal enuresis eliminated in 2 patients) 2. Increased duration between catheterizations for 3 patients treated during the day.

Chancellor et al. 1994; USA Downs & Black score=6 Case Series N=7

Discussion The neurotransmitter 5-hydroxytryptamine (5-HT; Serotonin) is known to affect the pudenal nerve which in turn causes the contraction of external urinary sphincter to prevent accidental voiding. Cisapride was previously indicated for use to assist with increasing movements or contractions in the stomach and intestines by interacting as a 5-hydroxytryptamine(4) receptor agonist. These 5-HT4 receptors have also been identified in in vitro preparations of the human urinary bladder (Tonini et al., 1994) and therefore there was a possibility that the dysfunctional bladder may also have been susceptible to the prokinetic actions of cisapride. Wyndaele & Van Kerrebroeck (1995), conducted a RCT to test the effects of 4 weeks of Cisapride or Placebo on the cystometric paramers in SCI patients and found no difference between groups. This type of robust evidence along with a FDA warning regarding the risk of serious cardiac arrhythmias should be sufficient to dissuade use of cisapride for the treatment of SCI bladder dysfunction. Since May 1, 2000, Cisapride is only available through an investigational limited access program. DDVAP, otherwise known as desmopressin, is a synthetic analogue of antidiuretic hormone (ADH) most commonly administered by intravenous infusion for treatment of bleeding disorders. It can also be taken in the form of a pill of intranasal spray and also has been used treat bedwetting, frequent urination and extreme thirst in diabetes, blood coagulation disorders and amnesia and memory loss. Chancellor et al., (1994) investigated the use of intranasal DDVAP as an alternative therapy for neurogenic bladder dysfunction that is unresponsive to conventional therapy. DDAVP is thought to bind to V2 receptors in renal collecting ducts to increase water resorption. After one month of DDAVP treatment, two patients had only one episode of nocturia per night and in the other two patients, nocturnal enuresis was completely 13-38

eliminated. Three patients used daytime DDAVP administration at work and were able to achieve an additional 3.5 hours between catheterizations. These improvements persisted for a mean of 12 months. This small scale (N=7), case series study provides only preliminary evidence and encourages further study in order to recommend intranasal DDVAP for the treatment of SCI neurogenic bladder. The use of Capsaicin as a topical temporary analgesic is not uncommon as evidenced by overthe-counter ointments available for purchase in local pharmacies. Localized and reversible antinociception by capsaicin is a result of induced C-fibre conduction and subsequent neuropeptide release inactivation (Dray, 1992). Although C-fibers are not involved in normal voiding, neuroplastic changes to C-fiber bladder afferent growth account for injury emergent Cfiber mediated voiding reflex (i.e. spinal detrusor hyperreflexia; deGroat, (1995)). By chemically decreasing C-fiber bladder afferent influence with intravesical vanilloids (i.e. capsaicin, resiniferatoxin) bladder contractility is decreased and bladder capacity is increased (Evans 2005). deSeze et al 1998 has provided level 1 evidence in support of capsaicins ability to improve bladder function (decrease frequency and leakages) by increasing bladder capacity. This corroborates other small, non-RCT studies that also reported significant capsaicin induced increases in bladder capacity (Das et al., 1996; Dasgupta et al., 1998). Although the Dasgupta group confirmed that metaplasia, dysplasia, flat carcinoma in situ, papillary or solid invasive cancer have not been detected after 5 years of follow-up, further surveillance is required up to 10 years when chemical carcinogenic morphologies are typically apparent. deSeze et al. (2004) later established that another vanilloid, resiniferatoxin (RTX) was similarily effective in increasing bladder capacity when compared to capsaicin (CAP). CAP was significantly more effective at increasing urgency delay (p<0.01) but there was only a trend to greater maximum bladder capacity in favour of CAP. There was also a statistically significant increase in the side effect, suprapubic pain, that was clinically tolerable and brief (p<0.04). The increase in persistent clinical improvements due to RTX over CAP at 90 days follow-up was not statistically significant. The efficacy of RTX vs placebo was confirmed an RCT conducted by Silva et al. (2005) where they found that RTX was responsible for significantly increased volume of first involuntary detrusor contraction (FDC; p=0.03)) and maximum cystometric capacity (MCC, p=0.02), and decreased urinary frequency (=0.01) and incontinence (p=0.03) with similar side effects as compared to placebo. Kim et al. (2003) confirmed the improvements in SCI bladder function and further investigated the effect of dose (single100ml instillation of 0.005, 0.025, 0.05, 0.10, 0.2, 0.5, 1.0 microM RTX or placebo). Despite the small sample size in each dose category, MCC increased by 53% and 48% for the two highest dosages by 3 weeks post-treatment. Similarly, incontinence episodes decreased by 51.9% and 52.7%. As with all bladder instillilations, autonomic dysreflexia remains a potential problem with RTX treatment. A heptadecapeptide (Meunier et al., 1995; Reinscheid et al., 1995), N/OFG (nociception/orphanin phenylalanine glutamine) that acts on sensory innvervation of the lower urinary tract in a similar fashion to CAP and RTX has been shown to be effective in inhibiting the micturition reflex in the rat (Lecci et al., 2000). Following a successful preliminary study, Lazzeri et al. (2003) confirmed that N/OFG versus placebo is responsible for a significant increase in the bladder capacity (p<0.001) and threshold volume of detrusor overactivity (p<0.001), and a non-significant decrease of maximum bladder pressure of the dysfunctional neurogenic bladder. The authors conclude that this inhibition of the micturition reflex supports nociceptin orphan peptide receptor agonists as a new treatment for neurogenic bladders of SCI patients.

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Conclusion Level 1 evidence for lack of efficacy, in combination with a FDA warning for risk of serious cardiac arrhythmias, supports not using Cisapride for treatment of SCI bladder dysfunction. Level 1 evidence supports the use of vanillanoid compounds such as capsaicin or resiniferatoxin to increase maximum bladder capacity and decrease urinary frequency and leakages in neurogenic detrusor overactivity of spinal origin. Level 4 evidence exists to suggest that intravesical capsaicin installation in bladders of SCI individuals does not increase the rate of common bladder cancers after 5 years of use. Level 1 evidence supports the use of N/OFG, a nociceptin orphan peptide receptor agonist for the treatment of neurogenic bladder in SCI. Level 4 evidence from one small, case series study, suggests that intranasal DDVAP may increase the time between the need to void or catheterization in SCI with neurogenic bladder that is unresponsive to conventional therapy. Cisapride should not be used for treatment of SCI bladder dysfunction due to lack of efficacy and risk of serious cardiac arrhythmias. Vanillanoid compounds (CAP or RTX) improve function of neurogenic detrusor overactivity of spinal origin. Capsaicin may not be linked to common bladder cancers within 5 years of use, when instilled in the bladders of individuals with SCI . N/OFG is effective for the treatment of neurogenic bladder in SCI. Intranasal DDVAP may decrease the frequency of voids or catheterizations in SCI neurogenic bladder otherwise unresponsive to conventional therapy 13.6 Non-pharmacological Interventions for Preventing and Treating UTIs Bladder dysfunction secondary to SCI leads to urinary tract infection (UTI). UTI and its complications continue to be a leading cause of secondary health problems and death after spinal cord injury (Stover et al., 1989; DeVivo & Stover, 1995; DeVivo et al., 1999). Clinicians often diagnose UTI based on their clinical experience and knowledge of each patients history. However, to objectively assess the use of clean, intermittent catheterization following SCI, Maynard and Diokno (1984) clearly defined urinary tract infections as potential infections that met 5 criteria: 1) purulent urethral discharge with positive urethral culture; 2) pyuria/foul smelling urine with positive urine culture and white blood cells more than 25/HPF (laboratory infection); 3) fever of more than 100F/chills/flank pain, with laboratory infection; 4) positive C-reactive protein with positive urine culture. Although the Maynard and Diokno definition can be useful, the National Institute on Disability and Rehabilitation Research (NIDRR) developed a statement on UTI that was derived by expert consensus.

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In January 1992, the NIDRR defined UTI as bacteriuria (102 bacteria/ml of urine) with tissue invasion and resultant tissue response with signs and/or symptoms. Asymptomatic bacteriuria represents colonization of the urinary tract without symptoms or signs. They further defined risk factors to include: over-distention of bladder, vesicoureteral reflux, high pressure voiding, large post-void residuals, presence of stones in urinary tract, and outlet obstruction. Possible physiologic/structural, behavioral, and demographic risk factors were identified also, Indwelling catheterization, including suprapubic, and urinary diversion and the drainage methods most likely to lead to persistent bacteriuria. The Centers for Disease Control and Prevention (CDC) have further defined asymptomatic bacteriuria (ASB) and other infections of the urinary tract (OUTI) as well as symptomatic urinary tract infections (SUTI) that apply to SCI and the general population. For a diagnosis of ASB, 5 criteria must be met provided that urine cultures are acquired using appropriate technique, such as clean catch collection or catheterization and the positive culture of a urinary catheter tip is not used. OUTIs include infections of the kidney, ureter, bladder, urethra, or tissues surrounding the retroperitoneal or perinephric spasces. A diagnosis for SUTI or OUTI must include at least 1 of 4 major criteria that include several subcriteria. Some examples of criteria include fever > 38, urgency, frequency, dysuria, or suprapubic tenderness; and 1) 105 microorganisms/cm3 of urine with no more than two species; 2) positive dipstick for leukocyte esterase and/or nitrate; 3) pyuria (urine specimen with 10 WBC/mm3), etc. Detailed definitions and criteria can be obtained from Horan & Gaynes (2004) or downloaded from www.cdc.gov. With a documented and widely accepted consensus on UTI, initial SCI rehabilitation should be able to include quality bladder management education that can provide a common consistent goal to reduce the incidence of UTI in SCI. Educational efforts can initially cover at least one of the following methods to empty the neuropathic bladder: intermittent, indwelling or external condom (males only) catheterization and/or manual forms of voiding encouragement (anal or rectal stretch, crede, tapping, valsalva). Bacteria is the source of UTI and the source of bacteria is usually introduced from the skin and urethra via catheters. Alternatively, normally occurring bladder bacteria have the opportunity to grow when the bladder is not completely emptied of urine. Therefore the best prevention of UTI is to prevent the introduction and growth of bacteria. Prevention can be encouraged by properly educating the patients on the following: 1) keeping urinary care supplies clean, 2) keeping skin clean, 3) proper bladder emptying technique 4) regular and sufficient scheduling of bladder emptying and 5) knowing the early signs of UTI. 13.6.1 Educational interventions All SCI patients with neurogenic bladder are educated to healthy bladder function while in initial and some continue to receive ongoing education as situational changes occur post discharge. Table 13.14 Individual Studies of Educational Interventions for Preventing and Treating UTIs
Author Year; Country Score Research Design Total Sample Size Anton et al. 1998; Canada PEDro=7 Methods Outcome

Population: Gender: m=30, f=8; age 1969; SCI Treatment: PUD; recording frequency of

1. 2.

A total of 19 participants (in both groups) dropped out of the study. PUD group - fewer catheters p=0.026.

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Author Year; Country Score Research Design Total Sample Size RCT Initial N=57; Final N=38

Methods

Outcome

Cardenas et al. 2002; USA PEDro=5 RCT Initial N=68; Final N=56

Anderson et al. 1983; USA Downs & Black score=8 Prospective Controlled Trial N=75

catheterizations, catheter volumes, episodes of UTI Outcome Measures: The frequency of overdistension of the bladder, the frequency of catheterization and patient satisfaction were measured Population: m=42, f=14; age: 20-77; level of injury: C1-S4/5; ASIA A-D; Bladder Management IC n=33, Condom Catheter n=11, Indwelling catheter n=11, spontaneous management n=1; Time since injury: .5 to 48 yrs Treatment: specialized educational program for the prevention of UTIs vs no program Outcome Measures: episodes of symptomatic UTI, white blood cell count, bacterial colony counts, # antibiotic treatments for UTI, UTI related symptoms, health belief questionnaire, multidimensional health locus of control, self efficacy. Population: Not specified Treatment: Urinary tract care education program (patient and staff training), 5 classes + manual Outcome Measures: Functional Impairment Scale for Bacteriuria, UTIs, UTI symptoms, time lost due to UTI Population: Not specified Treatment:Patients with no risk factors for UTI received intensive counseling with respect to proper CIC technique, daily external condom catheter application and care. If subjects had 2 or more UTIs in 6mths either nitrofuratoin or methenamine mandelate with ascorbic acid was initiated. Outcome Measures: Not specified. Population: m=45, f=10; Age: 15-75yrs Tetra/paraplegia/paresis; SCI Treatment: Suprapubic tapping every 4 hours with or without compression followed by catheterization (residual volume goal < 100 ml). Outcome Measures: not specified Population: m=11, f=1; Age: 17-72; 37mths since injury; complete/incomplete Treatment: Intermittent catheterization Outcome Measures: Residual urine volume as measured by utrasonography; urinary tract infections Population: m=35, f=1; age: mean=31.5yrs, level of injury: C5-C8; complete=16/incomplete=20.

3.

No significant difference for mean over distention per subject (p=0.61).

Significant changes in favour of treatment: 1. Fewer Urinary Colony Counts (p=0.009). 2. Fewer symptom reports (p=0.097). 3. Fewer episodes treated with antibiotics (p=0.232). 4. No significant difference between the groups for NIDRR defined UTI. 5. Increase in the perception of the severity of the UTI (p=0.042). 6. Higher locus of control (p=0.066). Lower self-efficacy (p=0.033).

Barber et al. 1999; USA Downs & Black score=4 Case Series N=17

Treatment vs Control following education: 1. No impairment: 71 vs 32%. 2. Symptomatic: 24 vs 57% 3. No time lost: 71 vs 50% 4. Lost various times: 5 vs 23% 5. Recognition of symptoms: no difference 6. No p values - between group stats tests conducted. 7. 11/17 responders 1. 8/11 required multiple counseling sessions. 2. 4/17 were placed on prophylactic methenamine mandelate and ascorbic acid with various treatment periods. 3. 3/17 were placed on prophylactic nitrofurantion for 1 to 2 3/4 yrs. At discharge 1. 45 (82%) successfully bladder trained, 2. 8 (15%) used clean intermittent selfcatheterization, 3. 2 had indwelling catheter. No statistical results reported Hyper vs hypoactive bladder changes 1. Max scored retention p=.06 2. Mean residual volumes p=.21 3. UTI p=.49 4. Mean & Max residual volumes/UTI correlations: r=.19 & .16 (p=.52 & .63) 1. 81% continued to use CISC at 5 years post-discharge. 2. 24/29: independent CISC

Menon & Tan 1991; Singapore Downs & Black score=4 Case Series N=55 Jensen et al. 1995; Norway Downs & Black score=14 Case Series N=12 Sutton et al. 2002; Australia Downs & Black score=16

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Author Year; Country Score Research Design Total Sample Size Observational N=36

Methods

Outcome

Craven & Etchells 1998; Australia Downs & Black score=8 Case Series N=27

Treatment: No treatment-survey mailed to participants Outcome Measures: bladder management method, degree of satisfaction, independence, ADLs with this method, reasons for CISC cessation, number and reason for hospitalizations, frequency of contact with local medical office and SI unit, current use of adaptive equipment, and modified barthel index. Population: SCI patients with ileostomy or urostomy Treatment: No treatment chart review Outcome Measures: questionnaire for physical, psychological, and lifestyle effects after surgery

16/18 patients who were screened by urinalysis had sterile urine. 4. Higher CISC success with earlier CISC education 5. Pre-/post-discharge ADL scores did not correlate with CISC success. Very little statistical analysis reported.

3.

Although 27 charts reviewed only 18 patients located to complete the questionnaire: 1. Bowel and bladder management greatly improved in most cases, resulting in improved quality of life for these patients. 2. Positive psychological effects Long-term impact on renal health not measured.

Discussion While in rehabilitative care, clinical staff have an excellent opportunity to provide proper bladder management education to significantly affect the quality of bladder management after discharge. Cardenas et al. (2003) sought to answer this question in a randomized controlled trial of 56 SCI patients suffering from UTIs. The educational intervention included written material, a self-administered test, a review by nurse and physician, and a follow-up telephone call. The control group did not receive the intervention and final interventional data was compared to an equivalent baseline period. A significant decrease in urine colony count (UCC) and increased Multidimensional Health Locus of Control scale (MHLC) score reflected the beneficial effects of UTI educational intervention in improving bladder health and the patients perception of control over their own health behaviour. This finding confirms an earlier uncontrolled trial of educational intervention for urinary tract care (Anderson et al., 1983). When patients completed a special urinary tract care education program consisting of classes, reading material, written examinations, and demonstration of acquired skills, 71% of patients were asymptomatic of UTI. Only 32% of patients had asymptomatic UTI when a group of patients, 4 years earlier in 1975, did not undergo the education program. Furthermore, as a result of the education program only 5% of the educated group lost time from their usual daily activities compared to 23% of the non-educated group losing time. However, both groups registered the same incidence of confirmed or suspected UTI (62-63%). Therefore, the benefit translated into early detection and definitive action resulting in less impairment and less lost time due to the UTI. Once discharged, some SCI patients experience unacceptable recurrence of UTIs. These high risk individuals can be identified and re-educated with respect to proper technique and hygiene. Barber et al. (1999), identified and re-educated 17 patients over 1000 consecutive outpatient SCI clinic days, and found that 65% of these patients were able to reduce their number of UTIs to be reclassified as not high risk (2 UTI/6months). A further subset of these patients (N=8) required multiple counseling sessions to realize an effective reduction of number of UTIs. 13-43

Although the authors suggest that education intervention by a clinic nurse is a simple, costeffective means of decreasing the risk of UTIs in at risk SCI individuals, the sample size is small and the study was neither randomized nor controlled. Patients can also be educated with respect to additional definitive action for the prevention of UTI in SCI such as anal or rectal stretch, crede, tapping, valsalva or more frequent catheterization. With the aid of tapping and compression, Menon and Tan, (1991) (N=55, case series study) reported that acceptable residual urine volumes (<100mL) were maintained by patients who were catheter free (N=45), utilizing clean intermittent self-catheterization (N=8) or had an indwelling catheter (N=2). Another tool that may be useful in the bladder management education of SCI individuals is a portable ultrasound device (PUD) to assist with optimization of SIC frequency and with decrease in number of episodes of bladder over distension. Anton et al. (1998) randomized 57 SCI patients with neuropathic bladder into groups using a PUD (or not) where SIC frequency, bladder volumes and patient satisfaction were measured. The PUD group used significantly fewer catheters per day while no significant difference was found between the two groups for episodes of over distension. The authors felt that the change in number of episodes of over distension (12.45 vs 14.76 episodes of over distension) would still be clinically significant even if statistically non-significant. The majority (16/18) of PUD users expressed satisfaction with the use of the device although less than half expressed that they would be willing to purchase such a device to assist with their SIC program. Of note is the 33% drop out rate which may indicate that not all patients would find the PUD an acceptable part of their SIC program. Perhaps reporting a reduced incidence of UTIs would have been a more persuasive finding to advocate for consistent PUD usage in this population. The contribution of small residual volumes on UTI incidence was demonstrated in a case series of 12 SCI patients having documented residual urine volumes after SIC as measured by ultrasonography (Jensen et al., 1995). There was a low and non-significant correlation found between residual volume and frequency of urinary tract infections. All but 2 patients had residual volumes after an initial catheterization while residual volumes were reduced to <50ml after the 2nd or 3rd catheterization. Seven (19%) of the 36 catheterizations resulted in residual volumes exceeding 50ml and 2 of these patients had residual volumes exceeding 100ml. It appears that even small residual volumes may predispose patients to urinary tract infections. Even though SIC had been popularized since the early 1970s (Lapides et al., 1972; 1974), quadriplegic patients did not have access to this area of independence due to the fears of clinicians that insufficient hand function would create greater risk of UTI due to their inability to maintain clean technique (Dailey and Michael, 1977). However, Sutton et al. (2002) have provided evidence to the contrary where 81% of the 36 quadriplegic patients, taught CISC during hospitalization, continued to use CISC at follow-up 2-9 years later. Similar findings were reported by Maynard and Glass (1987) following a telephone interview and medical record review of 40 SCI patients (para and quadriplegic) with neuropathic bladder. At least 80% of patients who were discharged with CISC continued using CISC at 5 years post-discharge. The majority of the Sutton et al. (2002) patients (24/29) performed CISC with total independence and 16/18 patients who were screened by urinalysis had sterile urine. This group also found that there was a higher chance of CISC success with earlier CISC education. However, pre-/postdischarge activities of daily living (ADL) scores did not correlate with CISC success. In some instances, common bladder management techniques yield unsatisfactory results such as chronic UTIs, hydronephrosis, recurrent renal calculi, vesico vaginal fistula, persistent urethral or catheter leakages. For these patients, one option is for the elective formation of a 13-44

stoma via surgery. Craven and Etchells (1998) reviewed 27 medical records of SCI patients who had undergone colostomy, ileostomy or urostomy. Eighteen of these patients were then interviewed or completed a comprehensive questionnaire to assess the long-term physical, psychological or lifestyle effects of the surgery. Although the impact of the stoma on lifestyle was positive, the long-term impact to renal impairment could not be ignored for individuals with neuropathic bladder secondary to SCI. Conclusion Level 1 evidence supports the use UTI educational intervention to provide benefits of increased bladder health (i.e. decreased urine colony counts) that increase a patients perception of the control they have of their own health behaviours and that may translate into less impairment and less lost time due to UTI in SCI. Weak level 4 evidence suggests that outpatient, nursing-mediated re-education of SCI individuals at high risk of UTIs may be a cost-effective method of reducing the number of UTI. Level 4 evidence exists to support additional utilization of tapping and compression to augment bladder management as expressed as acceptable residual urine volumes (<100mL). Level 1 evidence supports the acceptance and use of a portable ultrasound device to significantly reduce the number of catheterizations required each day in individuals with SCI who perform SIC to empty their bladder. Level 5 evidence supports that quadriplegic patients educated to CISC may continue to use CISC successfully for many years after discharge. Level 4 evidence suggests that for SCI individuals with chronic or significant medical issues related to common bladder management techniques, urostomy may not be a viable alternative due to long-term renal impairment. UTI educational intervention improves bladder health and a patients perception of the control that they have of their own health behaviours. Out-patient, nursing-mediated, re-education may be cost-effective in reducing the number of UTIs in SCI individuals identified as high risk for UTI. Adjunct tapping and compression may help to maintain acceptable residual urine volumes in SCI bladder management. The use of portable ultrasound devices is accepted by patients and the number of intermittent catheterizations per day are reduced in patients using these devices. Quadriplegic patients can be successful with clean intermittent catheterizations for many years post-discharge. Quadriplegic patients taught clean intermittent catheterizations may continue to use this technique successfully for many years after discharge. Urostomy as an alternative to insufficient common bladder management methods may lead to long-term renal impairment.

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13.6.2 Managing Possible Sources of Contaminants Keeping the skin clean is one of the simplest methods to limit the source of bacteria that can be introduced into the bladder of SCI individuals. Using clean versus sterile catheterization supplies and instilling anti-bacterial solutions directly into the bladder are other alternative methods to reduce the level of contaminants residing in the bladder. Table 13.15 Individual Studies of the Effect of Managing Possible Contaminants in Preventing and Treating UTIs
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Giannantoni et al. 2001; Italy PEDro=9 RCT N=18

Population: SCI; Mean Age: 38.216.4 years; C5-Cauda Equina; AIS A-D; Postinjury time: 18-60 days. Treatment: Assessment of Instacath nonhydrophilic pre-lubricated catheter vs conventional uncoated PVC Nelaton catheter for IC (crossover design). Outcome measures: symptomatic UTI, incidence of urethral complications (ultrasound, CUG), urinalysis, visual analog scale of patient satisfaction. Collected at the start and end of 7 week study period.

1.

2.

3. 4. 5.

6.

Lower incidence of UTIs (p=0.03) and asymptomatic bacteriuria (p=0.0244) of those using pre-lubricated catheters vs PVC. More epithelial cells found on conventional vs pre-lubricated catheter (p=0.01) indicative of possible microtrauma. 2 people had urethral bleeding with conventional catheter, 0 with prelubricated. Pre-lubricated catheters had significantly higher satisfaction scores for 4 of 5 items on the scale. 3 subjects requiring assistance with the conventional catheter became independent with the pre-lubricated catheter (order effect unreported) No subject had impaired renal function of upper & lower tract abnormalities with either catheter. Lower incidence of UTIs of those using SpeediCath hydrophilic vs PVC (p=0.02). No difference in number of bleeding episodes or occurrence of hematuria, leukocyturia and bacteriuria between 2 catheters. More individuals expressed greater satisfaction with various aspects of the hydrophilic catheter, although these differences were not significant. 54% dropout rate (slightly more so in hydrophilic group) partially due to the fact that many subjects no longer needed to catheterize when bladder function was retained within the 1 year period. Urine pH lower in methenamine and hemiacidrin group (p<0.01). Control group had double the number of positive cultures (p<0.001). UTI higher in controls (p<0.02). Higher rate of symptomatic UTI in

De Ridder et al. 2005; Belgium, Spain PEDro=5 RCT N=123

Population: SCI using hydrophilic vs PVC catheter; Mean Age: 37.514.6 vs 36.714.6 years; AIS A-D. Treatment: SpeediCath hydrophilic catheters vs conventional uncoated PVC catheter for IC. Outcome measures: Occurrence of symptomatic UTIs, hematuria, strictures, convenience of use, satisfaction with catheter collected over a 12 month period.

1. 2.

3.

4.

Krebs et al. 1984; USA PEDro=4 RCT N=40

Population: m=40; level of injury: T6 & above=27, T7 & below=13 Treatment: Control group: intermittent catheterization without bacterial prophylaxis. Treatment group: instillation of 45 ml. 5% hemiacidrin solution at each

1. 2. 3. 4.

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

Sanderson & Weissler 1990a; UK PEDro=4 RCT N=19

catheterization and 2 mg methanamine mandelate orally 4*daily. Outcome Measures: Urinary pH determination culture and antibiotic susceptibility Population: m=16, f=3 Treatment: Patients washed daily in chlorhexide or unmedicated soap. Outcome Measures: Not specified

controls (chi-square 3.84, p<0.05)

1. 2. 3.

Prieto-Fingerhut et al. 1997; USA PEDro=2 RCT N=29

Population: m=16, f=13; ASIA: A-D; SCI. Treatment: rehab nursing catheterization every 4 to 6 hours over a 3 month period. Outcome Measures: Number or % of urinary tract infections. Population: Traumatic SCI on inpatient rehabilitation; No-touch vs traditional straight IC method groups; Median Age: 30.5 vs 30 years; 2 groups were similar with respect to age, gender, paraplegics vs quadriplegics, level of lesion and extent of lesion; LoS: 4.8 vs 11 weeks. Treatment: Assessment of no-touch vs traditional straight IC method. Outcome measures: UTIs, infection free days, duration of infection, Cost of antibiotics, nurse satisfaction with method. Population: SCI, approx age 26.5, 70 Treatment: External urinary collection system (EUCS): Group 1-continuous EUCS, Group 2-EUCS during day only, Group 3-no EUCS Outcome Measures: # of Pseudomonas and Klebsiella in swab cultures of urethra, perineum, rectum; Significant bacteriuria (10,000 bacteria/ml urine)

1. 2. 3. 1.

Charbonneau-Smith 1993; Canada Downs & Black score=18 Prospective Controlled Study (retrospective control group) N=110

2. 3. 4. 1. 2. 3.

Gilmore et al. 1992; USA Downs & Black score=10 Prospective Controlled Trial N=119

Bacteriuria reduced by washing with chlorhexidine vs soap. (X2=12.2, p<0.01). Bacteriuria less for those on antibiotics 2 and using chlorhexidine (X =3.2, 0.05<p<0.01). Antibiotics usage resulted in significant increase in perineal swabs negative for coliforms (p<0.01) No statistically significant results were reported. Non-sterile catheterization programs = more urinary tract infections (not significant). Sterile catheterization program 277% more costly. No-touch experimental group had fewer infections (p=0.0001), and reduced duration of infections (p=0.0004). No difference on total cost (including antibiotics) and # of infection-free days (trends were in favour of No-touch). Similar number of catheters used despite > 2x longer LoS for traditional method. Majority of nurses reported they preferred No touch catheter. Reduced Pseudomonas and Klebsiella in urethra, perineum or rectum only if no EUCS (p<.05), EUCS did not influence rate of bacteriuria. Removal of the EUCS at night reduced urethral colonization with Pseudomonas only (p=.03)

Discussion Although the use of standard soap for cleansing is routine in rehabilitation facilities, the prevention of bacterial colonization may require further measures. Sanderson and Weissler (1990b) found that perineal colonization of SCI individuals was significantly correlated with bacteriuria and may be a source of contamination of the environment and indirectly of the hands of patients and staff. As a result of this finding, this group further examined the effect of chlorhexidine antisepsis on bacteriuria, perineal colonization and environmental contamination in spinally injured patients requiring intermittent catheterization (Sanderson and Weissler, 1990a). In male patients not receiving antibiotics, daily body washing in chlorhexidine and

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application of chlorhexidine crme to the penis after every catheterization significantly reduced bacteriuria to 60% from 74% in patients who were only washed with standard soap. Chlorhexidine antisepsis did not affect perineal coliform colonization or contamination of the environment. Limiting the source of contaminants through the use of sterile vs clean catheter supplies may superficially sound like a viable solution to reducing the rate of UTI but not surpisingly, costs of sterile supplies may become prohibitive. Prieto-Fingerhut et al. (1997) conducted a randomized trial on 29 SCI patients using sterile or nonsterile urethral catherization. Predictably, the incidence of UTI was higher in the non-sterile group (incidence of 42.4% vs 28.6%) and the subsequent cost of antibiotic treatment in the sterile group was only 43% of the non-sterile group. However, the total cost of the sterile management group was 277% higher than the non-sterile group. Charbonneau-Smith (1993), had previously reported that using no-touch method of catheterization in a convenience sample of 18 traumatic SCI patients resulted in a 44.5% reduction of UTI rate. Athough a nurse satisfaction questionnaire revealed that this method of intermittent catheterization was preferred over the traditional method, no reference was made to a formal cost analysis between methods. Sterility aside, the type of catheter also has an effect of the incidence of UTI in those who practice IC to mange SCI neurogenic bladder. For example, Giannantoni et al. (2001) employed a double-blind, crossover RCT design (N=18) to examine the difference between a prelubricated nonhydrophillic Instantcath catheter as compared to a conventional polyvinyl chloride (PVC) silicon-coated Nelaton catheter with respect to the occurrence of UTIs and urethral trauma. The subjects were randomized to 1 of 2 groups which tried each catheter for a period of 7 weeks in an A-B, B-A design. Both incidence of UTIs and presence of asymptomatic bacteriuria was reduced for the pre-lubricated catheter vs the conventional PVC catheter. In terms of general satisfaction with use, subjects rated the pre-lubricated catheter significantly higher than the conventional catheter with respect to ease of inserting and extracting, comfort and handling. A similar finding of reduced incidence of UTIs was reported by De Ridder et al. (2005), but in this case the comparison was between a hydrophilic catheter as compared to the conventional PVC catheter, with the hydrophilic catheter associated with fewer infections. There were no other significant differences noted between the two groups including the number of bleeding episodes or occurrence of hematuria, leukocyturia and bacteriuria. This multi-centre investigation also employed a RCT design (N=123) but had a high drop-out rate (54%) with slightly more individuals not completing the study from the hydrophilic catheter group. A probable cause for many of these drop-outs was the lengthy treatment period of 1 year during which many individuals were likely to improve bladder function such that IC was no longer required. Although catheters inserted into the body are an obvious source of bacterial introduced into the bladder, condom catheters also can potentially be a source of bacterial colonization externally where external colonization, especially of the perineum, has been suggested by Sanderson and Weissler (1990b) to be significantly correlated with bacteriuria in SCI individuals. By discontinuing night time use of the external urinary collection system (EUCS), Pseudomonas colonization of the urethra was found to be significantly reduced where Klebsiella colonization was not affected significantly (Gilmore et al., 1992, N=119). However, the prevalence of bacteriuria caused by either gram-negative bacilli, did not have any significant correlation with EUCS use.

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Ensuring that the bladder is not a bacteria friendly environment, without the risk of encouraging antibiotic resistance, is another way to combat the source of contaminants during intermittent catheterization. Methenamine mandelate is a formaldehyde releasing compound that is rapidly absorbed and excreted in the urine. In combination with a 5% hemiacidrin bladder instillant (a citric acid solution), two 2mg oral methenamine mandelate tablets 4 times per day achieved significantly lower urine pH and lower incidence of UTI in SCI patients requiring intermittent catherterization than those who received the control treatment (Krebs et al., 1984, N=40). Conclusion Level 1 evidence (based on one high quality and several low quality RCTs) supports the use of daily body washing in chlorohexidine and application of chlorhexidine crme to the penis after every catheterization verses using standard soap in the endeavour to significantly reduce bacteriuria. Although the rate of UTI requiring antibiotic treatment is less with the use of sterile catheterization technique, level 1 evidence supports the use of clean versus sterile catheter supplies as a result of the prohibitive cost of the latter. Level 4 evidence suggests that the prevalence of bacteriuria caused by gram-negative bacilli, did not have any significant correlation with differing practices of external urinary collection systems (i.e. continual vs discontinuation at night). Poor quality level 1 evidence is supportive of the use of oral methenamine mandelate in combination with hemiacidrin bladder instillant to lower urine pH and incident of UTI.

External chlorohexidine application or methenamine mandelate with hemiacidrin bladder instillant are separate techniques that are likely to reduce the incidence of UTI. Sterile vs clean catheterization technique is more effective at reducing rate of UTI but is much more costly to maintain. The prevalence of gram-negative bacteriuria is not affect by continual use or night-time discontinuation of condom drainage. Oral methenamine mandelate in combination with hemiacidrin bladder instillant likely lowers the rate of UTI. 13.6.3 Bladder Management Techniques Each type of bladder management technique comes with its own set of advantages and disadvantages that the clinical team must assess at the time of initial bladder dysfunction secondary to spinal cord injury. There is discussion amongst clinicians over the bladder management technique that can best achieve optimum bladder control and rate of UTIs.

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Table 13.16 Individual Studies of the Effect of Various Bladder Management Techniques in Preventing and Treating UTIs
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Lloyd et al. 1986; USA Downs & Black score=16 Case control Initial N=204; Final N=203

Yadav et al. 1993; India Downs & Black score=7 Case control Group A: n=27 Group B: n=21

Wyndaele & De Taeye 1990; USA Downs & Black score=8 Case Series N=73

Population: Age:13-18yrs, level of injury: SCI; time since injury: within 36hrs; complete/incomplete. Treatment: Initial bladder management Outcome Measures: excretor urogram (IVP) graded by 2 MDs for pyelocaliectasis, renal plasma flow, episodes of chills and fevers. Population: Group A: m=26, f=1; SCI, 1296 hrs post injury. Group B: 19 para and 2 tetra; SCI, long-term clean intermittent catheterization (CIC) Treatment: Group A-CIC started on day 1 of hospitalization. Group B-Long term CIC (1-12 years) Outcome Measures: number of bladder infections Population: m=22,f=3; age=6-59yrs, level of lesion D7-D12 Treatment: Self-catheterizations. Outcome Measures: Not specified

No statistically significant differences between groups at 1 year post injury: 1. # chills and fevers 2. rate of urinary infections 3. upper tract changes, 4. genitourinary complications 5. frequency of urological procedures 1. Group A: 5 subjects had symptomatic UTI between 10 days-3mos (18.5%). 2. Group B: 0.07 episodes per patient per month symptomatic UTI (33%) CIC is safe and effective for acute and chronic SCI with acceptably low infective complications. 1. 72% of self-catheterization groups achieved a state of balanced bladder able to empty bladder by tapping or straining after a mean of 5 weeks. Urinary tract infections varied amongst the group - all subjects had at least one UTI . Relief of symptoms within 3-4 days of appropriate antibiotic treatment. Multiple organisms isolated in 62% of urine cultures. Pyuria decreased by at least 65% and 87% at midpoint and end of therapy, respectively.. ICP group had lower residual pyuria at mid and endpoint (p<0.05). Pyuria response to treatment, best and earlier assessed in ICP No statistical results reported. Nine percent of patients (46/520) over 6 years utilizing IUSC at discharge. 22/46 patients continue to use IUSC after 4.6y for males, 6.6 y for females. Only 4.3% complication rate from IUSC.

2. Population: m=29; Age: 28-61 years, mean=45 yrs; ASIA Level A; SCI; Itermittent catheterization program (ICP): 10; Suprapubic tube (SPT): 10; Indwelling foley catheters (IFC): 9. Treatment: 7-day course of an appropriate antibiotic with urine sampled at mid and endpoint. Outcome Measures: Not specified Population: m=27, f=19; age 18-64yrs. Treatment: Intermittent Urethral Self-Catheterization (IUSC) status at discharge and up to 5 yrs later. Outcomes Measures: bacteriological evolution, sterile vs. clean IUSC, frequency of daily catheterization, complications, continence and acceptance of the method. 1. 2. 3. 4. 5. 1. 2. 3. 4.

Joshi & Daroucihe 1996; USA Downs & Black score=10 Case Series Initial N=41; Final N=29

Kuhn et al. 1991; Switzerland Downs & Black score=7 Case Series N=46

Discussion Lloyd et al. (1986) studied a group of 204, young (13-18yo) SCI patients grouped according to urological management techniques as follows: A) intermittent catheterization within 36h of injury, B) suprapubic trocar drainage within 36 h of injury, C) urethral catheter drainage for >36h prior to intermittent catheterization, D) indwelling urethral catheter drainage throughout and after discharge from hospitalization, and E) intermittent catheterization placed in 13-50

community hospital. Overall, this group found that the method of initial bladder management does not affect the incidence of UTI, genitourinary complications or frequency of urological procedures at 1 year after injury. The only exception was group D who had a greater rate of UTIs as a result of the placement and maintenance of indwelling urethral catheter drainage throughout and after discharge from hospitalization. This corroborates the finding of Yadav et al. (1993) that reported CIC to be superior to indwelling catheter for management by reducing the clinical UTI rate in SCI individuals. Wyndaele and De Taeye (1990) found that the rate of UTI or urethral trauma did not differ between those patients who were taught intermittent self-catheterization (ISC) early after injury compared to those where the procedure was done by a catheter team. However, of interest was the finding that those who achieved early ISC also went home earlier for the weekend. The results of this case control study should be interpreted cautiously as the sample size was quite small (N=8). However, Yadav et al. (1993) in contrast, reported that patients managed with clean intermittent catheterization from day 1 of hospitalization (i.e. early vs late) experienced a lower (18.5%) clinical UTI rate compared to 26% reported for patients indwelling catheter in a separate study (Maynard and Diokno, 1984). Although the influence of the initial type of bladder management technique on rate of UTI is considered by some to be equivocal (Lloyd et al., 1986), Joshi & Darouiche (1996) report that the response to pyuria is better and can be assessed earlier in patients who utilize SIC over those whos bladder drainage is reliant on suprapubic tube or indwelling foley catheters. All patients experienced relief from proper antibiotic therapy after 3-4 days, but the level of residual pyuria was lowest at mid-therapy and after therapy completion in those patients using SIC as measured by the hemocytometer chamber method. A five-year follow-up study also showed results favouring the preparation of SCI patients to use of SIC at time of discharge. Kuhn et al. (1991) found that of the 46 (9% of 520) patients who met the criteria of achieving SIC at time of discharge, less that half (22) continued with ISC at the 5-year follow-up. Also at the 5-year follow-up, six had switched to indwelling catheters, 13 had switched to other methods of bladder emptying and 5 had died. The rate of complications was very low at 4.3% and pharmacological intervention was non-existent (no anti-cholinergic, alpha-stimulating or continuous antibiotic-prophylaxis) and the degree of continence remained stable throughout the 5 years. The authors concluded that with proper patient selection and quality instruction during hospitalization, SIC has been a successful method of neurogenic bladder management for their patients. 4 Conclusion There is Level 3 evidence that sterile intermittent catheterization may lead to a lower rate of UTI and complications with a maintained continence level after discharge as compared to other bladder management techniques such as use of indwelling catheter.

Sterile intermittent catheterization is likely to provide successful bladder management with a lower rate of UTI and complications with a maintained continence level after discharge.

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13.7 Pharmacological Interventions for Preventing and Treating UTIs The most common medical complication secondary to SCI neurogenic bladder is urinary tract infection (UTIs). The latter can be responsible for a decline in quality of life and an increased mortality rate in persons with SCI. Although prevention is the best medicine, many UTIs (symptomatic or asymptomatic) will require treatment with pharmacological agents. Choosing the right pharmacologic agent is dependent on the treatment stage, and the type of bacteria found in the patients urine. Choosing the length of treatment depends on the patients history (i.e. symptomatic or asymptomatic; occasional or chronic symptoms). The most common antibiotics used for routine UTIs include fluoroquinolones, trimethorprin, sufamethoxazole, amoxicillin, nitrofurantoin and ampicillin. Although antibiotic treatment is the most common option, alternative treatments are also gaining momentum not only due to the increase in antimicrobial resistance but also for health reasons and for reasons of cost reduction. 13.7.1 Preventative Pharmacological Interventions Prevention of SCI UTI is the treatment option of choice and patients are educated in this endeavour prior to hospital discharge. However, sterile technique is sometimes difficult for those who have limited independent function, attendant care or access to sterile supplies. Table 13.17 Individual Studies Assessing Pharmacological Interventions for Preventing UTIs
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Pearman et al. 1988; Australia PEDro=3 RCT Initial N=18; Final N=15

Population: m=15; Age:18-49yrs Treatment: Trisdine bladder instillation following intermittent catheterisation vs kanamycin + colistin bladder instillation Outcome Measures: Episodes of bacteriuria, number of catheterizations, duration of catheterizations Population: age 23-84 males matched to age, type of bladder drainage, location of UTI, route of antibiotic admin, etc. Treatment: Limited vs full microbiological investigation for management of symptomatic polymicrobial urinary tract (limited = cultures for specific organisms not used to guide antibiotic selection) Outcome Measures: Clinical improvement following symptomatic UTI (criteria defined as presence of bacteria + one symptom) by 4 days after treatment with antibiotic, time to start antibiotic, cost of entire therapy and lab tests

Darouiche et al. 1997; USA PEDro=7 RCT (study 1) Pre-post (study 2) Study 1 Initial N=45 Study 1 Final N=40 Study 2 N=12

Horton et al. 1998; USA PEDro=6 RCT

Population: SCI, inpatients. Treatment: urine sampleprocessing within 4 hrs of sampling (fresh) vs 24

No significant difference (chi square, no p value given) in number of episodes of bacteriuria between Trisdine vs kanamycin-colistin bladder instillations; 2. 0.56% (9 of 1609) vs .53% (9 of 1704) of instillations were associated with episodes of bacteriuria for Trisdine vs kanamycin-colistin respectively. 1. No difference in therapy response between full vs limited approach (p=.4); 2. Limited approach antibiotic initiation earlier at 1.2+/-1.4 days vs 3.3+/-2.5 days for full approach (p=.01); 3. Higher proportion of people in limited group required no change in initial antibiotic than with full approach 85% vs 33% (p=.006); 4. Recurrence at 1 month due to at least 1 of the originally infecting species was similar for both groups (p=1.0); 5. Costs for limited investigation-directed therapy less @ $157+/- $174 vs $252 +/- $237 for full approach but not significantly different (p=.18) No significant difference between fresh and refrigerated samples in: 1. WBC (z =-0.353, p=0.724),

1.

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Author Year; Country Score Research Design Total Sample Size N=40

Methods

Outcome

(refrigerated ) hours of refrigeration. Outcome Measures: cultures, colony counts, urinalysis.

2. 3. 4.

# bacteria (z -0.772, p = 0.440) leukocytes (z = -0.277, p = 0.782), or colony counts of E. fecalis & Pseudomonas (z=-1.00, p =0.317), E. coli, Citrobacter, Streptococcus, Yeast, or Acinetobacter (z=0.00, p=1.0). Sig diff btwn fresh & refrigerated samples with colony counts <50 k: 1. "mixed" organisms (z = -2.565, p = 0.010) 2. Staph aureus trend only (z=1.841, p=0.066) No cultures/colony count changes in up to 24h refrigeration to alter treatment or clinically significant urinalysis/culture results.

Discussion Practicality of treatment methods is a valid issue for consideration as evidenced by the study conducted by Pearman and colleagues (1988, N=15). They investigated the use of two different medicated bladder instillations used to prevent bacteriuria and UTI in SCI. They concluded that although there was no difference between incidence of bacteriuria in catheterized patients instilled with Kanamycin-Colistin versus Trisdine, the latter is preferred based on its stabilitiy at room temperature, reduced likelihood of selecting antibiotic-resistant bacteria than antibiotics and reduced cost compared to Kanamycin-Colistin. It is important to note that the preference of Trisdine is not based on a reduced incidence of bacteriuria but rather by cost savings and practicality. Although the latter are important factors for treatment choice, this study presents no evidence for preferential beneficial effects based on incidence of bacteriuria. Another practical approach to prevention and treatment of UTI in SCI patients was undertaken by Salomon et al. (2006). They utilized a weekly oral cyclic antibiotic (WOCA) program that was beneficial in preventing UTI in SCI patients, decreasing antibiotic consumption and decreasing the number and length of hospitalizations, without severe adverse events or the emergence of multi-drug resistant (MDR) bacteria. This paper will be discussed in more detail below along with other antibiotic interventions for the treatment of acute UTI in SCI individuals. Practicality and cost savings and practicality in UTI prevention and treatment may not have been the prime motive in an investigation by Dariouche et al. (1997), but they did find that an adequate clinical response to treatment was not significantly different as a result of limited vs full microbial investigation. As well, the cost savings, at an average of $183 US per patient, was significant between limited and full investigation. Althought this provides level 1 evidence in favour of deferring to a limited microbial investigation for SCI UTI treatment selection, the sample size was small (N=15) and warrants further study. Sample deterioration between the time of sampling and processing is controversial. Horton et al (1998) conducted a prospective blinded study to investigate the effects of refrigeration on urinalysis and culture results. Samples were split and analyzed at 4 (fresh) and 24 (refrigerated) hours post-refrigeration. The bacterial counts of mixed organisms (p=0.10) and 13-53

Staph aureus (p=066) were altered with refrigeration but no changes in colony counts would have altered the treatment regimen chosen based on urinalysis or culture results. This level 1 evidence provides a level of confidence for urine samples refrigerated (up to 24 hours) prior to analysis. Conclusion There is level 2 evidence (based on a single poor quality RCT) reporting no difference between incidence of bacteriuria in catheterized patients. However, Trisdine is the more often chosen between the 2 treatments, based on the fact that it is not likely to contribute to antiobiotic resistance, its stability at room temperature, and its lower cost. Level 2 (based on a single RCT) evidence suggests that both limited and full microbial investigation result in adequate clinical response to UTI treatment with antibiotics. Therefore the cost savings attributed to a limited microbial investigation favours this practice in the investigation of UTI. Refrigeration (up to 24 hours) of urine samples prior to sample processing does not alter urinalysis or urine culture results in SCI patients.

There is no difference between incidence of bacteriuria in catheterized patients instilled with Kanamycin-Colistin versus Trisdine. Both limited and full microbial investigation result in adequate clinical response to UTI treatment with antibiotics. Urinalysis and urine culture results of SCI patients is not affected by sample refrigeration (up to 24 hours).

13.7.2 Antibiotic Interventions for Treating UTIs Even though patients are thoroughly educated with regard to UTI prevention, the incidence of UTI in SCI remains high at ~1.8 episodes/person/year at risk as estimated by Waites et al. (1993). Detecting UTI is the first step towards treatment and in a prospective case review undertaken by Linsenmeyer and Oakley (2003), only 61% (90/147) of patients were able to correctly predict the presence of an UTI based on their symptoms. However, once a UTI has occurred, selection of the appropriate treatment depends on microbial investigation. Furthermore, it has been noted that 33% of SCI UTIs are polymicrobial (Dow et al., 2004). The clinician must then decide between a limited or full microbial investigation in selecting the appropriate treatment. The obvious benefit of a full microbial investigation (i.e. accuracy) is offset with adverse effects due to the time delay for the bacterial sensitivity results and with the cost of a full investigation.

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Table 13.18 Individual Studies Examining Antibiotic Interventions for Treating UTIs
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Dow et al. 2004; USA PEDro=10 RCT Initial N=60; Final N=52

Reid et al. 2000; Canada PEDro=8 RCT N=42

Population: m=51, f=9; age: mean 39yrs; SCI; voiding mangament: intermittent catheterization n=50, condom drainage n=10 Treatment: 250 mg of ciprofloxacin orally b.i.d for 3 days followed by 11days of placebo or they received ciprofloxacin (250mg) b.i.d. for 14 days. Outcome Measures: Urinalysis with leukocyte count, urine culture and surveillance cultures were taken before and throughout the study Population: Age: 18-75yrs, m=28, f=14; Treatment: ofloxacin ( 300 mg bid) vs trimethoprim-sulphamethoxazole (TMPSMX 160/800 mg bid) or another antibiotic if resistant to TMPSMX, either for 7 days Outcome Measures: presence of bacteria in urine, biofilm presence (# of bacteria / epithelial cell) Population: SCI, other neurological disease; Mean Age: 45.8 years; Gender: 49 male, 40 female; Mean Post-injury time: 11.2 years. Treatment: Assessment of normal saline vs 0.25% acetic acid vs neomycinpolymyxin (N-P) GU irrigant for treatment of bacteriuria. Outcome measures: Numbers and types of bacteria, urinary pH, urinary leukocytes, generation of antimicrobial-resistant organisms. Population: SCI with asymptomatic UTI Treatment: standard and low-dose tobramycin and amikacin (IM x5d) Outcome Measures: UTI rate, persistence, relapse, reinfection with other bacteria.

Waites et al. 2006; USA PEDro=6 RCT Initial N=89; Final N=52

Sapico et al. 1980; USA PEDro=6 RCT N=29

Biering-Sorensen et al. 1994; Denmark PEDro=8 RCT N=21 Gribble & Puterman 1993; Canada PEDro=8 RCT N=129

Population: SCI with neurogenic bladder dysfunction; m=18, f=3; median age 38y (19-73y). Treatment: Six months Ciprofloxacin (100mg/night) vs placebo prophylaxis Outcome Measures: # UTI, urine and fecal cultures, side effects Population: acute SCI; m=112, f=17; median age 38y (19-73y). Treatment: efficacy of trimethoprimsulfamethoxazole (TMP-SMX id; TMP 40 mg, SMX 200 mg ) for UTI prophylaxis in

Statistically significant results: 1. Higher microbiological cure for 14 day treatment (p<0.02). 2. Lower rates of clinical & microbiological relapse at short & long term follow-up (p<.01) 3. E. faecalis associated with treatment failure compared to other isolates (p<0.03). Improved microbiological outcomes in favour of 14 vs 3 day course for treatment of symptomatic UTI in SCI. 1. Clinical cure rate in favour of Ofloxacin vs TMPSMX or other antibiotic at day 4 (p=.003) and day 7 (p=.015); 2. Biofilm clearance rate in favour of Ofloxacin vs TMPSMX or other antibiotic at day 4 (p=.005); and day 7 (p=.014); 3. Both treatments effective at reducing bacterial biofilms at day 4 and 7 (p<.001). 1. Most common urine organism was Enterococcus spp.; increased significantly for N-P group only (p=0.02) 2. Mean urinary pH for all 3 groups increased from mean of 6.6 to 7.0 7.2 range (p=0.01) at wk 8. No sig increase in: 3. Urinary leukocytes in any group (p0.6). 4. MRSA (p0.37) or gram-negative resistance to common UTI antimicrobials (p0.11). 1. No difference between: dose strengths. tobramycin and amikacin. 2. Low cure rate. 3. High urine antibiotic concentrations in all subjects Tobramycin and amikacin not recommended for use in this popln. 1. Ciprofloxacin vs placebo prophylaxis (6mos): # UTIs 5 vs 59 (p<0.00005) 2. 1 instance of ciprofloxacin resistant E. coli found in the feces of 1 Cipro patient 3. No severe side effects. TMP-SMX more efficacious than placebo (P) prophylaxis: 1. Lower incidence/freq/relapse of bacteriuria and symptomatic UTI in males (p<0.003 /0.0001/0.0001 and

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

acute SCI, during the first 4 mos of intermittent catheterization (IC) Outcome Measures: Clinical:, wkly rectal and urethral swab, and urine cultures. Breakthrough bacteriuria treated with conventional antimicrobial therapy and prophylaxis was continued.

Waites et al. 1991; USA Downs & Black score=12 Case Series N=69

Population: m=66, f=3; SCI, Complete n=58, incomplete n=11; Age: 18-69yrs; injured <6 mths n=5, injured >/=6mths n=64. Treatment: Oral norfloxacin 400 mg bid for 14 days after initial bacteriologic confirmation of UTI Outcome Measures: bacterial strain/species identification, culture results mid and post treatment periods.

Salomon et al. 2006; France Downs & Black score=12 Case Series N=38

Reid et al. 1994b; Canada Downs & Black score=11 Case Series N=14

Population: Gender: m=22, f=16; Age: mean=45.9 13.9 yrs (SD); SCI: # of daily catheterizations: mean 6 1.4 Treatment: Weekly oral cyclic antibiotic (WOCA): Wk 1-one antibiotic + wk 2 another antibiotic (over 2 yrs). Antibiotic choice based on urine culture results: amoxicillin 3000mg; trimethoprim/ sulfamethoxazole 320-1600mg; fosfomycin trometamol 6000mg; nitrofurantoin 300mg; cefixime 40mg. Outcome Measures: Number of UTI's Population: SCI inpatients; m=11, f=3; 20-66y Treatment: urine samples for culture and sonication for 8 wks; monitored for UTI signs and symptoms and treated with appropriate antibiotic: ciprofloxacin 500mg bid, norfloxaqcin 400mg bid, amoxicillin 500mg q8h, ampicillin 250mg qid, cotrimoxazole (TMPSMX 160/800 mg bid), gentamycin (100mg q8h or nitrofurantoin 50mg qid. Outcome Measures: infection rate, extent of biofilm formation, level of bacterial adhesion

0.0003). 2. Similar trends in women. Other results: 3. Adv. events similar btwn grps 4. 1 TMP-SMX-resistant bacteriuria in all P subj. by yr 3. 5. Rectal/urethral swab TMP-SMXresistant organisms-both grps. TMP-SMX UTI prophylaxis effective in acute SCI/IC but emergent TMP-SMXresistance limits usefulness. No statistical results reported. 1. 58/79 (73%) negative for UTI midtreatment 2. 5 to 7 days after administration of norfloxacin, infection was eradicated in 42 cases (53%) while 37 cases (47%) had evidence of infection (>/=105 cfu/mL on one or more of the categories listed. 3. 8-12 wks after administration, 84% (27/32) infected after previous eradication. 4. Clinical cure in 67% (4/6) symptomatic UTIs 5. Side effects in 8% of patients. 6. 16% treatment emergent resistance to norfloxacin. Before/after WOCA programme: 1. Symptomatic UTIs/ pt/yr p<0.01 2. Febrile UTI/pt/yr, p<0.04 3. Hospitalizations p<0.01. 4. Decreased antibiotic consumption correlated with decreased incidence of UTIs over the course of the study.

Non-prophylaxis vs TMPSMX prophylaxis subjects: 1. 68% vs 54% (not significant; no p value reported) 2. E coli replaced by E faecalis as dominant uropathogen with TMPSMX use. 3. 4449 vs 3942 adherent bacteria/bladder cell (not significant; no p value reported) Laboratory results: 1. Counts of >20 adherent bacteria may be predictive of symptomatic UTI. 2. Reduced adhesion counts in favour of Fluoroquinolone vs TMPSMX (63% vs 44%)

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome

3. Population: Gender: m=7, f=3; SCI; ASIA: A, B &D. Treatment: installed 30 cc of neomycin/polymyxin solution 3 x with each session (3 session/day for 5 days) Outcome Measures: Not clear

Linsenmeyer et al. 1999; USA Downs & Black score=10 Case Series N=10

92%, 71%, 56% biofilm reduction with ciprofloxacin, ofloxacin & norfloxacin NO statistical results reported. 1. 9 bladder irrigation trials led to changed resistance. 2. Of these 6 were able to receive an oral antibiotic and 3 had change in the sensitivities so that an oral antibiotic could be used (one subject not allergic to antibiotic). 3. The remaining 3 bladder irrigations were not successful.

Discussion Once UTI presence is confirmed, the most common antibiotics chosen for UTI treatment include fluorquinolones, trimethorprin, sufamethoxazole, amoxicillin, nitrofurantoin and ampicillin. Fluorquinolones are chosen often because of their effectiveness over a wide spectrum of bacterial strains (Waites et al., 1991). Although Waites et al. (1991) showed norfloxacin to be 73% effective in eradicating UTIs by mid-treatment, the rate of reinfection was 84% after 8 to 12 weeks post initial eradication. Furthermore, 16% of strains isolated after eradication became resistant to norfloxacin. The authors concluded that norfloxacin is a reasonable treatment choice for SCI UTI but the subsequent and problematic emergence of resistance must be monitored (as with other antimicrobials). Despite the efforts in reducing antimicrobial resistance, the incidence is still high and continues to add further challenges to successful SCI UTI treatment. A novel approach to prevention and treatment of UTI in SCI patients was undertaken by Salomon et al. (2006). After a prospective, observational study with 2 year follow-up, they concluded that a weekly oral cyclic antibiotic (WOCA) program was beneficial in preventing UTI in SCI patients, decreasing antibiotic consumption and decreasing the number and length of hospitalizations, without severe adverse events or the emergence of multi-drug resistant (MDR) bacteria. The WOCA regimen involved alternating between two antibiotics, chosen based on allergy and antimicrobial susceptibility, once per week over at least 2 years. The most frequent combination of antibiotics utilized were trimethoprim / sulfamethoxazole and cefixime (30%) followed by cefixime and nitrofurantoin (25%). The combination of antibiotics was modified in 40% of the patients once, 20% twice and 10% on three occasions during the follow-up. This level 4 evidence for the effectiveness of WOCA in SCI UTI prevention, treatment and cost, and would serve well as guidance in design of a randomized, double-blind, placebo-controlled study to confirm these results. Although the WOCA approach is promising for prevention and treatment, this once weekly dosing is not common practice. However, shorter courses of antibiotic treatment are currently considered by clinicians and patients who are concerned with side effects, cost and antimicrobial resistance due to longer term use. Treatment course durations as short 3 days are not uncommon while the more common treatment duration is 14 days. Reid et al. (2000), suggested that a 3-day regimen in the treatment of SCI UTI could be sufficient based on significant biofilm eradication detected in bladder epithelial cells in patients treated with Ofloxacin compared to trimethoprim-sulfamethoxazole. Ofloxacin is a fluoroquinolone antibiotic 13-57

shown to be promising in its ability to penetrate and eradicate bacterial biofilms in the bladder in vitro and in SCI patients (Reid et al., 1994a;1994b). The earlier study (Reid et al., 1994a) concluded that fluoroquinolone therapy was more effective at reducing bladder cell adhesion counts in 63% of asymptomatic SCI UTIs vs 44% of SCI subjects treated with trimethoprimsulfamethoxazole. The difference in effective treatment duration, compared to the findings of Dow et al. (2004), is likely due to the difference in anti-microbial used. However, further study comparing the 2 antimicrobials (and others) and differing treatment durations are required to clarify the question of optimum treatment duration for the antimicrobial being considered for use. While the range of effective antibiotic treatment duration can vary widely depending on the antibiotic used and the patients UTI history, there is a need for objective research to clarify optimal treatment durations for individual antimicrobials. Dow et al. (2004), undertook to compare a 14 vs 3 day course of ciprofloxin treatment in SCI patients with UTI symptoms or microbially documented bacteriuria and concluded that a 14 day Ciprofloxin treatment results in improved clinical and microbiological outcomes. Microbiological relapse rates were significantly lower for those patients treated for 14 vs 3 days. Although, this high quality level 1 evidence advocates for the use of a 14 vs 3 day course of ciprofloxacin in SCI UTI, it does not address the optimal treatment period. Further studies comparing 7 and 10 day treatments vs the 14 day treatment would be warranted. As well, optimal treatment periods may be antimicrobial specific as evidenced by the study of Reid et al. (2000), where it was suggested that a 3-day regimen in the treatment of SCI UTI could be sufficient based on significant biofilm eradication detected in bladder epithelial cells in patients treated with Ofloxacin compared to trimethoprimsulfamethoxazole. On the other end of the dose duration spectrum is the use of long-term, low-dose, prophylactic use of antibiotics for the prevention of SCI UTI. An RCT comparing low-dose, long-term treatment with ciprofloxacin (100mg each night) vs placebo concluded that ciprofloxacin prophylaxis for up to 39 months resulted in a marked reduction from the pre-study infection rate. (p<0.00005, corrected) with no severe side effects and 1 instance of ciprofloxacin resistant E. coli found in the feces of 1 patient (Biering-Sorensen et al. 1994). Although prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX; TMP 40mg, SMX 200mg once daily) over placebo was also found to significantly reduce incidence (p=0.003) and frequency of bacteriuria (p=0.0001) and symptomatic urinary tract infection (p=0.0003) in persons with recent acute spinal cord injury using intermittent catheterization for bladder management, treatment emergent adverse reactions were common with frequent colonization and breakthrough bacteriuria with TMP-SMX-resistant organisms (Gribble and Puterman, 1993; RCT, N=129). Gram-negative bacteria such as Pseudomonas, Acinetobacter, Enterobacter and mycobacteria are susceptible to aminoglycosides such as tobramycin and amikacin which are often chosen for complicated UTI treatment. Due to their toxicity and inconvenient route of administration (i.e. intramuscular injection), their use is limited. To investigate the effectiveness of a lower dose of these aminoglycosides, Sapico et al. (1980) compared infection, persistence and reinfection rates of SCI UTI against a standard dose. An overall low rate of success and no differences between the dose strengths and between tobramycin and amikacin even though high antibiotic concentrations were found in the urine of all subjects suggested that alternative antimicrobial agents were considered for use in this population. The clinician is sometimes faced with additional treatment option challenges when multi-drug resistant bacteria or the patients allergy to the appropriate antibiotic are encountered. Linsenmeyer et al. (1999) investigated the use of medicated bladder irrigation as a method to alter the existing antimicrobial resistance. They found that intermittent neomycin/polymyxin 13-58

bladder irrigation was effective in altering the resistance of the offending bladder organism(s) to allow for appropriate antibiotic treatment. An RCT (Waites et al., 2006) comparing sterile saline acetic acid and neomycin-polymyxin solution bladder irrigants did not have an effect of the degree of bacteriuria/pyuria, or development of antimicrobial resistance. The first study utilized a 3 times per day for 5 day treatment regimen with assessments done immediately pre- and post-intervention while the latter study required twice daily irrigation for 8 weeks with assessments done at baseline and 2, 4 and 8 weeks post-treatment. Both studies do not recommend bladder irrigation for the treatment of bacteriuria in neurogenic bladder. However, Linsenmeyer et al. (1999) do provide level 4 evidence advocating for a short course treatment of neomycin/polymyxin irrigant to alter existing antimicrobial resistance. Conclusion Level 4 evidence suggests that norfloxacin may be a reasonable treatment choice for UTI in SCI but subsequent resistance must be monitored. Level 4 evidence supports weekly oral cyclic antibiotic (WOCA) use for UTI prevention in SCI patients. It decreases antibiotic consumption, the number and length of hospitalizations, and is used without severe adverse events or the emergence of multidrug resistant (MDR) bacteria. Optimum antimicrobial treatment duration is controversial due to the lack of comparative trials. High quality level 1 evidence supports the use of 14 vs 3 days of Ciprofloxcin for improved clinical and microbiological outcomes in the treatment of UTI in SCI individuals. Similarily level 1 evidence suggests that 3 day Ofloxacin treatment is sufficient based on significant biofilm eradication detected in bladder epithelial cells in SCI patients with UTI. Successful SCI UTI treatment with low-dose, long-term antibiotic prophylaxis without a high rate of treatment emergent adverse events is recommended for ciprofloxacin but not trimethoprim-sulfamethoxazole (TMP-SMX) as confirmed by level 1 evidence. A low success rate of aminoglycosides in the treatment of SCI UTI is supported by level 1 evidence. Bladder irrigation is not effective in treating bacteriuria in neurogenic bladder as confirmed by level 1 evidence Level 4 evidence is reported for Intermittent neomycin/polymyxin bladder irrigation being effective in altering the resistance of the offending bladder organism(s) to allow for appropriate antibiotic treatment.

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Norfloxacin may be a reasonable treatment choice for UTI in SCI but subsequent resistance must be monitored. Weekly oral cyclic antibiotic (WOCA) may be beneficial in preventing UTI in SCI patients. Improved clinical and microbiological SCI UTI treatment outcome is achieved after 14 (vs 3) days of treatment with Ciprofloxin. Aminoglycosides have a low success rate in the treatment of SCI UTI. Ofloxacin, after a 3 day treatment regimen resulted in significant UTI cure rate and bladder cell biofilm eradication rate. Successfully SCI UTI prophylaxis without appreciable side effects is possible with low-dose, long-term ciprofloxacin but not TMP-SMX. Bladder irrigation is ineffective to treat neurogenic bladder bacteriuria. Intermittent neomycin/polymyxin bladder irrigation may be effective in altering the resistance of the offending bladder organism(s) to allow for appropriate antibiotic treatment.

13.7.3 Dietary supplementation Based Interventions for Preventing UTIs There is a trend to alternative health care use in individuals with physical disabilities (Krauss et al, 1998). Given this milieu, it is not surprising that use of dietary supplementation based interventions such as cranberries to acidfy the urine (Kinney & Blount 1979) and prevent UTIs have been reported. Other dietary supplementation based interventions are also discussed below. Table 13.19 Individual Studies Dietary Supplementation Based Interventions for Preventing UTIs
Author Year; Country Score Level Total Sample Size Methods Results

Linsemeyer et al. 2004; USA PEDro=6 RCT Initial N=37; Final N=21

Waites et al. 2004; USA PEDro=5 RCT Initial N=74; Final N=48

Population: m=16m f=5; Level of injury: C4-L1; # of UTI: 0 to 2. Treatment: Randomized, crossover: placebo or cranberry tablets (400 mg) 3 times daily for 4 weeks. Outcome measures: urinary bacterial counts, white blood cell counts, combination of both counts. Population: Age: 20-73yrs, m=42, f=6; SCI; time since injury: 1-30yrs; Complete=40/incomplete=6; Treatment: Randomized to cranberry or placebo capsules. Microscopic and dipstick urinalyses pre enrollment and monthly. Bacteriuria defined as a urine colony of >/= 104 colonies/ml urine. Pyuria defined as >/=10 urinary leukocytes/ml urine. Outcome measures: bacterial counts and urinalysis.

No statistically significant findings for the effect of cranberry tablets vs placebo: 1. Urinary bacterial count (t20=-0.05, p=0.96), 2. WBC count (t20=1.14, p<0.27)or 3. Urinary bacterial + WBC count combination (t20=1.14, p<0.27). No significant differences between groups: 1. Bacterial colony counts, bladder management method, or within groups over time (p=0.758, 0.170, 0.302). 2. Urinary leukocyte counts /ml urine, bladder management method, or within groups over time (p=0.929, 0.888, 0.499). 3. pH of urine, or within groups over time (p=0.659, 0.246). 4. For each outcome, no interaction between groups, bladder management method, and time (p>0.05). 5. pH higher for external collection vs

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Author Year; Country Score Level Total Sample Size

Methods

Results

Castello et al. 1996; Spain PEDro=4 RCT Initial N=38; Final N=13 Reid et al. 2001; Canada Downs & Black score=16 Case Conrol N=15

Population: SCI; Age: 27.8311.75 vs 25.579.91 years; 9 male, 4 female; tetra/para 1/12 Treatment: Ascorbic acid vs placebo (lactose) UTI prophylaxis Outcome measures: Urine pH, culture. Population: SCI, 21-78y; m=10, f=4. Treatment: 250 ml water / cranberry juice with meals, each for 7days treatment arms separated by 2 days. Outcome Measures: biofilm load, bacterial adhesion Population: neurogenic bladder caused by myelomeningocele (N=5), and traumatic SCI (N=2), and using clean intermittent catheterization; Age: 18-29 years; Gender: 3M, 4F; Level of Injury: L2 & 4, T6, 8 & 12(x2) and Sacral; Post-injury time: 2 or more years (SCI=5yrs post injury). Treatment: phosphorus supplement (Neutra-phos) as urine-acidifying agent. Outcome measures: urinalysis (Urine pH st measured 3x/day (1 morning, afternoon, evening) for 4 wks; wk 2 and 3, patient drank a phosphorus supplement 3x/day, (4 wk study period); urine sample cultured2x/wk.

intermittent catheter (p=0.046) for all time periods for both groups combined. No significant difference in 1. baseline or post- treatment urine pH for ascorbic acid or placebo. 2. number of patients developing UTI between groups. Cranberry juice vs water significantly reduces: 1. Biofilm load (p=0.028); and compared to baseline (p=0.013,). 2. Bacterial Adhesion counts (p<0.033). 3. Gram positive counts (p=0.022). 4. Gram negative counts (p=0.054). No significant change in urine pH during the 2-week period when patient was on phosphorus supplement (vs when off supplement). 1. In 3 patients, mean pH dropped 0.10.4 units during suppl. 2. In 3 patients, mean pH increased by 0.2-0.6 units during suppl. 3. In 1 patient, no change in mean pH during suppl. 4. Urine acidification not achieved with phosphate suppl. 5. Frequency of bacteriuria in an individual patient was similar on and off supplementation.

Schlager et al. 2005; USA Downs & Black score=14 Case Control N=7

Discussion An RCT (PEDro=6) conducted by Linsenmeyer et al. (2004) (N=21) found that cranberry tablets were not effective in changing bacterial or white blood cell (WBC) counts. This was confirmed by an RCT (PEDro= 5) conducted by Waites et al. (2004) (N=48) which showed no difference between cranberry extract or placebo in reducing bacteriuria or pyuria in individuals with SCI. Both of these RCTs lacked an Intent To Treat (ITT) statistical analysis and therefore were not of the highest quality. However evidence does exist in 2 good quality RCTs (Jepson et al., 2004 Cochrane Review) that cranberry product (juice or tablet) does reduce the number of UTIs in women in the general population. Furthermore a pilot study conducted by Reid et al 2001 (N=15) showed that cranberry juice intake significantly reduced the adhesion of bacteria to bladder cells where water intake did not significantly reduce the bacterial adhesion or biofilm presence in individuals with SCI. The conflicting conclusions may be influenced by the different populations studied, the spectrum of dose of cranberry product and outcome measures used in the various studies discussed. In order to make valid conclusions regarding the use of cranberry product for the treatment of UTI in SCI, properly designed studies with optimum cranberry product dose and consistent outcome measures are required. Acidifying urinary pH for the prevention of UTIs is based on the long known fact that pH reduction to 5.0 will inhibit growth of urinary E. coli (Shohl and Janney, 1917), the most

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prevalent bacteria in bacteriuria. Waites et al. (2006) in addition, found that 8 weeks of bladder irrigation with some irrigants (saline, acetic acid and neomycin/polymycin solution) did significantly increase the urinary pH (p=0.01) to a range that was favourable for the growth of E. coli (i.e. pH 6.0-7.0; Shohl and Janney, 1917). Urine acidification with cranberry tablets vs placebo was also ineffective (Waites et al., 2004). Similarily, 2 weeks of phosphate supplementation or 2 gram per day of ascorbic acid in SCI neurogenic bladder managed with IC or indwelling catheter were also ineffective in acidifying urine (Schlager et al., 2005; Castello et al., 1996). Conclusion Conflicting level 1 evidence exists for the effectiveness of cranberry juice or extract in the treatment of UTI. However, the negative evidence involved poorer quality studies involving specifically SCI while the positive evidence was the result of higher quality studies involving women in the general population. Further complicating the burden of evidence is level 2 evidence supporting the use of cranberry juice over placebo (i.e. water) in the reduction of bacterial adhesion or biofilm presence. Level 1 evidence does not recommend the use of cranberry, phosphate or ascorbic acid supplementation to acidify urine in SCI neurogenic bladder.

Conflicting evidence exists for the effectiveness of cranberry juice or extracts used in the treatment of UTI. Use of cranberry, phosphate or ascorbic acid supplementation is not efficacious in acidifying the urine in SCI. 13.8 Bladder Function and Quality of Life Table 13.20 Individual Studies Quality of Life
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Kuo 1998; Taiwan Downs & Black score=15 Case Series N=251

Population: Gender: m=212, f=39, SCI, complete/incomplete. Treatment: Various voiding techniques and drugs to facilitate urination to reduce residual urine or to decrease urinary incontinence. Outcome measures: Quality of life index for urination

1. 2.

3.

4. Liguori et al. 1997; USA Downs & Black score=12 Observational Population: age: Mean=42yrs m=67, f=14; SCI; complete/incomplete Treatment: No treatment, survey mailed 1. 2.

UTIs occurred in majority of patients regardless of level of injury. Those with complete SCI (88%)and those with incomplete SCI (65%) experienced an episode of symptomatic UTI per yr (X2=16.89, p<0.05) For those (n=77) who had surgical interventions the QofL improved from 0.27+ 0.39 (preoperatively) to +1.54+0.38 postoperatively. This contrast to those who had other forms of active urological management (mean QofL = +0.34+1.09) Higher functioning scores with para vs tetraplegia, p<0.01. Higher # UTI compared to normal

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Author Year; Country Score Research Design Total Sample Size Initial N=360; Final N=81

Methods

Outcome

home. IC=intermittent catheterization CON=condom catheters IND=chronic indwelling catheterization Outcome Measures: Information on: UTI, bladder management, functioning, productivity and life satisfaction, was asked in the mailed questionnaire.

3. 4. 5. 6. 7.

8. 9.

Craven & Etchells 1998; Australia Downs & Black score=6 Case Series N=27 patients (31 procedures)

Population: para/tetra: 21/6; m=16, f=11; time since injury to stoma formation 0-31y with majority at 10y; age at time of procedures 16-74y. Treatment: No treatment, chart review (n=27) and patient interviews (n=18). Outcome Measures: Content analysis; grouped themes.

1.

2.

voiding: IC p<0.01; CON p<0.07; IND p<0.05. Higher UTI rate with IND (p<0.05) and CON (p<0.01) than IC. More prophylactic antibiotic with IC vs normal voiding, (T=3.06, p<0.01). Negative correlation between # UTIs / functioning (1yr r= -.23, p<0.05; 3yr r=-.23, p<0.05). Positive correlation between functioning/productivity (r=.21, p<0.05); functioning/life satisfaction (r=.21, p<0.05). Negative correlation between productivity/UTI (1 yr r=-.24, p<0.5; 3 yr r=-.26, p<0.01). Positive correlation between productivity/global satisfaction (r=-.20, p<0.01) and productivity/functioning (r=.20, p<0.05). Reason for urostomy: paraplegicschronic UTI, hydronephorosis, recurrent renal calculi, bladder trauma, fistula, persistent catheter leakage. Tetraplegics-chronic UTIs, recurrent renal calculi, persistent catheter leakage. Improved QoL: freedom, independence, hygiene, productivity, less dysreflexia, less UTI.

Discussion The quality of life of individuals having bladder management problems secondary to SCI is affected by the urological management that they receive immediately after initial injury. Kuo et al. (1998) assessed the quality of life of 251 SCI patients before and after treatment for voiding or urological problems over an 8 year period. Thirty-one percent of the patients continued to have voiding or urological problems after unsuccessful attempts to achieve satisfactory voiding through voluntary means, intermittent self-catheterization (CISC) or Foley catheters. For these patients, various surgical procedures (external sphincterotomy, entercystoplast, autoaugmentation, continent urinary diversion, periurethral Teflon injection and transurethral resection of the prostate) resulted in an improvement in the total satisfaction rating on the quality of life after the surgical procedures. Some complications persisted after enterocystolast and continent diversion. Repeat sphincterotomy was required in 16.7% of patients and half were not satisfied with total incontinence after external sphinterotomy. This group concluded that mandatory long-term follow-up for urological management was essential to eliminate indwelling catheters, hydronephrosis and frequent UTIs in patients with SCI. Once discharged from the hospital, the factors determining bladder health and the functional, behavioural and social characteristics of the individual with SCI and how these factors relate to incidence of UTIs is not well understood. Liguori et al. (1997), via a mail-out questionnaire reported that higher functioning and work-productive individuals suffered from a lower incidence 13-63

of UTIs per year and over a 3 year period. One can speculate between the interpretation that fewer UTIs allowed for more hours worked per week versus higher productivity benefiting behavioural or psychological factors that in turn place these individuals at less risk for UTIs. Regardless of the choice of interpretation, productivity correlated positively with global satisfaction and functioning. The results were derived from 35% of 360 completed questionnaires sent to a volunteer sample of SCI in- and out-patients previously treated at a university rehabilitation center over a 3 year period. Please note that, common to many quality of life studies, no intervention was delivered in this study. However results were included in this analysis in lieu of the scarcity of interventional studies measuring quality of life of the impact of UTI on patients with spinal cord injury. Although some procedures improve quality of life in individuals with neuropathic bladder secondary to SCI, other physical or psychological impacts may render the procedure ultimately undesirable. The elective formation of a stoma via surgery is one procedure that has been undertaken in some patients who do not have adequate bladder health with the more common bladder management methods. Craven and Etchells (1998) reviewed 27 medical records of SCI patients who had undergone colostomy, ileostomy or urostomy. Eighteen of these patients were then interviewed or completed a comprehensive questionnaire to assess the long-term physical, psychological or lifestyle effects of the surgery. Although the impact of the stoma on lifestyle was positive, the long-term negative impact to renal health could not be ignored for individuals with neuropathic bladder secondary to SCI. This study is an illustrative example how no single outcome measure can capture the multi-dimensional nature of interventions and highlights the importance of choosing effective outcome measures to monitor the range of medical outcomes as suggested by Goldberg (1991): 1) technical outcome; 2) functional outcome; 3) patient satisfaction and 4) cost effectiveness. Conclusion Level 4 evidence suggests that urological management and follow-up is essential to optimize post-discharge bladder management techniques and improve quality of life in patients with neurogenic bladder secondary to SCI. There is Level 5 evidence to support the notion that higher functioning and workproductivity correlates with higher global satisfaction. Individuals with higher productivity suffered from a lower incidence of UTIs per year over a 3 year period. Level 4 evidence suggests that although urostomy may improve quality of life in SCI individuals with otherwise insufficient bladder health management methods, the procedure is not likely to be a good alternative due to the long-term negative impact to renal impairment. Mandatory post-discharge urological management may improve quality of life in patients with neurogenic bladder secondary to SCI. Higher functioning and work-productive individuals seem to have fewer UTIs per year and this is likely associated with higher global satisfaction. Urostomy may not be a good long-term bladder management method although it may improve quality of life when other methods fail.

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13.9 Overall Comment An overall comment that can be made regarding the study of UTI intervention treatments is the lack of consistent outcome measures to allow a meaningful comparison between treatment options. Studies under review in this chapter utilized the following UTI definitions and/or outcome measures: 1) symptomatic UTI = >100,000 bacteria/ml catheter urine plus fatigue or spasm or foul smelling urine or haematuria; 2) presence of bacteria plus one symptom; 3) presence of bacteria in urine plus biofilm presence (number of bacteria/epithelial cell); 4) clinical improvement following symptomatic UTI by 4 days after treatment; 5) time to start of antibiotic; 6) bacteriologic confirmation; 7) bacteriuria defined as a 104 colonies per ml of urine and pyuria defined as 10 urinary leukocytes per l of urine; 8) number of episodes of bacteriuria; 9) number or duration of catheterizations; 10) routine bacterial and WBC counts. 13.10 Summary There is Level 4 evidence that indwelling urethral catheterization, employed acutely, has abated is associated with a higher rate of acute urological complications than intermittent catheterization. There is Level 4 evidence that prolonged indwelling catheterization, whether suprapubic or urethral, may result in a higher long-term rate of urological and renal complications than IC, condom catheterization or triggered spontaneous voiding. There is Level 4 evidence that intermittent catheterization, whether performed acutely or chronically, has the lowest complication rate. Chronic use of a spontaneous triggered voiding method has comparable long-term complication rates to intermittent catheterization. There is Level 4 evidence that acute use of intermittent catheterization is associated with reduced time to become catheter-free in comparison with indwelling urethral or suprapubic catheterization. There is likely no difference among these methods for the likelihood with which one will become catheter-free. There is Level 4 evidence that those who use intermittent catheterization at discharge from rehabilitation may have difficulty continuing with particular difficulty for those with tetraplegia and complete injuries. To a lesser degree females also have more difficulty than males in maintaining compliance with IC procedures. There is Level 2 evidence that early treatment with electroacupuncture may shorten the time that it takes for urine to pass at low pressure with minimal residual volume, no matter the primary method of bladder management. There is Level 1 evidence based on 1 RCT that pre-lubricated hydrophilic catheters are associated with fewer UTIs and reduced incidence of urethral bleeding and microtrauma as compared to conventional Poly Vinyl Chloride catheters. There is Level 2 evidence based on 1 RCT that fewer UTIs, but not necessarily urethral bleeding may result with the use of hydrophilic catheters as compared to conventional PVC catheters.

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There is Level 4 evidence that those with neurogenic bladder due to SCI and managed with IC may have a lower health-related quality of life on most domains assessed by the SF-36. There is Level 4 evidence that incontinence may be reduced with intermittent catheterization and even moreso when oxybutynin is administered as well. There is Level 4 evidence that triggering mechanisms such as the Valsalva or Crede maneuvers may assist some individuals with neurogenic bladder to void spontaneously but these are also associated with high intra-vesical pressures which could conceivably lead to renal complications. There is Level 4 evidence that penile implants may allow easier use of condom catheters, thereby reducing incontinence. There is Level 4 evidence that despite a significant incidence of urological and renal complications associated with acute and chronic indwelling suprapubic catheterization, this is still a reasonable choice for bladder management for some people. There is Level 4 evidence that ongoing use of sacral anterior root stimulation (accompanied in most cases by posterior sacral rhizotomy) results in reduced incontinence for the majority of those implanted. This is associated with increased bladder capacity and reduced post-void residual volume. There is Level 4 evidence that sacral anterior root stimulation (accompanied in most cases by posterior sacral rhizotomy) may be associated with reducing UTIs and autonomic dysreflexia. There is Level 4 evidence that other forms of neuroanatomically-related stimulation (e.g., dorsal penile nerve stimulation or direct bladder stimulation) may have similar effects to sacral stimulation but require further study. There is Level 4 evidence that epidural dorsal spinal cord stimulation originally intended for reducing muscle spasticity may have little effect on bladder function. There is Level 4 evidence that a program of functional electrical stimulation exercise involving the quadriceps muscle originally intended for enhancing muscle function and reducing muscle spasticity has only marginal (if any) effects on bladder function. There is Level 2 evidence based on 1 RCT comparative study that both sphincterotomy and implantation of a sphincteric stent resulted in enhanced bladder function, with little need for subsequent catheterization. The only significant difference in these 2 treatments was the reduced initial hospitalization associated with the stent, given the lesser degree of invasiveness. There is Level 2 evidence that both sphincterotomy and implantation of a sphincteric stent are associated with reduced detrusor pressure and reduced post-void residual volume but not changes in bladder capacity. There is Level 4 evidence that implantation of a sphincteric stent may result in reduced incidence of UTIs and bladder-related autonomic dysreflexia.

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There is Level 4 evidence from long-term follow-up of those having a previous sphincterotomy that the incidence of various upper and lower tract urological complications is quite high. There is Level 4 evidence that transurethral balloon dilation of the external sphincter may be associated with enhanced bladder function, notably reduced detrusor pressure and reduced post-void residual volume but not changes in bladder capacity. Most individuals undergoing the procedure were able to discontinue use of indwelling catheters in favour of condom catheterization. There is Level 4 evidence that most individuals undergoing cutaneous ileal conduit (ileoureterostomy) diversion became newly continent and were more satisfied than with their previous bladder management method. Long-term follow-up demonstrated the presence of a high incidence of urological or renal complications. Level 1 evidence supports the use of propiverine to treat detrusor hyperreflexia by significantly improving bladder capacity. Early experience in the form of level 4 evidence (1 before/after trial with N=10 and 1 N=14, case series study) exists to support the potential benefits of controlled-release oxybutynin. Standard oxybutynin may be enhanced by co-verapamil administration, in the treatment of detrusor hyperreflexia in individuals with SCI. Level 1 evidence supports the use of tolterodine vs placebo to significantly increase intermittent catheterization volumes and decrease incontinence in neurogenic detrusor overactivity. There is level 2 evidence that for neurogenic detrusor overactivity, efficacy of tolterodine and oxybutynin is equivocal except that tolterodine results in less dry mouth as confirmed by level 2 evidence. Level 1 evidence supports the use of trospium chloride to increase bladder capacity and compliance, and decrease bladder pressure with very few side effects in SCI individuals with neurogenic bladder. Level 1 evidence supports the use of Tamsulosin to improve bladder neck relaxation and subsequent urine flow in SCI individuals. Level 1 evidence suggests that moxisylyte decreases maximum urethral closure pressure by 47.6% at 10 minutes after an optimum dose of 0.75mg/kg in individuals with SCI. Level 4 evidence (two non-RCT, N=28 & 9), supports Terazosin as an alternative treatment for bladder neck dysfunction in SCI individuals provided that side effects and drug tolerance are monitored. Level 4 evidence derived from a single, case series study involving 46 subjects (41 completers) indicates a potential for phenoxybenzamine as an adjunct treatment for neuropathic bladder following SCI, when tapping or crede is insufficient to achieve residual urine volume of <100mL.

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Level 4 evidence from 1 small retrospective chart review suggests that 6 months of alpha 1-blocker therapy may improve upper tract stasis secondary to SCI in men by decreasing the duration of involuntary contractions. Level 4 evidence is available from a single, small (N=9), case series study for the use of intra-thecal clonidine to improve detrussor hyperreflexia in individuals with SCI when a combination of oral treatment and sterile intermittent catheterization are insufficient. There is Level 1 evidence that Intrathecal Baclofen may be beneficial for bladder function improvement in individuals with SCI when oral pharmacological interventions are insufficient. Level 4 evidence based on 3 studies supports the use of Botox A injections into the detrusor muscle to provide targeted treatment for detrusor hyperreflexia and urge incontinence resistant to high-dose oral anticholinergic treatments with intermittent selfcatheterization in SCI. Additional level 4 evidence supports Botox A injected into the external sphincter to assist with SCI related voiding dysfunctions including neurogenic detrusor-sphincter dyssynergia, pelvic floor spasticity, or acontractile detrusor. Level 1 evidence for lack of efficacy, in combination with a FDA warning for risk of serious cardiac arrhythmias, supports not using Cisapride for treatment of SCI bladder dysfunction. Level 1 evidence supports the use of vanillanoid compounds such as capsaicin or resiniferatoxin to increase maximum bladder capacity and decrease urinary frequency and leakages in neurogenic detrusor overactivity of spinal origin. Level 4 evidence exists to suggest that intravesical capsaicin installation in bladders of SCI individuals does not increase the rate of common bladder cancers after 5 years of use. Level 1 evidence supports the use of N/OFG, a nociceptin orphan peptide receptor agonist for the treatment of neurogenic bladder in SCI. Level 4 evidence from one small, case series study, suggests that intranasal DDVAP may increase the time between the need to void or catheterization in SCI with neurogenic bladder that is unresponsive to conventional therapy. Level 1 evidence supports the use UTI educational intervention to provide benefits of increased bladder health (i.e. decreased urine colony counts) that increase a patients perception of the control they have of their own health behaviours and that may translate into less impairment and less lost time due to UTI in SCI. Weak level 4 evidence suggests that outpatient, nursing-mediated re-education of SCI individuals at high risk of UTIs may be a cost-effective method of reducing the number of UTI.

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Level 4 evidence exists to support additional utilization of tapping and compression to augment bladder management as expressed as acceptable residual urine volumes (<100mL). Level 1 evidence supports the acceptance and use of a portable ultrasound device to significantly reduce the number of catheterizations required each day in individuals with SCI who perform SIC to empty their bladder. Level 5 evidence supports that quadriplegic patients educated to CISC may continue to use CISC successfully for many years after discharge. Level 4 evidence suggests that for SCI individuals with chronic or significant medical issues related to common bladder management techniques, urostomy may not be a viable alternative due to long-term renal impairment. Level 1 evidence (based on one high quality and several low quality RCTs) supports the use of daily body washing in chlorohexidine and application of chlorhexidine crme to the penis after every catheterization verses using standard soap in the endeavour to significantly reduce bacteriuria. Although the rate of UTI requiring antibiotic treatment is less with the use of sterile catheterization technique, level 1 evidence supports the use of clean versus sterile catheter supplies as a result of the prohibitive cost of the latter. Level 4 evidence suggests that the prevalence of bacteriuria caused by gram-negative bacilli, did not have any significant correlation with differing practices of external urinary collection systems (i.e. continual vs discontinuation at night). Poor quality level 1 evidence is supportive of the use of oral methenamine mandelate in combination with hemiacidrin bladder instillant to lower urine pH and incident of UTI. There is Level 3 evidence that sterile intermittent catheterization may lead to a lower rate of UTI and complications with a maintained continence level after discharge as compared to other bladder management techniques such as use of indwelling catheter. There is level 2 evidence (based on a single poor quality RCT) reporting no difference between incidence of bacteriuria in catheterized patients. However, Trisdine is the more often chosen between the 2 treatments, based on the fact that it is not likely to contribute to antiobiotic resistance, its stability at room temperature, and its lower cost. Level 2 (based on a single RCT) evidence suggests that both limited and full microbial investigation result in adequate clinical response to UTI treatment with antibiotics. Therefore the cost savings attributed to a limited microbial investigation favours this practice in the investigation of UTI. Refrigeration (up to 24 hours) of urine samples prior to sample processing does not alter urinalysis or urine culture results in SCI patients. Level 4 evidence suggests that norfloxacin may be a reasonable treatment choice for UTI in SCI but subsequent resistance must be monitored.

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Level 4 evidence supports weekly oral cyclic antibiotic (WOCA) use for UTI prevention in SCI patients. It decreases antibiotic consumption, the number and length of hospitalizations, and is used without severe adverse events or the emergence of multidrug resistant (MDR) bacteria. Optimum antimicrobial treatment duration is controversial due to the lack of comparative trials. High quality level 1 evidence supports the use of 14 vs 3 days of Ciprofloxcin for improved clinical and microbiological outcomes in the treatment of UTI in SCI individuals. Similarily level 1 evidence suggests that 3 day Ofloxacin treatment is sufficient based on significant biofilm eradication detected in bladder epithelial cells in SCI patients with UTI. Successful SCI UTI treatment with low-dose, long-term antibiotic prophylaxis without a high rate of treatment emergent adverse events is recommended for ciprofloxacin but not trimethoprim-sulfamethoxazole (TMP-SMX) as confirmed by level 1 evidence. A low success rate of aminoglycosides in the treatment of SCI UTI is supported by level 1 evidence. Bladder irrigation is not effective in treating bacteriuria in neurogenic bladder as confirmed by level 1 evidence Level 4 evidence is reported for Intermittent neomycin/polymyxin bladder irrigation being effective in altering the resistance of the offending bladder organism(s) to allow for appropriate antibiotic treatment. Conflicting level 1 evidence exists for the effectiveness of cranberry juice or extract in the treatment of UTI. However, the negative evidence involved poorer quality studies involving specifically SCI while the positive evidence was the result of higher quality studies involving women in the general population. Further complicating the burden of evidence is level 2 evidence supporting the use of cranberry juice over placebo (i.e. water) in the reduction of bacterial adhesion or biofilm presence. Level 1 evidence does not recommend the use of cranberry, phosphate or ascorbic acid supplementation to acidify urine in SCI neurogenic bladder. Type 4 evidence suggests that urological management and follow-up is essential to optimize post-discharge bladder management techniques and improve quality of life in patients with neurogenic bladder secondary to SCI. There is Level 5 evidence to support the notion that higher functioning and workproductivity correlates with higher global satisfaction. Individuals with higher productivity suffered from a lower incidence of UTIs per year over a 3 year period. Level 4 evidence suggests that although urostomy may improve quality of life in SCI individuals with otherwise insufficient bladder health management methods, the procedure is not likely to be a good alternative due to the long-term negative impact to renal impairment.

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Waites KB, Canupp KC, Roper JF, Camp SM, Chen Y. Evaluation of 3 methods of bladder irrigation to treat bacteriuria in persons with neurogenic bladder. J Spinal Cord Med 2006; 29(3):217-226. Waller L, Telander M, Sullivan L. The importance of osmolality in hydrophilic urethral catheters: a crossover study. Spinal Cord 1997; 35(4):229-233. Weld KJ, Dmochowski RR. Effect of bladder management on urological complications in spinal cord injured patients. J Urol 2000; 163(3):768-772. Wheeler JS, Jr., Robinson CJ, Culkin DJ, Bolan JM. The effect of thigh muscle reconditioning by electrical stimulation on urodynamic activity in SCI patients. J Am Paraplegia Soc 1986; 9(12):16-23. Wheeler JS, Jr., Walter JS, Chintam RS, Rao S. Botulinum toxin injections for voiding dysfunction following SCI. J Spinal Cord Med 1998; 21(3):227-229. Wyndaele JJ, De Sy WA, Claessens H. Evaluation of different methods of bladder drainage used in the early care of spinal cord injury patients. Paraplegia 1985; 23(1):18-26. Wyndaele JJ, De TN. Early intermittent self-catheterisation after spinal cord injury. Paraplegia 1990; 28(2):76-80. Wyndaele JJ, Madersbacher H, Kovindha A. Conservative treatment of the neuropathic bladder in spinal cord injured patients. Spinal Cord 2001; 39(6):294-300. Wyndaele JJ, Van KP. The effects of 4 weeks treatment with cisapride on cystometric parameters in spinal cord injury patients. A double-blind, placebo controlled study. Paraplegia 1995; 33(11):625-627. Yadav A, Vaidyanathan S, Panigrahi D. Clean intermittent catheterisation for the neuropathic bladder. Paraplegia 1993; 31(6):380-383. Yavuzer G, Gok H, Tuncer S, Soygur T, Arikan N, Arasil T. Compliance with bladder management in spinal cord injury patients. Spinal Cord 2000; 38(12):762-765.

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CHAPTER FOURTEEN
Pain Following Spinal Cord Injury
Robert W Teasell, MD FRCPC Jo-Anne Aubut, BA Dalton L Wolfe, PhD Jane TC Hsieh, MSc Andrea F Townson, MD FRCPC

Key Points Pain post SCI has a significant effect on quality of life. Post SCI pain is common and often severe beginning relatively early post-injury. Post-SCI pain can most commonly be divided into neuropathic or musculoskeletal pain. Massage and heat might be helpful for post-SCI pain. Acupuncture may reduce post-SCI pain. Shoulder exercise protocol reduces post-SCI shoulder pain intensity. Hypnosis may reduce pain intensity post-SCI. Gabapentin improves pain post-SCI. Tricyclic antidepressants do not reduce post-SCI pain. Lidocaine through a subarachnoid lumbar catheter, I.V. Ketamine and Aflentanil improve post-SCI pain short term. Mexilitene does not improve SCI dysesthetic pain. Intrathecal Baclofen improves musculoskeletal pain post-SCI and may help dysethetic pain related to spasticity. Cannabinoids are a potential new treatment for post-SCI pain in need of further study. Intrathecal Clonidine alone does not provide pain relief although it may be helpful in combination with Intrathecal Morphine Spinal cord stimulation may improve post-SCI pain.

Table of Contents
14.1 Introduction ..................................................................................................................14-1 14.2 Incidence, Quality and Significance...........................................................................14-1 14.2.1 Incidence of Pain Post-SCI .........................................................................................14-1 14.2.2 Impact on Quality of Life .............................................................................................14-1 14.2.3 Severe Pain and SCI Location....................................................................................14-2 14.2.4 Natural History of SCI Pain .........................................................................................14-2 14.3 Location and Quality of SCI Pain ...............................................................................14-2 14.4 Classification of SCI Pain............................................................................................14-3 14.5 Musculoskeletal or Mechanical Pain..........................................................................14-4 14.6 Central or Neurogenic Dysesthetic Pain ...................................................................14-4 14.7 Borderzone or Segmental Pain...................................................................................14-5 14.8 Psychological Factors.................................................................................................14-6 14.9 Non-Pharmacological Management of Post-SCI Pain ..............................................14-7 14.9.1 Massage and Heat......................................................................................................14-7 14.9.2 Exercises for Shoulder Pain......................................................................................14-10 14.9.3 Hypnotic Suggestions ...............................................................................................14-12 14.10 Pharmacological Management of Post-SCI Pain ..................................................14-12 14.10.1 Pharmacological Measures Overall ........................................................................14-13 14.10.2 Anticonvulsants in SCI Pain....................................................................................14-14 14.11 Tricyclic Antidepressants in Post-SCI pain...........................................................14-16 14.12 Anaesthetic Medications.........................................................................................14-17 14.12.1 Antispasticity Medications.........................................................................................14-19 14.12.2 Opioids for Post-SCI Pain .......................................................................................14-21 14.12.3 Cannabinoids in Post-SCI Pain...............................................................................14-21 14.12.4 Clonidine for Post-SCI pain.....................................................................................14-22 14.13 Surgical Interventions .............................................................................................14-24 14.13.1 Spinal Cord Stimulation ..........................................................................................14-24 14.13.2 Destructive Neurosurgical Procedures ...................................................................14-24 14.13.3 Dorsal Rhizotomy....................................................................................................14-25 14.13.4 Sympathectomy ......................................................................................................14-25 14.13.5 Lateral Spinothalamic Tractotomy ..........................................................................14-25 14.13.6 Spinal Cordotomy ...................................................................................................14-25 14.14 Summary...................................................................................................................14-25 References............................................................................................................................14-27
This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Teasell RW, Aubut J, Wolfe DL, Hsieh JTC, Townson AF (2006). Pain Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 14.1-14.32. www.icord.org/scire

Pain Following Spinal Cord Injury

14.1 Introduction The last few decades have witnessed increasing sophistication and advances in the rehabilitation of spinal cord injured (SCI) patients with marked improvements in the quality of care accompanied by significant reductions in morbidity and mortality. Despite these impressive gains in bladder, skin, cardiovascular and respiratory care, the treatment of chronic pain in SCI has proven largely refractory to medical management. This lack of treatment efficacy has been complicated by an incomplete understanding of pain in individuals with spinal cord injuries and lack of a standardized framework upon which to classify these injuries (Burchiel and Hsu 2001). 14.2 Incidence, Quality and Significance 14.2.1 Incidence of Pain Post-SCI Pain is a frequent complication of traumatic spinal cord injury. Reported estimates of the incidence of pain following SCI range anywhere from 11 to 94% (Botterell 1953, Burke 1973, Davidoff 1987, Davis 1947, Donovan 1982, Kaplan 1962, Kennedy 1946, Munro 1948, 1950, Nashold 1981) with more recent studies reporting an incidence from 48-94% (Davidoff et al. 1987, Cohen et al. 1988, Rose et al. 1988, Britell and Mariano 1991, Mariano 1992, Cairns et al. 1996). Estimates of debilitating or disabling pain range from 11-34% (Botterell 1953, Davis 1947, Kaplan 1962, Munro 1948, Nepomunceno 1979). Bonica (1991) noted that on combining the data on 6 reported studies of pain in SCI and 1,028 subjects (Botterell 1953, Burke 1973, Davis 1947, Nepomunceno 1979, Rose 1988, Woolsey 1986), 53% had various types of deafferent pain. These wide ranging estimates are felt to be a relfection of significant heterogenicity in defining pain in this population. Bonica (1991) reviewed data contained in 10 reports that surveyed 2,449 SCI patients (Botterell 1953, Britell 1986, Burke 1973, Davis 1947, Kaplan 1962, Munro 1950, Nepomunceno 1979, Richards 1980, Rose 1988, Woolsey 1986). Chronic pain was present in 1,695 (69%) and in 30% of these patients it was rated as severe. Six of the reports (Botterell 1953, Burke 1973, Davis 1957, Nepomunceno 1979, Rose 1988, Woolsey 1986) analyzed the different types of pain. Out of a total of 1,965 patients, 608 (31%) of the patients had central pain/dysesthesia/phantom limb pain, 219 (12%) had root pain, and 198 (10%) had visceral pain caused by a central mechanism. There were 1,028 (53%) SCI patients with deafferentation pain. 14.2.2 Impact on Quality of Life It is estimated that 30-40% of patients with SCI experience severe disabling pain (burke and Woodward 1976). Pain is often reported as the most important factor for decreased quality of life. Nepomuceno (1979) noted that 23% of individuals with cervical or high thoracic SCI and 37% of those with low thoracic or lumbosacral injury would trade the loss of sexual and/or bowel and bladder function as well as hypothetical possibility for cure to obtain pain relief. Rose et al. (1988) sent a questionnaire to 1,091 spinal cord injured individuals. 885 "suitable" replies were received with a total of 615 subjects reporting pain at or below the level of the

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injury. In 110 subjects this occurred in a nerve root distribution with the remainder below the level of SCI. Pain, which was reported as constant in 43%, was considered severe at some point in the day in half the sample and mild to moderate in 21% of respondents. Prior to the SCI, 595 of the sample were employed; afterwards only 325 were employed. Interestingly 98 SCI individuals (11%) reported it was the severity of their pain and not their paralysis, which stopped them from working. 269 of the 325 SCI subjects (83%) who were employed reported that the pain interfered with their work. A total of 118 SCI subjects found that the pain was severe enough to stop social activity. Pain appeared to be more severe in the evening and at night, interfering with sleep in 325 of respondents (37%). This study clearly pointed out the importance of chronic pain in determining disability and morbidity in SCI patients (Rose 1988). Pain post-SCI has a significant effect of quality of life.

14.2.3 Severe Pain and SCI Location Persons with SCI who complain of severe pain are more likely to have low spinal cord or cauda equina lesions (Ragnarsson 1997, Davis and Martin 1947, Botterell et al. 1953, Nepomuceno et al. 1979). Severe pain was noted in 10-15% of persons with quadriplegia; 25% of those with thoracic paraplegia and 42-51% of those with lesions of the cauda equina (Ragnarsson 1997) 14.2.4 Natural History of SCI Pain One study examining the timing of the development of pain post-SCI noted that in 901 patients with SCI, pain started immediately after SCI in 34%, within the first year in 58%, pain increased over time in 47% and decreased over time in 7%. (Turner et al 2001). Turner et al. (2001) noted that pain most often started within the first 6 months following SCI. This has also been noted in several other studies (Turner and Cardenas 1999, Stormer et al.1997, Nepomuceno et al. 1979, Siddall et al. 1999). Conclusion For many SCI patients, pain has a significant impact on quality of life. Over 50% of SCI patients develop chronic pain. Severe pain is more common the lower down the lesion in the spinal cord. Pain post-SCI most often begins within the first 6-12 months post-SCI. Post SCI pain is common and often severe beginning relatively early post-injury.

14.3 Location and Quality of SCI Pain Widerstrom-Noga et al. (2001) conducted a careful analysis of the relationship between the location of the pain and the patients description of the pain. In this study 217 of 330 patients reporting chronic pain in a previous survey agreed to participate in the study. Participants had been injured for an average of 8.2 5.1 years and 55.4% were quadriplegic. Most subjects in this study marked multiple areas on a pain drawing with the back area being most frequently

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implicated (61.8%). 59.9% complained of a burning pain while 54.9% described an aching pain. Interestingly burning pain was significantly associated with pain localized to the front of the torso and genitals, buttocks and lower extremities. In contrast, aching type pain was significantly associated with pain localized to the neck, shoulders and back. Widerstrom-Noga et al. (2001) noted that the descriptor burning is often associated with neuropathic pain (Siddall et al. 1999, Ragnarsson 1997, Fenollosa et al. 1993) whereas aching is often associated with musculoskeletal pain (Siddall et al. 1999, Tunks 1986). However, the authors do note the substantial overlap in the clinical picture of SCI pain makes such relationships uncertain (Eide 1998, Bowsher 1996, (Widerstrom-Noga et al. 2001). The authors then go on to suggest that musculoskeletal-type pain (best characterized by the aching pain in the neck, shoulders and back) is potentially amenable to therapeutic interventions and aggressive attempts should be made to ameliorate this type of pain. All of this underscores the need for a reproducible classification system of the pain experienced following SCI. Conclusion The most common types of pain post SCI are: 1) a burning pain (likely neuropathic) usually localized to the front of torso, buttock or legs or 2) an aching pain (likely musculoskeletal) usually localized to the neck, shoulders and back. Post-SCI pain can most commonly be divided into neuropathic or musculoskeletal pain.

14.4 Classification of SCI Pain Siddall et al. (1997) noted that one of the concerns regarding SCI-related pain was a lack of consensus over a classification system for SCI pain. This has in part led to "large variation in the reported incidence and prevalence of pain following spinal cord injury." Twenty-eight (28) classification schemes have been published between 1947 and 2000. A Task Force on Pain Following Spinal Cord Injury of the International Association for the Study of Pain has introduced a taxonomy, which classified SCI pain based on presumed etiology (Burchiel and Hsu 2001, Siddall 2000). Table 14.1 Proposed IASP Classification of Pain Related to SCI (Burchiel & Hsu 2001)
Broad Type (Tier 1) Broad System (Tier 2) Musculoskeletal Nociceptive Visceral Above Level Specific Structure/Pathology (Tier 3) Bone, joint, muscle trauma, or inflammation Mechanical instability Muscle spasm Secondary overuse syndromes Renal calculus, bowel, sphincter dysfunction, etc. Dysreflexic headache Compressive mononeuropathies Complex regional pain syndromes Nerve root compression (including cauda equine) Syringomyelia Spinal cord trauma/ischemia (transitional zone, etc.) Dual-level cord and root trauma (double lesion syndrome) Spinal cord trauma/ischemia (central dysesthesia syndrome, etc.)

Neuropathic

At Level

Below Level

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14.5 Musculoskeletal or Mechanical Pain Musculoskeletal or mechanical pain occurs at or above the level of the lesion and is due to changes in bone, tendons or joints (Guttmann 1973). This is referred to as nociceptive pain caused by a variety of noxious stimuli to normally innervated parts of the body. (Ragnarsson 1997). Overuse of remaining functional muscles after spinal cord injury or those recruited for unaccustomed activity may be of primary importance in some patients (Farkash 1986). Pain may also be secondary to spinal osteoporosis or facet arthropathy (Farkash 1986). Instability of the vertebral column may also be a problem (Farkash 1986). Pain is usually dull and aching in character and although more common soon after SCI, it may become chronic. Sie et al. (1992) studied 239 SCI outpatients for the presence of upper extremity pain. Of the 136 patients with quadriplegia, 55% reported upper extremity pain, most commonly at the shoulder (46% of all subjects). In the case of shoulder pain, 45% were orthopedic-related including tendonitis, bursitis, capsulitis and osteoarthritis. Of the 103 paraplegics, 66 reported upper extremity pain with two-thirds reporting symptoms of carpal tunnel syndrome and 13 reporting musculoskeletal-related shoulder pain. 14.6 Central or Neurogenic Dysesthetic Pain "Central" dysesthesia or "deafferentation" pain is the most common type of pain experienced below the level of SCI and is generally characterized as a burning, aching and/or tingling sensation. In many cases this dysesthetic or deafferentation pain has defied a pathophysiological explanation (Britell,1991) although most researchers firmly support a central nervous system origin for this pain. Nashold (1991) goes as far as stating that except for radicular pain, all other pains of paraplegia are central or deafferentation in origin. This pain is most often perceived in a generalized manner below the level of the lesion, often a diffuse burning type of pain (Britell 1991, Tunks 1986). Burning pain is reportedly most common with lesions at the lumbar levels, although it may be found with SCI at thoracic and cervical levels (Tunks 1986). Nashold (1991) reported this pain occurred almost immediately after SCI and persisted. Beric (1997) refers to this pain as central dysesthetic pain (CDP) and found dissociative sensory loss and absence of spinothalamic-anterolateral functions, with different degrees of dorsal column function preservation present almost exclusively in incomplete SCI patients. CDP takes weeks or months to appear and is often associated with recovery of some spinal cord function. Paradoxically CDS is often characterized by complete loss of temperature, pinprick, and pain perception below the level of the lesion. It rarely occurs in spinal cord Injuries with complete sensory loss or loss of both sensory and motor functions below the level of the lesion. Davidoff et al. (1987a) concurred and further noted dysesthetic pain was more likely to be found in incomplete paraplegia resulting from penetrating wounds of the spinal cord, and in spinal fractures treated with conservative management. A number of factors may contribute to exacerbations of these "central" pain syndromes; these include visceral diseases or disturbances, movement, smoking or alcohol, emotional factors, fatigue, and even weather changes (Botterell 1953, Davis 1947, Davis 1975, Tunks 1986). Pressure sores, particularly if infected, or an occult injury such as a fracture, may result in an increase in burning, dysesthetic pain. These stimuli often provoke autonomic dysreflexic-like symptoms and simultaneously also may aggravate this "burning" pain.

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14.7 Borderzone or Segmental Pain Individuals with SCI frequently experience a band of pain and hyperalgesia at the border zone between diminished or abnormal and preserved sensation (Tunks 1986, Botterell 1953, Davis 1975, Heliporn 1978, Kaplan 1962, Maury 1978, Melzack 1978, Michaelis 1970). In the more recent literature, this segmental pain is further described as occurring at or just above the level of sensory loss in the cutaneous transition zone from the area of impaired/lost sensation to areas of normal sensation, involving at least one to three dermatomes (Friedman 1989, Nashold 1991, Ragnarsson 1997) and is often associated with spontaneous painful tingling or burning sensations in the same area. Ragnarsson (1997) also noted that in an individual with a cervical cord injury, segmental pain may be described as tingling, burning or numbing pain in the shoulders, arms or hands, those with a thoracic cord injury frequently describe a circumferential, feeling of tightness and pain around the chest and abdomen while lumbar lesions tend to be localized to the groins and different parts of the lower extremities. According to Nashold (1991) paraplegics often complain that touching the skin in the pain region activates the pain causing it to radiate into the lower parts of the body, especially the legs. Pain can be triggered by stroking and/or touching the skin in adjacent painful dermatomes (Nashold 1991). Even light touch or the pressure of clothing or bed sheets over this region may provoke marked discomfort (Tunks 1986). It may be accompanied by sweating or vasodilation at or below the level of hyperalgesia. Segmental pain is generally symmetrical although a partial spinal cord injury with asymmetrical neurological involvement will produce asymmetries (Nashold 1991). This pain has also been described as "neuropathic at level pain" (Siddall et al 1997) Although several theories have been proposed (Tunks 1986, Nashold 1981, Pollock 1951, Matthews 1972, Levitt 1983, Melzack 1978) the neurological mechanism responsible for this area of hyperalgesia after spinal injury is not well understood (Farkesh 1986). Although radicular pain is most severe in incomplete SCI lesions, it is also seen in transected cauda equina lesions which are by definition radicular types of pain (Heaton 1965, Siddall et al. 1997). It may also be secondary to spinal cord instability by facet or disc material, or to direct damage to the nerve root during the initial injury (Burke 1973, Nashold 1991). This radicular pain is associated with sensory change in the involved painful dermatome (Nashold 1991) and is most common to cervical or lumbosacral nerve roots. Non-neural structures, such as the dura mater, have also been suggested as a source of radicular pain (Cyriax 1969, Farkash 1986). In addition, it has been suggested that central borderzone pain may be generated in the damaged spinal cord just proximal to the spinal cord injury (Nashold 1991, Pollock 1951). Unfortunately, unless there is definitive evidence on imaging of nerve root damage, it is difficult to distinguish between these various mechanisms of pain. To reflect this uncertainty Siddall et al. (1997) in their proposed classification of SCI pain note that this "neuropathic at level pain" is divided into radicular and central pain. Radicular pain is due to nerve root pathology while central pain is due to changes within the spinal cord or possibly supraspinal structures. Pain attributable to nerve root damage is suggested by features of neuropathic pain (ie. burning, stabbing, shooting, electric-like pain, allodynia) and increased pain with spinal movement. Sjolund (2002) notes that this pain is thought to occur from nerve root entrapment and may occasionally benefit from decompression. However, pain, which appears radicular in nature, may occur in the absence of nerve root damage. This leads to the second grouping of borderzone pain, namely central pain or that which is due to pathology within the spinal cord thought to be the result of damage to the gray matter of the dorsal horn of the spinal cord (Ragnassaron 1997, Woolsey 1995). According to Ragnassaron (1997), such an injury has been said to result in hyperactivity of the nociceptor 14-5

cells within the dorsal horn (Nashold and Bullitt 1981, Nashold and Ostdahl 1979) which can be electrically recorded (Nashold and Alexander 1989). Sojlund(2002) notes that this second type of at level neuropathic pain is experienced as a girdle pain uni- or bilaterally in 2-4 segments of the transitional region. This pain is described as stimulus independent, often accompanied by troublesome alldodynia or hyperalgesia and thought to arise from segmental deafferentation (Sjolund 2002). 14.8 Psychological Factors Most studies of chronic SCI pain have focused on the medical causes and clinical manifestations of pain while much less is understood about how psychosocial factors impact SCI pain (Summers 1991). A negative psychosocial environment along with increased age, depression, anxiety and intellect were found to be associated with reports of greater post-SCI pain severity interfering with activities of daily living (Richards et al. 1980). Greater pain severity was not associated with physiological factors such as injury level, completeness of injury, surgical fusion and/or instrumentation or veteran status. The authors were unable to distinguish whether the psychological factors were a consequence of, or contributors to, greater pain severity. In the Summers et al (1991) study 54 SCI patients (19 with quadriplegia and 35 with paraplegia) were studied, and of these 42 patients "revealed that anger and negative cognitions were associated with greater pain severity after a careful psychological assessment and Pain Questionnaire. Patients who reported pain in response to a general prompt experienced more severe pain than patients who reported pain only when directly questioned about the presence of pain, but these different reporting groups did not differ on emotional variables. Those who were less accepting of their disability reported greater pain severity. Additionally, patients who perceived a significant other expressing punishing responses (e.g., expressing anger at the patients or ignoring the patients) to their pain behaviours reported more severe pain. Finally, pain was associated with emotional distress over and above the distress associated with the SCI itself." The authors concluded that, "Overall, psychosocial factors, not physiological factors were most closely associated with the experience of pain. Multidimensional aspects of pain are used to explain these findings and suggest that treatment should be directed at the emotional and cognitive sequelae of chronic SCI pain." Cohen et al. (1988) found that patients with complete SCIs reported significantly less severe pain than did pain clinic patients. However, they did not differ from patients with incomplete lesions. Patients with complete SCIs and pain clinic patients showed a significantly more disturbed MMPI (Minnesota Multiphasic Personality Inventory) profile than did patients with incomplete SCIs. It was hypothesized that those patients with complete lesions view themselves as more functionally limited than patients with incomplete lesions, and the completeness of the SCI may be more important in determining psychosocial adjustment than pain per se. Rintala (1998) in community-based men with SCI found that chronic pain was associated with more depressive symptoms, more perceived stress and poorer self-assessed health. 14.8.1 Catastrophizing and Pain Post-SCI When pain post-SCI is refractory to pharmacological and surgical treatment, it is important to fully understand the negative impact of the patients psychosocial environment prior to undertaking more invasive approaches to treatment.

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Table 14.2 Catastrophizing and Pain Post-SCI

Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=60, f=13, age: 2164yrs. Treatment: no treatment, questionnaire. Outcome Measures: Coping strategies questionnaire (CSQ), Short form McGill Pain Questionnaire (SF-MPQ), West Haven-Yale Multidimensional Pain Inventory (WHYMPI) solicitous subscale and CES-D scale. 1. Outcome CSQ catastrophizing was associated with WHYMPI (p<0.05), CES-D (p<0.001), SF-MPQ (sensory pain) (p<0.01) and CSQ SF-MPQ (affective pain) (p<0.001). Catastrophizing also accounted for significant variance in sensory pain scores (t=2.63, p<0.05). An interaction between relationship type and catastrophizing was also found (p<0.05). A significant relationship was noted between affective pain score and solicitousness (p<0.05) and catastrophizing and solicitousness (p<0.05). Catastrophizing itself accounted for a significant amount of variance in affective pain scores (p<0.01).

2.

Giardino et al. 2003; USA Downs & Black score=14 Case Series N=74

3.

4.

Giardino et al (2003) noted that pain-related catastrophizing, or exaggerating the negative consequences of a situation has been associated with greater pain intensity, emotional distress and functional disability in patients with chronic pain conditions and SCI. This was thought to provide partial support for a communal coping model of catastrophizing, where catastrophizing in persons with pain may function as a social communication directed toward obtaining social proximity, support or assistance. 14.9 Non-Pharmacological Management of Post-SCI Pain Before moving to pharmacological and surgical interventions, it is important to deal with those factors which may intensify or worsen the experience of pain. As mentioned previously, SCI pain may be worsened by decubitus ulcers, a urinary tract infection or stone, autonomic dysreflexia, increased spasticity, anxiety, depression, psychosocial factors and other contributors to post-SCI pain (Davis 1998, Tunks 1987). There are a number of nonpharmacological interventions for post-SCI pain which have been studied from massage to hypnosis. 14.9.1 Massage and Heat Massage and heat are used primarily to treat musculoskeletal pain. Their benefit is well known in a number of musculoskeletal pain disorders, although there are significant differences among therapists as to how treatment is delivered. Table 14.3 Massage and Heat in Post-SCI Pain
Author Year; Country Score Research Design Total Sample Size Budh & Lundeberg 2004; Sweden Downs & Black score=19 Methods Population: Gender: m=44, f=46, age:783, time since injury: 14.4 yrs. Treatment: No treatment questionnaire. Outcome The authors noted that massage and heat appeared to be the best nonpharmacological treatments.

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Author Year; Country Score Research Design Total Sample Size Case Series Initial N=100; Final N=90

Methods Outcome Measures: Pain questionnaire (looked at the use of pain relieving techniques, pain intensities and pain unpleasantness). Participants also completed a life questionnaire, hospital anxiety and depression scale, and a pain drawing.

Outcome

It stands to reason that local heat and massage therapy would be most effective for musculoskeletal pain post-SCI. Budh and Lundeberg (2004) in a survey of SCI patients 3 years post-injury found massage and heat were the best non-pharmacological treatments. No prospective studies examining heat and massage as treatment modalities for post-SCI pain have conducted. Conclusion There is limited level 4 evidence that massage and heat are the best nonpharmacological treatments for pain post-SCI. Massage and heat might be helpful for post-SCI pain.

14.9.1.1 Acupuncture and TENS Acupuncture is a component of traditional Chinese medicine that has been used for the treatment of pain for thousands of years and is based on the premise that illness arises from the imbalance of energy flow (Qi) through the body (Dyson-Hudson et al. 2001). Needle acupuncture involves inserting fine needles into specific points to correct these imbalances (Pomeranz 1995; NIH Consensus 1998; Wong & Rapson 1999; Dyson-Hudson et al. 2001). Acupuncture has been shown to activate type II and type III muscle afferent nerves or A delta fibers, blocking the pain gate by stimulating large sensory neurons as well as releasing endogenous opioids, neurotransmitters and neurohormones (Pomeranz 1995; Wong & Rapson 1999; Dyson-Hudson et al. 2001). Table 14.4 Acupuncture in Post-SCI Pain
Author Year; Country Score Research Design Total Sample Size Dyson-Hudson et al. 2001; USA PEDro=7 RCT N=21 Methods Population: Gender: m=18, f=6, age: 2869yrs, time since injury: 5-33 yrs, Level of injury: both paraplegic and tetraplegic, length of shoulder pain: 4mths-22yrs. Treatment: Subjects received either acupuncture treatments (sessions lasted 20 to 30 min) or Tager Psychophysical Integration - sessions lasted approx 45 min. Consisted for both table work and mentastic exercises. Outcome Measures: Intake questionnaire 1. Outcome Analysis of treatment on PC-WUSPI scores using ANOVA showed a significant effect of time for both treatments (Acupuncture p<0.001 and Trager p=0.001). Overall a reduction of the PC-WUSPI could be seen when looking at the data from the beginning of treatment to the end for both groups (p<0.05). Looking at the effect of treatment on the numeric rating scores, the ANOVA

2.

3.

14-8

Author Year; Country Score Research Design Total Sample Size

Methods (demographics and medical history), Weekly log, Wheelchair users shoulder pain index (WUSPI), Numeric rating scale, Verbal rating scale, range of motion.

Outcome showed a significant effect of time for both acupuncture and Trager groups for average pain & most severe pain (p<0.01, p<0.001 respectively), for the least severe pain the acupuncture group showed a significant reduction (p<0.01) compared to the Trager group. Verbal response scores-Looking at the effect of treatment on the VRS scores for both groups; there was a statistically significant effect for both groups (p=0.001). When looking at the 3 pain measures, pain intensity decreased over timeworst pain: (p<0.05), average pain: (p<0.01), present pain: (p<0.01). Post-treatment decline in pain intensity was maintained at 3mth follow-up (pretreatment vs follow-up: p<0.01). A difference in the ratings of pain intensity between pre and posttreatment (p<0.001) was noted and this was maintained 3 mths after the end of treatment (pretreatment vs follow-up: p<0.01). Those that did report pain relief at 3mth follow up reported only moderate levels of pain intensity on the NRS at the beginning of the study (7.83 .75) compared to those who did not report pain relief (9.67 .58, p<0.01). Pain interference: a decrease in pain interference with ADLs was also noted (p<0.05). Respondents showed a reduction in interference with ADLs at post-treatment (p<0.01). 24 participants improved in response to electro-acupuncture while 12 showed no improvement. Bilateral pain (n=21) more likely to respond to electro-acupuncture than those with unilateral pain (n=3) (p=0.014). Those with symmetric pain had a higher response to treatment than those who asymmetric pain (p=0.26). It was also noted that those with burning pain that was bilateral and symmetric (p=0.006) was more likely to improve after electro-acupuncture. Similar findings were noted for those who experienced bilateral symmetric constant burning pain (p=0.005).

4.

Nayak et al. 2001; USA Downs & Black score=21 Pre-post Initial N=31; Final N=22

Population: Gender m=15, f=7, age: mean=43.14, Injury level: C1-L3, ASIA: A, C & D, complete and incomplete, injury duration: 8.49yrs, pain duration: 8.46yrs. Treatment: 15 acupuncture treatments were administered over a 7.5-week period using a specific set of acupuncture points with additional points being selected by subjects based on individual history and clinical examination. Outcome measures: Pain intensity: numeric rating scale, general health: individualized symptom rating scale, pain impact and interference: activity scale, mood, psychological well being-general well being schedule and expectations.

1.

2. 3.

4.

5.

Population: Gender: m=23, f=23, age: 1775, injury level: cervical to lumbar, pain duration: <1mth->15yrs, # of tx:2-26. Treatment: SCI patients were given acupuncture treatment s. Outcome measures: pain. Rapson et al. 2003; Canada Downs & Black score=14 Pre-Post N=36

1. 2.

3. 4.

5.

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Discussion Dyson-Hudson et al. (2001) in an RCT compared acupuncture treatment to Trager Psychosocial Integration performed by a certified Trager practitioner. Trager therapy is a form of bodywork and movement re-education to induce relaxation and encourage the patient to identify and correct painful patterns. The theory is that chronically contracted muscles shortened by stress led to pain (Dyson-Hudson et al. 2001). There was a significant effect over time for both treatments in reducing shoulder pain but there was no difference between the two groups. Nayak et al. (2001) administered 15 acupuncture treatments over a 7.5-week period of time. Pain intensity decreased from pre-treatment to post-treatment with post-treatment decline in pain intensity being maintained at 3 month follow-up. Despite these results, 54.5% of those treated reported a worsening of pain after treatment. Those that reported pain below their injury did not respond to treatment (p<.05). Those who reported pain relief at 3 month follow-up reported only moderate levels of pain intensity at the beginning of the study compared to those who did not report pain relief at follow-up (p<.01). With the overall reduction in pain intensity there were also a decrease in pain interference with ADLs and an improvement in overall well being. The authors felt that 50% of patients demonstrated improvement in their pain with acupuncture. Rapson et al. (2003) asked patients to rate their pain intensity according to a visual analogue scale after electroacupuncture treatments. Sixty-seven percent (24/36) of patients reported improvement, with improvement best for those with bilateral symmetric constant burning pain. Table 14.5 Summary of Acupuncture in SCI Pain
Study Dyson-Hudson et al. 2001 Nayak et al. 2001 Rapson et al. 2003 Study Type RCT Pre-Post Pre-Post N 24 22 36 Intervention Acupuncture or Trager therapy Acupuncture Electro-acupuncture Outcome + +/+

Banerjee (1974) reported on five patients who developed burning, distressing pain below the level of SCI and who responded to transcutaneous electrical nerve stimulation (TENS) strong enough to lead to muscle contraction below the level of injury. The exact mechanism of action for this analgesic response was not delineated. Conclusion There is level 2 evidence that in general acupuncture is no more effective than Trager therapy for shoulder pain. There is level 4 evidence that acupuncture reduces the pain of some patients with SCI. Acupuncture may reduce post-SCI pain.

14.9.2 Exercises for Shoulder Pain Shoulder pain is a common form of musculoskeletal pain following SCI and is often the result of increased physical demands, awkward or over-use of the upper extremities as the individual

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with SCI compensates for loss of lower limb functioning (Curtis et al, 1999). Curtis et al. (1999) has noted, tightness of the anterior shoulder musculature, combined with weakness of the posterior shoulder musculature both seem to contribute to development of shoulder pain in wheelchair users (Curtis et al 1999, Burnham et al. 1993, Powers et al. 1994, Millikan et al. 1991) and may be further complicated by paralysis and spasticity in the individual with tetraplegia (Silverskiold and Waters 1991, Powers et al. 1994). The prevalence of shoulder pain in SCI individuals ranges between 30-100% (Curtis et al. 1999) and is a consequence of increased physical demands and overuse (Pentland and Twomey 1991, 1994, Nichols et al. 1979). Table 14.6 Shoulder Pain Management Post-SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=35, f=7, age: mean=35yrs, duration of wheelchair use: mean=24yrs, Injury level: cervical to lumbar, mixed etiology. Treatment: The experimental group attended a 60min educational session where they were instructed in 5 shoulder exercises. Outcome Measures: Self report questionnaire (demographic and medical info), Wheelchair User's Shoulder Pain Index (WUSPI), and a visual analog scale (VAS) used to rate intensity of pain. 1. Outcome When looking at the effect of exercise intervention on performance corrected (PC) WUSPI, a 2 factor repeated measures ANOVA showed a significant effect of time only (p=0.048). There were no significant differences between control and experimental group in age, years of wheelchair use or activity levels although the control group had much lower pain scores at baseline.

Curtis et al. 1999; USA PEDro =5 RCT N=42

2.

Discussion Curtis et al. (1999) in a RCT studied the effectiveness of a 6-month exercise protocol on shoulder pain experienced by wheelchair users where 42 patients were randomized into a treatment and a control group. Over 75% of all subjects reported a history of should pain since beginning wheelchair use and 50% in both groups had current shoulder pain at the start of the study. The treatment group performed two exercises designed to stretch the anterior shoulder musculature and 3 exercises for strengthening the posterior shoulder musculature. Compliance rates were higher-over 83% of the subjects completed the 6-month protocol. Subjects in the treatment group decreased their average PC-WUSPI score by an average of 39.9% vs only 2.5% in the control group. Despite this very significant change, 48.3% decreased in the paraplegic group and 27.2% in the tetraplegic group, the treatment group still had a higher mean score than the control group at the end of the study because of disparate baseline scores. Conclusion There is level 2 evidence (from one RCT) that a shoulder exercise protocol reduces the intensity of shoulder pain post-SCI. Shoulder exercise protocol reduces post-SCI shoulder pain intensity.

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14.9.3 Hypnotic Suggestions Hypnosis has been used to reduce pain in a number of painful clinical conditions as well as experimental pain (Jensen et al 2000). Hypnosis is appealing as a potential treatment because it is nonpharmacological although its use is controversial given the variability in hypnotic responsiveness. Table 14.7 Hypnotic Suggestion and Post-SCI Pain
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=64%, age: 2476yrs, time since injury: 1.75-42.33 yrs, pain duration: mean 13.88yrs. Treatment: Hypnotic suggestions for pain relief were given to each subject. Outcome Measures: Pain intensity and unpleasantness and hypnotic responsiveness (modified version of the Standford Hypnotic Clinical scale-SHCS. Jensen et al. 2000; USA Downs & Black score=16 Pre-post N=22 1. 2. 3. Outcome 86% reported decrease in pain intensity and unpleasantness from preinduction to just after induction. A significant time effect emerged for both pain intensity (p<0.001) and pain unpleasantness (p<0.001). Significant effect for analgesic suggestion on pain intensity over and above the effects of the induction alone, with a significant decrease occurring in reported pain intensity before and after the analgesic suggestion (p<0.05). Pre-induction, post-induction, and post-analgesia suggestion pain intensity ratings were all significantly lower than average pain during the previous 6 months (p<0.01, p<0.0001, P<0.0001 respectively). Statistical significance was noted for 2 of the associations: Effect of pain plus analgesia suggestion on pain intensity (P<0.01) and effect of induction alone relative to least pain (p<0.05).

4.

5.

Discussion Jensen et al. (2000), in a before and after study, examined the impact of hypnosis on pain postSCI. Eighty-six percent (86%) of the SCI patients reported a decrease in pain intensity and unpleasantness after hypnosis. There was no control group. Conclusion There is level 2 evidence that hypnosis reduces pain intensity post-SCI. Hypnosis may reduce pain intensity post-SCI.

14.10 Pharmacological Management of Post-SCI Pain Pharmacological interventions are the standard treatment for SCI pain. The limited effectiveness of non-pharmacological treatments has led to the increasing use of pharmacological interventions to deal with what is often very severe and disabling pain. 14-12

14.10.1 Pharmacological Measures Overall Table 14.8 Pharmacological Interventions and Post-SCI Pain
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=94, f=26, age: mean=40.6, time since injury: mean=9.8 yrs, level of injury: cervical and noncervical. Treatment: No treatment-questionnaire. Outcome Measures: Sociodemographic data and characteristics of injury, intensity of pain, location of pain, quality of pain, allodynia (pain in response to a stimulus that would not provoke pain), MPI (designed to assess the impact of pain and adaptation to chronic pain), difficulty in dealing with pain and pain treatments. Widerstrom-Noga & Turk 2003; USA Downs & Black score=14 Case Series N=120 1. Outcome Overall 59.2% of participants used pharmacological or nonpharmacological treatments to control pain. 40.8% indicated they had not used nor had they been prescribed any medication for pain. Pain Severity: Pain severity was found to be higher for those who had received pain medications (PM) (3.9 + 1.3, p=0.001) compared to those who had not used any pain treatment. The intensity of pain was higher for those on PM than for those not on PM (p=0.022). Pain Locations: Those using PM reported more painful areas than those not using PM (p=0.001) with frontal/genital pain reported more often (p<0.000). Quality of Pain: Those on PM used more descriptive adjectives to describe their pain compared to those not using PM (p=0.031). Difficulty in Dealing with Pain: Those using PM reported having more difficulty dealing with pain than those not using PM (p<0.000). Pain impact: Those using PM had higher scores for the pain severity scale and the life interference scale compared to the group not using PM (p<0.002).

2.

3.

4.

5.

6.

Discussion Widerstrom-Noga and Turk (2003), not unexpectedly, found that SCI patients with more severe pain, in more locations, those with allodynia or hyperalgesia, and those in whom the pain was more likely to interfere with activities were more likely to use pain medications. Trials of simple non-narcotic analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen or non-narcotic muscle relaxants are common clinical practice in SCI pain. Unfortunately, these medications are often ineffective in complete SCI neuropathic pain relief and have potential risks such as gastric ulceration with prolonged use. For neuropathic or "central" pain seen following SCI, psychotropic drugs such as antidepressants and anticonvulsants are reportedly the most effective (Donovan 1982). Despite increasing popularity, few drugs (with the exception of Gabapentin) have regulatory approval for use in neuropathic pain and selection for individual patients is largely based on anecdotal evidence, of off-labeled use.

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14.10.2 Anticonvulsants in SCI Pain Anticonvulsant medications are often utilized in treating neurogenic or deafferent pain following SCI based on the theory that these drugs alter sodium conduction in uncontrolled hyperactive neurons (convulsive environment) in the spinal cord. Carbamazepine has been recognized as being somewhat effective in the paroxysmal, sharp, shooting pain of trigeminal neuralgia (Swerdlow 1984). Gibson and White (1971) described relief resulting from carbamazepine treatment in two cases of L2 and T8 SCI with intractable pain below the level of SCI. A similar effect of Carbamazepine (200 mg 2 x daily in combination with Amitriptyline 50 mg 3 x daily) was reported in a complete C8 patient with dysesthesias below the level of the injury (Sandford et al. 1992). Again controlled studies utilizing these drugs in SCI pain are lacking with the exception of gabapentin. Gabapentin is now regarded as a first-line treatment of neuropathic pain and post SCI neuropathic pain (Ahn et al. (2003). have noted that although the analgesic mechanism of action of Gabapentin is not fully understood, Gabapentin appears to potentiate GABA effects centrally through enhancement of GABA synthesis and release. Levendoglu et al. (2004) note that neuropathic pain is ultimately generated by excessive firing of pain-mediating nerve cells, insufficiently controlled by segmental and nonsequental inhibitory circuits. Gabapentin works by increasing GABA and reducing the release of glutamate thereby suppressing the sensitivity of N-metyl-D-asparate (NMDA) receptor. This has been shown to reduce neuronal hyperexcitability recorded at the spinal dorsal horn near the level of injury (Ahn et al. 2003). Gabapentin is relatively well tolerated with only a few transient side effects, lack of organ toxicity, and no evidence of significant interaction with other medications (Levendoghu et al. 2004). Table 14.9 Anticonvulsants for SCI Pain
Author Year; Country Score Research Design Total Sample Size Methods Population: Age: range 23 to 62 yrs, Gender: m=13, f=7; Onset of pain post injury: range 1 to 8 mths, Duration of pain: range 6 to 45 mths. Treatment: Subjects were randomized to gabapentin or placebo for a 4 weeks titration period. Following this 4 week period subjects continued to receive max tolerated doses. After a 2 week washout period the treatments were switched in a crossover design. Outcome Measures: Neuropathic pain scale, Short Form Beck Depression scale, Visual Analogue Scale, and Lattinen test were used to assess pain and quality of sleep. 1. Outcome Both placebo and the gabapentin improved pain scores for the following: pain intensity (p<0.000), shape (p<0.000), hot (p<0.001), unpleasantness (p<0.000), deep and surface pain (p<0.001), at the 4th week and again at the 8th week of administration. Intensity of pain decreased significantly for the gabapentin groups during treatment p<0.001) and the intensity of pain differed between the two groups at all time periods (p<0.001). VAS scores indicated that there was significant pain relief, which began at week 2 and continued until week 6 (p<0.05) and pain relief between the two groups at the end of the stable dosing periods was significantly different p<0.000. More experienced side effects in the EX gr then in the placebo gr (p<0.05).

2.

Levendoglu et al. 2004; Turkey PEDro=9 RCT N=20

3.

4.

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Author Year; Country Score Research Design Total Sample Size

Methods Population: Gender: m=6,f=1, age: 27-47 yrs, level of injury C2-T7, duration of injury: 1mth-20yrs. Treatment: Subjects with neuropathic pain were treated with gabapentin or placebo. Outcome Measures: Neuropathic Pain Scale, which has 10 categories of pain types. 1. 2.

Outcome Significant reduction of "unpleasant feeling" with gabapentin vs placebo (p=0.028). Trends of reductions with gabapentin vs placebo for "pain intensity" (p=0.094) and "burning feeling" (p=0.065). No other differences for any other pain descriptors including "sharp", "dull", "cold", "sensitive", "itchy", "deep", "surface". 76% of subjects reported some improvement in pain after taking gabapentin. The visual analogue score (VAS) decreased from 8.86 pre-treatment to 4.13 post-treatment (6mths later) (p<0.001), with a significant curvilinear trend (p=0.001). At the end of the study, both groups (1 & 2) showed they had lower mean scores for pain and sleep interference score (p<0.05). Mean pain score for Group 1 decreased more than it did for Group 2 (p<0.05). This score decreased more for Group 1 during weeks 2-8 than it did for Group 2 (p<0.05). Mean sleep interference score for Group 1 decreased more than it did for Group 2 (p<0.05).

Tai et al. 2002; USA PEDro=6 RCT N=7

3.

To et al. 2002; Australia Downs & Black score=18 Case Series N=44

Population: Gender: m=28, f=10, age: 1575, paraplegia/tetraplegia. Treatment: Neuropathic pain were treated with gabapentin. Outcome Measures: Level of pain experienced by subjects. Population: Gender: m=19, f=12; level of injury: tetraplegia & paraplegia, Age: ~45yrs, Duration of pain: ~10yrs, Degree of lesion: complete & incomplete. Treatment: Subjects were started on 300 mg of gabapentin, which was increased over 18 days to 1500 mg, followed by a 5 wk maintenance period. If pain score did not decrease during this time period, meds were increased to 2400 and 3600 mg/day. Group1 had <6 mo of pain; group2 >6 mo. Outcome Measures: Pain and sleep interference scores of the 2 groups were compared.

1. 2.

1.

2. 3. 4.

Ahn et al. 2003; Korea Downs & Black score=17 Pre-post N=31

Discussion As mentioned previously, gabapentin is the only anticonvulsant which has a strong research basis for determining its effectiveness in treatment of pain post-SCI. To et al. (2002) studied the impact of gabapentin on pain in a case series of 44 SCI patients with neuropathic pain and reported a significant decrease (p<0.001) in visual analogue pain scale (VAS) in 76% of subjects. Tai et al. (2002) studied the impact of gabapentin for pain treatment in a small RCT of only 7 patients. There was a significant reduction of unpleasant feeling with gabapentin vs. placebo (p=0.028) while pain intensity and burning pain only trended to significance (p=0.094 and 0.065, respectively) and no differences were detected for other pain descriptors such as sharp, dull, cold, sensitive, itchy, deep, surface. Levendoglu et al. (2004) in a crossover design of 20 paraplegics with neuropathic pain > 6 months found that Gabapentin was more effective (p<0.05) than placebo in reducing neuropathic pain. Ahn et al. (2003) in a before and after trial found that Gabapentin was effective (p<0.05) in decreasing neuropathic pain which was refractory to conventional analgesics for SCI patients with pain < 6 months and > 6 months and that the impact was greater for those patients with pain < 6 months in the post recent pain group.

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Table 14.10 Summary: Anticonvulsants to Treat Post-SCI Pain

Study To et al. 2002 Tai et al. 2002 Levendeglu et al. 2004 Ahn et al. 2003 N 44 7 20 31 Study Type Case series RCT RCT Before and after Drug Gabapentin Gabapentin Gabapentin Gabapentin Outcome + + + + earlier onset

Despite the fact that none of the studies cited above involved large sample sizes, all showed a benefit to using Gabapentin for post-SCI pain. Conclusion There is level 1 evidence that the anticonvulsant Gabapentin improves pain post-SCI. There is level 4 evidence that the anticonvulsant Gabapentin is more effective when SCI pain is <6 months than >6 months. Gabapentin improves pain post-SCI.

14.11 Tricyclic Antidepressants in Post-SCI pain Tricyclic antidepressant drugs are thought to modulate pain by inhibiting the uptake of norepinephrine and serotonin in the CNS. Sandford et al. (1992) have suggested that the tricyclic antidepressants exert an analgesic effect by making more serotonin available in the CNS, thereby potentiating the inhibitory action of the dorsal horn of the spinal cord. Unfortunately, these medications are often sedating and produce a variety of anticholinergic side effects. The partial effectiveness of tricyclic antidepressants (TCA) in some SCI patients with dysesthetic pain suggests that this drug is simply affecting the pain by treating the depression. Sandford et al. (1992) noted that pain and depression maybe chemically linked. Depression can lower pain thresholds or pain tolerances thereby increasing the patient's experience of pain. However Max et al. (1987) were able to show that tricyclic antidepressants (TCA) had analgesic properties despite low doses or short treatment cycles with analgesic activity occurring independent of mood changes. Davidoff et al. (1987) reported trazodone's in-effictiveness in relieving pain in 19 SCI patients with chronic dysesthetic pain, using a double-blind placebo controlled trial. Trazodone reportedly selectively inhibits serotonin and norepinephrine uptake in a ratio of 25:1, and is thought to produce greater analgesia and less anticholinergic side-effects compared to nonselective agents such as amitriptyline. Table 14.11 Tricyclic Antidepressants in Post-SCI Pain
Author Year; Country Score Research Design Total Sample Size Cardenas et al. 2002; USA PEDro=9 1 RCT Methods Population: Gender: m=80%, f=20%, age: ~41yrs, level of injury: Cervical-lumbar, ASIA: A-D, duration of SCI: ~169 mths Treatment: Subjects with chronic pain 1. Outcome There were no significant differences between the 2 groups at baseline and at the 6 week time period for any of the measures except satisfaction with

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Author Year; Country Score Research Design Total Sample Size N=84

Methods randomized to a 6 wk course of amitriptyline or placebo 1-2 hrs before bedtime. Outcome Measures: Average pain measure (scale 0-10), Short form McGill pain questionnaire (SF-MPQ), Brief pain inventory (BPI), Center for epidemiologic studies-depression scale (CES-D scale), Functional independence measure (FIM). Population: Gender: m=16, f=2, Age: 39 yrs, SCI, DIO: approx 49 mths. Treatment: Subjects underwent a 2 week placebo lead-in period with a 6 week randomization to 150 mg trazadone per day or placebo. Outcome Measures: McGill Pain Questionnaire, Sternbach Pain Intensity & Zung Pain and Distress Index.

Outcome life which showed higher scores for those in the placebo group (p=0.004). For those who remained on the two medications, it was noted that those in the amitriptyline group had significantly higher severity ratings for increased spasticity (p=0.005) than those in the control group. No significant differences were noted between the groups when looking at the MPQ, SPI, PAD. More subjects reported side effects in the experimental gr (p<0.05). More subjects in the placebo group completed the 8 wk study (p<0.01).

2.

1. 2. 3.

Davidoff et al. 1987; USA PEDro=6 RCT Initial N=19; Final N=18

Discussion Tricyclic antidepressants are often recommended for the treatment of neuropathic pain following non-SCI causes. Therefore, it is important to study the use of tricyclic antidepressants in the treatment of post-SCI pain. Cardenas et al. (2002) reported no significant difference in randomized spinal cord injury patients receiving either amitriptyline or placebo given 1-2 hours before bedtime for a period of 6 weeks. Heilporn (1977) using combinations of melitracin and TENS reported relief of pain in 8 of 11 SCI patients with dysesthetic pain. Conclusion There is level 1 evidence (based on two RCTs) that tricyclic antidepressants do not reduce post-SCI pain. Tricyclic antidepressants do not reduce post-SCI pain. 14.12 Anaesthetic Medications Anaesthetic medication such as lidocaine and ketamine can be delivered by a number of routes. Ketamine is a noncompetitive N-methyl-D-Aspartate (NMDA) receptor antagonist can be administered epidurally and intrathecally to treat neuropathic pain syndromes (Hocking & Cousins 2003). Table 14.12 Anaesthetic Medications for Post-SCI Pain
Author Year; Country Score Research Design Total Sample Size Loubser & Donovan 1991; USA PEDro=8 Methods Population: Gender m=15, f=6, age: 1858, injury: cervical-lumbar, chronic pain >6mths duration. 1. 2. Outcome All 21 patients tolerated the injection (anaesthetics and placebo) well. Negative placebo response was noted

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Author Year; Country Score Research Design Total Sample Size RCT N=21

Methods Treatment: Subjects had a lumbar subarachnoid catheter inserted. Subjects recorded their pain intensity at baseline. This was followed by 2 separate injections (placebo and 5% lidocaine in dextrose). A decrease in pain was considered a positive response to the treatment. Outcome Measures: pain. Population: Gender: m=11, f=2, Age: mean=44yrs, SCI, ASIA A-E, time since injury: avg 7yrs. Treatment: Following a 1 wk washout period subjects were given either 150 mg of mexiletine or placebo (150mg-3 x daily) followed by another 1 wk washout period then subjects placed in opposite group. Outcome Measures: McGill pain score. Population: Gender: m=8, f=1, age: 25-72, level of injury: cervical to thoracic, ASIA: AD, onset of pain: <6 mths post injury, length of pain: 14-94 mths Treatment: Ketamine hydrochloride, alfentanil or a placebo was given as combination of bolus and continuous intravenous infusions. The bolus dose was administered for 60 secs and the continuous intravenous infusion started simultaneously and was delivered by IVAC syringe pump. This lasted 17 to 21 minutes while the testing was performed. Outcome Measures: Continuous pain was measured by a 100 mm visual analogue scale (no pain to unbearable pain (0 to 100)) before and after each drug treatment.

Outcome in 17 pts. Following lidocaine (n=13) patients showed a mean reduction in pain (p<0.01) for an average of 123.1 95.3 mins. The decrease in pain reduction following lidocaine was significant (p<0.01) for the EX gr only. Visual analogue showed no significant differences for average pain levels over the past week and pain at time of test regardless of which medication (drug or placebo) subject was taking. Results of the McGill Pain score also showed no significant differences between the groups. No change in level of function for either group at any time of the study. Freidmann's two-way analysis by ranks showed differences between the various treatments (p=0.005). The effect of alfentanil and ketamine was also significant (p<0.01 & p<0.04 respectively) No significant differences were noted between the actions of ketamine and alfentanil (Wilcoxon p=0.19). Significant differences were noted between the treatment groups (p=0.008). It was also noted that allodynia was not more changed by ketamine than by alfentanil (Wilcoxon p=0.93). Alfentanil reduced wind-up-like pain (p=0.014) compared to the placebo group. The effect of ketamine on wind-up-like pain was not significantly reduced (p=0.07). A high correlation between the serum concentration of ketamine and the reduction of continuous pain (r=0.78, p<0.002) and the reduction of wind-uplike pain (r=0.83, p<0.002) was noted.

3.

1.

Chiou-Tan et al. 1996; USA PEDro=8 RCT Initial N=15; Final N=11

2. 3. 1. 2. 3. 4.

Eide et al. 1995; Norway PEDro=7 RCT N=9

5.

6.

Discussion Given the severity of post-SCI pain, treatments such as lumbar epidural and subarachnoid infusions or anaesthetics are sometimes tried. There is some evidence for these treatments. Loubser and Donovan (1991) conducted an RCT of 21 patients who were provided 2 separate lumbar subarachnoid injections of placebo and 5% lidocaine in dextrose. Following lidocaine (n=13) there was a significant mean reduction in pain (p<0.01) for an average of 2 hours although 8 patients showed no changes. However, this treatment provided short-term relief of pain only. The authors regarded the value of this treatment as more a diagnostic procedure than a therapeutic one. Eide et al. (1995) in an RCT of intravenous ketamine hydrochloride

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(NMDA receptor antagonist), alfentanil (-opioid receptor agonist) or placebo were provided as combination of bolus and continuous intravenous infusions. There was a significant benefit to ketamine or alfentanil vs. placebo for allodynia. Alfentanil reduced wind-up pain compared to placebo but not ketamine overall; however, there was a high correlation between the serum concentration of ketamine and the reduction in continuous pain and wind-up pain. The effects of ketamine and alfentanil were significant when compared to placebo. Conclusion There is level 1 evidence (based on one RCT) that Lidocaine delivered through a subarachnoid lumbar catheter provides short-term relief of pain greater than placebo. There is level 1 evidence (based on one RCT) that intravenous Ketamine and Alfentanil significantly reduces Allodynia when compared to placebo. There is level 1 evidence (based on one RCT) that mexilitene (a derivative of lidocaine) does not improve SCI dysesthetic pain when compared to placebo. Lidocaine through a subarachnoid lumbar catheter, I.V. Ketamine and Aflentanil improve post-SCI pain short term. Mexilitene does not improve SCI dysesthetic pain.

14.12.1 Antispasticity Medications Herman et al. (1997) note that baclofen is an -aminobutyric acid (GABA)B receptor agonist and acts to suppress spasticity in SCI patients centrally within the spinal cord itself. GABA is known to be involved in several analgesics pathways (Savynok 1987) and experimentally induced allodynia has been shown to be suppressed by baclofen (Henry 1982). However, baclofen, by treating spasticity, may reduce the musculoskeletal pain associated with spasticity. Continuous intrathecal infusion of baclofen can be effective, when oral baclofen is ineffective, in further reducing post-SCI spasticity and/or pain (dysesthetic, musculoskeletal, neurogenic) (Penn & Kroin 1987; Herman & DLuzamsteg 1991). Table 14.13 AntiSpastic Medications for Post-SCI Pain
Author Year; Country Score Research Design Total Sample Size Methods Population: Age: range 33 to 63; Diagnosis: MS=4, TMy=2, SCI=2, epiduaral absess=1; Gender: m=3, f=6; spasm related pain (SRP): range 1 to 10yrs; Dysesthesia: 2-4 yrs. RCT n=5/Non-RCT n=2 Treatment: Baclofen and placebo were randomly administered into the L1-2 interspace of each subjects. Outcomes Measures: Ashworth Scale and tendon tap; VAS for dysesthetic pain intensity; threshold/EMG relationships after controlled pinch as an indication of nociceptive pain. 1. Outcome Intrathecal baclofen also significantly suppressed the dysethetic (burning quality) pain among 6 of the 7 RCT subjects (p<0.001). One of the ononRCT subjects who also noted dysesthetic pain was abolished. Pinch inducted pain was not affected by either placebo or baclofen.

Herman et al. 1992; USA PEDro=8 RCT & Non RCT N=7

2.

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Author Year; Country Score Research Design Total Sample Size

Methods Population: Age: 21 to 63: Gender: m=15, f=1; Frankel classification: A to C; Type of pain: neurogenic=6, musculosketal=6, mixed pain=3. Treatment: Baclofen infusion pump implantation. Outcome Measures: pain. 1. 2.

Outcome 12 out of 16 patients described chronic pain prior to the procedure. No significant differences were noted between the visual analogue score (VAS) at the 6 and 12-month period following the pump implantation. For those with neurogenic pain symptoms, ANOVA revealed a nonsignificant effect of intrathecal baclofen on pain at both 6 and 12 months. (F2, 16), adjusted p=0.26. In 5 of 6 patients with musculoskeletal pain symptoms pain severity decreased in conjunction with control of spasticity. Musculoskeletal pain responded to the Baclofen infusion while neurogenic pain did not.

Loubser & Akman1996; USA Downs & Black score=13 Pre-post N= 16

3.

4.

Discussion Similar to above, the severity of post-SCI pain has led to the use of intrathecal Baclofen to treat post-SCI pain. Herman et al. (1992) in a RCT found that intrathecal baclofen significantly suppressed the dysesthetic (burning) pain among 6 of the 7 subjects (p<0.001). Only one of the placebo patients noted the dysesthetic pain was abolished. Intrathecal baclofen did not have a significant impact on pinch induced pain. Therefore, in this study, intrathecal baclofen appeared to have an impact on post-SCI dysesthetic pain in addition to treating the spasticity. Loubser and Akman (1992) performed a before and after study of implanted Baclofen infusion pumps provided for spasticity. Twelve (12) of 16 patients described pre-existing chronic pain but there was no significant difference in the VAS neurogenic pain symptoms at 6 and 12 months (p=0.26) while musculoskeletal pain symptoms and pain severity decreased in conjunction with control of spasticity in 5 of 6 patients. In this study, it appeared musculoskeletal pain was reduced more with intrathecal baclofen, presumably by reducing spasticity. Hence it would appear that intrathecal baclofen improves chronic post-SCI pain but the actual mechanism has not been adequately established. It is treating neuropathic deafferentation type pain or musculoskeletal pain associated with spasticity? The answer may actually be both neuopathic and musculoskeletal pain, although some of the difficulties in coming to this determination may in fact reflect difficulties chemically in being able to consistently distinguish between neuropathic and musculoskeletal pain states. However, there is evidence that Baclofen infusion pumps may provide positive benefits for both neuropathic and musculoskeletal pain post-SCI. Conclusion There is level 1 evidence (based on one RCT) that Intrathecal Baclofen reduces dysesthetic pain post-SCI. However, the sample size was small and a before and after trial reported contradictory results. There is level 4 evidence that Intrathecal Baclofen reduces musculoskeletal pain postSCI in conjuctiton with spasticity reduction.

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Intrathecal Baclofen improves musculoskeletal pain post-SCI and may help dysethetic pain related to spasticity.

14.12.2 Opioids for Post-SCI Pain To date there are not research studies examining opioids in the treatment of SCI pain. There is a substantial body of research investigating the benefits of opioid analgesics in the treatment of non-cancer chronic pain and some of those studies examined the impact of opioids on neuropathic pain. There are no studies employing opioid analgesics in post-SCI pain. Furton et al (2006) conducted a meta-analysis of effectiveness and side-effects of opioid analgesics for chronic non-cancer pain. Their meta-analysis found that opioids reduced pain and improved functional outcomes when compared to placebo for both nociceptive and neuropathic pain syndromes. Strong opioids (oxydone and morphine) were significantly superior to naproxen and nortriptyline for pain relief but not functional outcomes. Weak opiods (propylene, tromadol and codeine) did not significantly do better than NSAIDS or tricyclic anti-depressants for either pain relief or functional outcomes (Furton et al. 2006). The same authors found that clinically, only constipation and nausea were significantly more common with opioids (Furher et al 2006). The big concern with opioids is of course addiction or opiod abuse. Unfortunately, as Furton et al. (2006) notes in their meta-analysis, the existing randomized trials were not designed to evaluate addiction. 14.12.3 Cannabinoids in Post-SCI Pain Wade et al. (2003) note that delta-9-tetra hydrocannabinol (THC) and other cannabinoids have been shown to improve both tremor and spasticity in animal models of multiple sclerosis supported by anecdotal reports that cannabis relieves some of the troublesome symptoms of multiple sclerosis and spinal cord injury (Dunn & Davis 1974; Petro & Ellenberger 1981; Ungeleider et al. 1987; Meinck et al. 1989; Martyn et al. 1995; Consroe et al. 1997; Baker 2000). There is a clinical impression that marijuana smoking is very common among patients post-SCI; however, there are social and legal implication to its use and medical concerns about smoking as a delivery system. Table 14.14 Cannaboids and Post-SCI Pain
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=10, f=10; age: mean=48; MS=18, SCI=4, other=2. Treatment: Whole plant extracts of delta 9 tetrahydrocannabinol (THC) and cannabidiol in a 1:1 preparation were used. These drugs were presented in pump action sublingual spray that delivered 2.5 mg THC and/or CBD at each actuation. A placebo was also prepared and administered. Outcome Measures: Daily diary-scored target symptoms by means of VAS, Short orientation memory concentration, the Barthel Activities of Daily Living Index, the Rivermead Mobility Index, and the General 1. Outcome ANOVA scores indicate that Cannabidiol (CBD) Cannabis medicinal extracts (CME) improved pain significantly on VAS score when compared to placebo (mean=54.8 22.6, p<0.05). Similar results were also noted with THC CME, which improved pain muscle spasm, spasticity & appetite (p<0.05). THC:CBD significantly improved muscle spasm and sleep (p<0.05). Cannabis medicinal extracts (CME) produced significant improvements in ratings of spasticity (p<0.05), while

Wade et al. 2003; UK PEDro=8 RCT Initial N=24; Final N=20

2.

3. 4.

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Author Year; Country Score Research Design Total Sample Size

Methods Health Questionnaire, Ashworth scale for spasticity, Nine hole Peg test of manual dexterity, 10 metre timed walk.

Outcome using THC CME and THC:CBD reduced the muscle spasm frequency (p<0.05).

Discussion Given that marijuana has anecdotally been thought to have benefits for post-SCI pain, Wade et al. (2003) conducted an RCT of sublingual 2.5 mg tetrahydrocannabinol (THC) and/or cannabidiol and found that it helped to reduce pain, muscle spasm, spasticity and sleep in a group of largely multiple sclerosis patients with neuropathic pain. It is of note that only a small percentage of the patients in this study had spinal cord injuries. Cannabinoids are a promising treatment, which would benefit from other studies. Conclusion It is not known whether Cannabinoids are effective in treating pain post-SCI but good results have been seen in treating multiple sclerosis patients. Cannabinoids are a potential new treatment for Post-SCI pain in need of further study.

14.12.4 Clonidine for Post-SCI Pain Clonidine is an alpha-2 adrenoceptor agonist which has been shown to activate spinal receptors that reduce responses to painful stimuli (Yaksh 1985). Ackerman et al. (2003) note that clonidine inhibits nociceptive impulses by activating alpha-2 adrencoceptors in the dorsal horn of the spinal cord (Rainov et al. 2001). The anti-nociceptive effects of clonidine are thought to be mediated via inhibitory interaction with pre- and post-synaptic primary afferent nociceptive projections in the dorsal horn (Osenbach and Harvey 2001) and possibly by inhibition of substance P release (Hassenbusch et al. 1999; Ackerman et al. 2003). Ackerman et al. (2003) noted selective alpha-2 adrenergic antagonists (e.g. Yohimbine) have been shown to reverse clonidine-induced analgesia (Osenbach & Harvey 2001). Teasell and Arnold (2004) were able to show that venous alpha-adrenoceptor hyperresponsiveness was present in patients with RSD, in diabetic peripheral neuropathy (Arnold et al. 1993) and below the level of lesion in quadriplegics (Arnold et al. 1995). They speculated that this alpha-adrenoceptor hyperresponsiveness was in fact due to alpha-2 adrenoceptor dysfunction leading to overstimulation of the post-synaptic alpha-1 adrenoceptor peripherally. This would fit with the observation that clonidine reduces pain post-SCI below the level of the lesion, presumably through its alpha-2 adrenoceptor agonist function. Ackerman et al. (2002) noted that clonidine may be useful for patients who are non-responsive to opiods. Clonidine appears to work synergistically with opiods to provide pain relief (Plummer et al. 1992; Tollerida et al. 1999; Siddall et al. 2000; Osenbach & Harvey 2001)

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Table 14.15 Clonidine for Treatment of SCI Pain

Author Year; Country Score Research Design Total Sample Size Methods Population: Age: 26-78yrs; Neuropathic pain: 13 had below level neurpathic pain, 4 at level of neuropathic pain, 3 had both types of pain. Treatment: Placebo, morphine or Clonidine was delivered via catheter into lumbar intrathecal spase. The subjects were first given either: 2-1mg of morphine, 50 to 100 mcg of Clonidine or placebodosage was increased if the subject had no side effects and no pain relief. Subjects could receive up to 1.5 times the initial drug dosage if necessary. Once the subject received satisfactory pain relief or side effects from the drug they were on they were given a mixture of morphine and Clonidine. Outcome Measures: Numerical pain rating scale, numerical pain relief score, a verbal pain rating and a nausea scale and sedation scores were recorded. Population: Gender m=4, f=6; age 3477yrs; time since injury: 1-10yrs. Treatment: Subjects, once implanted with a medical pump, were originally given 3 ml of saline followed by 1 ml of morphine, this was followed by a second dose of morphine (0.02 mg) provided no side effects or benefits were noted. This was followed by Clonidine (30 ug in 1 ml) and then depending on side effects a final dose of Clonidine (50 ug in 1 ml.). After each drug administration the catheter was flushed with saline. Outcomes Measures: Not specified. 1. Outcome The administration of morphine or clonidine resulted in a mean reduction in pain levels but this was not statistically significant compared to the effect of placebo. When the mixture of morphine and clonidine was administered there was a significant reduction in pain when compared to those on placebo (p=0.0084).

2.

Siddall et al. 2000; Australia PEDro=8 RCT N=15

1.

Uhle et al. 2000; Germany Downs & Black score=9 Prospective Controlled Trial N=10

2.

Subjects reported a good to excellent pain reduction following the administration of Clonidine administration. After Clonidine bolus subjects experienced an optimum pain reduction. Average dose of Clonidine was initially 53 ug/day and this decreased (or stabilized) to 44 ug/day.

Discussion Siddall et al. (2000) in a RCT/cross over trial of 20 subjects with post-SCI neuropathic pain. Intracthecal morphine clonidine or placebo was given at the lumbar level. Once the subject received satisfactory pain relief or drug side effects they were given a mixture of clonidine and morphine. Morphine or clonidine showed a trend in pain reduction, which was not statistically significant but when the combination of morphine and clonidine was administered there, was a significant reduction in pain. Siddall et al. (2000) did postulate that by administering half the effective minimum dose of clonidine and morphine together resulted in a synergistic addictive effect above the simple summing up of each drug in isolation. Uhle et al. (2000) in a study of study 10 patients were given morphine followed by clonidine via a medical pump. Patients when given clonidine experienced a good to excellent reduction in their pain. Conclusion There is level 1 evidence (based on only one RCT) that Intrathecal Clonidine alone did not provide pain relief greater than placebo, although there was a trend.

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There is level 2 evidence (based on one prospective controlled study) that the combination of Intrathecal Morphine and Clonidine did provide pain relief greater than placebo. Intrathecal Clonidine alone does not appear to provide pain relief although it may be helpful in combination with Intrathecal Morphine.

4.13 Surgical Interventions 14.13.1 Spinal Cord Stimulation Spinal cord stimulation has been used to try to treat intractable pain. Table 14.16 Spinal Cord Stimulation Post-SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=19, f=6; age: 3376yrs; SCI; time since injury: 1-39yrs. Treatment: An epidural electrode was inserted percutaneously over the posterior columns of the spinal cord. Spinal cord stimulation was performed with the following parameters: 85 cycles/sec, duration of 210 msec and varied intensity for comfortable parasthesias30 mins every 3 hrs during the day. Mean follow-up was 37.25 mths. Outcome Measures: Pain relief. 1. 2. 3. Outcome Results reported as %'s only. No statistical results reported. During SC stimulation, 22 patients reported parasthesias overlapping the painful area. 9 pts enjoyed 50% pain relief at the end of the test period. No pain relief was found in 3 of the patients.

Cioni et al. 1995; Italy Downs & Black score=8 Case Series N=25

Cioni et al. (1995) in a case series reported inserting epidural electrodes percutaneously over the posterior columns of the spinal cord to allow for spinal cord stimulation. During spinal cord stimulation, 22 patients reported parasthesias overlapping the painful area. 9 patients reported 50% pain relief and 3 patients experienced no pain relief. Conclusion There is level 4 evidence that spinal cord stimulation improves post-SCI pain. Spinal cord stimulation may improve post-SCI pain. 14.13.2 Destructive Neurosurgical Procedures Destructive neurosurgical procedures work best on segmental and central dysesthetic pain (Nashold, 1991). Nashold (1991) notes that surgery for pain is best done earlier than later. The Dorsal Root Entry Zone (DREZ) procedure is reportedly the most successful procedure at the present time (Nashold 1991); however, in many cases pain is either unresponsive or returns.

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14.13.3 Dorsal Rhizotomy Dorsal rhizotomy is a procedure where the sensory roots are divided either intradurally or extradurally. According to Nashold (1991) a single one or two level root rhizotomy may be appropriate when the pain is localized as in those patients with paraparesis and single root pain. Moreover, Nashold (1991) reported the Dorsal Root Entry Zone (DREZ) procedure was more likely to be successful in these patients. 14.13.4 Sympathectomy Sympathectomy is not recommended for pain following SCI (Nashold 1991). As mentioned previously, sympathetic blockade and sympathectomy have reportedly failed to relieve the central pain of SCI (White 1969; Melzack 1978; Friedman 1986). 14.13.5 Lateral Spinothalamic Tractotomy Hazouri and Mueller (1950) described three selected cases of patients with intractable root pain, subsequent to severe trauma to the cauda equina which resulted in paraplegia (L2-4 lesions). All three patients demonstrated a distinct increase in the threshold for perception of pain and "an even more remarkable increase in the threshold for reaction to pain." Lateral spinothalamic tractotomy in all three of these patients resulted in complete relief from pain. Threshold studies subsequent to the tractotomy "revealed a striking return of perception and reaction thresholds to a normal range." 14.13.6 Spinal Cordotomy This procedure can be performed openly or percutaneously. Anterior spinothalamic tracts subserving pain and temperature function are sectioned, often requiring a bilateral approach. Spinal cordotomy is an option but is rarely employed and there is little evidence that it works. 14.14 Summary Pain following SCI is quite common. The most common type of pain post SCI is central or neuropathic in nature characterized by a dysesthetic, burning pain below the level of SCI. Borderzone or segmental pain is much less common; occurring along the border between normal and absent sensation. The precise etiology of central/neuropathic or borderzone segmental pain is not known. There is some evidence suggesting an association may exist between the central or neuropathic dysesthetic burning pain and abnormalities of the sympathetic nervous system. Musculoskeletal pain, either secondary to the original trauma or to overuse is both common and well understood. Unfortunately, the management of central or neuropathic pain remains difficult and largely ineffective. For many SCI patients pain has a significant impact on quality of life. Over 50% of SCI patients develop chronic pain. Severe pain is more common the lower down the lesion in the spinal cord. Pain post-SCI most often begins within the first 6-12 months post-SCI. The most common types of pain post SCI are: 1) is a burning pain (likely neuropathic) usually localized to the front of torso, buttock or legs; 2) an aching pain (likely musculoskeletal) usually localized to the neck, shoulders and back.

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There is limited level 4 evidence that Massage and Heat are the best nonpharmacological treatments for pain post-SCI. There is level 2 evidence that in general acupuncture is no more effective than Trager therapy for shoulder pain. There is level 4 evidence that acupuncture reduces the pain of patients with SCI. There is level 2 evidence (from one RCT) that a shoulder exercise protocol reduces the intensity of shoulder pain post-SCI. There is level 4 evidence that hypnosis reduces pain intensity post-SCI. There is level 1 evidence that the anticonvulsant Gabapentin improves pain post-SCI. There is level 4 evidence that the anticonvulsant Gabapentin is more effective when SCI pain is <6 mos than >6 mos. There is level 1 evidence (based on two RCTs) that tricyclic antidepressants do not reduce post-SCI pain. There is level 1 evidence (based on one RCT) that Lidocaine delivered through a subarachnoid lumbar catheter provides short-term relief of pain greater than placebo. There is level 1 evidence (based on one RCT) that Intravenous Ketamine and Alfentanil significantly reduces Allodynia when compared to placebo. There is level 1 evidence (based on one RCT) that mexilitene (a derivative of lidocaine) does not improve SCI dysesthetic pain when compared to placebo. There is level 1 evidence (based on one RCT) that Intrathecal Baclofen reduces dysesthetic pain post-SCI. However, the sample size was small and a before and after trial reported contradictory results. There is level 4 evidence that Intrathecal Baclofen reduces musculoskeletal pain postSCI by reducing spasticity. It is not known whether Cannabinoids are effective in treating pain post-SCI but good results have been seen in treating multiple sclerosis patients. There is level 1 evidence (based on only one RCT) that Intrathecal Clonidine alone did not provide pain relief greater than placebo, although there was a trend. There is level 2 evidence (based on only one prospective controlled study) that the combination of Intrathecal Morphine and Clonidine did provide pain relief greater than placebo. There is level 4 evidence that Spinal Cord Stimulation improves post-SCI pain.

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CHAPTER FIFTEEN
Venous Thromboembolism Following Spinal Cord Injury
Robert W Teasell, MD FRCPC Jane TC Hsieh, MSc Jo-Anne Aubut, BA Janice J Eng, BSc (PT/OT), PhD Andrei Krassioukov, MD, PhD Linh Tu, BHSc

Key Points
Deep venous thrombosis is very common in spinal cord-injured patients not receiving DVT prophylaxis. There is insufficient evidence for Coumadin as a prophylactic treatment for venous thrombosis post-SCI. 5,000 units s/c q12h of unfractionated heparin does not appear to prevent venous thrombosis post-SCI while higher doses adjusted according to serum measures of anticoagulation is more effective. Low molecular weight heparin more effectively reduces the risk of venous thromboembolism post-SCI than standard or unfractionated heparin prophylaxis with less bleeding complications. There appears to be no difference between Enoxaparin and Dalteparin in reducing the risk of venous thrombosis post-SCI. Mechanical compression may reduce the incidence of venous thromboembolism postSCI. The use of rotating treatment tables reduces the incidence of venous thromboembolism post-SCI. A combined regiment of pneumatic compression, pressure stockings and low-dose heparin given prophylactically may reduce the incidence of venous thrombosis and the effect is better in early post-SCI. Inferior vena cava filters significantly reduce the risk of pulmonary emboli in high-risk SCI patients. Enoxaparin subcutaneously can be considered as an alternative to intravenous Heparin for acute DVTs post-SCI although more research needs to be done.

Table of Contents
15.1 Introduction .................................................................................................................15-1 15.2 Incidence of Venous Thromboembolism Post SCI ..................................................15-1 15.3 Diagnosis of Venous Thromboembolism Post SCI .................................................15-2 15.3.1 Venous Ultrasound ....................................................................................................15-2 15.3.2 Venography.................................................................................................................15-2 15.3.3 D-Dimer Assay............................................................................................................15-3 15.3.4 Diagnosis of DVT ........................................................................................................15-3 15.3.5 Clinical Presentation of Pulmonary Embolus .............................................................15-3 15.3.6 Ventilation/Perfusion (V/Q) Scanning .........................................................................15-3 15.3.7 Pulmonary Angiography..............................................................................................15-4 15.3.8 Spiral CT Scan............................................................................................................15-4 15.4 Prophylaxis of Venous Thromboembolism Post SCI ..............................................15-4 15.4.1 Pharmacological Agents for DVT Prophylaxis ...........................................................15-5 15.4.1.1 Coumadin as Prophylaxis for Venous Thromboembolism .......................................15-5 15.4.1.2 Unfractionated Heparin as Prophylaxis for Venous Thromboembolism Post-SC I ..15-6 15.4.1.3 Low Molecular Weight Heparin (LMWH) as Prophylaxis ........................................15-8 15.4.1.4 Heparin Analogues .................................................................................................15-8 15.4.1.5 LMWH vs. UFH as Prophylaxis for Venous Thromboembolism ..............................15-9 15.4.1.6 LMWH as a Prophylaxis of Venous Thrombosis....................................................15-12 15.5. Prevention of DVT through Mechanical Methods .................................................15-13 15.6 Vena Cava Filtration .................................................................................................15-17 15.7 Treatment of Acute Venous Thromboembolism in SCI .........................................15-20 15.8 Summary.....................................................................................................................15-21 References ...........................................................................................................................15-23

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Teasell RW, Hsieh JTC, Aubut J, Eng JJ, Krassioukov A, Tu L (2006). Venous Thromboembolism Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 15.1-15.25. www.icord.org/scire

Venous Thromboembolism Following Spinal Cord Injury

15.1 Introduction Deep venous thrombosis (DVT) and subsequent pulmonary embolism (PE) remain a significant cause of morbidity and mortality in spinal cord injured (SCI) patient. The incidence of DVT has been reported by various authors to range between 9% - 100% during the acute stage of SCI, with most occurring in the first 2 weeks post-injury, sometimes leading to a pulmonary embolism which remains a common cause of death (Tribe 1963; Walsh & Tribe 1965; Watson 1968; Stover et al. 1983; Winchelli et al. 1999; Aito et al. 2002; Chiou-Tan et al. 2003). 15.2 Incidence of Venous Thromboembolism Post SCI The incidence of deep venous thrombosis in patients with acute spinal cord injury has been reported to be very high, more than 50% in early prospective studies (Joffe 1975; Todd et al. 1976; Brach et al. 1977; Rossi et al. 1980; Becker et al. 1997) with the incidence of fatal pulmonary embolism estimated to be as high as 2% in paraplegics (Joffe 1975). The prevalence of DVT in acute SCI has been found to range from 14% to 100% (Chiou-Tan et al. 2003) or 9% to 90% (Aito et al. 2002). Chiou-Tan et al. (2003) have noted that this has been examined in depth in the literature. Table 15.1
Author/Year Colachis & Clinchot (1993) Gundez et al. (1993) Yelink et al. (1991) Merli et al. (1988) Myllynen et al. (1985) Green et al. (1982) Rossi et al. (1980) Treatment (n size) Prophylaxis Treatment (n=209) Low-dose Heparin (n= 31) Prophylactic anticoagulant therapy (n=147) Untreated group Anticoagulant therapy (n=37) External pneumatic calf compression (ENCP) or ENCP + aspirin + dipyrid (n=28) N/A (n=18) % of DVTs 14% 53% 23% 47% 100% of SCI pts 78% untreated pts 33% treated pts 72% Test Contrast venography Ultrasound Venography Venography I125 fibrinogen scan Impedance Plethysmography Venography 125 I fibrinogen scan Venography Platelet aggregation studies I125 fibrinogen scan

More recent and widespread reports, according to Aito et al. (2002), place the incidence of DVTs at between 10-30% (Yelnick et al. 1991; Kulkarni et al. 1992; Colachis & Clinchot 1994; Powell et al. 1999; Winemiller 1999). The high risk of DVT in acute SCI patients is due to the simultaneous presence of the 3 factors of Virchows triad: hypercoagulability, stasis and intimal (inner vessel layer) injury (Aito et al. 2002). Venous thromboembolism usually begins with a calf DVT (Nicolaides et al. 1971; Philbrick et al. 1988; Cogo et al. 1998). Twenty percent of DVTs extend into the proximal veins (Kakka et al. 1969; Lagestedt et al. 1985; Brandstater et al. 1992) and when DVTs causes

15-1

symptoms, over 80% of those involve the popliteal or more proximal veins (Kearon et al. 1998). Non-extending distal (i.e. calf) DVTs rarely cause PEs and as such are rarely worrisome (Kakka et al. 1969). Proximal (i.e. knee or above) DVTs often do cause PEs and are the source of concern (Kakka et al. 1969). Pulmonary emboli (PE) are not uncommon post-SCI and most are asymptomatic or unrecognized. Symptomatic PEs are large and with most large PEs, if fatal, fatal within the first few minutes. Deep venous thrombosis is very common in spinal cord-injured patients not receiving DVT prophylaxis.

15.3 Diagnosis of Venous Thromboembolism Post SCI The signs and symptoms of DVT are varied and depend on the severity. Generally DVTs can cause pain, swelling, tenderness, skin discolouration and increased warmth of the affected area. The signs and symptoms of PE are nonspecific and can include: sudden chest pain, shortness of breath, difficulty breathing, or rapid breathing, coughing up blood, loss of consciousness (fainting), which often leads to difficulties with diagnosis. Several methods and techniques are currently used for diagnosis. Although the various methods of DVT detection will be discussed, it is important for health care professionals, patients, family members and caregivers to be educated in the early signs and symptoms. Expert consensus, as noted by the PVA Consortium of Spinal Cord Medicine 2005 guideline for the prevention of thromboembolism, suggests that all extremities should be inspected twice daily for an increase in the calf or thigh venous pattern or circumference, lowgrade fever of unknown origin or pain/tenderness/heaviness of an affected extremity. Since patients can sometimes be asymptomatic, it is also suggested that health care providers, including family and caregivers, be familiarized with risk factors such as lower limb fractures, dehydration, obesity, age, malignancy, congestive heart failure, estrogen therapy, pregnancy, and a history of thrombosis. Another measure, considered by expert consensus to be important and preventative, is the routine practice of active and passive range-of-motion exercises. Mobilization and movement of the extremities (with careful consideration of spinal stability in the acute phase) should be essential to the prevention of DVT in SCI. 15.3.1 Venous Ultrasound Venous ultrasound is often used to diagnose a DVT. The sensitivity of the test is 95% in all patients with symptomatic proximal DVTs. The sensitivity falls to 73% for distal DVTs. However, distal DVTs are generally not dangerous until they extend proximally at which they are at a much higher risk of travelling anteriorly to become a pulmonary embolus. Since the majority of DVTs that do so extend within the first week, serial venous ultrasounds are useful to detect clots extending in symptomatic patients even if initial tests are negative. 15.3.2 Venography Venography is an invasive study whereby contrast dye is injected into the leg veins and is considered a definitive test for DVT. Diagnosis of DVT is made if an intraluminal-filling defect is noted.

15.3.3 D-Dimer Assay D-dimer assay tests are rapid, noninvasive and inexpensive (Gill and Nahum 2000). Fibrin is the main component of thrombus formation and fibrin degradation products include d-dimers (Gill & Nahum 2000). A positive d-dimer test is highly sensitive but lacks specificity since ddimers are found in other disease states, including cancer, congestive heart failure and inflammatory conditions (Raimondi et al. 1993). D-dimer assays have a high negative predictive value, which means when it is negative it is unlikely that the patient has a DVT. However, it has poor positive predictive value so that when it is positive the cause could be a condition other than DVT (i.e. false positive). To illustrate, Akman et al. (2004) reported that the sensitivity and negative predictive values of the D-dimer test were high, at 95.2% and 96.2%, respectively in a group of 68 rehabilitating patients admitted with a diagnosis of stroke, spinal cord injury, hip arthroplasty or traumatic brain injury. The specificity and positive predictive value were low, at 55.3% and 48.7%. 15.3.4 Diagnosis of DVT A positive diagnosis of a DVT can only be made if the venogram is positive or there is a positive venous ultrasound at two or more sites of the proximal veins. A negative diagnosis for DVT can be made if there is a negative venogram, a negative d-dimer test or a normal venous ultrasound assuming the venous ultrasound is accompanied by one of the following findings: 1) low clinical suspicion for DVT, or 2) normal d-dimer test, or 3) normal serial testing with the test interval being no greater than 1 week. 15.3.5 Clinical Presentation of Pulmonary Embolus The clinical diagnosis of pulmonary emboli is unreliable, being both insensitive and nonspecific. Many cases are clinically silent with only 30% having the clinical features of a DVT and only 70% demonstrating a DVT on venography. Patients with a massive pulmonary embolus who suffer compromise of more than 60% of the pulmonary circulation are considered critically ill. Right heart failure may progress to cardiovascular collapse with hypertension, coma and death. A submassive pulmonary embolus presents with tachycardia, tachypnea and signs of pulmonary infarction with consolidation, rales, hemoptysis, pleuritic chest pain, pleural friction rub, pleural effusion and fever. In most cases there are usually only a few clinical findings and the presentation may be nonspecific with the major clinical complaints of malaise and fever. 15.3.6 Ventilation/Perfusion (V/Q) Scanning Nuclear ventilation/perfusion scans are often used to diagnose a PE. A normal perfusion scan excludes a PE but is found in the minority of patients with a PE. Perfusion defects are nonspecific; about a third of those with defects actually have a PE. The probability that a perfusion defect is a PE increases with the size, shape and number of defects as well as the presence of a normal ventilation scan. Mismatched perfusion defects (normal ventilation scan), which are segmental in size or larger are high probability defects and are associated with approximately an 80% prevalence of PE. Three or more mismatched defects are associated with a prevalence of approximately 90%. If a patient has a positive V/Q scan and high clinical suspicion of a PE then they should be treated.

Table 15.2 Probability of Pulmonary Embolism Based on Ventilation-perfusion Scan Results and Clinical Suspicion in Prospective Investigation of Pulmonary Embolism Diagnosis Study (PIOPED) Study
Ventilation-perfusion scan results High probability Intermediate probability Low probability Normal/near-normal probability * Percentage of patients with pulmonary embolism Adapted from the PIOPED Investigators (Gill and Nahum 2000, PIOPED Investigators 1990). Clinical suspicion of pulmonary embolism* Low High Intermediate 56% 88% 96% 16% 28% 66% 4% 16% 40% 2% 6% 0%

PIOPED (prospective investigation of pulmonary embolism diagnosis) demonstrated that a lowprobability or normal ventilation-perfusion scan with a low clinical suspicion of pulmonary embolism essentially excludes the diagnosis of pulmonary embolism (negative predictive values of 96% and 98% respectively) (Gill & Nahum 2000; PIOPED Investigators 1990). When clinical suspicion is high and the scan indicates a high probability of pulmonary embolism, the positive predictive value is 96% (Gill & Nahum 2000; PIOPED Investigators 1990). 15.3.7 Pulmonary Angiography Pulmonary angiography is the definitive diagnosis for pulmonary embolism (Gill & Nahum 2000). It involves percutaneous catheterization and injection of contrast dye into a pulmonary artery branch (Gill & Nahum 2000). It is used when the V/Q scan is nondiagnostic but the clinical suspicion remains high. It is an expensive test and is associated with some significant risk of complications. Relative contraindications include significant bleeding risk, allergy to contrast medium, and renal insufficiency (Gill & Nahum 2000). It is associated with a mortality rate of up to 0.5% (Newman 1989; Stein et al. 1992). Pulmonary angiography is most commonly used when ventilation-perfusion scanning is nondiagnostic but clinical suspicion remains high (Tapson et al. 1999). A negative pulmonary angiogram excludes clinically relevant pulmonary embolism (Tapson et al. 1999; Gill & Nahum 2000). 15.3.8 Spiral CT Scan A spiral CT scan is a quick, less expensive CT scan which can scan the entire thorax in one breath-hold. It has a sensitivity ranging from 64-93% with a specificity of 89-100% - it is most accurate when the embolism is large and less accurate when the clot is small. It actually visualizes the clot and has the added benefit of diagnosing other disease states in the differential diagnosis. The majority of ventilation perfusion scans have nondiagnostic results, requiring further testing (PIOPED Investigators, 1990). 15.4 Prophylaxis of Venous Thromboembolism Post SCI Anticoagulants can prevent thrombi from forming in the deep veins of the leg. The deep veins (DVTs) can break off and travel to the lungs, resulting in a pulmonary embolism (PE) the most clinically important consequence of DVT. However anticoagulants can lead to serious complications such as intracerebral hemorrhaging. The consortium for spinal cord medicine published clinical practice guidelines for the prevention of thromboembolism in SCI (2002). They recommended 5,000 units of unfractionated heparin for motor-incomplete patients for 8 weeks and either heparin adjusted to high normal activated partial thromboplastin time or low molecular weight heparin for motor-complete patients for 8-12

weeks. Chiou-Tan et al. (2003) note that this recommendation is based on studies that showed that the risk of thromboembolism in SCI increases rapidly after injury and is maximal between days 7 and 10 (Green et al. 1982; Merli et al. 1988; Geerts et al. 1994). 15.4.1 Pharmacological Agents for DVT Prophylaxis 15.4.1.1 Coumadin as Prophylaxis for Venous Thromboembolism Warfarin (Coumadin) is the most widely prescribed oral anticoagulant. As an agonist of vitamin K, warfarin acts by inhibiting the synthesis of clotting factors. Therapeutic doses of warfarin reduce the production of functional vitamin K dependent clotting factors by approximately 30 to 50 percent. Antagonism of vitamin K reduces the rate at which these factors and proteins are produced (Horton & Bushwick 1999). Clinical evidence indicates that an International Normalized Ratio (INR) of 2.0-3.0 is sufficient for prophylaxis and treatment of venous thromboembolism while minimizing the risk of hemorrhage associated with higher INRs. The antithrombotic effect of warfarin, or the inability to expand or form clots, is not present until approximately the fifth day of therapy. Therefore, concomitant use of heparin is usually required during the transition in therapy. To ensure continuous anticoagulation, it is advisable to continue full dose heparin therapy and therefore Coumadin needs to be overlapped with heparin for 4 to 5 days, until Coumadin has produced the desired therapeutic response as determined by the PT/ INR. When Coumadin has produced the desired PT/ INR or prothrombin activity, heparin may be discontinued. A small decrease in the INR will likely occur once unfractionated heparin therapy is discontinued. The presence of a therapeutic INR does not confer protection from clot formation and expansion during the first few days of warfarin therapy because of the delay in the therapeutic inhibition of prothrombin (Horton & Bushwick 1999). Table 15.3 Coumadin Anticoagulation as Prophylaxis for Venous Thromboembolism
Author Year; Country Score Research Design Total sample size Methods Population: Gender: m=8; age: 22-56 yrs; SCI; time since injury:10-38days; traumatic injury Treatment: Anticoagulation therapy Outcome Measures: Complete blood picture, coagulation profile Outcome No statistically significant results reported. 1. One patient developed thromboembolism 9 days after the disontiuation of prophylactic therpay; 2. Drug interaction was observed in 2 patients in whom marked potentiation of coumadin action occurred during simultaneous Co-trimoxazole therapy; 3. Thromboembolism occurred in 3 patients; due to inadequate dose, early discontinuation of coumadin theapy 4. Five patients had a total of seven episodes of minor bleeding

Perkash 1980; USA Downs & Black score=13 Case Series N=8

Discussion Coumadin is not tradionally used as a prophylactic treatment for venous thromboembolism and so it is not surprising that there is a dearth of studies. In the one study found, Perkash (1980) studied 8 male SCI patients who were treated with anticoagulation therapy. One patient developed thromboembolism 9 days after the discontinuation of prophylactic therapy, 2 patients developed drug interactions with Septra, while 3 patients developed thromoboembolism two occurred after early discontinuation of coumadin therapy and one as a consequence of

inadequate dosing while 5 patients suffered 7 episodes of minor bleeding. This one poor quality study with n=8 patients is really not sufficient to draw conclusions on coumadin alone as a prophylactic treatment. Although there is a strong logical basis for using coumadin, prophylactically focused research is lacking. Conclusion The data on Coumadin as a prophylactic treatment for venous thromboembolism postSCI is insufficient to come to any conclusions except that there were an exceptional numbers of minor bleeding episodes. There is insufficient evidence for Coumadin as a prophylactic treatment for venous thrombosis post-SCI.

15.4.1.2 Unfractionated Heparin as Prophylaxis for Venous Thromboembolism Post-SCI Heparin acts as an anticoagulant by forming a complex with antithrombin, catalysing the inhibition of several activated blood coagulation factors: XIIa, XIa, IXa, Xa and thrombin. Heparins onset of action is immediate. It is most often used in acute conditions, and must be given parenterally. Although low molecular weight heparin has become more popular in the treatment of DVT, the effects of intravenous heparin can be reversed rapidly. Bleeding is the most common adverse effect of heparin. Osteoporosis is associated with the prolonged use of high doses of heparin, although its occurrence is infrequent. Thrombocytopenia is an uncommon but serious side-effect of the treatment (Pineo 2004). Table 5.4 Efficacy of Unfractionated Heparin vs. Placebo as Prophylaxis
Author Year; Country Score Research Design Total sample size Merli et al. 1988; USA PEDro=4 RCT Initial N=53; Final N=48 Methods Population: SCI Treatment: administration of low-dose heparin combined electric stimulation Outcome Measures: incidence of Deep Vein thrombosis 1. 2. 3. Outcome Electric stimulation plus heparin significantly lowered (p<0.05) the incidence of DVT. No differences were noted between the heparin and placebo group. Pooled data (heparin and placebo group) and comparing it to the heparin plus electric stimulation group, level of significance was much greater (p<0.008). Venous thrombosis was unexpectedly uncommon in both the control (1/17) and the heparinised (1/15) group.

Frisbie & Sasahara 1981; USA Downs & Black score=10 Prospective Controlled Trial N=32

Population: mean age=2711 years (treatment) and 2812 years (control); cervical-lumbar; 24 tetraplegics and 8 paraplegics (determined from level of lesion); Treatment: Patients in the heparin group were treated with 5000 units aqueous sodium heparin subcutaneously every 12h until the 60th day post injury occurred Outcome Measures: incidence of deep venous thrombosis

1.

Table 5.5 Fixed vs. Adjusted Dose Heparin in Prophylaxis of Thromboembolism in Spinal Cord Injury
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=63, f=12 age 1381 years; SCI; all complete Treatment: Patients were randomized to one of 2 regimens of heparin treatment: fixed dose or adjusted dose heparin. Outcome Measures: incidence of deep vein thrombosis and bleeding 1. Outcome Patients on the adjusted-dose regimen received a mean of 132002200U of heparin per dose and had a APTT 1 and 1/2 times higher than those on a fixed-dose regimen. Thromboembolism was detected in 9/29 patients randomized to the fixeddose regimen and 2/29 on the adjusted-dose regimen. While no patient who received the adjusted-dose and whose APTT reached the target level had a thrombosis, bleeding occurred in 7 patients. No patient on the fixed-dose regimen bled.

Green et al. 1988; USA PEDro=7 RCT Initial N=75; Final N=58

2.

3.

Discussion Unfractionated heparin (UFH) has for a long time has been the standard treatment for venous thromboembolism post-SCI. Merli et al. (1988) evaluated 53 acute SCI patients who were randomly assigned to placebo saline (n=17), 5000 IU heparin (n=16) and heparin plus electrical stimulation of the tibialis anterior and gastrocnemius muscles (n=15) over 28 days. There was no difference between the placebo saline and heparin groups in the incidence of DVT while there was a significant improvement in the heparin and electrical stimulation group. The study was prematurely discontinued because of the benefit of the heparin plus electrical stimulation group and lack of efficacy in the control group. Frisbie and Sasahara (1981) in a controlled, nonrandomized trial of 32 SCI patients saw half the patients receive no treatment and the other group receive 5,000 units s/c q12h until day 60 post-SCI onset. Venous thrombosis was unexpectedly uncommon in both the control (1/17) and the heparinized group (1/15). Green et al. (1988) studied 75 SCI patients who were randomized to receive either fixed dose or adjusted dose heparin. The fixed dose heparin was 5,000 units s/c q12h while the second group started off at 5,000 units s/c q12h which was adjusted according to the aPTT (activated Partial Thromboplastin Time) to a maximum of 15,000 units s/c q12h. Patients on the adjusted-dose regimen received a mean of 13,200 units s/c q12h. Thromboembolism was detected in 9/29 on fixed dose regimen with no bleeding complications while 2/29 on the adjusted-dose regimen developed thromboembolism and 7 had bleeding complications. Typically prophylactic treatment involves 5,000 units s/c of heparin. One RCT and one controlled study examining the efficacy of this dose and a placebo found no difference in the incidence of venous thrombosis in both the treatment and the placebo groups. Interestingly, Merli et al. (1988) found that heparin plus electrical muscle stimulation significantly reduced the incidence of venous thrombosis when compared to heparin alone. Green et al. (1988) compared 5,000 units s/c of heparin q12h with an adjusted dose of heparin according to the APTT (mean dose of 13,000 units s/c q12h) and the adjusted dose significantly reduced the incidence of venous thrombosis. Hence, although it appears that 5,000 units s/c of heparin q12h was not an effective dose in reducing the incidence of thromboembolism, higher doses were more effective but had a higher risk of bleeding complications. Further research is needed before a definitive statement can be made.

Conclusion There is level 2 evidence (based on one low quality RCT and one non-randomized controlled trial) that 5,000 units s/c of unfractionated heparin is no more effective than placebo in the prophylaxis of venous thrombosis post-SCI. There is level 1 evidence (based on one RCT) that adjusted (higher) dose s/c heparin is more effective in prophylaxis of venous thromboembolism than 5,000 s/c heparin q12h and has a higher incidence of bleeding complications. 5,000 units s/c q12h of unfractionated heparin does not appear to prevent venous thrombosis post-SCI while higher doses adjusted according to serum measures of anticoagulation is more effective. 15.4.1.3 Low Molecular Weight Heparin (LMWH) as Prophylaxis Low-molecular-weight heparin (LMWH) is derived from standard heparin through either chemical or enzymatic depolymerization. Whereas standard heparin has a molecular weight of 5,000 to 30,000 daltons, LMWH ranges from 1,000 to 10,000 Daltons. LMWH binds less strongly to protein, has enhanced bioavailability, interacts less with platelets and yields a very predictable dose response. The clinical advantages of LMWH include predictability, dosedependent plasma levels, a long half-life and less bleeding for a given antithrombotic effect. Thrombocytopenia is not associated with short-term use of low-molecular-weight heparin. LMWH is administered once or twice daily, both during the high-risk period when prophylaxis for DVT is recommended and also while waiting for oral anticoagulation to take effect in the treatment of DVT. The activated partial thromboplastin time (aPTT) does not need to be monitored, and the dosage does not need to be adjusted (Rydberg et al. 1999). Table 5.6 Generic and Trade-names of Low Molecular Weight Heparin
Generic Name Dalteparin Danaparoid Enoxaparin Ardeparin Parnaparin, Reviparin Tinzaparin Certoporain Trade-name Fragmin Orgaran Lovenox Normiflo Clivarine Logiparin, Innohep Alphaparin, Sandoparin

15.4.1.4 Heparin Analogues Danaparoid sodium (Orgaran) is an alternative anticoagulant for patients who develop heparininduced thrombocytopenia from heparin therapy. Danaparoid is a low molecular weight heparinoid. Its active components consist of heparan sulfate, dermatan sulfate and chondroitin sulfate. The major difference between danaparoid and other low molecular weight heparins (LMWH) is that danaparoid is devoid of heparin or heparin fragments. However, it exerts effects similarly to other LMWHs. Danaparoid acts by inactivating thrombin.

15.4.1.5 LMWH vs. UFH as Prophylaxis for Venous Thromboembolism The most commonly studied LMWH is th prophylaxis of venous thromboembolism post-SCI is enoxaparin. Enoxaparin was the first LMWH in the United States. Enoxaparin has a plasma half-life of 4.4 hours compared with 0.35 hours for UFH and its subcutaneous bioavailability is 50%, compared to 20% for UFH (Tomaio et al. 1998) Table 5.7 Low Molecular Weight Heparin vs. Unfractionated Heparin as Prophylaxis
Author Year; Country Score Research Design Total Sample Size Spinal Cord Injury Thromboprophylaxis Investigators 2003; USA PEDro=9 RCT Initial N=476; Final N=107 Methods Population: Gender: m=389, f=87; SCI; ASIA: A-D, Acute; Traumatic SCI Treatment: Enrolled patients were assigned to receive thromboprophylaxis with either the combination of low-dose unfractionated heparin (UFH) (5000 U subcutaneously every 8 h) plus intermittent pneumatic compression (IPC) (to be used at least 22h/day) or enoxaparin (30 mg subcutaneously every 12 h). Outcome Measures: Deep vein thrombosis, pulmonary embolism, major bleeding. Population: Gender: f=7, m=34; Age: mean 28 yrs complete, SCI Treatment: Patients were assigned to receive either UFH LMWH (5000uts/8hrs or 3500 anti-Xa uts/daily). Outcome Measures: documentation of thromboembolism Population: Retrospective review of 173:Group1: age: 10->60: SCI; Acute; Traumatic; complete/incomplete Intervention: 101 received a combination of heparin followed by warfarin and mechanical treatments for thromboprophylaxis. 72 received enoxaparin as a thromboprophylactic agent, started on the day of admission. Outcome Measure: Documentation of DVT, PE, Complication and duration of anticoagulation, results of Doppler studies, V/Q scans and unexplained decrease in haemoglobin and platelet levels 1. Outcome Among 107 assessable patients, the incidence of venous thromboembolism was 63.3% with UFH-IPC versus 65.5% with enoxaparin (p=0.81). The incidence of pulmonary embolism was 18.4% with UFH-IPC versus 5.2% with enoxaparin (p=0.03). Among all randomized patients, the incidence of major bleeding was 5.3% with UFH-IPC versus 2.6% with enoxaparin (p=0.14).

2. 3.

1.

Green et al. 1990; USA PEDro=8 RCT Initial N=41; Final N=32

Thumbikat et al. 2002; UK Downs & Black score=18 Case Series N=173

Spinal Cord Injury Thromboprophylaxis Investigators 2001; USA Downs & Black score=17 Pre-post Initial N=119; Final N=117

Population: mean age ~ 34.0, SCI; ASIA:A-C; traumatic; duration of rehabilitation:~36days, Acute Treatment: Administration of low-dose (UFH n=60) UFH and enoxaparin (n=59) in a 6-wk rehab phase: UFH 5,000 U every 8 hours, but IPC was discontinued; Enoxaparin 40mg once daily Outcome Measures: thromboprophylactic efficacy and safety

The cumulative event rate was 34.7% (95% CI, 13.7%-55.2%). None of the patients treated with low-molecularweight heparin had thrombosis or bleeding (95% CI, 0%-14%). 2. The difference between the 2 groups was significant (p=0.006, log-rank test) No statistical results reported. 1. 4 patients in UFH and 13 patients in LMWH developed venous thromboembolic episodes. 2. 3 of 13 on enoxaparin 40mg OD and 10 of 59 on 20 mg OD. 3. UFH group, one of the thrombotic events occurred post-mobilization. 4. Six of the 13 thrombotic events in LMWH occurred after the patients had been mobilized and anticoagulation stopped. 5. 2 periods of peak incidence of venous thromboembolism were noticed in both groups - the first at 20-30 days following injury and the second at 90100 days post-injury. 1. New VTE was demonstrated in 13 of 60 UFH versus 5 of 59 enoxaparin patients (21.7% vs. 8.5%; p = 0.052). 2. Enoxaparin appeared more effective than heparin in the prevention of thromboembolic complications during rehabilitation after spinal cord injury. 3. Both interventions were safe in this population.

Author Year; Country Score Research Design Total Sample Size

Methods Population: Age: ~mean 25yrs SCI; Traumatic injuries; Acute; Frankel scores: A or B Treatment: prophylaxis on SCI patients with deep vein thrombosis or pulmonary embolism were put on antithrombotic prophylaxis for 42 days after injury. Outcome Measures: demographic characteristics; venous thromboembolism risk factors; methods of surveillance and prophylaxis, and thromboembolic events within the first 6 weeks following injury 1.

Outcome Multivariate analysis suggested that sequential pneumatic compression devices (SCD) or gradient elastic stockings (GES) were associated with a reduced risk of venous thromboembolism. Multivariate analysis also suggested an decreased risk of thromboembolism in patients with SCI treated with heparin within the first 14 days or anytime within 42 days. Although the estimated risk reduction for heparin was about twice that for SCD/GES, it was not statistically significant. The differences in bleeding between the two forms of heparin are significant (p=0.04) favoring LMWH, and that there is a trend toward fewer thrombotic events with LMWH (p=0.15).

Winemiller et al. 1999; USA Downs & Black score=13 Case Series N=285

2.

3.

Green et al. 1994; USA Downs & Black score=13 Pre-post N=48

Population: n=48 Gender: m=39, f=9 age range=14-83 years; SCI; Acute Treatment: LMWH in a dose of 3500antiXa U given subcutaneously once daily- all subjects received this medication at this dose for 8 wks, then if the venous colour flow ultrasonography was negative meds were discontinued. Outcome Measures: incidence of deep vein thrombosis, pulmonary embolism, and bleeding

1.

Discussion Low Molecular Weight Heparin (LMWH) is the newest treatment for prophylaxis of venous thromboembolism and has already been described in the introduction. Because UFH for years has been the standard treatment and LMWH appears to offer advantages over UFH it is not surprising that there are a number of trials comparing the 2 treatments. There have been three trials, which have compared UFH and LMWH. The SCI Thromboprophylaxis Investigators (2001) conducted a controlled non-randomized trial of low dose UFH (5,000 units s/c q8h) and enoxaparin (40 mg once daily) during a 6-week rehabilitation phase. A new venous thromboembolism was detected in 21.7% of UFH and 8.5% of enoxaprin patients (p = 0.052). Enoxaprin appeared to be more effective in this population than UFH. One trial compared UHF plus intermittent pneumatic compression to LMWH. SCI Thromboprophylaxis Investigators (2003) conducted a RCT of 476 SCI patients who were assigned to receive thromboprophylaxis with either a combination of low-dose UFH (5000 units s/c q8h) plus intermittent pneumatic compression (IPC) to be used at least 22 hours each day or enoxaparin 30 mg s/c q12h. Among 107 assessable patients, the incidence of venous thromboembolism was 63.3% with UFH/IPC versus 65.5% with enoxaparin (p=0.81). The incidence of PE was 18.4% in the UFH/IPC group versus 5.2% with enoxaparin (p=0.03). Among all the randomized patients, the incidence of major bleeding was 5.3% in the UFH/IPC versus 2.6% with enoxaparin (p=0.14). This is the only study where the incidence of venous thromoboemolism was not significantly less with LMWH when compared to UFH. However, there was a significant difference in favour of UFH/IPC for incidence of PEs which is

undoubtedly a result of the added benefit of pneumatic compression given with UFH only in this study Thumbikat et al. (2002) in a retrospective study compared one group of SCI patients (n=101) who received a combination of heparin followed by warfarin and another group (n=72) who received enoxaparin. Four patients in the UFH group and 13 patients in the LMWH group developed venous thromboembolic episodes. Of the 72 patients on enoxaparin, 2/13 on 40 mg daily (OD) and 10/59 on 20 daily developed DVT/PE. One patient in group 1 and 6 patients in group 2 developed DVT post-mobilization with discontinuation of anticoagulation. Green et al. 1990 in an RCT randomized 41 SCI subjects to either standard heparin or LMWH. Five patients in the standard heparin group had thrombotic events including 2 patients with fatal pulmonary embolism. Two other patients had bleeding severe enough to necessitate withdrawal of the heparin. The cumulative event rate was 34% while the LMWH group had no thrombotic events or bleeding. The difference between the 2 groups was significant (p=0.006). Green et al. 1994 studied 60 acute SCI patients with complete motor paraplegia all of who received low molecular weight heparin in a dose of 3500 units s/c daily. Forty-eight were able to complete the study. Treatment began within 72 hours of injury and continued for 8 weeks. Forty patients completed the 8 weeks of prophylaxis uneventfully while 8 suffered a thrombotic event. Of the thrombotic events, 2 were pulmonary emboli, 4 were proximal DVTs while 2 were distal calf DVTs. The differences in bleeding between standard heparin, when combining data from a previous study (68 LMWH (20 from previous study) and 79 UFH), were significant (p=0.04) favoring LMWH with a trend toward fewer thrombotic events with the LMWH (P=0.15). There is strong evidence based on the results for these RCTs that LMWH in particular enoxaparin is more effective than standard UFH. This strong evidence in favour of LMWH outweighs the conflicting conclusions of a large, nonrandomized study by Thumbikat et al. 2002. Table 5.8 Studies Evaluating Low Molecular Weight Heparin or Unfractionated Heparin
Author/Year SCI Thromboprophylaxis Investigators / 2001 SCI Thromboprophylaxis Investigators / 2003 Thumbakit et al. / 2002 Green et al. / 1990 Green et al. / 1994 N & Type of Study 119 nonrandomized 107 RCT 172 nonrandomized 41 RCT 147 nonrandomized Treatments UFH vs. Enoxaparin UFH plus intermittent pneumatic compression vs enoxaparin UFH followed by warfarin vs enoxaparin UFH vs LMWH UFH vs LMWH Results Enoxaparin more effective Enoxaparin more effective for PE only with less complications UFH and warfarin more effective LMWH more effective with less complcations Trend to LMWH more effective. Significantly less bleeding complications

- Indicates a reduction in the incidence of DVT compared to placebo/alternative treatment + Indicates no difference in the incidence of DVT compared to placebo/alternative treatment

Conclusion There is level 1 evidence (based on 2 RCTs) that low molecular weight heparin, in particular enoxaparin, is more effective in reducing venous thromboembolic events, when compared to the standard s/c heparin prophylaxis. Moreover, the incidence of bleeding complications was less in the LMWH group.

Low molecular weight heparin more effectively reduces the risk of venous thromboembolism post-SCI than standard or unfractionated heparin prophylaxis with less bleeding complications. 15.4.1.6 LMWH as a Prophylaxis of Venous Thrombosis Three studies were found which examined LMWH alone, compared different dosages of LMWH or compared different LMWHs. Table 5.9 LMW Heparin Alone in Prophylaxis of Venous Thromboembolism Post-SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Age ~36yrs, SCI; complete/incomplete; length of injury: <6wks Treatment: Enrolled patients were randomized into two treatment groups. One group received 30 mg of enoxaparin subcutaneously every 12 hr and the other received 5000 IU of dalteparin subcutaneously once daily. Outcome Measures: Daily Logbook, Short Form Health Status Survey, follow-up questionnaire Population: Retrospective review SCI, Acute Treatment: administration of subcutaneous Enoxaparin (40mg once daily or 30mg twice daily) Outcome Measures: safety and efficacy of enoxaparin, cost analysis Hebbeler et al. 2004; USA Downs & Black score=15 Case Control N=129 Outcome No statistically significant results reported 1. 6% of the patients developed DVT while receiving enoxaparin and 4% 2 while receiving dalteparin (X =.44, p=.51). 2. 4% developed bleeding while receiving dalteparin and 2% while receiving enoxaparin (X2=.13, p=.72). 3. There were no DVTs or hemorrhages reported after discharge to home. 4. There was 99% compliance (X2=.88, p=.5) with taking medication while in hosp. 1. Equivalent prophylaxis efficacy was seen in both enoxaparin groups. 2. Symptomatic venous thromboembolism did not differ, with deep vein thromboses occurring in 1 of 49 (2.0%) patients receiving twicedaily enoxaparin, and 1 of 80 (1.25%) patients receiving once-daily enoxaparin (X2 = 0.125, NS). 3. Pulmonary embolism was seen in 1 of 49 (2.0%) patients treated with twicedaily enoxaparin and in none of the 2 patients in the once-daily group (X = 1.64, NS). 4. Bleeding complications also did not differ between the 2 treatment groups; these were observed in 2 of 49 (4.1%) patients receiving twice-daily enoxaparin and in 5 of 80 (6.3%) patients receiving once-daily enoxaparin (X2 = 0.228, NS). No statistical results reported 1. No patient developed clinical evidence of thromboembolism, and none of the 60 venous ultrasound examinations showed a deep vein thrombus.

Chiou-Tan et al. 2003; USA PEDro=6 RCT N=95

Harris et al. 1996; USA Downs & Black score=7 Case Series Initial N=105; Final N=101

Population: age 15-84 years; complete/incomplete; SCI; length of injury=6-104 days Treatment: All patients received 30 mg of enoxaparin subcutaneously every 12 h beginning at the time of admission. Outcome Measures: Not specified.

Discussion From the previous discussion it is clear that LMWH is superior to UFH both in venous thromboembolism phrophylaxis and in reducing the risk of bleeding complications. In line with this Harris et al. 1996 studied 105 subjects of whom 66 had SCI in an observational retrospective study. All patients received 30 mg of enoxaparin s/c q12h beginning at the time of admission. If a patient was scheduled for surgery, the drug was withheld for the morning of the operation, resumed 24 hours later, and continued until the patients discharge. No patient developed clinical evidence of venous thromboembolism and none of the 60 venous ultrasound examinations showed a DVT. The optimal dose of enoxaparin has not been established to date. Hebbeler et al. 2004 reported on a nonrandomized trial of 129 acute SCI patients who received either enoxaparin 40 mg daily vs. 30 mg twice daily prophylactically. Symptomatic thromboembolism did not differ between the two groups with DVT occurring in only one patient in each group. There was no difference in bleeding complications between the 2 groups. There are many new LMWHs available and it is inevitable that there will be studies comparing their efficacy. Chiou-Tan et al. 2001 randomized 95 acute SCI patients into one group who received enoxaparin (30 mg s/c q12h) and another who received 5000 IU of dalteparin s/c daily. There were no significant groups between the two groups in terms of DVTs or bleeding complications. Enoxaparin was more expensive than the dalteparin. Conclusion There was level 4 (limited) evidence that 40 mg Enoxaparin is no more effective than 30 mg of Enoxaparin in reducing the incidence of deep venous thrombosis or bleeding complications when used prophylactically. There is level 1 evidence (based on one RCT) that Enoxaparin is no more effective than Dalteparin in reducing the risk of deep venous thrombosis or bleeding complications although Enoxaparin is more expensive. There appears to be no difference between Enoxaparin and Dalteparin in reducing the risk of venous thrombosis post-SCI.

15.5. Prevention of DVT through Mechanical Methods Although pharmacological measures have been generally the preferred treatment for venous thromboembolism prophylaxis post-SCI, mechanical means of limiting venous stasis can also serve to reduce the incidence of DVT post-SCI. Mechanical treatments are designed to limit stasis in the paralyzed lower extremities. However, it should be noted that use of these devices should be accompanied by the twice daily inspection for skin discolourations or breakdown, or broken blood vessels. As well, pneumatic compression devices are not suitable for patients with severe arterial insufficiency.

Table 5.10 Evaluating the Physical Methods for the Prevention of DVT

Author Year; Country Score Level Total Sample Size

Methods

Results

Spinal Cord Injury Thromboprophylaxis Investigators 2003; USA PEDro=9 Level 1 RCT Initial N=476; Final N=107

Becker et al. 1987; USA PEDro=6 RCT N=15

Population: Gender: m=389, f=87; SCI; ASIA: A-D, Acute; Traumatic SCI Treatment: Enrolled patients were assigned to receive thromboprophylaxis with either the combination of low-dose unfractionated heparin (UFH) (5000 U subcutaneously every 8 h) plus intermittent pneumatic compression (IPC) (to be used at least 22h/day) or enoxaparin (30 mg subcutaneously every 12 h). Outcome Measures: Deep vein thrombosis, pulmonary embolism, major bleeding Population: Age range 17 to 75 Gender: m=11, f=3, SCI complete/incomplete, Acute Treatment: rotating treatment tables Outcome Measures: impedance blood plethysmography Population: Age: ~mean 25yrs SCI; Traumatic injuries; Acute; Frankel scores: A or B Treatment: prophylaxis on SCI patients with deep vein thrombosis or pulmonary embolism were put on antithrombotic prophylaxis for 42 days after injury. Outcome Measures: demographic characteristics; venous thromboembolism risk factors; methods of surveillance and prophylaxis, and thromboembolic events within the first 6 weeks following injury

1.

2. 3.

Among 107 assessable patients, the incidence of venous thromboembolism was 63.3% with UFH-IPC versus 65.5% with enoxaparin (p=0.81). The incidence of pulmonary embolism was 18.4% with UFH-IPC versus 5.2% with enoxaparin (p=0.03). Among all randomized patients, the incidence of major bleeding was 5.3% with UFH-IPC versus 2.6% with enoxaparin (p=0.14). 4/5 control patients developed positive fibrinogen leg scans. All had also become positive by impedance plethysmography. Four of the treatment patients developed fibrinogen but not impedance plethysmography. This difference was significant with p=0.017. Multivariate analysis suggested that sequential pneumatic compression devices (SCD) or gradient elastic stockings (GES) were associated with a reduced risk of venous thromboembolism. Multivariate analysis also suggested an decreased risk of thromboembolism in patients with SCI treated with heparin within the first 14 days or anytime within 42 days. Although the estimated risk reduction for heparin was about twice that for SCD/GES, it was not statistically significant.

1. 2.

1.

Winemiller et al. 1999; USA Downs & Black score=13 Case Series N=285

2.

3.

Discussion WineMiller et al. (1999) did chart audits to conduct a case-control study of 285 SCI patients. Multivariate analysis suggested that sequential pneumatic compression devices (SCD) or gradient elastic stockings (GES) were associated with a reduced risk of venous thromboembolism. Multivariate analysis also suggested a decreased risk of venous thromboembolism in patients with SCI treated with heparin within the first 14 days or anytime within 42 days. Although the risk reduction was approximately twice that at of SCD/GES it was not statistically significant. Becker et al. (1987) studied whether rotating treatment tables would prevent the development and progression of DVT in acute SCI patients. The authors noted that rotating treatment tables had been used up to that time in acute SCI patients to maintain spinal cord alignment while facilitating nursing care, allowing even distribution of ventilation and preventing pressure sores. It was hypothesized that because these appliances rotated continuously, they might serve to inhibit thrombosis formation by reducing venous stasis. This randomized trial involved 15 patients with acute SCIs. Four of the 5 control (nonrotated) patients developed distal and

proximal thrombi, assessed by 125I fibrinogen scanning and impedance plethysmography while only one of the 10 treated (rotated) SCI patients developed both distal and proximal venous thrombi (p=0.007). Conclusion There was level 4 (limited) evidence that sequential pneumatic compression devices (SCD) or gradient elastic stockings (GES) were associated with a reduced risk of venous thromboembolism post-SCI. There is level 1 evidence (based on one small RCT) that rotating treatment tables reduce the incidence of venous thrombi in acute spinal cord injured patients. Mechanical compression may reduce the incidence of venous thromboembolism post-SCI. The use of rotating treatment tables reduces the incidence of venous thrombo-embolis post-SCI.

Table 5.11 Combined Pharmacological and Physical Measures for the Prophylaxis of Venous Thromboembolism Post-SCI
Author, Year; Country Score Research Design Total Sample Size Methods Population: Gender: f=4 m=24, all complete; SCI Treatment: Subjects were randomized to one of two regimens: external pneumatic calf compression (EPCC) alone (n=15), and EPCC combined with aspirin (ASA), 300 mg bid, and dipyridamole (Dip) 75 mg bid (n=13). Outcome Measures: Incidence of deep vein thrombosis; platelet aggregation ratios (PAR); Factor VIII coagulant activity 1. Outcome Of the 27 patients that completed the study, DVT was detected in 9/27 patients, an incidence significantly less than the 78 % they previously recorded in 37 patients not receiving prophylaxis (p<0.001). Thrombi developed in 6/15 patients treated solely with EPCC, and in 3/12 receiving ASA/Dip as well as EPCC (p<0.1). No differences were observed in the PAR of patients treated with EPCC alone or EPCC combined with ASA and Dip. Factor VIII levels of patients treated with EPCC alone as compared to those also receiving ASA and Dip revealed that the latter in general had lower levels. Of the 19 patients, 17 had negative fibrinogen scanning upon completion of the study. The 2 remaining patients developed a positive fibrinogen scan on days 6 and 8 of the study. In comparison, the control group developed positive 125 I fibrinogen scans in 6/17 patents and all were confirmed by venography. The incidence of thrombosis was significantly different than that of the

2.

Green et al. 1982; USA PEDro=7 RCT Initial N=28; Final N=27

3.

4.

Merli et al. 1992; USA Downs & Black score= 12 Case Series Initial N=38; Final N=36

Population: Gender: m=25, f=11 SCI; complete/incomplete Frankel: A&B; Acute Treatment: Patients received prophylaxis with external pneumatic compression plus gradient elastic stockings and low dose heparin for 2 weeks. Outcome Measures: incidence of deep vein thrombosis; Marder score

1. 2. 3.

4.

Author, Year; Country Score Research Design Total Sample Size

Methods

Outcome treated group (p=0.04). No statistical results reported. 1. DVT incidence in early admitted pts was 2%. The incidence of DVT in later admitted pts was 26%. 2. Of those 60% were detected on admission, while the remaining 40% developed in a period not exceeding 6 wks of hospitalization. 65% of detected DVT did not show any evident clinical sign. 3. ASIA A were more likely to develop DVT (36%) while in ASIA D on admission only 7% did so.

Aito et al. 2002; Italy Downs & Black score=12 Case Series N=275

Population: Age ~ 42 years; length of injury: within 72 hrs of being injured (n=99) or post 8 days (n=176); ASIA: A-D; SCI; SCI; Acute injury Treatment: Permanently dressed gradient elastic stockings (PGES). Subcutaneous low molecular weight heparin (LMWH) (nadroparin) .4 ml once a day. External sequential pneumatic compression (ESPC) Outcome Measure: diagnosis of DVT

Discussion Merli et al. (1992) studied 37 SCI patients who received 2 weeks of prophylaxis with external pneumatic compression plus gradient elastic stockings and low dose heparin 5,000 s/c q12h. Of 19 patients treated, 17 had negative fibrinogen scanning upon completion of the study while the 2 remaining patients developed a positive fibrinogen scan on days 6 and 8 of the study. In comparison, the control group developed positive I125 fibrinogen scans in 6/17 patients and all were confirmed by venography. The incidence of thrombosis was significantly different than that of the treated group (p=0.04). Aito et al. (2002) studied 275 SCI patients, 99 of whom were treated within 72 hours of injury while 176 were treated after 8 days post-SCI. The treatment involved permanently dressed gradient elastic stockings, s/c LMWH 0.4 ml once a day, and external sequential pneumatic compression (ESPC) of the lower limbs 3 hrs per day given in 2 applications. There was early mobilization of the lower limbs. The complete prophylactic treatment lasted at least 30 days post-SCI; LMWH and ESPC were continued for 2 more months depending on the patients progress. For the earlier treated group, DVT incidence was 2% while the incidence in the later treated group was 26%. Of those 60% were detected at the time of later admission, while the remaining 40% developed in a period not exceeding 6 weeks of hospitalization. Sixty-five percent of detected DVT did not show any obvious clinical sign. ASIA A patients were more likely to develop a DVT (36%) while only 7% of ASIA D patients did so on admission. Green et al. (1982) randomized 28 SCI patients with complete injuries, were randomized to either external pneumatic calf compression (EPCC) alone, and EPCC combined with aspirin (ASA) 300 mg bid and dipyridamole 75 mg bid. Twenty-seven subjects completed the study DVT was detected in 9/27 patients, an incidence significantly less than the 78% previously recorded in the 37 patients not receiving prophylaxis (p<0.001). Thrombi developed in 6/15 patients treated solely with EPCC and in 3/12 receiving ASA/Dipyridamole as well as EPCC (p<0.1). The authors concluded that early application of pharmacological plus mechanical treatments markedly reduced the risk of DVT complications. Although there was no moderate to strong evidence that combined measures to provide effective DVT prophylaxis this was a consequence of the quality of the studies. However, it makes sense intuitively, given Virchrows trial that different measures designed to treat different

risk factors would have an additive effect and hence be more effective than individual treatments. Conclusion There is level 4 (limited) evidence that a comprehensive prophylactic treatment of external pneumatic compression, gradient pressure stockings and low dose heparin reduces venous thrombosis post-SCI. There is level 4 (limited) evidence that a comprehensive prophylactic regimen of pharmacological and physical measures is more effective in preventing venous thrombosis post-SCI when instituted early rather than later. There was a trend (supported by one RCT) that pneumatic compression plus antiplatelet agents (ASA and Dipyridamole) was more effective than pneumatic compression alone. Although an RCT, the numbers were small thus the trend was non-significant (p<0.1). A combined regiment of pneumatic compression, pressure stockings and low-dose heparin given prophylactically may reduce the incidence of venous thrombosis and the effect is better in early post-SCI. 15.6 Vena Cava Filtration Vena cava filtration involves inserting a mechanical filter in the inferior vena cava to prevent devastating pulmonary emboli from occurring. Table 5.13 Prophylactic Greenfield Filter Placement in Selected High-Risk Trauma Patients
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=151 f=48; Age ~ 37 yrs; Traumatic age; Acute injuries; SCI, Acute Treatment: prophylactic Greenfield filter (PGF) placement Outcome Measures: Injury Severity Score, Glasgow Coma Scale, fluoroscopy, B-mode ultrasonography, ventilation/perfusion scanning, pulmonary arteriography Outcome There were no statistical differences between the two groups. 1. None of the patients in the PGF group had a PE. 2. In the control group, 13 patients had a PE, nine of which were fatal. 3. These differences were statistically significant for both PE (p < 0.009) and PE-related death (p < 0.03). 4. The overall mortality rate was reduced in the PGF group (18 of 108, 16%) versus the control group (47 of 216, 22%); not statistically significant.

Khansarinia et al. 1995; USA Downs & Black score=20 Case Control Initial N=324; Final N=259

Table 5.14 Prophylactic Vena Cava Insertion in Patients with Traumatic SCI
Author Year; Country Score Research Design Total Sample Size Maxwell et al. 2002; USA Downs & Black score=19 Methods Population: Age: range 15-91;average hospital length of stay 23.520.5 days; 1. Outcome 111/8269 SCI pts with an incidence of DVT and PE of 9.0% and 1.8%,

Author Year; Country Score Research Design Total Sample Size Case Series N=111

Methods SCI; Traumatic, Acute Treatment: DVT prophylaxis with sequential compression devices and unfractionated heparin 5,000 unites subcutaneously every 12 giyrs (then to 30 mg subcutaneously every 12 hours Outcome Measures: Injury Severity Score, incidence of DVT and PE

Outcome respectively. 41.4% were paraplegics and 58.6% were tetraplegics, and 17.1% of patients had severe closed-head injury. 3. Hospital stay: 2320 days for SCI patients. 4. The incidence of DVT and PE in those patients with SCDs alone was 7.1% and 2.3%; for SCDs plus subcutaneous heparin, the incidence was 11.1% and 2.8%; and for SCDs plus low-molecular-weight heparin, the incidence was 7.4% and 0%, respectively 5. The incidence of DVT in SCI patients with long bone fractures was 37.5%, which was significantly greater than the total SCI population (p < 0.02). 1. No complications were associated with vena cava filter insertion. 2. No patients developed venous thrombosis during acute hospitalization (median 22 d), and no patients have developed PE after filter insertion. 3. A follow-up deep abdominal Duplex scan of the vena cava was performed, with a 30-day patency of 100% and 1year follow-up is felt to represent the trapping of thrombus. 1. Time from admission to prophylactic insertion of a vena cava filter was 4.33.9 days. 2. 3 cases of deep vein thrombosis occurred after discharge from hospital. 3. Overall there were 19 patients (30%) with prophylactic vena cava filters who had deep vein thrombosis develop. 4. When the incidence of pulmonary embolism was compared in the highrisk trauma population before and after instituting a policy of inserting a prophylactic vena cava filter, there was a significant (p<0.00072) reduction in the incidence of pulmonary embolism in the group receiving filters. No statistical findings reported 1. All patients with an indication for the Kim-Ray Greenfield filter were technically capable of having the device inserted. 2. There has been one death due to PE in a patient with a filter to date. 3. There have been no other instances of suspected or proved PE after insertion of a filter since the institution of requiring a preoperative IVCgram and 2.

Wilson et al. 1994; USA Downs & Black score=18 Case Control N=22

Population: Age:18-49 yrs; Injury Severity Score: 25-41, SCI, Traumatic, Acute Treatment: Prophylactic Vena Cava Filter Insertion Outcome Measures: Injury Severity Score, Impedance Plethysmography, Lower extremity Duplex Ultrasound

Rogers et al. 1995; USA Downs & Black score=13 Case Control Initial N=71; Final N=63

Population: Gender: m=73%, f=27%; Age:38.919.3yrs; Injury Severity Score 31.59.4; SCI; Traumatic Injury Treatment: The insertion of prophylactic vena cava filters Outcome Measures: incidence of pulmonary embolism

Jarrell et al. 1983; USA Downs & Black score=11 Case Series N=21

Population: SCI, Acute Treatment: The Kim-Ray Greenfield filter is inserted into the IVC below the renal veins to interrupt the IVC. The patient remains on full anti-coagulation throughout the performance of the procedure. A repeat IVCgram is performed if there is any doubt about the position of the filter or patency of the IVC. Outcome Measures: documentation of DVT or PE

Author Year; Country Score Research Design Total Sample Size

Methods

Outcome postoperative studies to prove proper location. Follow-up on the 23 remaining patients revealed 2 instances of thrombosis of the IVC.

4.

Discussion The data supporting the use of inferior vena cava (IVC) filters in the prophylaxis of PE post-SCI is far from compelling. Observational trials and case series are the primary evidence. Jarrell et al. (1983) studied 21 acute SCI patients in whom a Kim-Ray Greenfield filter was inserted in the inferior vena cava. One patient with a filter died of a PE. On follow-up no other PEs were noted while there were two instances of thrombosis of the inferior vena cava . Wilson et al. (1994) in a retrospective chart audit studied 22 acute traumatic SCI patients who were treated with a vena cava filter insertion. No complications were associated with vena cava filter insertion. No patients developed venous thrombosis during acute hospitalization (median 22 days) and no patients developed PE after filter insertion. Khansarinia et al. (1995) in an experimental non-RCT compared 108 patients who sustained multiple trauma with known high risk of PE (including SCI patients) and who received a prospectively placed prophylactic Greenfiled filter (PGF), to 216 historically matched control patients. None of the patients in the PGF group had a pulmonary embolism while 13 patients in the control group had a PE (p<0.009), 9 of which were fatal (p<0.03). The overall mortality rate was reduced in the PGF group (18 of 108, 16%) versus the control group (47 of 216, 22%) but this result was not deemed to be statistically significant. Rogers et al. (1995) in a chart audit, pre-post and comparison with historical controls studied 63 patients receiving prophylactic vena cava filter 15 of these patients had head injuries, 25 had SCIs and 23 had pelvic fractures. Of 3151 admissions to a trauma service, 71 were considered to be in a high-risk category for PE of whom 63 received a prophylactic vena cava filter. The mean time to insertion of the vena cava filter was 4.3 days post-admission. Overall, there were 19 patients (30%) with prophylactic vena cava filters who developed a DVT. When the incidence of pulmonary embolism in a high-risk patient population was compared before and after the prophylactic vena cava filter policy was instituted, there was a significant reduction (p<0.00072) in the incidence of PE in the group receiving the filters. Maxwell et al. (2002) in a retrospective chart audit studied 111 SCI patients to determine if they were different than other trauma patients in terms of the incidence of DVT and PE. They concluded that inferior vena cava filters were not necessarily needed for SCI patients as the incidence of DVTs and PEs were not that much different than other trauma patients. Maxwell et al. have noted, there are high risk of patients with SCI that probably deserve phrophylactic IVC filter placement. They include patients that have failed DVT prohylaxis or have contraindications to anticoagulation. SCI patients with long bone fractures also appear to be at extreme risk for DVT and may also benefit from IVC filter placement (p. 902).

Conclusion There is level 3 evidence that inferior vena cava filters significantly reduce the risk of pulmonary emboli in high-risk SCI patients. Inferior vena cava filters significantly reduce the risk of pulmonary emboli in high-risk SCI patients.

15.7 Treatment of Acute Venous Thromboembolism in SCI Virtually all of the research to date has focused on the prevention of venous thromboembolism but there has been focus on the treatment of newly diagnosed venous thromboembolism in SCI. The standard treatment is anticoagulation, generally with intravenous unfractionated heparin immediately followed by a gradual transition to Coumadin which is generally maintained for 3-6 months. We were able to find one small study which compared UFH to LMWH. Table 5.15 Unfractionated Heparin vs. LMW Heparin
Author Year; Country Score Research Design Total Sample Size Methods Population: n=6; age 33-60; SCI; ASIA: AD Treatment: 3 were give IV Heparin followed by warfarin, while 3 were treated with SQ Enoxaparin followed by warfarin Outcome Measures: Cost analysis Tomaio et al. 1998; USA Downs & Black score=11 Case Series N=6 1. Outcome The average cost of initial anticoagulation of Group 1 (IV Heparin) patients was $413.33 (range $331.20-$502.80), which includes the cost of heparin, IV pump and tubing, and laboratory monitoring of the PTT. The average cost in Group 2 (enoxaparin) patients was $362.27 (range $197.60-$617.50), which includes only the cost of medication. Enoxaparin is slightly less expensive (mean cost of enoxaparin = $362.27, IV heparin = $413.33) when peripheral cost are taken into account. Subcutaneous enoxaparin is a safe, cost-effective, and less labor-intensive treatment, and can be of substantial benefit in the treatment of DVT in SCI patients in the rehabilitation setting.

2.

3.

4.

Discussion Again, there are remarkably few studies examining treatment of venous thrombolembolism postSCI with most of the research focus to date on prophylaxis. Tomaio et al. (1988) studied 6 SCI patients with acute DVT, half of whom were treated by IV Heparin followed by Warfarin and half who were treated by s/c enoxaparin followed by Warfarin. Though the study was extremely small the author did a careful cost analysis. S/C enoxaparin was regarded as a safe, costeffective and less labour intensive treatment and could be of substantial benefit in the treatment of DVT in SCI patients. Obviously more research needs to be done.

Conclusion There is level 4 (limited) evidence that Enoxaparin subcutaneously appears to be a safe, cost-effective and less labour-intensive treatment than intravenous heparin for acute DVTs post-SCI. Enoxaparin subcutaneously can be considered as an alternative to intravenous Heparin for acute DVTs post-SCI although more research needs to be done.

15.8 Summary Venous thromboembolism following SCI is a source of significant morbidity and mortality. Virtually all of the research is focused on prophylaxis of venous thromboembolism in this very high-risk population. Guidelines based on best evidence for DVT prophylaxis in SCI include use of sequential compression devices for 2 weeks and anticoagulant for 8-12 weeks after injury (Maxwell et al. 2002). There is evidence in the literature the 5,000 units S/C of unfractionated heparin delivered every 12 hours is this population may not be sufficient to provide adequate protection. The good news is that low molecular weight heparin with enoxaparin, being the primary drug studied, appears to be more effective and should be considered the new standard of treatment, given the added benefit of lower risk of bleeding complications. Physical measures in particular gradient pressure stockings and intermittent pneumatic compression are designed to reduce the impact of stasis due to prolonged and immobilized lower extremities and have been shown to have a limited impact. There is an intuitive benefit to combining treatment (i.e. pharmacological with mechanical treatment) although the evidence suggests pharmacological measures are the more important of the two in prophylaxis. The data on Coumadin as a prophylactic treatment for venous thromboembolism postSCI is insufficient to come to any conclusions except that there were exceptional numbers of minor bleeding episodes. There is level 2 evidence (based on one low quality RCT and one non-randomized controlled trial) that 5,000 units s/c of unfractionated heparin is no more effective than placebo in the prophylaxis of venous thrombosis post-SCI. There is level 1 evidence (based on one RCT) that adjusted (higher) dose s/c heparin is more effective in prophylaxis of venous thromboembolism than 5,000 s/c heparin q12h and has a higher incidence of bleeding complications. There is level 1 evidence (based on 2 RCTs) that low molecular weight heparin, in particular enoxaparin, is more effective in reducing venous thromboembolic events, when compared to the standard s/c heparin prophylaxis. Moreover, the incidence of bleeding complications was less in the LMWH group. There was level 4 (limited) evidence that 40 mg Enoxaparin is no more effective than 30 mg of Enoxaparin in reducing the incidence of deep venous thrombosis or bleeding complications when used prophylactically.

There is level 1 evidence (based on one RCT) that Enoxaparin is no more effective than Dalteparin in reducing the risk of deep venous thrombosis or bleeding complications although Enoxaparin is more expensive. There was level 4 (limited) evidence that sequential pneumatic compression devices (SCD) or gradient elastic stockings (GES) were associated with a reduced risk of venous thromboembolism post-SCI. There is level 1 evidence (based on one small RCT) that rotating treatment tables reduce the incidence of venous thrombi in acute spinal cord injured patients. There is level 4 (limited) evidence that a comprehensive prophylactic treatment of external pneumatic compression, gradient pressure stockings and low dose heparin reduces venous thrombosis post-SCI. There is level 4 (limited) evidence that a comprehensive prophylactic regimen of pharmacological and physical measures is more effective in preventing venous thrombosis post-SCI when instituted early rather than later. There was a trend (supported by one RCT) that pneumatic compression plus antiplatelet agents (ASA and Dipyridamole) was more effective than pneumatic compression alone. Although an RCT, the numbers were small thus the trend was non-significant (p<0.1). There is level 3 evidence that inferior vena cava filters significantly reduce the risk of pulmonary emboli in high-risk SCI patients. There is limited evidence that Enoxaparin subcutaneously appears to be a safe, costeffective and less labour-intensive treatment than intravenous heparin for acute DVTs post-SCI.

References Aito S, Pieri A, DAndrea M, Marcelli F, and Cominelli E. Primary prevention of deep venous thrombosis and pulmonary embolism in acute spinal cord injured patients. Spinal Cord 2000; 40:300-303. Akman MN, Cetin N, Bayramoglu M, Isiklar I, and Kilinc S. Value of the D-dimer test in diagnosing deep vein thrombosis in rehabilitation inpatients. Archives of physical Medicine and Rehabilitation 2004; 85:1091-4. Arnold JMO, Teasell RW, MacLeod AP, Brown JE, Carruthers SG. Increased venous alphaadrenoceptor responsiveness in patients with reflex sympathetic dystrophy. Annals of Internal Medicine 1993; 118(8):619-621. Becker DM, Gonzalez M, Gentili A, Eismount F, Green B. Prevention of deep venous thrombosis in patients with acute spinal cord injuries: Use of rotating treatment tables. Neurosurgery 1987; 20(5): 675-677. Brach BB, Moser KM, Cedar L, Minteer M, Convery R. Venous thrombosis in acute spinal cord paralysis. J Trauma 1977; 17:289-292. Brandstater Me, Roth EJ and Siebens HC. Venous thromboembolism in stroke: literature review and implication for clinical practice. Archives of Physical Medicine and Rehabilitation 1992; 75(5-S):S379-91. Chiou-Tan FY, Garza H, Chan K-T, Parsons KC, Donovan WH, Roberston CS, Homles SA et al. Comparison of dalteparin and enoxaparin for deep venous thrombosis prophylaxis in patients with spinal cord injury. American Journal of Physical Medicine and Rehabilitation 2003: 82(9):678-685. Colachis SC III, Clinchot DM. The association between deep venous thrombosis and heterotopic ossification in patients with acute traumatic spinal cord injury. Paraplegia 1993; 31:507-512. Davidson BL and Deppert EJ. Ultrasound for the diagnosis of deep vein thrombosis: where to now. British Medical Journal 1998; 316(7124):2-3 Eide PK, Stubhaug A, Stenehjam AE. Central dysesthesia pain after traumatic spinal cord injury is dependent on N-Methyl-D Aspartate receptor activation. Neurosurgery 1995; 37(6):10801087. Frisbie JH and Sasahara AA. Low does heparin prophylxis for deep venous thrombosis in acute spinal cord injury patients: a controlled study. Paraplegic 1981; 19:343-346. Gill P and Nahum A. Improving detection of venous thromboembolism. New technology holds promise for early, precise diagnosis. Postgraduate Medicine 2000; 108(4):24-6. Green D, Rossi EC, Yao JS, Flinn WR, Spies SM. Deep vein thrombosis in spinal cord injury: effect of prophylaxis with calf compression, aspirin and dipyridamole. Paraplegia 1982; 20(4):227-34. Green D, Lee MY, Ito MY, Cohn T, Press J, Fibrandt PR, VandenBerg WC, Yarkony GM, Meyer PR. Fixed-vs adjusted-dose heparin in the prophylaxis of thromboembolism in the spinal cord injury. Journal of the American Medical Association 1988; 260(9):1255-1258. Green D, Lee MY, Lim AC, Chmiel JS, Vetter M, Pang T, Chen D, Fenton L, Yarkony GM, Meyer PR. Prevention of thromboembolism after spinal cord injury using low-molecularweight heparin. Annals of Internal Medicine 1990; 113:571-574. Green D, Chen D, Chmiel JS, et al. Prevention of thromboembolism in spinal cord injury: Role of low molecular weight heparin. Arch Phys Med Rehabil 1994; 75:290-292. Gunduz S, Ogur E, Mohur H, et al. Deep vein thrombosis in spinal cord injured patients. Paraplegia 1993; 31:606-610. Harris S, Chen D, Green D. Enoxaparin for thromboembolism prophylaxis in spinal injury: Preliminary report on experience with 105 patients. American Journal of Physical Medicine and Rehabilitation 1996; 75(5):326-327.

Hebbler sl, Marciniak CM, Crandall S, Chen D, Nussbaum S, Mendelewski S. Daily vs twice daily enoxaparin in the prevention of venous thromboembolic disorders during rehabilitation following acute spinal cored injury. The Journal of Spinal Cord Medicine 2004; 27(3):236240. Joffe SN. Incidence of postoperative deep vein thrombosis in neurosurgical patients. J Neurosurg 1975; 42:201-203. Kakkar VV, Howe CT, Flanc C and Clarke MB. Natural History of postoperative deep-vein thrombosis. Lancet 1969;2(7614):230-232. Kearon C, Ginsberg JS and Hirsh J. The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Annuals of Internal Medicine 1998; 129(12):1044-9. Khansarinia S, Dennis JW, Veldenz HC, Butcher JL, Hartland L. Prophylactic Greenfield filter placement in selected high-risk trauma patients. Journal fo Vacular Surgery 1995; 22(3):231236. Kulkarni JR, Burt AA, Tromans AT, Constable PDL. Prophylactic low dose heparin anticoagulant therapy in patients with spinal cord injuries: A retrospective study. Paraplegia 1992; 30:169-172. Lagerstedt CI, Olsson CG, Fagher BO, Oqvist BW, Albrechtsson U. Need for long-term anticoagulant treatemtn in symptomatic calf-vein thrombosis. Lancet 1985; 2(8454):515-8. Maxwell RA, Chavarria-Aguilar M, Cockerham WT, Lewis PL, Parker DE, Durham RM, et al. Rountine prophylactic vena cava filtration is not indicated after acute spinal cord injury. The Journal of Trauma 2002; 52(5):902-906. Merli G, Herbison G, Ditunno J, et al. Deep venous thrombosis: Prophylaxis in acute spinal cord injured patients. Arch Phys Med Rehabil 1988; 69:661-664. Merli GJ, Doyle L, Ditunno JF, Herbision GJ. Mechanical plus pharmacological prophylaxis for deep vein trhrombosis in acute spinal cord injury. Parpalegia 1992; 30:558-562. Merli GJ. Management of deep vein thrombosis in spinal cord injury. Chest 1992;102(6 Suppl):625S-657S. Merli GJ, Crabbe S, Paluzzi RG, et al. Etiology, incidence, and prevention of deep vein thrombosis in acute spinal cord injury. Arch Phys Med Rehabil 1993; 74:1119-1120. Myllynen P. Kammonen M, Rokkanen P, et al. Deep venous thrombosis and pulmonary embolism in patients with acute spinal cord injury: A comparison with nonparalyzed patients immobilized due to spinal fractures. J Trauma 1985; 25:541-543. Newman GE. Pulmonary angiography in pulmonary embolic disease. J Thorac Imaging 1989;4(4):28-39. Nicolaides AN, Kakkar VV, Field ES, and Renney JT. The origin of deep vein thrombosis: a venographic study. British Journal of Radiology 1971; 44(525): 653-63. Paralyzed Veterans of America/Consortium for Spinal Cord Medicine. Prevention of thromboembolism in spinal cord injury. Washington (DC): Paralyzed Veterans of America (PVA); 1999 Sep. 29 p. Perkash A. Experience with the management of deep vein thrombosis in patients with spinal cord injury. Paraplegia 1980;18:2-14. Philbrick JT and Becker DM. Calf deep venous thrombosis. A wolf in sheeps clothing? Archives of Internal Medicine 1988; 148(10): 2131-8. PIOPED Investiagtors. Tissue plasminogen activator for the treatment of acute pulmonary embolism. A collaborative study of the PIOPED investigators. Chest 1990; 97(3): 528-33. Powell M, Kirschblum S, OConnor KC. Duplex ultrasound screening for deep vein thrombosis in spinal cord injured patients at rehabilitation admission. Arch Phys Med Rehabil 1999; 80:1044-1046.

Raimondi P, Bongard O, De Moeloose P, Reber G, Valdvogel F, Bounameau H. D-dimer plasma concentration in various clinical conditions: Implications for the use of this test in the diagnostic approach of venous thromboembolism. Thromb Res. 1993; 69(1):125-30. Rogers FB, Shackford SR, Ricci MA, Wilson JT, Parson S. Routine prophylactic vena cava filter insertion in severely injured trauma patients decreases the incidence of pulmonary embolism. Journal of the American College of Surgeons 1995:180(6):641-647. Rossi EC, Green D, Rosen JS, Spies ST, Jao JST. Sequential changes in factor VII and platelets preceeding deep venous thrombosis in patients with spinal cord injury. Br J Haematol 1980; 45:143-151. Spinal Cord Injury Thromboprophylaxis Investigators. Prevention of venous thromboembolism in the acute treatment phase after spinal cord injury: A randomized, multicenter trial comparing low-dose heparin plus intermittent pneumatic compression with enoxaparin. The Journal of Trauma 2003; 54(6):11616-1126. Spinal Cord Injury Thromboprophylaxis Investigators. Prevention of Venous thromboeblolismin the rehabilitation phase after spinal cord injury: Prophylaxis with low-dose heparin or enoxaparin. The Journal of Trauma 2003; 54(6):1111-1115. Stein PD, Athanasoulis C, Alavi A, Greenspan RH, Hales CA, Saltzman HA, et al. Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation 1992;85(2):462-8. Stover SL et al. University of Alabama in Birmingham Spinal Cord Injury Data Management Service. Quarterly Report for the period March 1, 1983 through June 30, 1983, pp 21-22. Tapson VF, Carroll Ba, Davidson BL, Elliott CG, Fedullo PF, Hales CA et al. Am J Respir Crit Care Med 1999;160(3):1043-1066. Thumbikat P, Poonnoose PM, Balasubrahmaniam P, Ravichandran G and McClelland MR. A comparison of heparin/warfarin and enoxaparin thromboprophylaxis in the spinal cord injury: the Sheffield experience. Spinal Cord 2002; 40:416-420. Todd JW, Frisbie JH, Rossier AB, Adams DF, Als AV, Armenia RJ, Sasahara AA, Tow DE. Deep venous thrombosis in acute spinal cord injury: A comparison of 125I-fibrinogen leg scanning, impedance plethysmography, and venography. Paraplegia 1976; 14:50-57. Tomaio A, Kirshblum SC, OConnor KC. Johnston M. Treatment of acute deep vein thrombosis in spinal cord injured patients with enoxaparin: A cost analysis. The Journal of Spinal Cord Medicine 1998;21:205-210. Tribe CR. Causes of death in early and late stages of paraplegia. Paraplegia 1963; 1:19-47. Walsh JJ, Tribe LR. Phlebothrombosis and pulmonary embolism in paraplegia. Paraplegia 1965; 3:209-213. Watson N. Venous thrombosis and pulmonary embolism in spinal cord injury. Paraplegia 1968; 6:113-121.Wilson JT, Rogers FB, Wald SL, Shackford SR, Ricci MA. Prophylactic vena cava filter insertion in patients with traumatic spinal cord injury: Preliminary results. Neurosurgery 1994; 35(2):234-9. Winchelli RJ et al. Risk factors associated with pulmonary embolism despite routine prophylaxis: implications for improved protection. J Trauma 1996; 2:600-605. Winemiller MH, Stolp-Smith KA, Silverstein MD, Therneau TM. Prevention of venous thromboembolism in patients with spinal cord injury: effect of sequential pneumatic compression and heparin. J Spinal Cord Med 1999; 22:182-191. Yelnik A, Dizien O, Bussel B, et al. Systematic lower limb phlebography in acute spinal cord injury in 147 patients. Paraplegia 1991; 29:253-260.

CHAPTER SIXTEEN
Orthostatic Hypotension Following Spinal Cord Injury
Andrei Krassioukov, MD, PhD Darren ER Warburton, PhD Robert W Teasell, MD, FRCPC Janice J Eng, BSc (PT/OT), PhD

Key Points Midodrine hydrochloride should be included in the management protocol of OH in individuals with spinal cord injury. There is limited evidence that fludrocortisone is effective for the management of OH in SCI. There is limited evidence that ergotamine is effective for the management of OH in SCI. There is little evidence that ephedrine is effective for the management of OH in SCI. There is limited evidence that L-DOPS is effective for the management of OH in SCI. The benefits of salt loading have not been sufficiently proven in individuals with SCI. There is insufficient evidence that elastic stockings or abdominal binders have any effect on the cardiovascular responses in SCI The use of FES is an effective adjunct treatment to minimize cardiovascular changes during changes in position. Simultaneous arm exercise during a tilt test is not effective for improving orthostatic tolerance. The benefits of body-weight supported treadmill training for management of OH have not been sufficiently proven in SCI.

Table of Contents
16.1 Introduction ..................................................................................................................16-1 16.2 Pharmacological Management of OH in SCI .............................................................16-2 16.3 Non-pharmacological Management of OH in SCI .....................................................16-6 16.3.1 Fluid and Salt Intake for Management of OH in SCI ...................................................16-6 16.3.2 Effect of Pressure Interventions in Management of OH in SCI ...................................16-8 16.3.3 Effect of FES on OH in SCI.........................................................................................16-9 16.3.4 Effect of Exercise on OH in SCI................................................................................16-12 16.4 Summary.....................................................................................................................16-14 References............................................................................................................................16-15

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Krassioukov A, Warburton DER, Teasell RW, Eng JJ (2006). Orthostatic Hypotension Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 16.1-16.17. www.icord.org/scire

Orthostatic Hypotension Following SCI

16.1 Introduction The Consensus Committee of the American Autonomic Society and the American Academy of Neurology (CCAAS&AAN 1996) defined orthostatic hypotension (OH) as a decrease in systolic blood pressure of 20mmHg or more, or a reduction in diastolic blood pressure of 10mmHg or more, upon the change in body position from a supine position to an upright posture, regardless of the presence of symptoms. Numerous studies have documented the presence of OH following SCI (Mathias 1995; Faghri et al. 2001; Cariga et al. 2002). This condition is evident in the acute period post-injury and persists in a significant number of individuals for many years (Frisbie & Steele 1997; Claydon et al. 2006). Standard mobilization treatment during physiotherapy (e.g., sitting or standing) are reported to induce blood pressure decreases that are diagnostic of orthostatic hypotension in 74% of SCI patients, and cause symptoms of orthostatic hypotension (such as lightheadedness or dizziness) in 59% of SCI individuals (Illman et al. 2000). This may have a negative impact upon the ability of SCI individuals to participate in rehabilitation. Management of OH consists of pharmacological and non-pharmacological interventions. The low level of efferent sympathetic nervous activity and the loss of the reflex vasoconstriction following SCI are among the major causes of OH. The decrease in blood pressure following the change to an upright position in individuals with SCI appears to be related to excessive pooling of blood in the abdominal viscera and lower extremities (Mathias 1995; Krassioukov & Claydon, 2005; Claydon et al. 2006). This is compounded by the loss of lower extremity muscle function post-SCI that is known to be important in counteracting venous pooling in the upright position. The excessive venous pooling in the lower extremities, and reduced blood volume in the intrathoracic veins leads to a decrease in ventricular end-diastolic filling pressure and enddiastolic volume leading to a decreased left ventricular stroke volume (Ten Harkel et al. 1994). The reduced ventricular filling and emptying ultimately leads to a reduction in cardiac output, and subsequently arterial pressure (provided the reductions in cardiac output are marked). Tachycardia may occur as a response to reduced cardiac parasympathetic (vagal) activity, reflexly induced by the unloading of the arterial baroreceptors. However, this tachycardic response is often not sufficient to compensate for the decreased stroke volume, leading to a reduction in cardiac output and in turn arterial blood pressure. Several other factors may predispose spinal cord-injured individuals to OH. These include low plasma volume, hyponatremia, and cardiovascular deconditioning due to a prolong bed-rest (Mathias 1995; Illman et al. 2000; Claydon et al. 2006). The prevalence of OH is greater in patients with higher spinal cord lesions, and thus it is more common in tetraplegia (Frisbie & Steele 1997; Claydon et al. 2006; Mathias 2006). Furthermore, individuals with cervical SCI also experience larger falls in blood pressure associated with postural change than those with paraplegia (Mathias 1995; Claydon et al. 2006). There is also an increased risk of OH in individuals who sustain a traumatic SCI than in nontraumatic injury such as spinal stenosis (Mckinley et al. 1999).

16-1

Table 16.1 Factors Predisposing to OH following SCI Multifactorial Loss of tonic sympathetic control Altered baroreceptor sensitivity Lack of skeletal muscle pumps Cardiovascular deconditioning Altered salt and water balance Claydon et al. 2006 Wallin & Stjernberg 1984; Houtman et al. 2000 Munakata et al. 1997; Wecht et al. 2003 Ten Harkel et al. 1994; Faghri & Yount 2002; Raymond et al. 2002 Hopman et al. 2002; Vaziri 2003 Frisbie 2004

The pooling of blood in the lower extremities and decrease in blood pressure results in a reduction in cerebral flow which presents as a number of signs and symptoms in Table 16.2. Table 16.2 Signs and Symptoms of OH 11HLight-headedness 12HDizziness 13HFainting 14HBlurred vision Fatigue Muscle weakness 15HSyncope (temporary loss of consciousness)

16.2 Pharmacological Management of OH in SCI The majority of our knowledge on management of OH is obtained from patients who are presenting OH consequent to non-SCI causes, such as heart disease, Parkinsons disease, and dyautonomia. Numerous medications have been successfully used to manage OH in these chronic conditions such Midodrine, fludrocortisone, and ephedrine. However, given that the mechanisms of development of OH are different in individuals with SCI, it is important to assess the effectiveness of these medications specifically in people with SCI. Table 16.3 Pharmacological Management of OH in SCI
Author Year; Country Score Research Design Total Sample Size Methods Outcome

Nieshoff et al. 2004; USA PEDro=5 RCT N=4

Population: Age range=28-41 years, SCI; 1. Midodrine, 10 mg elevated systolic chronic motor complete tetraplegia blood pressure during exercise in 3 Treatment: Midodrine 5mg, 10 mg, or participants. Peak systolic BPs ranged placebo (unmarked capsule). Double-blind, from 90 to 126 mmHg under baseline placebo-controlled cross-over design. and placebo conditions, 114-148 after 5 Measure of cardiovascular parameters mg of midodrine, and 104 to 200 mmHg during wheelchair ergometer test. after 10 mg. Outcome Measures: Oxygen consumption, 2. Two participants showed perceived blood pressure. exertion and VO2. 3. No adverse effects of midodrine.

16-2

Author Year; Country Score Research Design Total Sample Size

Methods Population: 45-year-old chronic complete traumatic paraplegia; 6 non-SCI male controls; age range=44-50 years Treatment: Clonidine (150 g, 2X/day) and midodrine (specific alpha 1-agonist) (10 mg, 2X daily) Heart rate assessed by blinded tester. Outcome Measures: Blood pressure, heart parameters, plasma catecholamine, alpha-adrenoceptor sensitivity. Population: 2 cases of acute motor complete tetraplegia. Treatment: Administration of fludrocortisone acetate 0.1 mg 4X/day or midodrine 10 mg 3X/day. Outcome Measures: Blood pressure, heart rate, and symptoms of OH. Population: 28-year-old with chronic C5 tetraplegia. Treatment: Administration of Ergotamine (2 mg), daily combined with fludrocortisone (0.1- .05 mg) Outcome Measures: Blood pressure.

Outcome 1. Individual with SCI showed significant alpha adrenergic supersensitivity. 2. The increase in systolic blood pressure induced by midodrine (10 mg) was significantly higher in the patient (change of 56 mmHg) than in controls (change of 15 mmHg). 3. Midodrine and clonidine alone or two drugs in combination led to an increase in resting BP and decrease severity of OH. 1. Fludrocortisone in both patients resulted in pitting edema of hands and lower limbs. No effect of fludrocortisone on OH. 2. Initiation of the midodrine hydrochloride resolved orthostatic symptoms in both individuals without any complications. 1. Following 10 days with fludrocortisone patient able to tolerate sitting. Following additional ergotamine, the patient able to tolerate an upright position without symptoms. 2. Supine BP was 94/70 mmHg. Sitting BP was 78/50mmHg after 30 seconds in a sitting position, and stabilized to 84/70mmHg after 3 minutes. 1. After salt supplement, a marked BP and NE were observed in response to sitting. There is also a decrease in basal plasma rennin activity was observed. 2. Addition of L-threo-3,4dihydroxyphenylserine for 2 weeks, showed elevation in catecholamines (E &NE) about 5 and 10 times without an apparent increase in resting BP level. 3. Significant improvement in the symptoms of the paroxysmal hypotension and patient able to participate in rehabilitation program. 1. Gradual increase of dose of midodrine from 2.5mg to 10 mg (at 0800, 1200 and 1600 hrs) resulted in resolution of ssymptoms and orthostasis. Patient able to participate fully in the rehab program.

Senard et al. 1991; France Downs & Black score=11 Pre-post N=7

Barber et al. 2000; USA Downs & Black score=7 Case Series N=2

Groomes et al. 1991; USA Downs &Black score=9 Case Series N=1

Muneta et al. 1992; Japan Downs & Black score=9 Case Series N=1

Population: 72-year old woman with nontraumatic SCI and paroxysmal hypotension. Treatment: Several weeks of salt supplement (7 then 15 g/day) was followed by L-threo-3,4-dihydroxyphenylserine (100 mg up to 600 mg/day) Outcome Measures: Blood pressure, catecholamines, plasma rennin activity.

Mukand et al. 2001; USA Downs & Black score=10 Case Series N=1

Population: 21-year old male; SCI; traumatic; C6 tetraplegia; ASIA C, with symptomatic orthostatic hypotension. Treatment: Administration of midodrine (2.5 to 15 mg 3X/day). Outcome Measures: Blood pressure (systolic and diastolic), pulse rate, and symptoms of OH.

16-3

Author Year; Country Score Research Design Total Sample Size

Methods Population: Age range=68-83 years;chronic cervical complete tetraplegia; ASIA A Treatment: Evaluation of urinary salt and water output in relation to prescribed dosage of ephedrine (doses range from 0 to 100 mg daily) Outcome Measures: Severity of OH, urinary output. Population: SCI; Ephedrine group: mean age=5715 years, duration of paralysis 2615 years; Non-ephedrine group: mean age=5115.2 years, 2213.5 years postinjury Treatment: Retrospective chart review of ephedrine, salt supplementation, fludrocortisone or physical therapy. Outcome Measures: OH symptoms, serum sodium and urine osmolality.

Outcome 1. With decreasing ephedrine dose (and OH severity), there was anmean daily output of urine sodium (from 50 to 181 mEq), water (from 1.5 to 5.3 L), rate of creatinine secretion, rates of water excretion, urine osmolality, and sodium concentrations. 1. OH was greatest in tetraplegic, motor complete patients (24 of 73 patients, 33%). 2. Symptoms of OH were reduced consciousness (100% of subjects), strength (75%), vision (56%) and breath (53%). Precipitating factors were hot weather (77%) bowel care (33%) and meals (30%). 3. Low blood sodium found in 54% of the OH patients and 16% of those without, P < 0.001.

Frisbie 2004; USA Downs & Black score=9 Observational N=4

Frisbie & Steele 1997; USA Downs & Black score=18 Observational N=231

Discussion Midodrine (ProAmatine) Midodrine is a selective apha1 adrenergic agonist, and exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure. The plasma levels of Midodrine peak after about half an hour, and decline with a half-life of approximately 25 minutes, while the metabolite reaches peak blood concentrations about 1 to 2 hours after a dose of Midodrine and has a halflife of about 3 to 4 hours. Usual doses are 2.5mg at breakfast and lunch or three times daily. Doses are increased quickly until a response occurs or a dose of 30 mg/day is attained (Wright et al. 1998). Midodrine does not cross the blood-brain barrier and it is thus not associated with CNS effects. The benefits of Midodrine in the management of OH in individuals with spinal cord injury were reported in a level 1 RCT (Nieshoff et al. 2004) and three level 4 studies (Senard et al. 1991; Barber et al. 2000; Mukand et al. 2001). Although only 4 studies with a total of 8 subjects have been reported, Nieshoff et al. (2004) was a double-blind placebo-controlled, randomized, crossover trial using a within-subjects design. Not only was systolic blood pressure increased during peak exercise (3/4 subjects), but exercise performance was also enhanced. Fludrocortisone (Florinef) Fludrocortisone is a mineralocorticoid which forces more salt into the bloodstream. It increase blood volume and may also enhance sensitivity of blood vessels to circulating catecholamine (Schatz 1984; Van Lieshout et al. 2000). The starting dose is 0.1 mg daily. Blood pressure rises gradually over several days with maximum effect at 1-2 weeks. Doses should be adjusted at weekly or biweekly intervals. Hypokalemia (low potassium) occurs in 50% of individuals, and hypomagnesemia in 5%. These may need to be corrected with supplements. Florinef should not be used in persons with congestive heart failure. Headache is a common side effect.

16-4

The benefit of Fludrocortisone has not been sufficiently proven in individuals with SCI. One level 3 retrospective study (Frisbie & Steele 1997) and level 4 case series (Groomes & Huang 1991; Barber et al. 2000) described its use for management of OH in the SCI population. Dihydroergotamine Dihydroergotamine or Ergotamine is an ergot alkaloid which interacts with alpha adrenergic receptors and has selective vasoconstrictive effects in peripheral and cranial blood vessels. Peak plasma levels are reached about 2 hours after ingestion. The benefit of Ergotamine has not been sufficiently proven in individuals with SCI since there is only one case report that combined Ergotamine with fludrocortisone to successfully prevented symptomatic OH in one individual with SCI (Groomes & Huang 1991). Ephedrine Ephedrine is a non-selective, alpha and beta receptor agonist, with central and peripheral action. Its peripheral actions are due partly to norepinephrine release and partly to direct effects on receptors. 12.5-25 mg orally 3X/day. Side effects may include tachycardia, tremor and supine hypertension. It raises blood pressure both by increasing cardiac output and inducing peripheral vasoconstriction. It has a plasma half-life ranging from 3 to 6 hours (Kobayashi et al. 2003). The benefits of Ephedrine have not been sufficiently proven in individuals with SCI. One retrospective chart review exists (Frisbie & Steele 1997) and a case report (level 4) (Frisbie 2004) which reported that daily urinary output of salt and water was inversely related to the prescribed ephedrine dose in patients with OH (but they did not monitor blood pressure). L-threo-3,4-dihydroxyphenylserine (L-DOPS) L-DOPS is an exogenous, neutral amino acid, precursor of noradrenalin. The benefits of LDOPS have not been sufficiently proven in individuals with SCI. Only one level 4 case series is published (Muneta et al. 1992) with evaluation of effects of the L-DOPS on OH in nontraumatic SCI. In this study, treatment with salt supplementation in combination with L-threo-3,4dihydroxyphenylserine, markedly improved the syncopal attacks, decreased drowsiness associated with hypotension and increased the patient's daily activity. General Discussion In summary, the studies addressing the pharmacological management of OH following SCI involve a small number of trials with low number of subjects and numerous case reports. Furthermore, it is often difficult to determine the effects of individual medications when used as combination therapies. Midodrine hydrochloride should be included in the management protocol of OH in individuals with spinal cord injury. Further research needs to quantify the effects of the many pharmacological interventions which have been shown to be effective in conditions other than spinal cord injury. Conclusion There is level 2 evidence that Midodrine enhances exercise performance in some individuals with SCI, similar to other clinical populations with cardiovascular autonomic dysfunction. There is level 4 evidence that the use of clonidine and midodrine resulted in successful treatment of OH based on one study using one individual.

16-5

There is level 4 evidence on case series that show evidence of fludrocortisone is effective for OH in SCI. There is level 4 evidence based on 1 case series that Ergotamine, daily combined with fludrocortisone, successfully prevented symptomatic OH in one individual with SCI (Groomes & Huang 1991). There is level 4 evidence that L-DOPS, in conjunction with salt supplementation in one individual is effective for reducing OH There is level 5 evidence that Ephedrine may prevent some symptoms of OH. Midodrine hydrochloride should be included in the management protocol of OH in individuals with spinal cord injury. There is limited evidence that fludrocortisone is effective for the management of OH in SCI There is limited evidence that ergotamine is effective for the management of OH in SCI There is little evidence that ephedrine is effective for the management of OH in SCI There is limited evidence that L-DOPS is effective for the management of OH in SCI

16.3 Non-pharmacological Management of OH in SCI Non-pharmacological management includes the regulation of fluids and salt intake, as well as physical modalities such as abdominal binders, physical activities, and electrical muscle stimulation. 16.3.1 Fluid and Salt Intake for Management of OH in SCI OH is common among patients with higher levels of paralysis, symptoms are variable, and abnormal salt and water metabolism often coexist. Increases in fluid intake and high salt diet can expand extracelular fluid volume and augment orthostatic responses. This simple intervention appears to be effective in patients with idiopathic OH without SCI (Davidson et al. 1976; Claydon & Hainsworth 2004). Table 16.4 Fluid and Salt Intake for Management of OH in SCI
Author Year; Country Score Research Design Total Sample Size Frisbie & Steele 1997; USA Downs & Black score=18 Observational N=231 Methods Population: SCI; Ephedrine group: mean age=5715 years, duration of paralysis 2615 years; Non-ephedrine group: mean age=5115.2 years, duration of paralysis 2213.5 years. Treatments: Retrospective review with more than 1 treatment provided to some: Ephedrine (n=30), salt supplementation (n=6), fludrocortisone (n=3) or physical Outcome 1. OH was greatest in tetraplegic, motor complete patients (24 of 73 patients, 33%). 2. Symptoms of OH were reduced consciousness (100% of subjects), strength (75%), vision (56%) and breath (53%). Precipitating factors were hot weather (77%) bowel care (33%) and meals (30%).

16-6

Author Year; Country Score Research Design Total Sample Size

Methods therapy (n=29). Outcome Measures: Symptoms of OH, incidence of hyponatremia, serum sodium and urine osmolality.

Outcome 3. Symptoms worsened with the duration of paralysis in 12 patients. 4. Chronic hyponatremia was found in 54% of the PH patients and 16% of those without, P < 0.001.

Frisbie 2004; USA Downs & Black score=9 Observational N=4

Muneta et al. 1992; Japan Downs & Black score=9 Case Series N=1

Population: Age range=68-83 years;chronic cervical complete tetraplegia; ASIA A. Treatment: Evaluation of urinary salt and water output in relation to prescribed dosage of ephedrine (0 to 100 mg daily). Outcome Measures: Severity of OH, urinary output of sodium and water. Population: 72-year old woman with nontraumatic SCI and paroxysmal hypotension. Treatment: Several weeks of salt supplement (7 then15 g/day) was followed by L-threo-3,4-dihydroxyphenylserine (100 mg up to 600 mg/day). Outcome Measures: Blood pressure to sitting, catecholamines (E, NE), plasma rennin activity.

1. The increasing OH severity in SCI patients, was characterized by decreasing rates of creatinine secretion, decreasing rates of water excretion, increasing urine osmolality and decreasing sodium concentrations. 1. After initiation of the salt supplement, BP and NE in response to sitting. There is also a decrease in resting plasma rennin activity. 2. Addition of L-threo-3,4dihydroxyphenylserine for 2 weeks, showed plasma E and NE about 5 and 10 times without in basal BP level. 3. Improvement in the symptoms of the paroxysmal hypotension and patient was able to participate in rehabilitation program.

Discussion The estimated daily intake of salt and water was inversely related to the ephedrine requirements in patients with OH and suggests greater salt and water intake may lead to a more balanced renal action (Frisbie 2004). OH is common among myelopathy patients with higher levels of paralysis, symptoms are variable, and abnormal salt and water metabolism often coexist. Few observational studies and one case report suggested that salt loading, was effective in the reduction of symptoms of OH (Frisbie 2004). Currently, guidelines that suggest appropriate water and salt intake specific to people with spinal cord injury do not exist. Conclusion The research studies used salt and fluid regulation in combination with other pharmacological interventions and thus, the effects of salt and fluid regulation cannot be determined. No evidence exists on the effect of salt or fluid regulation alone for OH management in SCI. The benefits of salt loading have not been sufficiently proven in individuals with SCI.

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16.3.2 Effect of Pressure Interventions in Management of OH in SCI The application of external counterpressure by devices such as abdominal binders or pressure stockings is thought to decrease capacitance of the vasculature beds in legs and abdominal cavity which are the major areas of blood pooling during standing. Table 16.5 Pressure Interventions for Management of OH in SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: m=9 SCI; mean age=349 years (5, tetraplegics) and 287 years (4, paraplegics); 8 complete & 1 incomplete; mean duration of injury=11.48.1 years (tetraplegics) and 7.04.5 years (paraplegics). Treatment: 5 discontinuous maximal arm ergometer tests on different days while: 1) sitting, 2) supine, 3) sitting plus an anti-G suit, 4) sitting plus stockings and abdominal binder, and 5) sitting plus FES of the leg muscles. Outcome Measures: Oxygen uptake, carbon dioxide output, respiratory parameters, HR, BP. Population: 5 tetraplegic SCI; 4 paraplegic SCI (same subjects as above study). Treatment: 5 conditions as above, except submaximal exercise at 20, 40 and 60% of maximum power output. Outcome measures: Oxygen uptake, carbon dioxide output, respiratory parameters, HR, BP. Population: 6 Tetraplegic complete, 5 Paraplegic complete, mean age=31.811.3 years; age range=21-55 years, ASIA A; 9 able bodied controls, mean age: 23.49.3 years, age range=19-48 years. Treatment: With and without harness for locomotor training during supine, sitting and standing (within subject analysis). Outcomes measures: Blood pressure, heart rate. Outcome 1. The supine posture increased VO2peak in tetraplegics, but reduced HR in paraplegics compared to sitting. 2. The anti-G suit, stockings plus abdominal binder or FES did not have any effect on VO2, HR, ventilatory exchange or power output. The anti-G suit did significantly reduce the perceived exertion for the tetraplegics only. 3. Results suggested that stockings and abdominal binders, FES or do not provide hemodynamic benefits.

Hopman et al. 1998; USA PEDro=5 RCT N=9

Hopman et al. 1998; Netherlands PEDro=5 RCT N=9

Krassioukov & Harkema; 2006 Canada Downs & Black score=17 Prospective Controlled Trial N=20

Raymond et al. 2002; Australia Downs & Black score=16 Prospective Controlled Trial N=16

Population: 8 male complete paraplegia, mean age=41.36.5 years; 8 male ablebodied controls, mean age=41.16.6 years. Treatment: Subjects were evaluated: (1) during supine rest, (2) supine with lowerbody negative pressure (LBNP), and (3) for SCI only, LBNP with leg electrical stimulation. Outcome measures: Heart rate, stroke

1. Tetraplegics: VO2, cardiac output, stroke volume, BP and stroke volume with FES; cardiac output, stroke volume and HR with binders and stockings ; HR and BP with anti-G suit. 2. Paraplegics: VO2 and HR with FES; VO2 and HR with anti-G suit; VO2 with stockings and binders. 1. Orthostatic stress significantly decreased arterial blood pressure only in individuals with cervical SCI (P<0.05). 2. Harness application had no effect on cardiovascular parameters in ablebodied individuals, whereas diastolic blood pressure was significantly increased in those with SCI. 3. Orthostatic changes in cervical SCI when sitting were ameliorated by harness application. However, while standing with harness, individuals with cervical SCI still developed orthostatic hypotension. 4. LBNP elicited a stroke volume (by 23% and 22%), cardiac output (by 15% and 18%), and HR (by 10% and 9%), total peripheral resistance (by 23% and 17%) and calf volume (by 1.51% and 4.04%) in SCI and controls, respectively. 5. LBNP + stimulation had stroke volume (by 20%), cardiac output (by 16%),

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Author Year; Country Score Research Design Total Sample Size

Methods volume, cardiac output, total peripheral resistance. Population: f=4,m=2;chronic complete paraplegia; age range=20-25 years; mean age=21.8 years. Treatment: Cross-over design: abdominal binder (experimental condition) or not wearing (the control condition). Outcome Measures: BP, HR, VO2max, respiratory parameters, and wheelchair propulsion.

Outcome and total peripheral resistance (by 12%) in SCI group compared to LBNP alone. 1. 5/6 subjects demonstrated a mean increase of 31 % in forced vital capacity with binder compared to without. No statistical significance but this may be because the sixth subject showed an 18% decrease in forced vital capacity when wearing the binder.

Kerk et al. 1995; USA Downs & Black score=13 Prospective Controlled Trial N=6

Discussion One expert opinion (Bhambhani 2002) and three small experimental studies showed conflicting data. Kerk et al. (1995) stated that there were no statistically significant effects of the abdominal binder on any of the cardiovascular or kinematic variables at submaximal or maximal levels of exercise (Kerk et al. 1995). Bhambhani in his review also concluded that the use of abdominal binders does not influence cardiovascular physiological responses (Bhambhani 2002). However, Hopman et al. (1998a) demonstrated in a small group of SCI subjects (n=9) that stockings and an abdominal binder do have effect on cardiovascular responses during submaximal exercises (Hopman et al. 1998a), but not during maximal exercises (Hopman et al. 2002). Conclusion There is conflicting evidence based on limited research that elastic stockings/abdominal binders have any effect on cardiovascular responses in individuals with SCI. There is level 2 evidence that application of a harness in individuals with SCI could alter baseline cardiovascular parameters and the response to orthostatic stress. There is insufficient evidence that elastic stockings or abdominal binders have any effect on the cardiovascular responses in SCI 16.3.3 Effect of FES on OH in SCI The application of FES activates the physiologic muscle pump via intermittent muscle contractions that produce a pumping mechanism of both the superficial and deep veins of the legs.

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Table 16.6 FES on OH in SCI

Author Year; Country Score Research Design Total Sample Size Methods Population: 2 tetraplegics, 3 paraplegics; complete; mean age=294.3; in acute period of SCI - 2-4 weeks post-injury. Treatment: Tilt table - 6 minutes at each tilt angle (0, 15, 30, 45 and 60 degrees), with 4 minutes of recovery between each, with or without bilateral ankle plantar flexor and knee extensor electrical stimulation. Application order or absence of FNS was counterbalanced. Outcome Measures: HR, blood pressure, perceived exertion. Population: n=14 SCI, mean age= 359.41 years; n=15 able-bodied, mean age=296 years; 7 paraplegia, 7 tetraplegia; 4 incomplete, 10 complete; time post-injury 7764 months. Treatment: Random order of standing with or without FES (30 mins) for SCI subjects; voluntary tiptoe contractions during 30 minutes standing for able-bodied subjects. Outcome Measures: Hemodynamics during supine-sitting-30 min standing. Population : n=14 SCI; Gender: m=11, f=3;mean age=359yrs (range 2056yrs);mean length post injury 77.364.4months (range 7-170 months);7 tetraplegia, 7 paraplegia; 4 incomplete, 10 complete. Treatment: FES augmented standing (active) and non-FES standing (passive), for 30min duration; tests were separated by at least 24hours. Outcome Measures: Hemodynamics. Population: 8 male complete paraplegia, mean age=41.36.5 years; 8 male ablebodied controls, mean age=41.16.6 years. Treatment: Subjects were evaluated: (1) during supine rest, (2) supine with lowerbody negative pressure (LBNP), and (3) for SCI only, LBNP with leg electrical stimulation. Outcome measures: Heart rate, stroke volume, cardiac output, total peripheral resistance. Population: Motor complete SCI (lesions above T6); (3 with recent injury, 3 with long standing injury); age range=17-46 years old; ASIA class A n=4, B n=2. Treatment: With and without lowerextremity FES while tilted by 10 increments every 3 minutes, from 0-90 with varying intensities of stimulation. Outcome Measures: Blood pressure, Outcome 1. At tilt angles of 15, 30, 45 and 60 degrees, systolic BP was significantly lower when FNS was not applied compared to when it was administered, and it was more marked with increasing tilt angles. 2. There was a progressive decrease in blood pressures with increasing tilt angle and this increase was less pronounced in the FNS condition. 3. Post hoc analysis showed that HR was significantly higher with FNS compared to without FNS at 60 degrees tilt. 1. Reductions (p < 0.05) up to 10% BP measures for SCI subjects from sitting to passive standing; but minimal changes when moving to FES standing. 2. After 30 min of passive standing (no FES), there is a reduction in stroke volume and cardiac output. After 30 min of FES standing, the pre-standing haemodynamics are maintained except for a significant reduction in stroke volume. 1. BP changed 8-9% when moving from sitting to passive standing (no FES). The augmented FES condition prevented BP change when moving from sitting to standing.

Elokda et al. 2000; USA PEDro=5 RCT N=5

Faghri & Yount 2002; USA PEDro=5 RCT N=29

Faghri et al. 2001; USA Downs & Black score=22 Prospective Controlled Trial N=14

Raymond et al. 2002; Australia Downs & Black score=16 Prospective Controlled Trial N=16

Sampson et al. 2000; USA PEDro=5 RCT N=6

1. LBNP elicited a stroke volume (by 23% and 22%), cardiac output (by 15% and 18%), and HR (by 10% and 9%), total peripheral resistance (by 23% and 17%) and calf volume (by 1.51% and 4.04%) in SCI and controls, respectively. 2. LBNP + stimulation had stroke volume (by 20%), cardiac output (by 16%), and total peripheral resistance (by 12%) in SCI group compared to LBNP alone. 1. HR increased for both groups with incline angle. Mean diastolic BP was lower for the recent SCI subjects (105 mmHg) with chronic (123 mmHg). 2. systolic and diastolic BP with stimulation intensities and BP with incline angle (p < .001) regardless of the site of stimulation. 3. Subjects tolerated higher angles of incline with FES than without. The

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Author Year; Country Score Research Design Total Sample Size

Methods heart rate, perceived syncope score. Population: m=15, f=1 SCI; motor complete tetraplegia; age range=15-70 years old; time since injury: 2-324 months (118.9104.2 months); ASIA class A n=11, B n=5. Treatment: Progressive head-up tilting maneuver with and without the FES to 4 muscle groups. Outcome Measures: BP, heart rate, perceived presyncope score. 1. 2.

Outcome higher the intensity of FES, regardless of stimulation site, the greater the tilt incline tolerated. With increasing tilt angle, systolic and diastolic BP and heart rate with and without FES. Adding FES to tilting significantly attenuated the drop in systolic BP by 3.71.1 mmHg (p = .005), the drop in diastolic BP by 2.30.9 mmHg (P = .018), and heart rate increase by 1.00.5 beats/min (p = .039) for every 15 degrees increment in the tilt angle. FES increased the overall mean standing time by 14.33.9 min (p = .003). After training, resting HR and systolic BP in tetraplegics and systolic and diastolic BP in paraplegics. In both groups, HR and BP during submaximal exercise significantly decreased and stroke volume and cardiac output significantly increased after program. These results suggest that FES-LCE training improves peripheral muscular and central cardiovascular fitness in SCI subjects.

Chao & Cheing 2005; China Downs & Black score=15 Post N=16

3. Population: n=6 paraplegics (T4-T10); n=7 tetraplegics (C4-C7); mean age=30.5 years; mean time post injury = 8 years. Treatment: FES-leg cycle ergometer training, 3X/week, for about 12 weeks (36 sessions). Outcome Measures: Oxygen uptake (VO2), pulmonary ventilation (Ve), respiratory exchange ratio (RER), BP, HR, stroke volume (SV) and cardiac output (Q). 1. 2.

Faghri et al. 1992; USA Downs & Black score=14 Pre-post N=13

3.

Discussion FES may be an important treatment adjunct to minimize cardiovascular changes during postural orthostatic stress in individuals with SCI. Several studies have suggested that FES-induced contractions of the leg muscles increases cardiac output and stroke volume, which is attributable to increased venous return (Raymond et al. 2002). This increases ventricular filling and left ventricular end-diastolic volume (i.e., enhanced cardiac preload). According to the Frank-Starling effect, an increase in ventricular preload will lead to a greater stretch of the myocytes and a concomitant increase in left ventricular stroke volume. The increased stroke volume may allow cardiac output and as such arterial blood pressure to be increased. Therefore, FES-induced contraction of the leg muscles may attenuate the drop in systolic BP in response to an orthostatic challenge. FES-induced contraction in the leg muscles may also artificially restore the bodys ability to redistribute blood from below the level of the lesion back to the heart. In fact, FES may be effective during the orthostatic challenge by redistributing blood volume from the regions of the body that are below the level of the SCI (Davis et al. 1990). FES of leg muscles resulted in increase of cardiac output and stroke volume (Davis et al. 1990). These studies suggested that FES of leg muscles could alleviate the lower limb pooling effect during the orthostatic challenge. FES causes a dose-dependent increase in blood pressure independent of stimulation site that may be useful in treating orthostatic hypotension (Sampson et al. 2000). FES may be an important treatment adjunct to minimize cardiovascular changes during postural orthostatic

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stress in individuals with acute spinal cord injury. Two level 2 RCTs and non-randomized controlled trials with small number of individuals provide support for use of FES in individuals with SCI. FES of the lower extremity could be used by persons with SCI as an adjunct during standing to prevent orthostatic hypotension and circulatory hypokinesis. An FES-induced leg muscle contraction is an effective adjunct treatment to delay orthostatic hypotension caused by tilting; it allows people with tetraplegia to stand up more frequently and for longer durations (Elokda et al. 2000; Sampson et al. 2000).This effect may be more beneficial to those with tetraplegia who have a compromised autonomic nervous system and may not be able to adjust their hemodynamics to the change in position (Faghri et al. 2001). Conclusion There is level 2 evidence from randomized controlled trials that FES is an important treatment adjunct to minimize cardiovascular changes during postural orthostatic stress in individuals with SCI. The use of FES is an effective adjunct treatment to minimize cardiovascular changes during changes in position. 16.3.4 Effect of Exercise on OH in SCI Following exercise, individuals with SCI could exhibit positive changes in autonomic regulation of cardiovascular system (Lopes et al. 1984). Exercise or even passive movement of the legs could potentially stabilize the reduced central blood volume in individuals with SCI during the orthostatic challenge (Dela et al. 2003). There is also some evidence that exercise training could enhance sympathetic outflow in individuals with SCI as shown by increase in catecholamine response to maximal arm ergometry exercise (Bloomfield et al. 1994) Table 16.7 Exercise on OH in SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: m=12 SCI, 6 experimental (5 tetraplegia, 1 paraplegia. mean age=40.3, mean 7.2 weeks post injury); 6 control (6 tetraplegia, mean age=22.5 years; mean 8.2 weeks post injury. Treatment: Random assignment to active exercise (60 bilateral forearm flexion and extension movements per minute during the first and third minute of each tilt angle) versus no upper limb exercises during tilt from 0-70 degrees by 10 degrees increments at five-minute intervals until blood pressure dropped below 70/40. Outcome measures: BP, hypotensive symptoms. Population: Sensory incomplete cervical SCI; m=6, f=2; mean age= 27.65.2 years; level of injury C4-C5; ASIA B-C; 9.67.5 years post-injury. Outcome 1. No significant difference between the active upper extremity exercise group versus non-exercise group with reference to tolerance to progressive vertical tilt.

Lopes et al. 1984; USA PEDro=2 RCT N=12

Ditor et al. 2005; Canada Downs & Black score=18 Pre-post N=8

1. Resting HR but no change in BP after BWSTT. 2. No effect on BP or HR on the 60 Head Up Test.

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Author Year; Country Score Research Design Total Sample Size

Methods Treatment: 6 month of body weightsupported treadmill training (BWSTT). Outcomes measures: HR, BP, and orthostatic responses, heart-rate variability.

Outcome 3. A trend (p=0.09) towards a relative exaggeration of the pressor response to orthostatic stress during tilt test (measured bylow frequency power of heart rate) and suggests improved orthostatic tolerance.

Only two exercise studies exist and are very diverse in protocol. Lopes et al. (1984) found no effects on orthostatic tolerance with the addition of upper extremity exercises during a progressive vertical tilt protocol. Such findings are not surprising given the small muscle mass involved in the upper limbs and the fact that venous pooling occurs primarily in the lower limbs. The study by Ditor et al. (2005) demonstrate that individuals with incomplete tetraplegia retain the ability to make positive changes in cardiovascular autonomic regulation with body weightsupport treadmill training. Six months of BWSTT did not substantially affect the ability of SCI subjects to tolerate orthostatic stress, however, the authors found this encouraging as it suggests that orthostatic tolerance is retained after exercise training, even though this intervention probably reduced peripheral vascular resistance. Conclusion There is level 2 evidence that simultaneous upper extremity exercises does not improve orthostatic tolerance during a progressive tilt exercise. There is level 4 evidence that 6 months of body-weight support treadmill training does not substantially improve orthostatic tolerance during a tilt test. Simultaneous arm exercise during a tilt test is not effective for improving orthostatic tolerance. The benefits of body-weight supported treadmill training for management of OH have not been sufficiently proven in SCI.

General Discussion The major part of our present understanding of pathophysiology and management of incapacitating symptoms of OH is derived from the management of this condition in individuals with both central autonomic neurodegenerative disorders, such as multiple system atrophy and Parkinsons disease, and peripheral autonomic disorders, such as the autonomic peripheral neuropathies and pure autonomic failure (Mathias 1995; Freeman 2003). From previous studies in non SCI individuals it is well established that combination of patient education and use of pharmacological and non-pharmacological modalities could lead to successful management of the OH. The therapeutic goal for management of OH is not to normalize the blood pressure values but rather to ameliorate symptoms while avoiding side effects. (Kaufmann et al. 2006) The general approach in management of OH is that the therapeutic interventions should be implemented in stages dependent upon the severity of symptoms (Kaufmann et al. 2006). It is also well known from previous studies in non SCI population that nonpharmacologic measures alone are often insufficient to prevent symptoms of OH. Pharmacological interventions are needed particularly in SCI patients with moderate to severe OH symptoms.

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Although a wide array of physical and pharmacological measures are recommended for the general management of OH (Kaufman et al. 2006), very few have been evaluated for use in SCI. Of the pharmacological interventions, only minodrine has some evidence, while the FES is one of the only non-pharmacological interventions which has limited evidence to support its utility. 16.4 Summary There is Level 1 evidence that Midodrine enhances exercise performance in some individuals with SCI, similar to other clinical populations with cardiovascular autonomic dysfunction. There is Level 4 evidence that the use of clonidine and midodrine resulted in successful treatment of OH based on one study using one individual. There is level 4 evidence on case series that show evidence of fludrocortisone is effective for OH in SCI There is level 4 evidence based on 1 case series that Ergotamine, daily combined with fludrocortisone, successfully prevented symptomatic OH in one individual with SCI (Groomes & Huang 1991). There is level 5 evidence that Ephedrine may prevent some symptoms of OH. There is level 4 evidence that L-DOPS, in conjunction with salt supplementation in one individual is effective for reducing OH The studies used salt and fluid regulation in combination with other pharmacological interventions and thus, the effects of salt and fluid regulation cannot be determined. No evidence exists on the effect of salt or fluid regulation alone for OH management in SCI. There is conflicting evidence that elastic stockings/abdominal binders have any effect on cardiovascular responses in individuals with SCI. There is level 2 evidence that an application of a harness in individuals with SCI could alter baseline cardiovascular parameters and the response to orthostatic stress. There is level 2 evidence from randomized controlled trials that FES is an important treatment adjunct to minimize cardiovascular changes during postural orthostatic stress in individuals with SCI. There is level 2 evidence that simultaneous upper extremity exercises does not improve orthostatic tolerance during a progressive tilt exercise. There is level 4 evidence that 6 months of body-weight support treadmill training does not substantially improve orthostatic tolerance during a tilt test.

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Senard JM, Arias A, Berlan M, Tran MA, Rascol A, Montastruc JL. Pharmacological evidence of alpha 1- and alpha 2-adrenergic supersensitivity in orthostatic hypotension due to spinal cord injury: a case report. Eur J Clin Pharmacol 1991;41:593-596. Ten Harkel AD, van Lieshout JJ, Wieling W. Effects of leg muscle pumping and tensing on orthostatic arterial pressure: a study in normal subjects and patients with autonomic failure. Clin Sci (Lond) 1994;87:553-558. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurol 1996;46:1470. Van Lieshout JJ, ten Harkel AD, Wieling W. Fludrocortisone and sleeping in the head-up position limit the postural decrease in cardiac output in autonomic failure. Clin Auton Res 2000;10:35-42. Vaziri ND. Nitric oxide in microgravity-induced orthostatic intolerance: relevance to spinal cord injury. J Spinal Cord Med 2003;26:5-11. Wallin BG, Stjernberg L. Sympathetic activity in man after spinal cord injury. Outflow to skin below the lesion. Brain 1984;107:183-198. Wecht JM, De Meersman RE, Weir JP, Spungen AM, Bauman WA. Cardiac autonomic responses to progressive head-up tilt in individuals with paraplegia. Clin Auton Res 2003;13:433-438. Wright RA, Kaufmann HC, Perera R, Opfer-Gehrking TL, McElligott MA, Sheng KN, Low PA. A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology 1998;51:120-124.

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CHAPTER SEVENTEEN
Autonomic Dysreflexia Following Spinal Cord Injury
Andrei Krassioukov, MD, PhD Darren ER Warburton, PhD Robert W Teasell, MD, FRCPC Janice J Eng BSc (PT/OT), PhD

Key Points The identification of the possible trigger and decrease of afferent stimulation to the spinal cord is the most effective prevention strategy in clinical practice. Botulinum toxin injections into the detrusor seem to be a safe and valuable therapeutic option in SCI patients who perform clean intermittent self-catheterization and have incontinence resistant to anticholinergic medications. Capsaicin and its analogue, resiniferatoxin, are effective in the management of AD in patients with SCI. Anticholinergics do not appear to be sufficient for the management of AD in SCI. It is not known whether sacral deafferentation reduces AD during urodynamic investigations. Enterocystoplasty has demonstrated long-term viability compared to sphincterotomy. Lidocaine anal block can limits the AD response in susceptible patients undergoing anorectal procedures. Topical lidocaine does not prevent AD during anorectal procedures. Adequate anesthesia (spinal or epidural if possible) is needed with vaginal delivery, cesarean delivery or instrumental delivery is required. Epidural anesthesia is preferred and effective for most women with AD during labor and delivery. Anesthesia should be used during surgical procedures in individuals with SCI despite apparent lack of sensation. Topical anesthetic is not effective for the prevention of AD during FES Nifedipine may be useful to prevent or control AD in SCI individuals. Nitrates are commonly used in the control of AD in SCI, but not studies have been done to show their effectiveness or safety in SCI. Preliminary evidence suggests that captopril is effective for the management of autonomic dysreflexia in SCI There is limited evidence for the use of Terazosin as an agent for control of AD in SCI individuals. Prazosin can reduce severity and duration of AD episodes in SCI. It is not known whether Phenoxybenzamine is effective for the management of AD in SCI Prostaglandin E2 may reduce BP responses during eletroejactulation. Sildenafil has no effect on AD responses in men with SCI during ejaculation.

Table of Contents
17.1 Introduction ..................................................................................................................17-1 17.2 Pathophysiology of AD ...............................................................................................17-1 17.3 Management .................................................................................................................17-2 17.4 Prevention strategies ..................................................................................................17-2 17.4.1 Prevention of AD during bladder procedures..............................................................17-3 17.4.1.1 Botulinum toxin and AD ...........................................................................................17-3 17.4.1.2 Capsaicin .................................................................................................................17-4 17.4.1.3 Anticholinergics........................................................................................................17-6 17.4.1.4 Sacral denervation ...................................................................................................17-6 17.4.1.5 Bladder and urethral sphincter surgery....................................................................17-7 17.4.2 Treatments to reduce AD during anorectal procedures ..............................................17-9 17.4.3 Prevention of AD during Pregnancy and Labour ......................................................17-10 17.4.4 Prevention of AD during surgery...............................................................................17-11 17.4.5 Prevention of AD during FES Exercise .....................................................................17-12 17.5 Pharmacological management of AD ......................................................................17-13 17.5.1 Nifedipine (Adalat, Procardia) ...................................................................................17-13 17.5.2 Nitrates (Nitroglycerine, Depo-Nit, Nitrostat, Nitrol, Nitro-Bid) ..................................17-15 17.5.3 Captopril....................................................................................................................17-16 17.5.4 Terazosin ..................................................................................................................17-16 17.5.5 Prazosin (Minipress ..................................................................................................17-18 17.5.5 Prazosin (Minipress ..................................................................................................17-18 17.5.6 Phenoxybenzamine (Dibenzyline) ............................................................................17-18 17.5.6 Phenoxybenzamine (Dibenzyline) ............................................................................17-18 17.5.7 Prostoglandin E2.......................................................................................................17-19 17.5.8 Sildanefil (Viagra)......................................................................................................17-20 17.5.9 Other pharmacological agents tested for management of AD. .................................17-20 17.6 Summary.....................................................................................................................17-21 References............................................................................................................................17-23

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Krassioukov A, Warburton DER, Teasell RW, Eng JJ (2006). Autonomic Dysreflexia Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 17.1-17.27. www.icord.org/scire

Autonomic Dysreflexia Following Spinal Cord Injury

17.1 Introduction Autonomic dysreflexia (AD) is a well-known clinical emergency in individuals with spinal cord injury (SCI). It commonly occurs in individuals with injury at level T6 and above. (Mathias & Frankel 1988; Teasell et al. 2000; Mathias & Frankel 2002) An episode of AD is characterized by acute elevation of arterial blood pressure (BP) and bradycardia (slow heart rate), although tachycardia (fast heart rate) may also occur. Objectively, an increase in systolic BP greater than 2030mmHg is considered a dysreflexic episode. (Teasell et al. 2000) Intensity of AD can vary from asymptomatic (Linsenmeyer et al. 1996), mild discomfort and headache to a life threatening emergency when systolic blood pressure can reach 300mmHg (Mathias & Frankel 2002). Untreated episodes of autonomic dysreflexia may have serious consequences, including intracranial hemorrhage, retinal detachments, seizures and death (Yarkony et al. 1986; Pine et al. 1991; Eltorai et al. 1992; Valles et al. 2005). It has been observed that the higher the level of the SCI, the greater the degree of clinical manifestations of cardiovascular dysfunctions (Mathias & Frankel 1992; Curt et al. 1997; Krassioukov et al. 2003). Another crucial factor for the severity of AD is completeness of spinal injury: only 27% of incomplete tetraplegics presented signs of AD in comparison with 91% of tetraplegics with complete lesions (Curt et al. 1997). AD is three times more prevalent in tetraplegics with a complete injury, in comparison to those with an incomplete injury (Curt et al. 1997). It is important to note, however, that although autonomic dysreflexia occurs more often in the chronic stage of spinal cord injury at or above the 6th thoracic segment, there is clinical evidence of early episodes of autonomic dysreflexia in the first days and weeks after the injury (Silver 2000; Krassioukov et al. 2003). 17.2 Pathophysiology of AD Most commonly AD is triggered by urinary bladder or colon irritation. However, many other causes were reported in the literature (Teasell et al. 2000; Mathias & Frankel 2002). AD is caused by massive sympathetic discharge triggered by either noxious or non-noxious stimuli below the level of the SCI (Krassioukov & Claydon, 2005). Numerous reports of AD have been described in the literature: these are usually short- lived either due to treatment or being selflimiting. However, there are reports of AD triggered by a specific stimulus, which then continued to be present for a period of days to weeks (Elliott & Krassioukov 2006). Numerous mechanisms have been proposed for the development of AD. It is known from animals experiments that autonomic instability following SCI result from plastic changes occurring within the spinal autonomic circuits in both the acute and chronic stages following injury (Mathias & Frankel 1988; Teasell et al. 2000; Mathias & Frankel 2002; Krassioukov 2005). The destruction of the descending vasomotor pathways results in the loss of inhibitory and excitatory supraspinal input to the sympathetic preganglionic neurons, and is currently considered as the major factor underlying the unstable blood pressure control following SCI (Furlan et al. 2003). Furthermore, there is numerous animal and human data suggesting that plastic changes within the spinal cord (specifically spinal sympathetic neurons and primary

17-1

afferents) underlies the abnormal cardiovascular control and AD following SCI. Altered sensitivity of peripheral alphaadrenergic receptors (receptors in the sympathetic nervous system) is one mechanism that may contribute to AD (Osborn et al. 1990; Arnold et al. 1995; Krassioukov & Weaver 1995, 1996; Karlsson 1999; Krassioukov et al. 1999; Krassioukov et al. 2002). Table 17.1 Signs and Symptoms
severe headache feeling of anxiety profuse sweating above the level of injury flushing and piloerection (body hair stands on end) above the injury dry and pale skin due to vasoconstriction below the level of injury blurred vision nasal congestion cardiac arrhythmias, atrial fibrillation

17.3 Management Presently there is a well established protocol of management of AD developed by the Consortium for Spinal Cord Medicine (Consortium for Spinal Cord Medicine 1997). In patients with spinal cord injury, appropriate bladder and bowel routines, in addition to pressure sore prevention are the most effective measures for prevention of autonomic dysreflexia. However, for each individual, the identification and elimination of specific triggers for autonomic dysreflexia should also be employed to manage and prevent episodes of autonomic dysreflexia (Teasell et al. 2000; Mathias & Frankel 2002; Blackmer 2003). When AD develops, the initial management of an episode involves placing the patient in an upright position to take advantage of an orthostatic reduction in blood pressure, and the loosening of any tight clothing (Consortium for Spinal Cord Medicine 1997). Throughout the episode, the blood pressure should be checked at 5 min intervals. It is then necessary to search for and eliminate the precipitating stimulus most commonly (in 85% of cases) related to either bladder distention or bowel impaction (Teasell et al. 2000; Mathias & Frankel 2002). The use of antihypertensive drugs should be considered as a last resort, but may be necessary if the blood pressure remains at 150 mmHg or greater following the steps outlined above (Consortium for Spinal Cord Medicine 1997). The goal of such an intervention is to alleviate symptoms and avoid the complications associated with uncontrolled hypertension (Yarkony et al. 1986; Pine et al. 1991; Eltorai et al. 1992; Valles et al. 2005). The identification of the possible trigger and decrease of afferent stimulation to the spinal cord is the most effective prevention strategy in clinical practice.

17.4 Prevention Strategies The most effective approach to AD is the prevention of occurrence of this disabling and life threatening condition (Braddom & Rocco 1991). This includes careful evaluation of individuals with SCI and early recognition of possible triggers that could result in AD. Improved clinician awareness of AD and greater attention on the need to eliminate noxious stimuli in individuals with SCI is a priority. Clinicians, family members, and care givers should be aware that

17-2

increased afferent stimulation (e.g., via surgery, invasive investigational procedures, labour) to persons with SCI will increase the risk for development of AD. A variety of procedures can be used to prevent occurrence of episodes of AD. 17.4.1 Prevention of AD during Bladder Procedures Urinary bladder irritation or stimulation is the major trigger of AD following SCI (McGuire & Kumar, 1986; Linsenmeyer et al. 1996; Giannantoni et al. 1998; Teasell et al. 2000; Mathias & Frankel 2002). A bladder management program and continuous urological follow-up are important elements of the medical care of individuals with SCI (Waites et al. 1993a; Vaidyanathan et al. 1994; Vaidyanathan et al. 2004). An established bladder management program with intermittent catheterization or an indwelling Foley catheter allows individuals with SCI to plan for bladder emptying when convenient or necessary. Urological follow up includes annual urodynamic evaluations and cystoscopy examinations depending on the bladder management program. During the last decade, these strategies have decreased the frequency of urinary tract infections and development of renal failure in individuals with SCI (Waites et al. 1993a; Waites et al. 1993b; DeVivo et al. 1999). Urodynamic procedures and cystoscopy are associated with significant activation of the urinary bladder afferents and have potential to trigger AD (Snow et al. 1977; Dykstra et al. 1987; Chancellor et al. 1993; Linsenmeyer et al. 1996). Therefore, numerous studies focus on strategies designed to decrease afferent stimulation to the urinary bladder to prevent development of AD. The ideal management of urinary bladder following SCI is the reduction of the intravesical pressure, allowing efficient drainage with intermittent self catheterization and preferably with minimal activation of bladder afferents that could lead to AD. This can be achieved either by addressing the detrusor or the urethral sphincter. 17.4.1.1 Botulinum Toxin and AD Injection of Botulinum toxin into the detrusor muscle is an effective method for treating urinary incontinence secondary to neurogenic detrusor overactivity. Table 17.2 Botulinum Toxin and AD
Author Year; Country Score Research Design Total Sample Size Methods Population: 11 men with SCI and detrusor-sphincter dyssynergia Treatment: low dose botulinum A toxin at the neuromuscular junction to denervate the rhabdosphincter. Outcome Measures: urethral pressure, symptoms of AD 1. Outcome All 10 patients evaluated by electromyography after injection showed signs of sphincter denervation. The urethral pressure profile in the 7 patients in whom it was measured before and after treatment decreased an average of 27 cm H20 after toxin injections. Post-void residual urine volume decreased by an average of 146 cc after the toxin injections in 8 patients. In the 8 patients for whom it could be determined, toxin effects lasted an average of 50 days.

2.

Dykstra et al. 1988; USA Downs & Black score=12 Pre-post N=11

3. 4.

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Author Year; Country Score Research Design Total Sample Size

Methods Population: traumatic SCI, mean age: 36.7 years, 18 paraplegia, 3 tetraplegia, 17 complete, 4 incomplete, 60.2 months postinjury, incontinence resistant to anticholinergic medication Treatment: Botulinum-A toxin was injected under cystoscopic control into the detrusor muscle. Outcome Measures: voiding and detrusor pressure, diary of incontinence, AD symptoms 1. 2.

Outcome At 6-week follow-up 17/19 patients were completely continent. Urodynamic evaluation in all 19 cases revealed significant increases in mean reflex volume (p<.016) and maximum cystometric bladder capacity (p<.016). 3 patients with tetraplegia with severe AD with bladder emptying found this disappeared after treatment.

Schurch et al. 2000; Switzerland Downs & Black score=11 Pre-post N=31

3.

Discussion The duration of effect seems to be last up to 9 months. Both studies were level 4 (Dykstra et al. 1988; Schurch et al. 2000) and showed positive effects. In fact, following Botulinum toxin treatment for AD associated with bladder emptying, the AD disappeared in 3 individuals with tetraplegia. Conclusion There is level 4 evidence (from 2 pre-post studies) that Botulinum toxin injections into the detrusor seem to be a safe and valuable therapeutic option in SCI patients who perform clean intermittent self-catheterization and have incontinence resistant to anticholinergic medications. Botulinum toxin injections into the detrusor seem to be a safe and valuable therapeutic option in SCI patients who perform clean intermittent self-catheterization and have incontinence resistant to anticholinergic medications.

17.4.1.2 Capsaicin Capsaicin is the pungent extract from red pepper and exerts a selective action on certain sensory nerves, most notably those involved in reflex contractions of the bladder after spinal cord injury. Table 17.3 Capsaicin
Author Year; Country Score Research Design Total Sample Size Methods Population: 22 males, 14 females, neurologically impaired patients (20 SCI, 7 multiple sclerosis, 9 other) with urodynamically verified detrusor hyperreflexia Treatment: Randomized double-bind, placebo-controlled trial. Intravesical instillation of Resiniferatoxin (RTX) 0.005, 0.025, 0.05, 0.10, 0.2, 0.5, or 1.0 microM of 1. 2. Outcome No statistical significance due to small sample sizes. Intravesical RTX administration was well-tolerated. This patient group was refractory to all previous oral pharmacologic therapy, yet some patients responded with improvement in bladder capacity and continence function shortly

Kim et al. 2003; USA PEDro=9 RCT N=36

17-4

Author Year; Country Score Research Design Total Sample Size

Methods RTX (n = 4 each group) or placebo (n=8). Outcome Measures: incontinence episodes, bladder capacity

Outcome after RTX administration. In some cases, mean cystometric capacity increased up to 500% over baseline. Incontinence episodes decreased by over 50% for the 2 highest doses. No data available on long term effect of RXT on AD. There was no significant urodynamic or clinical improvement in the capsaicin group at 30 and 60 days of follow-up. In the resiniferatoxin group the mean uninhibited detrusor contraction threshold increased from mean 176 54 to 250107 ml at 30 days and to 27598 ml at 60 days (p<.05) and bladder capacity increased from 19675 to 365113 ml at 30 days and to 357 101 ml. at 60 days (p <0.001). AD, limb spasms, suprapubic discomfort and hematuria developed in most patients who received capsaicin but in none who received resiniferatoxin. Bladder distension increased (p<.001) the mean blood pressure before capsaicin treatment at empty and full, but this response was attenuated (p<.01) after treatment.

3. 4. 5.

Giannantoni et al. 2002; Italy PEDro=6 RCT N=23

Population: 24 SCI patients with refractory detrusor hyperreflexia Treatment: Randomized two treatments a) single dose of 2 mM. capsaicin in 30 ml ethanol plus 70 ml 0.9% sodium chloride OR b) 100 mM. resiniferatoxin in 100 ml 0.9% sodium chloride Outcome Measures: Urodynamics, frequency of daily catheterizations, incontinence episodes and side effects was recorded

1.

2.

3.

Igawa et al. 2003; Japan Downs & Black score=13 Pre-post N=7

Population: 5 cervical and 2 thoracic SCI patients Treatment: bladder instillation with capsaicin solution under general anesthesia. Outcome Measures: blood pressure, heart rate, serum catecholamines, blood ethanol concentration

1.

Discussion One pre-post study (Igawa et al. 2003) demonstrated that intravesical capsaicin diminished episodes of AD in patients with SCI during catheterization which suggested that intravesical capsaicin may be a promising therapy for both AD and detrusor hyperreflexia in SCI patients. However, two studies (Giannantoni et al. 2002; Kim et al. 2003) used an analogue of capsaicin (resiniferatoxin RXT) which is more than 1,000 times more potent in desensitizing C-fiber bladder afferents and found reduced episodes of AD. In addition, in a randomized controlled trial, Giannantoni et al. (2002) found that intravesical administration of resiniferatoxin was superior to that of capsaicin in terms of urodynamic results and clinical benefits in SCI patients and it does not cause the inflammatory side effects associated with capsaicin. However, no data on long term effect on AD were presented. Conclusion There is level 4 evidence (from 1 pre-post study) that intravesical capsaicin is effective for reducing episodes of AD in SCI

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There is level 1 evidence (from 2 RCTs) that intravesical resiniferatoxin is effective for reducing episodes of AD in patients with SCI. There is level 1 evidence (from 1 RCT) that intravesical resiniferatoxin is more effective than intravesical capsaicin. Capsaicin and its analogue, resiniferatoxin, are effective in the management of AD in patients with SCI.

17.4.1.3 Anticholinergics Anticholinergics are a class of medications that inhibit parasympathetic nerve signals by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movements of smooth muscles such as those found in the urinary tract. Table 17.4 Anticholinergics
Author Year; Country Score Research Design Total Sample Size Methods Population: 48 SCI patients, prospective study Treatment: anticholinergic drugs Outcome Measures: neurological and urological examination and urodynamic evaluation with concurrent recording of blood pressure, heart rate, symptoms of AD 1. Outcome During urodynamic evaluation all the patients with lesion level above T6 showed signs of sympathetic stimulation, although only some showed dangerous blood pressure values. Presence of detrusor uninhibited contractions and bladder distension both contribute to AD crisis. Treatment with anticholinergic drugs is not sufficient to prevent AD starting from the bladder, unless it induces detrusor areflexia.

Giannantoni et al. 1998; Italy Downs & Black score=13 Observational N=48

2. 3.

Conclusion There is level 5 evidence that anticholinergics (from 1 observational study) are not sufficient for the treatment of AD. Anticholinergics do not appear to be sufficient for the management of AD in SCI. 17.4.1.4 Sacral Denervation When detrusor hyperreflexia post-SCI does not respond to conservative treatment, and patients are not eligible for ventral sacral root stimulation for electrically induced micturition, sacral bladder denervation may be considered as a stand-alone procedure to treat urinary incontinence and AD.

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Table17.5 Sacral Denervation

Author Year; Country Score Research Design Total Sample Size Methods Population: 10 SCI patients with AD Treatment: sacral deafferentation Outcome measures: continuous noninvasive recordings of BP and HR during urodynamic recordings, pre- and postoperative data Outcome 1. There was a marked elevation in systolic and diastolic BP with bradycardia during the urodynamic examination in all eight patients, despite complete intra-operative deafferentation of the bladder in five. 2. Even after complete sacral deafferentation, AD persisted in patients with SCI and always occurred during the stimulationinduced voiding phase. 1. Detrusor hyperreflexia and autonomic dysreflexia were eliminated in all cases. 2. Bladder capacity increased from 177.8 39.6 to 668.9 64.3 mL and intravesical pressure decreased from 89.3 19.1 to 20.2 2.7 cm H2O. 3. In the 5 patients with AD, the systolic blood pressure was lowered from 196 16.9 to 124 9.3 mmHg and the diastolic blood pressure from 114 5.1 to 76 5.1 mmHg.

Schurch et al. 1998; Switzerland Downs & Black score=17 Case Series N=10

Hohenfellner et al. 2001 Germany Downs & Black score=11 Pre-post N=9

Population: 9 patients (8 men and 1 woman), 21-58 years old, traumatic SCI, detrusor hyperreflexia Treatment: sacral bladder denervation Outcome Measures: bladder capacity, blood pressure, symptomatic AD

Two level 4 studies with sacral denervation reported conflicting results. Hohenfellner et al. (2001) reported that sacral bladder denervation is a valuable treatment option in patients with detrusor hyperreflexia. However, Schurch et al. (1998) showed that complete bladder deafferentation did not abolish AD during bladder urodynamic investigations. Conclusion There is conflicting evidence (from two level 4 studies) for sacral deafferentation for prevention of AD. It is not known whether sacral deafferentation reduces AD during urodynamic investigations.

17.4.1.5 Bladder and Urethral Sphincter Surgery The association between episodes of AD and the presence of detrusor sphincter dyssynergia, high intravesical pressure and urethral pressure has led to the development of numerous surgical procedures to alleviate voiding dysfunctions and consequently AD.

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Table 17.6 Bladder and Urethral Sphincter Surgery

Author Year; Country Score Research Design Total Sample Size Barton et al. 1986; USA Downs & Black score=12 Case Series N=16 Methods Population: 16 patients with SCI (5 thoracic, 8 cervical), mean age: 32.22 years (cervical), 353 years (thoracic), 47285 months post-injury Treatment: modified transurethral external sphincterotomy. Outcome Measures: bladder and urethral pressures and volumes, blood pressures Population: 12 adults with SCI, mean age: 22-53 years, C5-T11, 9 complete, 3 incomplete, 2-27 years post-injury Treatment: augmentation enterocystoplasty Outcome Measures: functional bladder capacity, levels of blood urea nitrogen, creatinine, electrolytes 1. Outcome intravesical and urethral pressures compared to before sphincterotomy (p<.001) and blood pressure (p<.01). Other responses related to AD also were markedly attenuated. By 4 months post-op, 11/12 patients were totally continent on clean intermittent self-catheterization every 4-6 hours. Of the 3 patients in whom an artificial urinary sphincter was implanted, 2 became continent after sphincter activation and 1 had achieved continence without sphincter activation. The mean functional bladder capacity post-op was 562 cc and the bladder compliance was excellent. The mean bladder capacity was increased from 180 ml (baseline) to 300 ml (intraoperation) and 800 ml (1 year post). No complications up to 1 year post except one subject with orchitis. At one year post, all still had continence and self-intermittent catheterization done via continent stoma at the abdominal wall.

1.

Sidi et al. 1990; USA Downs & Black score=11 Pre-post N=12

2.

3. Population: 12 patients with suprasacral SCI, mean age: 35 years, mean 3.5 years post-injury, failure of treatment to suppress hyperreflexic bladder. Treatment: follow-up of Mitrofanoff procedure with enterocystoplasty. Outcome Measures: bladder capacity, adverse effects 1.

Kochakarn & Muangman 2001; Thailand Downs & Black score=6 Case Series N=12

2. 3.

External sphincterotomies are not commonly done as they are associated with significant risks, including hemorrhage, erectile dysfunction and the need for repeat procedures. Thus, alternatives have been investigated, such as urethral stents and botulinum toxin injection (Ahmed et al. 2006). The augmentation enterocystoplasty has demonstrated long-term success based on urodynamic evaluation and clinical assessment of individuals with SCI (ChartierKastler et al. 2000). Enterocystoplasty with a Mitrofanoff Procedure has now become a frequent choice of bladder augmentation in individuals with SCI (Kochakarn & Muangman 2001). Conclusion There is level 4 evidence (based on three pre-post/case series) that urinary bladder surgical augmentations resulted in a decrease of intravesical and urethral pressure and significantly diminished or completely resolved episodes of AD. Enterocystoplasty has demonstrated long-term viability compared to sphincterotomy. Enterocystoplasty has demonstrated long-term viability compared to sphincterotomy.

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17.4.2 Treatments to Reduce AD during Anorectal Procedures Pain or irritation within the colorectal area is the second most common cause of AD. Constipation, hemorrhoids, and anal fissures are frequently can be observed in patients with SCI and be responsible for episodes of AD (McGuire & Kumar 1986; Hawkins, Jr. et al. 1994; Teichman et al. 1998; Teasell et al. 2000). Furthermore, bowel routines in SCI individuals frequently involves digital stimulation that can trigger AD. Rectosignmoid distension and anal manipulation can thus be iatrogenic triggers of AD in this population (Cosman & Vu 2005). Table 17.7 Treatments to Reduce AD during Anorectal Procedures
Author Year; Country Score Research Design Total Sample Size Cosman & Vu 2005; USA PEDro=11 RCT N=25 Methods Population: complete SCI, mean 46-49 years, mean 15-25 years post-injury, C73 level of injury Treatment: intersphincteric anal block with 300 mg 1% lidocaine or normal saline (placebo) before sigmoidoscopy or anoscopic hemorrhoid ligation procedure. Outcome Measures: blood pressure Population: 45 patients (44 male, 1 female) with chronic, complete SCI, injury level of T6 or above Treatment: Double-blind, placebocontrolled trial. Patients undergoing anoscopy and/or flexible sigmoidoscopies were randomized to receive 2% topical lidocaine jelly (n=18) or nonmedicated lubricant (control, n=32) just prior to the procedure. Outcome Measures: blood pressure 1. Outcome The mean maximal systolic blood pressure increase for the lidocaine group (2214 mmHg) was lower than the placebo group (4731 mmHg) (p = 0.01) suggesting that AD risk was reduced with lidocaine. Topical lidocaine had no significant effect on mean maximal systolic blood pressure (SBP; 3525 mmHg in the lidocaine group vs. 45 30 mmHg in the control group). Greater SBP increase with anoscopic procedure compared to sigmoidoscopic procedures (4929 vs. 25 20 mmHg, respectively).

2.

Cosman et al. 2002; USA PEDro=9 RCT N=45

3.

Discussion Rectosigmoid distention and anal manipulation are among the common stimuli that may trigger AD. In two small RCTs, investigators evaluated effect of topical versus local anesthesia of anorectal area for prevention of AD during the anorectal procedures. Investigators demonstrated that anoscopy, which involves stretching of the anal sphincters, was a more potent stimulus for AD than flexible sigmoidoscopy, which involves gaseous distention of the rectosigmoid. Anal sphincter stretch and rectosigmoid distention, rather than a mucosal stimulus, are likely nociceptive triggers for procedure-associated AD (Cosman et al. 2002). In one randomized, double-blind, placebo-controlled trial AD was not abolished during the anorectal procedure by topical lidocaine in the rectum (Cosman et al. 2002). However, the same investigators in a latter RCT demonstrated that lidocaine anal sphincter block was effective in limiting anorectal procedure-associated AD (Cosman & Vu 2005). Conclusion Both anoscopy and flexible sigmoidoscopy caused significant blood pressure elevation. There is level 1 evidence (from 1 RCT) that lidocaine anal block significantly limits the AD response in susceptible patients undergoing anorectal procedures.

17-9

There is level 1 evidence (from 1 RCT) that topical lidocaine did not significantly limit or prevent AD in susceptible patients during anorectal procedures. Lidocaine anal block can limits the AD response in susceptible patients undergoing anorectal procedures. Topical lidocaine does not prevent AD during anorectal procedures. 17.4.3 Prevention of AD during Pregnancy and Labour Based on North American statistics, women represent a third of the SCI population, not an insignificant proportion (Ackery et al. 2004). In the United states, 3,000 women of childbearing age are affected by SCI (Cross et al. 1992). The ability of women to have children is not usually affected once their menstrual cycle resumes (Jackson & Wadley 1999). There are increasing numbers of women with SCI who become pregnant and have healthy babies (Cross et al. 1992). However, women with SCI are at high risk of developing uncontrolled AD during labor and delivery (Sipski 1991; Sipski & Arenas 2006). Recognition and prevention of this life threatening emergency is critical for the management of labor in women with SCI (McGregor & Meeuwsen 1985). Table 17.8 Prevention of AD during Pregnancy and Labour
Author Year; Country Score Research Design Total Sample Size Methods Population: 22 woman with SCI, 11 cervical, 11 thoracic, 10 incomplete, 12 complete Treatment: epidural anesthesia Outcome Measures: presence of autonomic hyperreflexia, type of anesthesia, type of delivery, complications 1. 2. 3. Outcome AD was experienced in 9/16 pregnancies of patients whose injury level was above T6. Most of the patients who experience AD had motor complete injuries. One patient had two grand mal seizures during labour, which may have been triggered by her severe AD and the subsequent intravenous administration of diazepam. Six patients had epidural anesthesia, which was effective for the control of AD. Labour tended to be diagnosed by dysreflexic symptoms or membrane rupture with confirmation by palpation of contractions and vaginal examination. Initial management of AD included elevation of head of the bed, nifedipine and nitrates. The most effective measure for controlling AD was to identify the cause and interrupt the triggering afferent input to the spinal cord. Of the 16 women, 25 pregnancies occurred, resulting in 22 babies & 3

Cross et al. 1992; USA Downs & Black score=4 Case Series N=22

4. Population: 17 pregnancies in 15 women with SCI, age range: 19-39 years, level of injury: T4-L3, length of injury not reported Treatment: management and outcome of pregnancies in women with SCI. Outcome Measures: antenatal care and problems, labour diagnosis and outcome 1.

Hughes et al. 1991; UK Downs & Black score=5 Observational N=15

2. 3.

Cross et al. 1991; USA Downs & Black score=4

Population: 7 cervical, 9 thoracic SCI, length of injury: 1-11 years

1.

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Author Year; Country Score Research Design Total Sample Size Observational N=16

Methods Treatment: questionnaire (in person or telephone) and hospital records review. Outcome Measures: outcomes of pregnancies - # of babies, # of abortions, fetal birth weights & Apgar scores, complications

Outcome abortions. 2/15 vaginal deliveries and 5/7 caesarian section had AD during delivery with 4 of these receiving epidural anesthesia for the control of AD. 1 patient required epidural catheter 5 days postpartum to control AD.

2.

3.

In women with SCI the onset of AD during the labor is intermittently timed with uterine contractions. In the majority of women with SCI above T10, the uterine contractions may present as only abdominal discomfort, an increase in spasticity and AD (Hughes et al. 1991). Numerous observational studies, case reports and expert opinions recommend adequate anesthesia in women with SCI during labor and delivery despite the apparent lack of sensation. Epidural anesthesia was reported as the best choice for the control of AD. The American College of Obstetrics and Gynecology (2002) emphasized that it is important that obstetricians caring for these patients are aware of the specific problems related to SCIs (2002). Autonomic dysreflexia is the most significant medical complication seen in women with SCIs, and precautions should be taken to avoid stimuli that can lead to this potentially fatal syndrome (McGregor & Meeuwsen 1985). Conclusion There is level 4 evidence that women with SCI may give birth vaginally. With vaginal delivery or when cesarean delivery or instrumental delivery is indicated, adequate anesthesia (spinal or epidural if possible) is needed. There is level 4 evidence (from 1 case series and 2 observational studies) that epidural anesthesia is preferred and effective for most patients with AD during labor and delivery. Adequate anesthesia (spinal or epidural if possible) is needed with vaginal delivery, cesarean delivery or instrumental delivery is required. Epidural anesthesia is preferred and effective for most women with AD during labor and delivery. 17.4.4 Prevention of AD during Surgery AD may be precipitated by a host of somatic and visceral noxious or non-noxious stimuli below the level of injury. Therefore a variety of interventions have been used to decrease afferent information to the spinal cord by either peripheral anesthetic blocks, epidural anesthesia, general anesthesia, or even dorsal rhizotomy (McGregor & Meeuwsen 1985; Barton et al. 1986; Cosman et al. 2002; Cosman & Vu 2005; Kutzenberger et al. 2005). Despite the partial or total loss of sensation below the level of injury, it is important to recognize that surgical procedures or manipulations can potentially initiate episodes of AD. Anesthesiologists and surgeons undertaking surgery with SCI patients must be aware of the interactions of the anesthetic and its effects on AD and how to prevent or manage AD during these procedures.

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Table 17.9 Prevention of AD during Surgery

Author Year; Country Score Research Design Total Sample Size Lambert et al. 1982; USA Downs & Black score=13 Observational N=50 Methods Population: 50 SCI patients, injury above T6, complete, mean of 6.5 years post-injury Treatment: retrospective review of 78 procedures. Three groups: 1) topical or no anesthesia sedation (n=19), 2) general anesthesia (n=13), and 3) spinal anesthesia (n=46). Outcome Measures: blood pressure Population: mean age: 53.5 yrs, range: 23-81 yrs, level of injury C1-T10, mean length of injury: 22.3 yrs, range: 0-50 yrs Treatment: retrospective review of anesthetic methods during surgery Outcome Measures: blood pressure 1. Outcome Hypertension occurred more significantly with topical or no anesthesia (15/19) compared to general anesthesia (3/13) (p=.011) and spinal anesthesia (3/46) (p<.001). No difference between general and spinal anesthesia groups (p=.114). AD occurred most commonly during the start of anesthesia (induction) with the greatest frequency when no anesthesia was provided. During induction, systolic blood pressure increased in 68.7% of procedures during combined local anesthesia and intravenous (IV) sedation, in 65.4% of IV sedation alone, in 62.1% of local anesthesia alone, in 51.5% of spinal or epidural anesthesia, in 51.5% of general anesthesia, and in 88.8% of no anesthesia.

2. 1.

Eltorai et al. 1997; USA Downs & Black score=4 Observational N=591

2.

Two observational studies presented evidence that AD is a common complication during the general surgery in individuals with SCI. Up to 90 % of individuals undergoing surgery with topical anesthesia or no anesthesia developed AD. Both studies concluded that patients at risk for AD could be protected by either general or spinal anesthesia. Conclusion There is level 5 evidence (from 2 observational studies) that indicate that patients at risk for autonomic dysreflexia are protected from developing intraoperative hypertension by either general or spinal anesthesia. Anesthesiologists and surgeons dealing with SCI patients must know how to recognize the AD syndrome, how to prevent its occurrence and how to manage it aggressively. Anesthesia should be used during surgical procedures in individuals with SCI despite apparent lack of sensation. 17.4.5 Prevention of AD during FES Exercise Functional electrical stimulation (FES) is a popular modality during the rehabilitation of individuals with SCI ( Sampson et al. 2000; Wood et al. 2001). Unfortunately, similar to any non-noxious or noxious stimuli below the level of injury, FES can result in significant afferent stimulation and trigger the development of AD (Ashley et al. 1993; Matthews et al. 1997).

17-12

Table 17.10 Prevention of AD during FES Exercise

Author Year; Country Score Research Design Total Sample Size Matthews et al. 1997; Canada PEDro=7 RCT N=7 Methods Population: 7 subjects with cervical (C4C7) complete SCI, 23-44 years, 3-21 years post-injury Treatment: Double-blind and randomized to topical anaesthetic or placebo creams. This was applied to the quadriceps muscles during graded FES exercise. Outcome Measures: heart rate, blood pressure, serum catecholamines 1. Outcome Decrease in HR and increase in systolic and diastolic BP were seen (p<.05), which is typical of the previously reported FES-induced AD response. No differences in HR, BP or catecholamine responses or FES force were seen between the two conditions.

2.

One RCT evaluated the effect of topical anaesthetic or placebo creams on two different days applied to the skin area over quadriceps muscle 1 hr prior to FES (Matthews et al. 1997). Cardiovascular and AD responses during FES were unaffected by the use of topical anaesthetic cream on the skin at the stimulation site. The authors suggested that mechanisms other than skin nociception contribute to the FES-induced AD. Conclusion There is level 1 evidence (from one RCT) supporting no effect of topical anesthetic for the prevention of AD during FES. Topical anesthetic is not effective for the prevention of AD during FES

17.5 Pharmacological Management of AD Episodes of AD in individuals with SCI can vary in severity, be asymptomatic and be managed by the individual once they are familiar with their own triggers and symptoms (Linsenmeyer et al. 1996). However, in some individuals it is difficult to find the trigger for the acute blood pressure elevation and immediate medical attention is required (Elliott & Krassioukov 2006). Antihypertensive drugs with a rapid onset and short duration of action should be used in management of acute episodes (Blackmer 2003). The Consortium for Spinal Cord Medicine (1997) recommends that if non-pharmacological measures (sit patient upright, loosen clothes, reduce irritation to the bladder and bowel) fail and arterial blood pressure is 150 mmHg or greater, then pharmacological management should be initiated. However, the Consortium for Spinal Cord Medicine (1997) does not identify any particular medication for management of AD. Numerous pharmacological agents have been proposed for management of episodes of autonomic dysreflexia (Naftchi & Richardson 1997; Blackmer, 2003). The majority of the recommendations are based on the clinical practice of management of hypertensive crises in able-bodied population. 17.5.1 Nifedipine (Adalat, Procardia) Nifedipine is a calcium ion influx inhibitor (Ca-channel blocker) which selectively inhibits calcium ion influx across the cell membrane of cardiac muscle and vascular smooth muscle without changing serum calcium concentrations. In man, Nifedipine causes decreased peripheral vascular resistance and a modest fall in systolic and diastolic pressure (5-10mm Hg systolic),

17-13

but sometimes larger. Nifedipine is generally given using the "bite and swallow" method, in a dose of 10 mg. Table 17.11 Nifedipine (Adalat, Procardia)
Author Year; Country Score Research Design Total Sample Size Methods Population: 10 SCI males with a history of AD, mean age: 30 years (range 26-38), injury levels above T5, mean 9 years postinjury (range 3-21 years) Treatment: 10-30 mg nifedipine sublingually 15 min prior to electroejaculation. 25 trials with nifedipine pretreatment and 56 trials without (1-3 trials per patient). Outcome Measures: blood pressure, voltage and current delivered during electroejaculation Population: 12 tetraplegic individuals Treatment: phenoxybenzamine (10mg bid) versus nifedipine (20mg bid) administration during cystometry. Outcome Measures: blood pressure Population: 10 patients with cervical or high thoracic SCI Treatment: 10 mg nifedipine sublingually during cystometry Outcome Measures: blood pressure 1. 2. Outcome In all but one case, blood pressures were markedly lower after nifedipine pretreatment. Systolic BP during electroejaculation was lower with nifedipine pretreatment (168 mmHg) compared to no treatment (196 mmHg). In all but one patient, tolerance to electrical stimulation was equal or greater after nifedipine pretreatment. Given as regular medication twice daily, neither drug was effective in preventing AD responses to bladder filling, and a significant number of patients developed troublesome hypotension. In each patient there was a decrease in the maximum systolic and diastolic BP after the administration of nifedipine. The group mean maximum systolic pressure decreased significantly from 147 mmHg (range 119-165 mmHg) to 118 mmHg (range 99-145 mmHg). The in blood pressure was due to a of the baseline pressure and in the blood pressure response during cystometry. All but one SCI patient demonstrated AD during ESWL with maximal increase in systolic BP of 74 mmHg. Nifedipine was administered sublingually and controlled BP elevation. For severe, acute increases in BP, ESWL stimulation was momentarily discontinued until pharmacological control of the BP was achieved, after which treatment was continued. Nifedipine alleviated AD when given sublingually during cystoscopy and prevented autonomic hyperreflexia when given orally 30 minutes before cystoscopy. No adverse drug effects were observed.

Steinberger et al. 1990; USA Downs & Black score=9 Prospective Controlled Trial N=10

3.

Lindan 1985; USA Downs & Black score=8 Prospective Controlled Trial N=12

1.

1.

Thyberg et al. 1994; Sweden Downs & Black score=13 Pre-post N=10

2.

3.

Kabalin et al. 1993; USA Downs & Black score=10 Case Series N=20

Population: 19 men and 1 woman with SCI, mean age: 45 years (range 20-63 years), 10 tetraplegia, 10 paraplegia Treatment: 10-30 mg nifedipine sublingually during Estracorporal shock wave lithotripsy (ESWL) for kidney stone treatment. Outcome Measures: electrocardiogram, blood pressure, pulse rate, peripheral oxygen saturation Population: 7 males, 21-48 years, 2-15 years post-injury, complete, cervical injuries Treatment: 10 mg nifedipine during cystosopy procedure Outcome measures: blood pressure, presence of AD

1. 2. 3.

1.

Dykstra et al. 1987; USA Downs & Black score=9 Pre-post N=7

2.

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Nifedipine was successfully tested in one non-randomized controlled trial with SCI individuals undergoing electroejaculation (Steinberger et al. 1990). Steinberger and co-investigators reported that sublingual nifedipine decreased peak systolic, diastolic, and mean BB during the procedure (Steinberger et al. 1990). Furthermore, Braddom surveyed 86 physicians with an average of 16.8 years experience in management of patients with SCI and management of AD (Braddom & Rocco 1991). They found that current pharmacologic treatment of AD varies greatly from physician to physician. Antihypertensive medications are the most frequently used medications. Nifedipine was a drug of choice in 48% of minor AD and in 58% of severe symptomatic AD. Although nifedipine has been the most commonly used agent for management of AD in individuals with SCI (Dykstra et al. 1987; Braddom & Rocco 1991; Thyberg et al. 1994; Esmail et al. 2002), its use has declined recently (Frost 2002; Anton & Townson 2004). There have been no reported adverse events from the use of nifedipine in the treatment of autonomic dysreflexia (Blackmer 2003), although all had very small samples. However, a review of nifedipine for the management of hypertensive emergencies not specific to SCI, found serious adverse effects such as stroke, acute myocardial infarction, death and numerous instances of severe hypotension (Grossman et al. 1996). Due to several reports of serious adverse reactions occurring after administration of immediate-release nifedipine, the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (1997) has discouraged use of this drug. Conclusion There is level 2 evidence (from 2 prospective controlled trials) that Nifedipine may be useful to prevent dangerous blood pressure reactions, e.g. during cystoscopy and other diagnostic or therapeutic procedures in SCI injured patients with AD.

Nifedipine may be useful to prevent or control AD in SCI individuals.

17.5.2 Nitrates (Nitroglycerine, Depo-Nit, Nitrostat, Nitrol, Nitro-Bid) Nitrates cause relaxation of vascular smooth muscle, producing vasodilator effects on peripheral arteries and veins. Dilation of postcapillary vessels, including large veins, promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular enddiastolic pressure (preload). Arteriolar relaxation reduces systemic vascular resistance and arterial pressure (after-load). Before nitrates are administered (such as nitroglycerin, isosorbide dinitrate, or sodium nitroprusside), a person with spinal cord injury presenting with acute AD should be questioned regarding their use of sildenafil. If this agent has been used within the last 24 hours, it is recommended that an alternative short-acting, rapid-onset antihypertensive agent be used. Nitrates are the second after nifedipine most commonly used agent for management of AD in individuals with SCI ( Braddom & Rocco 1991; Consortium for Spinal Cord Medicine 1997). However, no studies exist to support their use in SCI. Conclusion

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There is level 5 evidence (clinical consensus from Braddom & Rocco 1991), but no clinical studies which support the use of nitrates in the control of AD in SCI. Nitrates are commonly used in the control of AD in SCI, but not studies have been done to show their effectiveness or safety in SCI. 17.5.3 Captopril Captopril is a specific competitive inhibitor of angiotensin I-converting enzyme (ACE). During an episode of AD, captopril 25mg is recommended to administer sublingually. Table 17.12 Captopril
Author Year; Country Score Research Design Total Sample Size Methods Population: 26 consecutive patients older than 15 years with SCI above T6 Treatment: administration of a) captopril 25mg sublingually if systolic blood pressure (SBP) was at or above 150mmHg, b) 5mg of immediate-release nifedipine if SBP remained elevated 30 minutes after captopril administration Outcome Measures: systolic BP 1. Outcome A total of 33 autonomic dysreflexia episodes were documented, of which 18 episodes in 5 patients were treated with drug therapy. Captopril alone was effective in 4 of 5 initial episodes (80%). Mean SBPs at baseline and 30 minutes after captopril were 17818mmHg and 13328mmHg, respectively. The addition of nifedipine successfully reduced SBP in the remaining patient. 94% of episodes were successfully treated with the protocol.

Esmail et al. 2002; Canada Downs & Black score=9 Case Series N=7

2. 3.

Discussion Captopril appears to be safe and effective for autonomic dysreflexia management. One prospective open labeled study (Esmail et al. 2002) and numerous experts opinion suggest the use of the captopril as a primary medication in management of AD (Frost 2002; Anton & Townson 2004). Conclusion There is level 4 evidence (from one case series) for the use of captopril in the management of AD in SCI. Preliminary evidence suggests that captopril is effective for the management of autonomic dysreflexia in SCI 17.5.4 Terazosin Terazosin is a long-acting, alpha-1adrenoceptor selective blocking agent. Selective alpha 1 blockade has been suggested as a good pharmacological choice in the management of AD because of its dual effect at the bladder level (inhibition of urinary sphincter and relaxation of the smooth muscles of blood vessels). 17-16

Table 17.13 Terazosin

Author Year; Country Score Research Design Total Sample Size Methods Population: 18 adults with tetraplegia (17 male, 1 female), 3 children with ventilatordependent tetraplegia and 3 adult males with paraplegia. All had AD in the absence of an acute predisposing factor. Treatment: Terazosin with starting dose of 1 mg (adults) or 0.5 mg (children). Step-wise increments of these doses were given at 3-4 day intervals. Outcome Measures: drug-induced hypotension, adverse effects, AD symptoms Population: 6 paraplegic, 6 quadriplegic, 6 cervical, 5 thoracic, 1 lumbar, 7 complete, 5 incomplete, age range: 22-65 yrs, 13-120 months post-injury Treatment: nightly Terazosin administration for 4 weeks (5 mg starting dose). Outcome Measures: physical examination, symptom score and synchronous cystoscopy and cystometry before, during and after Terazosin therapy Population: 21 individuals with complete SCI; mean age: 34 years (range 20-53 years), C3-T5 Treatment: Terazosin administration. Outcome Measures: blood pressure and autonomic dysreflexia frequency and severity scores 1. 2. 3. Outcome The AD symptoms subsided completely with the Terazosin therapy in all the patients. Adult patients required a dose between 1-10 mg and children required between 1-2 mg. The side effects of postural hypotension and drowsiness were transient and mild. One tetraplegic patient developed persistent dizziness and therapy was discontinued. Detrusor compliance improved in all patients during the treatment phase. The change in bladder pressure and the safe bladder volume were statistically and clinically significant.

Vaidyanathan et al. 1998; UK Downs & Black score=12 Pre-post N=24

1. 2.

Swierzewski et al. 1994; USA Downs & Black score=11 Pre-post N=12

1.

Chancellor et al. 1994; USA Downs & Black score=10 Pre-post N=21

2. 3. 4.

There was a statistically significant decrease in the AD severity score from baseline at one week, 1 month and 3 months. Degree of muscle spasm and degree of headache did not improve. There was decrease in the frequency of AD at 1-week follow-up and was maintained at 1 and 3 months. Systolic blood pressure did not statistically change after 3 months of Terazosin (p=.26).

Discussion Terazosin was evaluated in several level 4 experimental studies and appears to be effective in preventing AD without erectile function impairment (Chancellor et al. 1994). Patients report moderate to excellent improvement (Chancellor et al. 1994) or even complete termination of the dysreflexic symptoms (Vaidyanathan et al. 1998). Conclusion There is level 4 evidence (from 3 pre-post studies) that Terazosin may have positive effects on incontinence and AD.

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There is limited evidence for the use of Terazosin as an agent for control of AD in SCI individuals. 17.5.5 Prazosin (Minipress) Prazosin is a postsynaptic alpha-1 adrenoceptor blocker, which lowers blood pressure by relaxing blood vessels. Prazosin has a minimal effect on cardiac function due to its alpha-1 receptor selectivity. The recommended starting dose in adults is 0.5 or 1 milligram (mg) two or three times a day. Table 17.14 Prazosin (Minipress)
Author Year; Country Score Research Design Total Sample Size Krum et al. 1992; Australia PEDro=9 RCT N=15 Methods Population: T6 or above, at least 2 episodes of AD in last 7 days Treatment: double-blind, randomized to Prazosin 3 mg bid. (n=8) or placebo (n=7) for 2 weeks. Outcome Measures: frequency and severity of AD, blood pressure 1. Outcome Prazosin was well tolerated and did not significantly lower resting BP. Compared to baseline, the Prazosin group had fewer severe episodes of AD (reduced rise in BP, shorter symptom duration and less need for acute antihypertensive medication). The severity of headache during individual AD episodes was also diminished with Prazosin therapy.

2.

Discussion Prazosin is well tolerated and does not affect the baseline blood pressure, and AD episodes were less severe and shorter in duration (Krum et al. 1992). Conclusion There is level 1 evidence (from one RCT) that Prazosin is superior to placebo in the prophylactic management of AD. Prazosin can reduce severity and duration of AD episodes in SCI. 17.5.6 Phenoxybenzamine (Dibenzyline) Phenoxybenzamine is a long-acting, adrenergic, alpha-receptor blocking agent and can increase blood flow to skin, mucosae, and abdominal viscera and lower supine and erect blood pressures. The initial does is 10 mg of Dibenzyline (phenoxybenzamine hydrochloride) bid with increases once daily, usually to 20-40 mg 2-3 times/days. Table 17.15 Phenoxybenzamine (Dibenzyline)
Author Year; Country Score Research Design Total Sample Size McGuire et al. 1976; USA Methods Population: 9 SCI individuals with severe 1. Outcome Subjects had a dramatic relief of

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Author Year; Country Score Research Design Total Sample Size Downs & Black score=9 Case Series N=9

Methods AD Treatment: phenoxybenzamine (alphasympatholytic agent) Outcome Measures: blood, bladder and urethral pressures Population: 12 tetraplegic individuals Treatment: phenoxybenzamine and nifedipine Outcome Measures: blood pressure 1. symptoms.

Outcome

Lindan 1985; USA Downs & Black score=8 Pre-post N=12

Given as regular medication twice daily, neither drug was effective in preventing AD responses to bladder filling and a significant number of patients developed troublesome hypotension.

Conclusion There is level 4 evidence for use of Phenoxybenzamine in the management of AD, however, the results are conflicting with no effects in one study (Lindan et al. 1985) and positive effects in the other (McGuire et al. 1976). It is not known whether Phenoxybenzamine is effective for the management of AD in SCI

17.5.7 Prostaglandin E2 Prostaglandin E2 is a group of hormone-like substances that participate in a wide range of body functions such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels and control of blood pressure. Table 17.16 Prostaglandin E2
Author Year; Country Score Research Design Total Sample Size Frankel & Mathias 1980; UK Downs & Black score=11 Prospective Controlled Trial N=4 Methods Population: 5 patients with complete SCI, age range: 25-37 years, C5-T4, 5-108 months post-injury Treatment: trans-rectal electrical ejaculation with and without intravenous administration of Prostaglandin E2. Outcome Measures: heart rate, blood pressure, electrocardiogram. 1. 2. Outcome Resting BP decreased and resting HR increased with Prostaglandin E2. BP decreased during electrical stimulation, which enabled tolerance of more intense stimulation and successful ejaculation in 2 patients.

Conclusion There is level 2 evidence from a very small prospective controlled study which used subjects as their own controls which showed that the level of BP recorded during electrical ejaculation was substantially reduced with Prostaglandin E2. Prostaglandin E2 may reduce BP responses during eletroejactulation.

17-19

17.5.8 Sildanefil (Viagra) Sildanefil is an inhibitor of phosphodiesterase type 5 (PDE5) and causes increased levels of cGMP in the corpus cavernosum, smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation. The recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity, but may be taken anywhere from 4 hours to 0.5 hour before sexual activity. Sildanefil is known to potentiate the hypotensive effects of nitrates and nitrates in any form is therefore contraindicated with sildanefil use. Table 17.17 Sildanefil (Viagra)
Author Year; Country Score Research Design Total Sample Size Methods Population: males with cervical (n = 8) or thoracic (n = 5) SCI Treatment: oral dose of sildenafil citrate (25-100 mg) or no medication during penile vibratory stimulation Outcomes Measures: ECG, blood pressure 1. 2. Outcome Sildenafil decreased base BP in cervical SCI. Men with cervical SCI had more pronounced AD during penile vibrostimulation than men with thoracic injuries. Administration of sildenafil had no effect on HR or BP during AD triggered by penile vibratory stimulation in men with SCI.

Sheel et al. 2005; Canada PEDro=5 RCT N=13

3.

The effect of sildenafil on AD was reported in one small prospective study (Sheel et al. 2005). Although sildenafil decreased the resting BP, there was no effect on magnitude of AD resulting from vibrostimulation in men with SCI. Conclusion There is level 1 evidence (from 1 RCT) that sildaenafil citrate had no effect on changes in BP during episodes of AD initiated by vibrostimulation in man with SCI Sildenafil has no effect on AD responses in men with SCI during ejaculation. 17.5.9 Other Pharmacological Agents Tested for Management of AD There are several other pharmacological agents supported by case reports or expert opinion for the management of AD in individuals with SCI. These agents are listed below but do not have sufficient evidence to warrant their recommendation. Table 17.18 Other Pharmacological Agents Tested for Management of AD
Drug Name Hydralazine (Apresoline) Beta blockers Mecamylamine (Inversine) Magnesium sulphate Diazoxide (Hyperstat) Phenazopyridine Evidence Expert opinion Case report Case report Case report Expert opinion Case report Author Erickson 1980 Pasquina et al. 1998 Braddom & Rocco 1991 Jones & Jones 2002; Maehama et al. 2000 Erickson 1980 Paola et al. 2003

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17.6 Summary There is level 4 evidence (from 2 pre-post studies) that Botulinum toxin injections into the detrusor seem to be a safe and valuable therapeutic option in SCI patients who perform clean intermittent self-catheterization and have incontinence resistant to anticholinergic medications. There is level 4 evidence (from 1 pre-post study) that intravesical capsaicin is effective for reducing episodes of AD in SCI There is level 1 evidence (from 2 RCTs) that intravesical resiniferatoxin is effective for reducing episodes of AD in patients with SCI. There is level 1 evidence (from 1 RCT) that intravesical resiniferatoxin is more effective than intravesical capsaicin. There is level 5 evidence that anticholinergics (from 1 observational study) are not sufficient for the treatment of AD. There is conflicting evidence (from two level 4 studies) for sacral deafferentation for prevention of AD. There is level 4 evidence (based on three pre-post/case series) that urinary bladder surgical augmentations resulted in a decrease of intravesical and urethral pressure and significantly diminished or completely resolved episodes of AD. Enterocystoplasty has demonstrated long-term viability compared to sphincterotomy. Both anoscopy and flexible sigmoidoscopy caused significant blood pressure elevation. There is level 1 evidence (from 1 RCT) that lidocaine anal block significantly limits the AD response in susceptible patients undergoing anorectal procedures. There is level 1 evidence (from 1 RCT) that topical lidocaine did not significantly limit or prevent AD in susceptible patients during anorectal procedures. There is level 4 evidence that women with SCI may give birth vaginally. With vaginal delivery or when cesarean delivery or instrumental delivery is indicated, adequate anesthesia (spinal or epidural if possible) is needed. There is level 4 evidence (from 1 case series and 2 observational studies) that epidural anesthesia is preferred and effective for most patients with AD during labor and delivery. There is level 5 evidence (from 2 observational studies) that indicate that patients at risk for autonomic dysreflexia are protected from developing intraoperative hypertension by either general or spinal anesthesia. Anesthesiologists and surgeons dealing with SCI patients must know how to recognize the AD syndrome, how to prevent its occurrence and how to manage it aggressively. There is level 1 evidence (from one RCT) supporting no effect of topical anesthetic for the prevention of AD during FES.

17-21

There is level 2 evidence (from 2 prospective controlled trials) that Nifedipine may be useful to prevent dangerous blood pressure reactions, e.g. during cystoscopy and other diagnostic or therapeutic procedures in SCI injured patients with AD. There is level 5 evidence (clinical consensus from Braddom & Rocco 1991), but no clinical studies which support the use of nitrates in the control of AD in SCI. There is level 4 evidence (from one case series) for the use of captopril in the management of AD in SCI. There is level 4 evidence (from 3 pre-post studies) that Terazosin may have positive effects on incontinence and AD. There is level 1 evidence (from one RCT) that Prazosin is superior to placebo in the prophylactic management of AD. There is level 4 evidence for use of Phenoxybenzamine in the management of AD, however, the results are conflicting with no effects in one study (Lindan et al. 1985) and positive effects in the other (McGuire et al. 1976). There is level 2 evidence from a very small prospective controlled study which used subjects as their own controls which showed that the level of BP recorded during electrical ejaculation was substantially reduced with Prostaglandin E2. There is level 1 evidence (from 1 RCT) that sildaenafil citrate had no effect on changes in BP during episodes of AD initiated by vibrostimulation in man with SCI

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McGuire TJ, Kumar VN. Autonomic dysreflexia in the spinal cord-injured. What the physician should know about this medical emergency. Postgrad Med 1986;80:81-4, 89. Naftchi NE, Richardson JS. Autonomic dysreflexia: pharmacological management of hypertensive crises in spinal cord injured patients. J Spinal Cord Med 1997;20:355-360. Osborn JW, Taylor RF, Schramm LP. Chronic cervical spinal cord injury and autonomic hyperreflexia in rats. Am J Physiol 1990;258:R169-R174. Paola FA, Sales D, Garcia-Zozaya I. Phenazopyridine in the management of autonomic dysreflexia associated with urinary tract infection. J Spinal Cord Med 2003;26:409-411. Pasquina PF, Houston RM, Belandres PV. Beta blockade in the treatment of autonomic dysreflexia: a case report and review. Arch Phys Med Rehabil 1998;79:582-584. Pine ZM, Miller SD, Alonsa JA. Atrial fibrillation associated with autonomic dysreflexia. Am J Phys Med Rehabil 1991;70:271-273. Sampson EE, Burnham RS, Andrews BJ. Functional electrical stimulation effect on orthostatic hypotension after spinal cord injury. Arch Phys Med Rehabil 2000;81:139-143. Schurch B, Knapp PA, Jeanmonod D, Rodic B, Rossier AB. Does sacral posterior rhizotomy suppress autonomic hyper-reflexia in patients with spinal cord injury? Br J Urol 1998;81:7382. Schurch B, Stohrer M, Kramer G, Schmid DM, Gaul G, Hauri D. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol 2000;164:692-697. Scott MB, Morrow JW. Phenoxybenzamine in neurogenic bladder dysfunction after spinal cord injury. J Urol 1978;119:483-484. Sheel AW, Krassioukov AV, Inglis JT, Elliott SL. Autonomic dysreflexia during sperm retrieval in spinal cord injury: influence of lesion level and sildenafil citrate. J Appl Physiol 2005;99:5358. Sidi AA, Becher EF, Reddy PK, Dykstra DD. Augmentation enterocystoplasty for the management of voiding dysfunction in spinal cord injury patients. J Urol 1990;143:83-85. Silver JR. Early autonomic dysreflexia. Spinal Cord 2000;38:229-233. Sipski ML, Arenas A. Female sexual function after spinal cord injury. Prog Brain Res 2006;152:441-447. Sipski ML. The impact of spinal cord injury on female sexuality, menstruation and pregnancy: a review of the literature. J Am Paraplegia Soc 1991;14:122-126. Snow JC, Sideropoulos HP, Kripke BJ, Freed MM, Shah NK, Schlesinger RM. Autonomic hyperreflexia during cystoscopy in patients with high spinal cord injuries. Paraplegia 1977;15:327-332. Steinberger RE, Ohl DA, Bennett CJ, McCabe M, Wang SC. Nifedipine pretreatment for autonomic dysreflexia during electroejaculation. Urol 1990;36:228-231. Swierzewski SJ, Gormley EA, Belville WD, Sweetser PM, Wan J, McGuire EJ. The effect of terazosin on bladder function in the spinal cord injured patient. J Urol 1994;151:951-954. Teasell RW, Arnold JM, Krassioukov A, Delaney GA. Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system following spinal cord injuries. Arch Phys Med Rehabil 2000;81:506-516. Teichman JM, Barber DB, Rogenes VJ, Harris JM. Malone antegrade continence enemas for autonomic dysreflexia secondary to neurogenic bowel. J Spinal Cord Med 1998;21:245-247. Thyberg M, Ertzgaard P, Gylling M, Granerus G. Effect of nifedipine on cystometry-induced elevation of blood pressure in patients with a reflex urinary bladder after a high level spinal cord injury. Paraplegia 1994;32:308-313. Vaidyanathan S, Singh G, Soni BM, Hughes PL, Mansour P, Oo T, Bingley J, Sett P. Do spinal cord injury patients always get the best treatment for neuropathic bladder after discharge from regional spinal injuries centre? Spinal Cord 2004;42:438-442.

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CHAPTER EIGHTEEN
Heterotopic Ossification Following Spinal Cord Injury
Robert W Teasell, MD FRCPC Jo-Anne Aubut, BA Maureen C Ashe, PhD, PT Linh Tu, BHSc

Key Points Anti-inflammatory medications given early post-SCI reduces development of heterotopic ossification. Warfarin may inhibit the development of heterotopic ossification post-SCI. Etidronate can halt the progression of heterotopic ossification. Radiotherapy can reduce the progression of heterotopic ossification.

Table of Contents
18.1 Introduction ..................................................................................................................18-1 18.2 Pathophysiology of Heterotopic Ossification ..........................................................18-1 18.3 Clinical Presentation and Natural History .................................................................18-1 18.4 Treatment of Heterotopic Ossification.......................................................................18-2 18.4.1 Non-Steroidal Anti-Inflammatory Drugs as Prophylaxis ..............................................18-2 18.4.2 Warfarin as Prophylaxis ..............................................................................................18-3 18.4.3 Etidronate....................................................................................................................18-3 18.4.4 Radiation Therapy.......................................................................................................18-5 18.5 Summary.......................................................................................................................18-6 References..............................................................................................................................18-7

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Teasell RW, Aubut J, Ashe MC, Tu L. (2006). Heterotopic Ossification Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 18.1-18.8. www.icord.org/scire

Heterotopic Ossification Following Spinal Cord Injury

18.1 Introduction Heterotopic ossification (HO) is the formation of pathological bone in muscle or soft tissue. In patients following a spinal cord injury, the incidence has been thought to vary greatly, ranging from 10-78% (van Kuijk et al. 2002, Banovac 2001). Banovac et al. (2001) notes HO occurs most frequently in the first 2 months after SCI below the level of paralysis. The etiology of HO is not fully understood which creates challenges in determining appropriate diagnostic and therapeutic approaches. 18.2 Pathophysiology of Heterotopic Ossification The mechanism underlying heterotopic ossification following spinal cord injury is not well understood but it is believed to be initiated by a change of mesenchymal cells into bone precursor cells (Schuetz et al. 2005). HO forms through a typical process beginning with the formation of a protein mixture created by bone cells (osteoid) that eventually calcificies within a matter of weeks (Pape et al. 2001). Over the next few months, the calcified osteoid remodels and matures into well-organized trabecular bone (Pape et al. 2001). Months following the initial trauma patients develop bone formation in muscle and the soft tissues adjacent to a joint (paraarticular) with resultant restriction in range of motion, pain and ankylosis (Banovac and Gonzalez 1997, Garland et al. 1980). The bony lesion has a high metabolic rate, adding new bone tissue more than three times the rate of normal bone and an osteoclastic (bone removal cell) density more than twice the number of osteoclasts found in healthy bone (Puzas et al. 1987). Pape and coworkers (2004) noted that mesenchymal stem cells can differentiate into osteogenic cells under the right stimuli within the right environment, even within soft tissues (Chalmers et al. 1975). These mesenchymal stem cells can generate cartilage, bone, muscles, tendons, ligaments or fat (Williams et al. 1999) and are thought to play a pivotal role in the development of HO (Pape et al. 2004). It is suspected there may be a neurogenic factor contributing to HO but the mechanism is poorly understood (Hurvitz et al. 1992, Pape et al. 2001, Pape et al. 2004). 18.3 Clinical Presentation and Natural History Schuetz and coworkers (2005) has noted that the symptoms of heterotopic ossification appear 3-12 weeks after spinal cord injury. SCI patients typically present with joint and muscle pain, parasthesias and tissue swelling in the involved region, accompanied by mild fever (Thomas & Amstutz 1987; Orzel and Rudd 1985; Smith 1998; Shehab et al. 2002). In the initial stages of HO, clinical signs of inflammation are nonspecific (Neal 2003). Measurement of biochemical markers such as osteocalcin and alkaline phosphatase, as well as three-phase bone scan have allowed earlier diagnosis of HO and earlier treatment (Banovac & Gonzalez 1997; Wilkinson et al. 2003).

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18.4 Treatment of Heterotopic Ossification Treatment of HO consists of four treatments: non-steroidal anti-inflammatory drugs, warfarin, etidronate and radiation. 18.4.1 Non-Steroidal Anti-Inflammatory Drugs as Prophylaxis This is a broad range of medications that act to reduce inflammation within the offending tissues. Table 18.1: Anti-Inflammatory Drugs as Prophylaxis
Author, Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=65 , f= 11; complete/incomplete; SCI; ASIA A-C; Time since injury: mean 24 days Interventions: The treatment group received PO rofecoxib 25 mg daily X 4 wks. Outcomes Measures: incidence of heterotopic ossification and swelling of joint(s). Population: Gender: m=33; Age: Mean=33 yrs, SCI; ASIA A-D; Treatment n=16, placebo n=17. Treatment: Treatment was slow-release indomethacin 75mg daily vs placebo X 3wks. Pts were followed up clinically until they showed signs and symptoms of HO; all were followed up with x-rays q2mos X 6mos. Where pts had evidence of a +ve nuclear bone scan for HO, the study was D/C and patient initiated on disodium etidronate. Outcomes: The effect of indomethacin administration on the incidence of heterotopic ossification. 1. Outcome A significantly lower incidence of HO was found in rofecoxib group (13.4%) than in the placebo group (33.3%, p<0.05). In patients receiving rofecoxib, there was 2.5X lower relative risk of developing HO than in the placebo group. There was a significantly higher incidence of early HO, diagnosed on nuclear bone scan, in the placebo group (11/17) than in the group taking indomethacin (4/16) (p<.001). In the placebo group, 7/17 pts developed x-ray evidence of HO as did 2/16 in the indomethacin treated group (p<.001).

Banovac et al. 2004; USA PEDro=10 RCT N=76

2.

1.

Banovac et al. 2001; USA PEDro=9 RCT N=33

2.

There were two highly rated RCTs examining the use of non-steroidal anti-inflammatory drugs in the early phase after a SCI in an attempt to reduce the incidence of HO Banovac and coworkers (2001) randomized 33 SCI patients approximately 3 weeks post-SCI and treated them prophylactically with either slow-release indomethacin 75 mg daily or placebo for a total of 3 weeks. Patients were carefully followed with regular clinical follow-up and nuclear bone scans. There was a significantly higher incidence of HO, diagnosed on nuclear bone scan and on X-ray, in the placebo group compared with the group taking indomethacin (p<.001). Banovac and coworkers (2004) in a more recent study randomized 76 patients in the early phase post-SCI into 2 goups: the treatment group who received 25 mg rofecoxib 25 mg daily for weeks and a placebo group. A significantly lower incidence of HO was found in the rofecoxib group (13.4%) than in the placebo group (33.3%) (p<.05). Both of these RCTs provided compelling evidence that anti-inflammatory drugs, given prophylactically reduce the likelihood of developing HO. Rofecoxib is no longer available due to cardiovascular side effects.

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Conclusions There is Level 1 evidence that non-steroidal anti-inflammatory medications can reduce the incidence of heterotopic ossification when administered early after a spinal cord injury. Anti-inflammatory medications given early post-SCI reduces development of heterotopic ossification.

18.4.2 Warfarin as Prophylaxis Warfarin is a well-known anti-coagulant which may also be useful in the prevention of heterotopic ossification post-SCI. Table 18.2: Warfarin as a Prophylaxis
Author, Year; Country Score Research Design Total Sample Size Buschbacher et al. 1992; USA Downs &Black score=9 Observational Retrospective (chart review) N=227 Methods Population: Gender M=94%, F=6%; Age: 17-75 yrs complete/incomplete; SCI Treatment: Patients treated with warfarin for 5.4 weeks (mean time) post-SCI for DVT with no X-rays taken to rule out HO. HO diagnostic tests only if clinical signs suggested. Outcome Measures: not specified 1. 2. Outcome Warfarin administration and development of HO were found to be significantly related (p<.01). None of the pts treated with Warfarin (n=33) developed HO and none of the patients with HO (n=34) had been treated with Warfarin.

There is only one observational retrospective study examining the association between Warfarin use and heterotopic ossification post-SCI. Buschbacher et al. (1992) studied 227 patients with SCI. None of the 33 patients treated with Warfarin an average of 5.4 weeks post-SCI were diagnosed as suffering from heterotopic ossification; of the remainder 34 patients were diagnosed as suffering from HO and no patient with a diagnosis of HO had been treated with Warfarin. The authors speculated that Warfarin provided a protective or inhibitory effect against HO. Conclusion There is Level 5 evidence that Warfarin inhibits the development of heterotopic ossification post spinal cord injury. Warfarin may inhibit the development of heterotopic ossification post-SCI. 18.4.3 Etidronate
Etidronate was introduced in the 1970s for treatment of heterotopic ossification post-SCI and is still commonly used today (Banovac et al. 1997; Fleisch 1991). The medication works by inhibiting the transformation of amorphous calcium phosphate into crystalline hydroxyapetite (Fleisch 1991; Fleisch et

18-3

al. 1969; Banovac et al. 1997). Although commonly used its efficacy in prophylaxis has been questioned (Finerman & Stover 1981).

Table 18.3: Etidronate in the Treatment of Heterotopic Ossification

Author, Year; Country Score Research Design Total Sample Size Banovac et al. 1993; USA Downs & Black score=12 Prospective Controlled Trial N=27 Methods Population: Gender: m=25, f=2 Age:15-64 yrs; Time since injury: 2-6 wks : Frankel Class: A=15, B=12 ; SCI; complete/incomplete Treatment: 300mg of Etidronate Disodium was administered by IV over a 3 hr period for 3-5days. After parenteral therapy 20 mg of etidronate was administered orally for 6 months Population: Gender: m=44, f=2; Age:1655 yrs SCI; Time since injury:,2-5 wks : ASIA A-C Treatment: 3 hrs of IV disodium etidronate on day of HO dx and continued for 3 successive days followed by PO etidronate X6 mos. Outcome Measures: degree of heterotopic ossification 1. Results After initial IV therapy, 20 pts showed prompt reduction in swelling 1st 48 hrs, while 7 pts had no change or an increase in swelling. 2. Overall, treatment reduced swelling (p<0.01). 3. No significant differences noted between the IV and orally treated groups in effect on HO. 1. Group 1 (+ve bone scan and ve xray for HO, n=33), 5 pts discontinued therapy and showed gradual development of HO. Of the remaining 28 pts, 22 had no x-ray evidence of HO while 6 developed x-ray dx HO by F/U. 2. Group 2 (+ve bone scan and x-ray, n=13) 6 patients progression of soft tissue ossification was inhibited by etidronate while the remaining 7 did not respond to Rx and showed progression of HO. No statistical results reported 1. None of the pts treated with pamidronate showed clinical, x-ray or lab signs of HO recurrence or new forming HO at time of F/U 5-54 months post-op.

Banovac et al. 1997; USA Downs & Black score=9 Prospective Controlled Trial N=46

Schuetz et al. 2005; Switzerland Downs & Black score=9 Case Series N=7

Banovac 1999; Denmark Downs & Black score=7 Case Series N=40 Subbarao et al. 1986; USA Downs & Black score=8 Case Series N=5

Population: Gender: m=7; Age: 47-68 yrs; 1 thoracic lesion, 2 tetraplegics. Treatment: All pts underwent excisionsurgery for removal of HO. Pamidronate was administered IV peri- and post-op, starting at a dose level of 120 mg for 1st 12 hrs and gradually increasing for a total of 614 days. Outcome Measures: not specified Population: Gender: m=39, f=1 Age: mean=23 yrs: SCI; Time since injury: mean 2-5 wks, ASIA A& B. Treatment: All pts with +ve clinical findings and +ve nuclear bone scan were treated with IV etidronate sodium and then PO 20mg/kg/day X 6mos. Outcome Measures: Not specified Population: Age 29-41 yrs,: SCI; Time since injury: 18-197mths Treatment: Didronel given 10 days 2 wks preoperatively, medication withheld for immediate postop period (72 hrs) and continued for min. of 3 mos. All 5 pts underwent wedge resection at hip to permit free movement of hip in flexion. Outcome Measures: Not specified

No statistical results reported 1. 11/40 patients developed radiographic evidence of HO from 1.5 to 6 yrs post treatment. 2. In 95% of cases of recurrent HO in developed in different areas involving different joints. No statistical results reported 1. All pts at last F/U were able to function independently in their wheelchairs except one but was able to function independently in a semireclining W/C. 2. Pts had severe restriction of ROM in involved joints.

Banovac et al. (1993) provided IV etidronate for 3-5 days followed by PO etidronate for 6 months to 27 SCI patients following diagnosis of heterotopic ossification and then compared to 11 SCI patients treated with PO etidronate for 6 months alone. After initial IV therapy, 20

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patients showed prompt reduction in swelling over the first 48 hours while 7 patients had no change or an increase in swelling. Overall, treatment reduced swelling (p<.01). There was no significant difference noted between the IV and orally treated groups in its effect on heterotopic ossification. Banovac et al. (1997) subsequently studied 46 patients (of whom 5 were excluded because of discontinuation of therapy) who were treated with 3 days of IV disodium etidronate followed by PO etidronate for 6 months. 33 patients had a positive bone scan but a negative xray for HO and of these 5 discontinued treatment and showed gradual progression of HO. Of the remaining 28 patients, 22 had no x-ray evidence of HO while 6 developed HO on x-ray. 13 patients had a positive bone scan and a positive x-ray, 6 patients progression of soft tissue ossification was inhibited by etidronate while the remaining 7 did not respond to treatment and showed progression of HO. Banovac (1999) studied 40 SCI patients with HO, diagnosed early with positive bone scan and negative x-rays, were treated with etidronate (IV x 3days and then PO x 6months). 11 of the 40 (27.5%) developed radiographic evidence of HO from 1.5-6.0 years post initiation of therapy. Subbarao et al. (1986, N=5) and Schuetz et al. (2005, N=7) used edridonate pre and post surgical hip wedge resection and pamidronate pre and post heterotopic ossification surgical removal with no occurrence of heterotopic ossification. However, numbers were small. These results are difficult to interpret because of the lack of RCTs and the different treatment scenarios. It appears that etidronate is able to delay or inhibit HO progression once it is diagnosed and it tends to work with early after the SCI rather than waiting. Conclusions There is Level 2 evidence that etidronate can stop the progression of heterotopic ossification once the diagnosis is made; it is most effective if given at the time the nuclear bone scan is positive but the radiographs are negative.

Etidronate can halt the progression of heterotopic ossification.

18.4.4 Radiation Therapy Radiation therapy or radiotherapy is the use of ionizing therapy in the treatment of heterotopic ossification. Table18. 4: Radiation Therapy in Treatment of Heterotopic Ossification Post-SCI
Author, Year; Country Score Research Design Total Sample Size Sautter-Bihl et al. 2000; Germany Downs & Black score =9 Experimental Non-RCT N=36 Methods Population: Gender: m-32, f=4; age: 17-59 yrs; Follow-up: 4-98 months. Treatment: 25/36 subjects received 10 Gy in fraction of 2-2.5Gy, while 4 pts received higher doses. In phase 2- 7 subjects received a single does of irradiation with 8Gy. In total 46 joints were irradiated. Outcome measures: not specified Results No statistically significant results reported. 1. 16 of the 32 hips treated with radiotherapy only did not show any abnormalities on F/U 2. No progression of HO was noted in 30/36 subjects. 3. Reossification after therapy, which led to a decrease in joint mobility, was noted in 3 subjects.

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Sautter-Bihl et al. (2000) studied 36 patients with heterotopic ossification of whom 27 patients (32 joints) received radiotherapy only to treat myositis initiated ASAP when ossification was minimal. 11 patients (13 joints) had manifest ossifications, which had to be resected. Post-op radiotherapy was performed 24-36 hours post-op. 2 patients received radiotherapy both before and after surgery. Mean duration of follow-up was 23.6 months. 30 of the 36 irradiated patients showed no progression of HO. In 3 patients reossifications after therapy caused a moderate decrease in joint mobility. Conclusion

There is Level 2 evidence that radiotherapy reduces the progression of heterotopic ossification.
Radiotherapy can reduce the progression of heterotopic ossification

18.5 Summary Schuetz and coworkers (2005) note that after a SCI, heterotopic ossification still remains a therapeutic challenge. Anti-inflammatory medications provided early on prevents the development of HO while warfarin was associated with a decreased risk of HO but this needs further investigation. Both radiotherapy and etidronate appear to halt the progression of heterotopic ossification once it is diagnosed. Although more research is needed, early work in encouraging suggesting that heterotopic ossification post-SCI is treatable. There is strong Level 1 evidence that anti-inflammatory medications provided early on post spinal cord injury reduces the likelihood of developing heterotopic ossification. There is Level 5 evidence that Warfarin inhibits the development of heterotopic ossification post spinal cord injury. There is Level 2 evidence that etidronate can stop the progression of heterotopic ossification once the diagnosis is made; it is most effective if given at the time the nuclear bone scan is positive but the radiographs are negative. There is limited Level 2 evidence that radiotherapy reduces the progression of heterotopic ossification.

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References
Banovac K, Gonzalez F, Wade N & Bowker JJ. Intravenous disodium etidronate therapy in spinal cord injury patients with heterotopic ossification. Paraplegia 1993;31:660-666. Banovac K & Gonzalez F. Evaluation and management of heterotopic ossification in patients with spinal cord injury. Spinal Cord 1997;35:158-162. Banovac K, Gonzalez F & Renfree KJ. Treatment of heterotopic ossification after spinal cord injury. J Spinal Cord Med 1997;20:60-65. Banovac K, Renfree KJ & Hornicek FJ. Heterotopic ossification after brain and spinal cord injury. Crit Rev Physic Rehab Med 1998;10:223-256. Banovac K. The effect of etidronate on late development of heterotopic ossification after spinal cord injury. The Journal of Spinal Cord Medicine 2000;23(1):40-44. Banovac K, Williams JM, Patrick LD & Haniff YM. Prevention of heterotopic ossification after spinal cord injury with indomethacin. Spinal Cord 2001;39:370-374. Banovac K, Williams JM, Patrick LD & Levi A. Prevention of heterotopic ossification after spinal cord injury with COX-2 selective inhibitor (rofecoxib). Spinal Cord 2004;42:707-710. Blane CE & Perkash I. True heterotopic bone in the paralyzed patient. Skel Radiol 1981;7:21-25. Bravo-Payno P, Esclarin A, Arzoz T, Arroyo O & Labarta C. Incidence and risk factors in the appearance of heterotopic ossification in spinal cord injury. Paraplegia 1992; 0:740-745. Buschbacher R, McKinley W, Buschbacher L, Devaney CW & Coplin B. Warfarin in prevention of heterotopic ossification. American J Phys Med Rehabil 1992;71:86-91. Chalmers J, Gray DH, Rush J. Observations on the induction of bone in soft tissues. J Bone Joint Surg Br 1975; 57:36-45. Colachis SC & Clinchot DM. The association between deep venous thrombosis and heterotopic ossification in patients with acute traumatic spinal cord injury. Paraplegia 1993;31:507-512. Dejerine A & Cellier A. Paraosteoarthopathies of paraplegic patients by spinal cord lesion: Clinical and roentgenographic study (translated, condensed, and abridged from Ann Med 5:497, 1918). Clin Ortho Rel Res 1991;263:3-12. Finerman GA & Stover SL. Heterotopic ossification following hip replacement or spinal cord injury. Two clinical studies with EHPD. Metab Bone Dis Rel Res 1981;3:337-342. Fleisch H. Biphosphonates. Pharmacology and use in the treatment of tumour-induced hypercalcaemic and metastatic bone disease. Drugs 1991;42:919-944. Fleisch H, Russell RG & Francis MD. Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science 1969;165:1262-1264. Freed JH, Hahn H, Menter R & Dillon T. The use of the three-phase bone scan in the early diagnosis of heterotopic ossification (HO) and in the evaluation of Didronel therapy. Paraplegia 1982;20:208-216. Garland DE & Orwin JF. Resection of heterotopic ossification in patients with spinal cord injuries. Clin Orthop 1989;242:169-176. Garland DE. A clinical perspective on common forms of acquired heterotopic ossification. Clin Ortho Rel Res 1991;263:13-29. Garland DE. Surgical approaches for resection of heterotopic ossification in traumatic brain-injured adults. Clin Orthop 1991;263:59-70. Hardy AG & Dickson JW. Pathological ossification in traumatic paraplegia. J Bone Joint Surg 1963;45B:76-87. Hencey JY, Vermess M, van Geertruyden HH, Binard JE & Manchepalli S. Magnetic resonance imaging examination of gluteal decubitus in spinal cord injury patients. J Spinal Cord Med 1996;19:5-8. Hernandez AM, Forner JV, de la Fuenta T, Gonzalez C & Miro R. The para-articular ossification in our paraplegics and tetraplegics: a survey of 704 patients. Paraplegia 1978;16:272-275. Hurvitz EA, Mandac BR, Davidoff G, Johnson JH, Nelson VS. Risk factors for heterotopic ossification in children and adolescents with severe traumatic brain injury. Arch Phys Med Rehabil 1992; 73:459462. Lal S, Hamilton BB & Heinemann A. Risk factors for heterotopic ossification in spinal cord injury. Arch Phys Med Rehabil 1989;70:387-390. Liberson M. Soft tissue calcification in cord lesions. JAMA 1953;152:1010-1013. Neal B. Effects of heterotopic bone formation on outcome after hip arthroplasty. ANZ J Surg 2003; 73:422-426.

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Orzel JA & Rudd TG. Heterotopic bone formation: clinical, laboratory, and imaging correlation. J Nucl Med 1985; 26:125-132. Pape HC, Lehmann U, van GM, Gansslen A, von GS, Krettek C. Heterotopic ossifications in patients after severe blunt trauma with and without head trauma: incidence and patterns of distribution. J Orthop Trauma 2001; 15:229-237. Pape HC, Marsh S, Morley JR, Krettek C, Giannoudis PV. Current concepts in the development of heterotopic ossification. J Bone Joint Surg Br 2004; 86:783-787. Perkash A, Sullivan G, Toth L, Bradleigh LH, Linder SH & Perkash I. Persistent hypercoagulation associated with heterotopic ossification in patients with spinal cord injury long after injury has occurred. Paraplegia 1993; 31:653-659. Puzas JE, Evarts CM, Brand JS. The stimulus for bone formation. Hip 1987;25-38. Sautter-Bihl ML, Liebermeister E & Nanassy A. Radiotherapy as a local treatment option for heterotopic ossifications in patients with spinal cord injury. Spinal Cord 2000; 38:33-36. Sazbon L, Najesnon T, Tartakovsky M, Becker E & Grosswasser Z. Widespread periarticular new-bone formation in long-term comatose patients. J Bone Joint Surg 1981; 63B:525-528. Schuetz P, Mueller B, Christ-Crain M, Dick W & Haas H. Amino-biphosphonates in heterotopic ossification: first experience in five consecutive cases. Spinal Cord 2005; 43:604-610. Shehab D. Elgazzar AH & Collier BD. Heterotopic ossification. J Nucl Med 2002; 43:346-353. Smith R. Fibrodysplasia (myositis) ossificans progressive. Clinical lessons learned from a rare disease. Clin Orthop 1998; 346: 7-14. Stover SL, Hataway CJ & Zeiger HE. Heterotopic ossification in spinal cord-injured patients. Arch Phys Med Rehabil 1975; 56:199-204. Subbarao JV, Nemchausky BA & Gratzer M, Hines E. Resection of heterotopic ossification and didronel therapy regaining wheelchair independence in the spinal cord injured patient. J AM Paraplegia Soc. 1987;10(1):3-7. Thomas BJ & Amstutz HC. Prevention of heterotopic bone formation: clinical experience with diphosphonates. Hip 1987; 59-69. van Kuijk AA, Geurts AC & van Kuppevelt HJ. Neurogenic ossification in spinal cord injury. Spinal Cord 2002; 40:313-326. Williams JT, Southerland SS, Souza J, Calcutt AF, Cartledge RG. Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes. Am Surg 1999; 65(1):22-26. Wilkinson JM, Stockley I, Hamer AJ, Barrington NA & Eastell R. Biochemical markers of bone turnover and development of heterotopic ossification after total hip arthroplasty. J Orthop Res 2003; 21:529534. Wittenberg R, Peschke U & Botel U. Heterotopic ossification after spinal cord injury. J Bone Joint Surg 1992; 74B:215-218.

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CHAPTER NINETEEN
Nutrition Issues Following Spinal Cord Injury
Chris Fraser, HBSc, RD Stephanie Muir-Derbyshire, MSc SLP(C) Reg CASLPA Candice A Rideout, PhD (Candidate) Robert W Teasell, MD FRCPC

Key Points A combined diet and exercise program can help patients reduce weight following SCI without compromising total lean mass and overall health. Participation in a holistic wellness program is positively associated with improved eating and weight-related behaviours in persons with SCI. Dietary counseling results in improved lipid profile; consultation with a registered dietitian should be obtained, because individualized diets may enhance compliance. Blood concentrations of DHA and EPA increased as the result of n-3 fatty acid supplementation; however, no significant changes in lipid profile were identified. Individuals with SCI should be screened for vitamin D deficiency and, if needed, replacement therapy should be initiated. Creatine supplementation does not result in improvements in muscle strength, endurance or function in weak upper limb muscles. Clinicians should conduct early screening for and treatment of vitamin B12 deficiency. Creatine supplementation does not result in improvements in muscle strength, endurance or function in weak upper limb muscles. More research is needed to evaluate the role of nutrition in the management of postacute SCI to provide the evidence base required for optimal clinical decisions.

Table of Contents
19.1 Introduction .................................................................................................................19-1 19.2 Nutrition-related Complications .................................................................................19-1 19.2.1 Altered Glucose Metabolism .......................................................................................19-1 19.2.2 Neurogenic Bowel.......................................................................................................19-1 19.2.3 Neurogenic Bladder and Risk for Urinary Tract Infections ..........................................19-2 19.2.4 Pressure Ulcers ..........................................................................................................19-2 19.2.5 Osteoporosis...............................................................................................................19-2 19.3 Nutritional Intervention Programs for Obesity & Wellness .....................................19-2 19.3.1 Energy Imbalance ......................................................................................................19-2 19.3.2 Health Promotion .......................................................................................................19-4 19.4 Nutritional Interventions for Dyslipidemia ................................................................19-5 19.4.1 Nutrition Counseling for Dyslipidemia and Cardiovascular Disease Risk ...................19-5 19.4.1.1 Omega-3 Fatty Acid Supplementation .....................................................................19-6 19.5 Vitamin Deficiencies and Supplementation ..............................................................19-7 19.5.1 Vitamin D Supplementation ........................................................................................19-7 19.5.2 Vitamin B12.................................................................................................................19-9 19.6 Creatine Supplementation for Muscle Function ....................................................19-10 19.5 Summary.....................................................................................................................19-11 References ...........................................................................................................................19-12

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Fraser C, Muir-Derbyshire S, Rideout CA, Teasell RW (2006). Nutrition Issues Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 19.1-19.13. www.icord.org/scire

Nutrition Issues Following Spinal Cord Injury

19.1 Introduction Given that traumatic spinal cord injuries tend to occur among young previously well-nourished persons, declines in nutritional status most likely occur post injury. These declines are likely due to the combined effects of altered metabolism and lifestyle choices. Many secondary complications of SCI are related to changes in energy, glucose, lipid and vitamin metabolism, including undesirable weight gain, cardiovascular disease risk, insulin resistance and osteoporosis. Additional nutrition-related complications which can negatively impact quality of life include pressure ulcers and neurogenic bowel and bladder. At this point, little is known about the most effective health promotion activities, including nutrition interventions, required to promote long-term wellness for persons after SCI. However, it is clear that adequate nutrition following SCI will help reduce the likelihood of further morbidity associated with post-SCI physiological and metabolic changes. This chapter will summarize what is currently known regarding nutrition issues in the post-acute SCI population. 19.2 Nutrition-related Complications 19.2.1 Altered Glucose Metabolism Many factors contribute to increased risk of insulin resistance and hyperinsulinemia, glucose intolerance, cardiovascular disease and obesity in persons with SCI. These factors tend to correlate with the severity and level of the neurological deficit (Javierre et al. 2005). It is hypothesized that the decreased lean muscle mass and increased adipose tissue which follow a SCI lead to impaired glucose uptake and affect whole body glucose homeostasis (Javierre et al. 2005). Pathogenesis of SCI and lifestyle factors impact blood glucose management and increase the risk of morbidity and mortality due to cardiovascular diseases, the principal cause of death among persons with SCI (Arrowwood et al. 1987; Yekutiel et al. 1989; Javierre et al. 2005). Abnormalities in lipid metabolism in SCI develop early following injury and tend to progress over time (Brenes et al. 1986; Bauman et al. 1992; Kocina 1997; Szlachcic et al. 2000). Insulin resistance and exaggerated hyperinsulinemia in response to an oral glucose challenge are associated with the development of Type II diabetes mellitus, atherosclerosis and ischemic heart disease in the SCI population (Duckworth et al. 1983; Defronzo et al. 1991; Bauman et al. 1992; Mohr et al. 2000). 19.2.2 Neurogenic Bowel Alterations in the central or peripheral nervous system can result in delayed gastric emptying, prolongation of intestinal transit time, and poor colonic motility, collectively known as neurogenic bowel. Neurogenic bowel has a significant impact on the quality of life of spinal cord injured patients, causing morbidity and even death (Correa & Rotter 2000). Modifications to dietary fibre consumption may assist with the management of neurogenic bowel following SCI. For further discussion on neurogenic bowel and specific nutrition interventions, see Chapter 12.

19-1

19.2.3 Neurogenic Bladder and Risk for Urinary Tract Infections Functional foods are products that are demonstrated to have health benefits and/or reduce the risk of chronic disease beyond their basic nutritional functions (Health Canada 2002). Cranberry juice as it pertains to urinary tract infection risk may fall under the category of a functional food. Refer to Chapter 13 for further information on the potential impact of cranberry juice on urinary tract infection in the SCI population. 19.2.4 Pressure Ulcers Pressure ulcers are common following SCI, and healing can be compromised by suboptimal nutrition status. SCI patients with pressure ulcers have lower zinc, albumin and prealbumin levels than those without pressure ulcers (Cruse et al. 2000a). Impaired nutritional status contributes to delayed or incomplete wound healing (Cruse et al. 2000b). Refer to Chapter 20 for additional information regarding pressure ulcers in the SCI population. 19.2.5 Osteoporosis Osteoporosis is a common sequelae of SCI resulting in increased bone fragility and fracture risk (Warden et al. 2001). In addition to pharmacological and other management strategies, supplementation with nutrients such as calcium and vitamin D may play a role in bone health following SCI. Refer to Chapter 9 for further details. 19.3 Nutritional Intervention Programs for Obesity & Wellness 19.3.1 Energy Imbalance Obesity is a common secondary complication of chronic SCI and is associated with adverse metabolic sequelae. In order to maintain a healthy weight, one must stay in energy balance, with energy intake equaling energy expenditure. Total daily energy expenditure is determined by three factors: resting metabolic rate, physical activity and the thermic effect of food. Each of these factors is altered following a SCI, rendering it challenging for SCI patients to achieve and maintain energy balance. The resting metabolic rate of people with chronic SCI is estimated to be 1427% lower than their able-bodied counterparts, largely due to reductions in fat-free mass and reduced sympathetic nervous system activity (Buchholz & Pencharz 2004). Physical activity levels of persons with SCI are generally lower than that of able-bodied persons (Buchholz & Pencharz 2004. In addition, a lower thermic effect of food has been reported in persons with a SCI compared to able-bodied controls (Monroe et al. 1998). Without appropriate modification of dietary intake following SCI, energy intake readily exceeds daily energy expenditure, thus predisposing persons with SCI to undesirable weight gain (Cox et al. 1985). Given alterations in resting energy expenditure, it can be challenging to accurately estimate daily energy requirements for individuals with post-acute SCI. Equations validated and used in able-bodied populations to predict resting metabolic rate overestimate actual measured energy needs in the SCI population (Buchholz & Pencharz 2004). For this reason, it has been suggested that energy needs following SCI are best assessed by indirect calorimetry using a metabolic cart (Hadley 2002). Because not all health care centers have access to metabolic carts to measure resting metabolic rate, validated equations specific to the SCI population are needed.

It is important to note that despite widespread emphasis on obesity-related health risks in persons with SCI, limited research has been carried out to address this problem. There is a lack of information regarding the health outcomes of weight loss in this population. In addition, there are limited educational resources available on nutrition issues and weight control for this high-risk group (Chen et al. 2006). Table 19.1 Energy Expenditure and Overweight/Obesity
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=9, f=7; SCI, ASIA: A D: family history of overweight/obesity: yes n=11, no n=5 Treatment: Attended 12 wks (90 min/wk) of classes that were focused on nutrition and exercise on weight control, weight reduction, and 6 wks (30-min exercise session was introduced). (Clarify) Outcome measures: Physiologic measures, diet behaviour, psychosocial well being. 1. 2. Outcome During intervention: 14 subjects lost weight (4.2 2.7kg) Decreases were noted in BMI (p<0.05), waist circumference (p<0.0005), neck circumference (p<0.02), skinfold thickness (p<0.0005). HDL levels decreased significantly (p<0.03). Post intervention follow-up (n=13): 6 continued to lose wt (2.1 1.8 kg), 4 kept wt off, 3 gained wt (3.0 2.2 kg).

Chen et al. 2006; USA Downs & Black score=16 Pre-post Initial N=17; Final N=16

3. 4.

Discussion Chen et al (2006) conducted a study to assess the effect of a weight loss program on body weight, body mass index, waist and neck circumference, skinfold thickness, fat vs. lean mass, bone mineral content, blood pressure, serum lipids, hemoglobin, albumin, eating habits, nutrition knowledge, bowel function and indicators of psychosocial well-being. A total of 16 subjects with chronic SCI who were overweight or obese completed the intervention program (15 = traumatic SCI; 1 = spina bifida). Subjects attended 90 minute counseling sessions once per week for 12 weeks, led primarily by a registered dietitian. The dietary approach emphasized high-fibre, nutrient-dense foods (fruits, vegetables, grains, cereals) and the moderation of meats, cheeses, sugars and fats (Weinsier et al. 1983). The program included exercise and behaviour modification. Reported results included an average weight loss of 3.5 kg (3.8% of initial weight), significant reductions in body mass index, anthropometric measures and fat mass. Lean mass, hemoglobin, albumin and bone mineral content were maintained. There was no significant change in blood pressure or LDL cholesterol. There was a decrease in HDL cholesterol. There was a trend between weight lost and decrease in waist circumference, increase in nutritional quality of diet, increase in fibre consumption and decrease in time required for bowel movement. Changes in psychosocial and physical functioning were also reported. Conclusion There is level 4 evidence (from one pre-post trial) that an intervention program combining diet and exercise is effective for reducing weight among overweight persons with SCI. A combined diet and exercise program can help patients reduce weight following SCI without compromising total lean mass and overall health.

19.3.2 Health Promotion Little is known about the most effective health promotion activities, including nutrition interventions, to meet the long-term wellness needs for persons after SCI. A holistic wellness program intervention was developed, conducted and assessed by Zemper et al. 2003. Table 19.2 Nutritional Intervention and Long-Term Wellness Needs for Individuals after SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=30, f=13;Age:2280; Time since injury: 1-49yrs; Incomplete/complete, SCI Treatment: Subjects attended a series of six 4 hr workshop sessions over a 3mth period Outcome measures: Wellness survey, Health Promoting Lifestyle Profile-II (HPLP), Secondary Conditions Scale, SelfRated Abilities for Health Practices Scale (SAHP), Perceived Stress Scale, & Physical Activities with Disability (PADS) , Questionnaire. 1. Outcome Treatment groups scores on the SAHP improved following treatment (p<0.05) as well as on the HLPH-II (total score) & the HPLP-II health related subscale score (p<0.001). Treatment group scores improved post-treatment on the HELP-II (nutrition subscale) (p<0.05). Mean scores for the treatment groups improved significantly for the HPLP-II stress management subscale (p=0.001). Treatment group's stress scores also improved, indicating less stress (p<0.05). HPLP-II physical activity scores improved post treatment for the treatment group only (p=0.001). No significant differences were noted for the PADS score for either group post treatment. Secondary Conditions Scale score decreased for the treatment group, post treatment (p=0.001), indicating fewer and less sever problems with secondary conditions. Number of secondary conditions was decreased for the treatment group post treatment (p<0.01).

2. 3.

Zemper et al. 2003; USA PEDro=8 RCT Initial N=76; Final N=43

4.

5.

Discussion In this study, 43 adults with SCI were randomly assigned to intervention or control groups. The intervention group attended 6 half-day wellness workshops over a 3-month period which included nutrition, physical activity, lifestyle management and prevention of secondary conditions. Among other measurements, total cholesterol and body mass index were assessed. Health Promoting Lifestyle Profile-II (HPLP-II) was used to assess nutrition and other health promotion habits. There was improvement in the HPLP-II nutrition subscale mean score for the intervention group. Mean body mass index values actually increased for both groups. Total cholesterol values rose for both groups (the study reported on total cholesterol only; changes in HDL and LDL cholesterol values were not reported). There were significant improvements in reported eating and weight related behaviours.

Conclusion There is level 1 evidence (based on one RCT) that improved health related behaviours are adopted following a holistic wellness program for individuals with SCI. Participation in a holistic wellness program is positively associated with improved eating and weight-related behaviours in persons with SCI.

19.4 Nutritional Interventions for Dyslipidemia 19.4.1 Nutrition Counseling for Dyslipidemia and Cardiovascular Disease Risk Cardiovascular disease appears prematurely in SCI patients. It is the most frequent cause of death among persons surviving more than 30 years following injury and accounts for 45% of all SCI deaths (Devivo et al. 1999). Abnormalities in lipid metabolism in individuals with SCI develop shortly after injury and tend to progress over time (Brenes et al. 1986; Bauman et al. 1992; Kocina 1997; Szlachcic et al. 2000). Despite the high risk for CVD morbidity and mortality in individuals with SCI, few studies have addressed the benefits of risk reduction interventions aimed at modifiable factors and those that exist have been limited to exercise interventions. This section discusses what is known about the value of nutrition counseling in improving dyslipidemia in persons with SCI. Table 19.3 The Effect of Nutrition Counseling on Dyslipidemia and Cardiovascular Disease Risk
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender m=198, f=24; minimum 2 years post-injury, SCI; complete/incomplete. Treatment: Subjects who had a cholesterol level >200mg/dL (n=86) were referred to dietary consultation and advised to modify daily intakes as follows: total fat <30% of kcal, saturated fat <10% of kcal, cholesterol <300 mg, carbohydrate = 60% of kcal. Compliance was assessed twice. The remaining subjects acted as a control group. Outcome measures: change in blood lipid profile. 1. Outcome Total cholesterol decreased in the dietary counseling group (from 234 to 224 mg/dL, P < 0.001) and slightly increased in the control group (from 162 to 166 mg/dL, P = 0.006). LDL was reduced (from 159 to 151 mg/dL, P = 0.004) in the dietary counseling group and did not change significantly among controls. Neither group experienced significant changes in HDL or triglyceride values.

Szlachcic et al. 2001; USA Downs & Black score=20 Prospective Controlled Trial N=222

2.

3.

Discussion Szlachcic et al. 2001 evaluated the effects of dietary education for individuals with SCI at least 2 years post-injury who had moderately elevated total cholesterol levels (>200 mg/dL) and reported significant decreases in total and low-density lipoprotein (LDL) cholesterol. Individuals who were assessed at baseline as having total cholesterol values greater than 5.2 mmol/L (200 mg/dL) (N = 86; control group) were referred to the staff registered dietitian for counseling. Specifically, individuals were advised to limit daily fat intake to <30% of total daily calories, daily saturated fat intake to <10%, daily cholesterol intake to <300 mg and to consume 60% of total

daily calories as carbohydrate. Subjects in the treatment group were seen by a dietitian at least twice to assess their dietary compliance. The remaining 136 subjects (control group) did not receive nutrition consultation. Subjects in the treatment group were significantly older and had a greater number of years post-injury than those in the control group; therefore, changes in lipid profile were analyzed controlling for differences in age and duration post-injury. A summary of results is as follows Total cholesterol Treatment group demonstrated a significant decrease in TC; control group showed a significant increase in TC; 69% of those in the treatment group had decreases in TC compared to 43% in the control group. LDL The treatment group demonstrated significant declines in LDL while LDL in the control group showed a nonsignificant increase between baseline and follow-up. In the treatment group, 67% had decreases in LDL compared with 47% of those in the control group. High-density lipoprotein cholesterol (HDL) Although there were no significant changes in either group, one third of all subjects in both groups had HDL-C values below the recommended range at baseline. Triglycerides (TG) Although there was a significant group-by-examination interaction for the mean triglyceride values, univariate analyses did not detect a significant difference between the initial and follow-up values for either groups; 60% of the treatment group compared with 45% of control group had declines in TG values. Conclusions There is level 2 evidence that standard dietary counseling (total fat <30% of daily kcal, saturated fat <10% of kcal, cholesterol <300 mg, carbohydrate 60% of kcal) can reduce total and LDL cholesterol among individuals with SCI who have total cholesterol >200 mg/dL. Dietary counseling results in improved lipid profile; consultation with a registered dietitian should be obtained, because individualized diets may enhance compliance. 19.4.1.1 Omega-3 Fatty Acid Supplementation Recent studies suggest that n-3 polyunsaturated fatty acids (found primarily in fatty fish, and in smaller amounts in flax, soy, canola, olive and wheat germ oils and black walnuts) have beneficial effects on cardiovascular disorders including anti-inflammatory, antithrombotic, hypolipemic and vasodilatory effects and contribute to primary and secondary prevention of ischemic heart disease in the general population (Hirafuji et al. 2003; Simopoulos 1999). Table 19.4 Nutrient Supplementation and Lipid Profile Post SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: SCI, ASIA: A D, Time since injury >12 yrs. Treatment: Subjects were administered daily doses of DHA (1.5g) and EPA (.75g) in the form of gelatin pearls, 6 per day to be taken with their principal meals. Outcome Measures: Plasma DHA, EPA, cholesterol (total, HDL, LDL, VLDL), triglycerides, and glucose measured following an overnight fast at baseline, 3 and 6 months. 1. 2. Outcome Plasma EPA and DHA increased significantly (p<0.05) in response to the intake of the supplement. An increase was noted when comparing the levels before and after EPA was administered in the 3rd month period and again at the 6-month period (p<0.05). The same could be seen when looking at the percentages of DHA between the 3 time periods. A significant increase was noted

Javierre et al. 2005; Spain Downs & Black score=15 Pre-post N=10

Author Year; Country Score Research Design Total Sample Size

Methods

Outcome (p<0.05) No differences in cholesterol (total, HDL, LDL, VLDL), triglycerides, or glucose were observed.

3.

Discussion Javierre et al. (2005) assessed the effects on lipid profile and fasting blood glucose in 19 adult males with SCI at 3 and 6 months following daily supplementation of 1.5 grams docosahexaenoic acid (DHA) and 0.75 grams of eicosapentaenoic acid (EPA). Despite significant increases in the plasma concentration of DHA and EPA, plasma concentrations of glucose, total, HDL and LDL cholesterols, very low density lipoprotein cholesterol and triglycerides did not show differences as the result of n-3 fatty acid supplementation. Conclusion There is level 4 evidence that daily supplementation with DHA (1.5 g) and EPA (0.75 g) increases plasma DHA and EPA levels but does not alter total cholesterol, HDL, LDL, VLDL, triglycerides, or glucose. Blood concentrations of DHA and EPA increased as the result of n-3 fatty acid supplementation; however, no significant changes in lipid profile were identified.

19.5 Vitamin Deficiencies and Supplementation Although little work has been done examining the vitamin profiles of individuals following SCI it is generally thought the vitamin deficiency is a significant issue. Moussavi et al. (2003) reported that 16 to 37% of community-dwelling SCI subjects had serum levels below the reference range for vitamins A, C and E compared with general population norms. A case controlled study by Lynch et al. (2002) assessed complete blood count, white blood cells, iron status, ferritin, red blood cell folate, vitamin B12, magnesium, zinc, albumin and prealbumin in persons with chronic SCI and compared values to those of age and gendermatched non-SCI controls. Results were not outside the normal ranges for either group; however, the SCI group had significantly different median values than the control group for hemoglobin, white blood cell count, albumin, prealbumin, serum iron and % saturation. 19.5.1 Vitamin D Supplementation Individuals with SCI have an increased occurrence of vitamin D deficiency, resulting from a number of factors including decreased exposure to sunlight, inadequate dietary intake and the effect of medications. In turn, vitamin D deficiency promotes calcium deficiency and secondary hyperparathyroidism, resulting in further bone loss and exacerbating osteoporosis. Myopathy and nonspecific musculoskeletal pain may also develop as a consequence of vitamin D deficiency (Bauman et al. 2005; Holick 2005).

Observational studies have shown that vitamin D deficiency is common among individuals with SCI. Bauman et al. (1995) reported that 32 of100 SCI subjects had 25(OH)D levels below normal range; 11 of the 32 had elevated serum PTH levels. Zhou et al. (1992) measured the 25(OH)D, serum calcium, magnesium and albumin concentrations of 92 men with SCI, 38 of whom had single or multiple pressure ulcers, and compared these values with those of ablebodied controls. The SCI group had lower serum 25(OH)D, total calcium and albumin concentrations. Quadriplegics had lower 25(OH)D levels than paraplegics. Additionally, the SCI subgroup with pressure ulcers demonstrated significantly lower serum 25(OH)D, calcium and magnesium levels than the SCI subjects without ulcers. Table 19.5 Vitamin D Supplementation Post SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Study 1: Age: mean=5315yrs; SCI. Study 2: Age: mean=4313 yrs; SCI Treatment: Study 1: All were given 50g (2000 IU) vitamin D (25-hydroxyvitamin D3) twice weekly and 1.5 g elemental calcium daily for 2 weeks. Blood and urine were collected at baseline and after 2 weeks. Study 2: 10g (400 IU) vitamin D3, a multivitamin with an additional 10g (400 IU) vitamin D3, and 0.5 g elemental calcium daily for 12 months. Blood and urine were collected at baseline, 6 and 12 months. Outcome measures: Changes in serum 25(OH)D, calcium and PTH, and urinary calcium. Results Study 1: 1. After 2 weeks, serum 25(OH)D increased (from 8.8 to 14.7 ng/mL, P < 0.005) but 8 of 10 subjects still had values below the normal range (< 16 ng/mL). 2. Serum PTH decreased from 35 to 18 pg/mL (P < 0.05), serum calcium was not significantly different, and urinary calcium increased from 103 to 239 mg/d (P = 0.01). Study 2: 1. After 6 and 12 months, serum 25(OH)D increased (from 10.7 to 19.6 to 22.5 ng/mL, P < 0.0001). 2. At baseline, 33 subjects were vitamin D deficient (< 16 ng/mL) compared to 9 after 12 months. 3. Serum PTH decreased (from 37 to 27 to 25 pg/mL, P < 0.005), and measures of calcium were not significantly different.

Bauman et al. 2005; USA Downs & Black score=16 Pre-post Study 1: N=10 Study 2: N=40

Discussion Bauman et al. (2005) determined that healthy individuals with chronic SCI living in the community have vitamin D deficiency. Ten subjects with chronic SCI and a diagnosis of absolute vitamin D (25(OH)D) deficiency received 50 ug (2000 IU) of 25-hydroxyvitamin D3 twice per week for 2 weeks in addition to 1.5 grams (1500 mg) of elemental calcium daily. Serum 25(OH)D levels significantly increased by day 14; however, levels remained below normal range in 8/10 subjects. Serum calcium level was not significantly different but urinary calcium significantly increased. Serum PTH levels significantly decreased. Forty subjects with chronic SCI, regardless of initial serum vitamin D status, received 10 ug (400 IU) of vitamin D3 daily in addition to a multivitamin that contained 10 ug (400 IU) vitamin D3 for a total of 20 ug (800 IU) daily for 12 months. Subjects were encouraged to have at least 0.8 grams (800 mg) of calcium in their daily diet and were supplemented daily with 0.5 grams (500 mg) elemental calcium. Vitamin D levels significantly increased from baseline at 6 and 12 months. There was no significant association of level of injury with baseline 25(OH)D levels. Serum and ionized calcium were not significantly different after 12 months of treatment. Serum PTH was significantly reduced at 6 and 12 months. It is important to note that at baseline, 33 of the 40

subjects had 25(OH)D levels that were below the lower limit of normal, and that after 12 months of supplementation at 800 IU, only 8 of the 40 subjects had serum 25(OH)D values greater than 30 ng/mL which is not adequate to reverse elevated parathyroid levels and reduce bone turnover, despite significant decreases in PTH at 12 months. Finally, 40 subjects were simultaneously enrolled in a placebo-controlled study on the effect of a vitamin D analog (4 ug/day of 1-alpha hydroxyvitamin D2) on lower extremity bone mineral density. Following randomization, 19 of the 40 subjects received the analog or placebo. The vitamin D analog was not considered to appreciably affect the serum 25(OH)D response to vitamin D supplementation. Subjects were encouraged to have at least 0.8 grams (800 mg) of calcium in their daily diets and were supplemented daily with 0.5 g (500 mg) elemental calcium. There was no significant difference at 6 and 12 months in serum PTH level between individuals who were receiving 1-alpha hydroxyvitamin D2 or placebo. Vitamin D supplementation resulted in significant increases in 25(OH)D levels and reductions in parathyroid hormone; however, suboptimal 25(OH)D levels persisted, suggesting the need for higher doses of vitamin D supplementation and/or longer periods of administration. Conclusion There is level 4 evidence that vitamin D supplementation raises serum 25(OH)D levels in persons with chronic SCI. However, the dose and duration required to ensure vitamin D sufficiency remains unclear. Individuals with SCI should be screened for vitamin D deficiency and, if needed, replacement therapy should be initiated. 19.5.2 Vitamin B12 The prevalence of vitamin B12 deficiency in persons with SCI is reported to be between 5.7 and 19% (Petchkrua et al. 2002). Symptoms may include declining gait, depression or fatigue, upper limb weakness, memory loss and worsening pain (Petchkrua et al. 2002; Petchkrua et al. 2003). Vitamin B12 deficiency usually responds to supplementation. Petchkrua et al. (2003) conducted a cross-sectional study with prospective blood collection and retrospective medical record review to assess the prevalence of vitamin B12 deficiency in persons with SCI. Biochemical vitamin B12 deficiency was reported in 13% of the subjects. While hematologic abnormalities were infrequent, neuropsychiatric symptoms were observed in half of the subjects. The age range most associated with vitamin B12 deficiency was 40 59 years; among subjects older than 59 years, 9% had B12 deficiency. No deficiency was noted in subjects within the age range of 20 39 years. Deficiency was more predominant in subjects with complete SCI. Petchkrua et al. (2002) followed a retrospective chart review of patients with SCI who had received serum vitamin B12 testing over a 10 year period. The most common symptoms among subjects identified as having deficient, subnormal or low normal vitamin B12 levels were declining gait, depression, fatigue, upper limb weakness, memory loss or worsening pain. In this report, greater than half of the cases of probable vitamin B12 deficiency occurred in young persons with no known risk factors. Neurologic and/or psychiatric symptoms improved in 88% of SCI subjects following high-dose oral or monthly parenteral vitamin B12 supplementation. It is

recommended that clinicians conduct early screening and treatment of vitamin B12 deficiency. However, definitive trials have not been done. Given the potential for permanent neurological deficits, the relatively low cost of screening and the low cost and high efficacy of high-dose oral supplementation, Petchkrua et al. (2002) suggest that clinicians conduct early screening and treatment of vitamin B12 deficiency. Additional investigations into the predisposing risk factors for vitamin B12 deficiency in persons with SCI are warranted. Clinicians should conduct early screening for and treatment of vitamin B12 deficiency. 19.6 Creatine Supplementation for Muscle Function Creatine serves as a short duration reservoir for the energy required for muscle contraction in skeletal muscle. Low levels of intramuscular creatine are seen in some neuromuscular diseases. Creatine supplementation improves muscle strength in some patient populations with neurological disorders (Kendall et al, 2005). Table 19.6 Creatine Administration Post SCI
Author Year; Country Score Research Design Total Sample Size Methods Outcome No significant findings were noted between: 1. Placebo and supplementation conditions; 2. Endurance times between the two treatments; 3. Or the mean summed GRT scores for creatine and placebo.

Population: SCI; Cause of SCI was not stated; time since injury-mean 16.5yrs; Kendall et al. 2005; USA ASIA-A-C; level of injuryC5/C6. Treatment: Subjects were randomized into PEDro=9 RCT one of two groups. They either received Initial N=9; Final N=8 creatine or placebo, then following a wash out period they received the other medication. Outcome Measures: Hand function was assessed by using the GRT. Subjects completed the Functional Independence Measure. Looked at eating, grooming, dressing and transferring. GRT = Grasp and Release Test

Discussion Kendall et al (2005) reported findings of a study that sought to determine whether creatine supplementation improves muscle strength, endurance and function in weak upper limb muscles in person with tetraplegia. Eight individuals with tetraplegia and mild wrist extensor weakness were randomized to receive creatine or a placebo in a double-blind crossover design. During creatine supplementation, participants received oral doses of creatine monohydrate powder (10 grams orally twice per day for 6 days then were maintained on 5 grams daily until they underwent testing). There was no change in any of the functional tests performed by the participants and none of the participants had a change in self-reported motor Functional Independence Measure (FIM) scores.

Conclusion There is level 1 evidence (based on one RCT) that creatine supplementation did not result in improvements in wrist extensor strength or muscle function. Creatine supplementation does not result in improvements in muscle strength, endurance or function in weak upper limb muscles. 19.7 Summary There is a paucity of intervention studies investigating nutritional status and associated risk of persons with SCI. Many descriptive and observational publications address the risk for obesity, dyslipidemia and cardiovascular disease, impaired glycemic control and diabetes mellitus. Blood lipid profiles and indicators of impaired glucose tolerance and hyperinsulinemia of persons with SCI have been compared with those of able-bodied controls. Despite the high risk for CVD morbidity and mortality in individuals with SCI as evidenced by blood values, metabolic and lifestyle factors, few studies have addressed the benefits of risk reduction interventions aimed at modifiable factors and have been limited to exercise. Other studies have compared vitamin and mineral status of persons with SCI and compared values to those of able-bodied controls or to general population norms and have found lower levels of a variety of nutrients in the SCI population. Few publications have suggested screening and supplementation strategies to address these trends. There is level 4 evidence (from one pre-post trial) that an intervention program combining diet and exercise is effective for reducing weight among overweight persons with SCI. There is level 1 evidence (based on one RCT) that improved health related behaviours are adopted following a holistic wellness program for individuals with SCI. There is level 2 evidence that standard dietary counseling (daily total fat <30% of kcal, saturated fat <10% of kcal, cholesterol <300 mg, carbohydrate 60% of kcal) can reduce total and LDL cholesterol among individuals with SCI and total cholesterol >200 mg/dL. There is level 4 evidence that daily supplementation with DHA (1.5 g) and EPA (0.75 g) increases plasma DHA and EPA levels but does not alter total cholesterol, HDL, LDL, VLDL, triglycerides, or glucose. There is level 4 evidence that vitamin D supplementation raises serum 25(OH)D levels. However, the dose and duration required to ensure vitamin D sufficiency remains unclear. There is level 1 (based on one RCT) that creatine supplementation did not result in improvements in wrist extensor strength or muscle function. More research is needed to evaluate the role of nutrition in the management of postacute SCI to provide the evidence base required for optimal clinical decisions.

References Arrowwood JA, Mohant PK, Thames MD. Cardiovascular problems in the spinal cord injury patient. Phys. Med. Rehabil. State Art Review. 1987; 1:443-456. Bauman WA, NG Morrison and AM Spungen. Vitamin D replacement therapy in persons with spinal cord injury. J Spinal Cord Med 2005;28:203-207. Bauman WA, YG Zhong and E Schwartz. Vitamin D deficiency in veterans with chronic spinal cord injury. Metabolism 1995;44:1612-1616. Bauman Wa, Spungen AM, Raza M, Tothstein J, Zhang RL, Zhong YG et al, Coronary artery disease: metabolic risk factors and latent disease in individuals with paraplegia.1992; 59(2):163-8. Brenes G. Dearwater S, Shapera R. Laporte RE & Collins E. High density lipoprotein cholesterol concentration in physically active and sedentary spinal cord injured patients. Arch Phys Med Rehabil 1986; 67(7):445-450. Buchholz AC and PB Pencharz. Energy expenditure in chronic spinal cord injury. Curr Opin Clin Nutr Metab Care 2004;7:635-639. Chen Y, Henson S, Jackson AB, Richards JS. Obesity intervention in persons with spinal cord injury. Spinal Cord 2006; 44:82-91. Correa GI and Rotter KP. Clinical evaluation and management of neurogenic bowel after spinal cord injury. Spinal Cord 2000;38(5):301-308. Cox SA, Weiss SM, Posuniak EA, Worthington P, Prioleau M, Heffley G. Energy expenditure after spinal cord injury: an evaluation of stable rehabilitating patients. J Trauma 1985;25:419-423. Cruse JM, RE Lewis, S Dilioglou, DL Roe, WF Wallace and RS Chen. Review of immune function, healing of pressure ulcers, and nutritional status in patients with spinal cord injury. J Spinal Cord Med 2000a;23:129-135. Cruse JM, RE Lewis, DL Roe, S Dilioglou, MC Blaine, WF Wallace and RS Chen. Facilitation of immune function, healing of pressure ulcers, and nutritional status in spinal cord injury patients. Exp Mol Pathol 2000b;68:38-54. DeFonzo RA and Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerotic cardiovascular disease. Diabetes Care 1991; 14(3):173-194. DeVivo MJ, Stover SL. Long-term survival and causes of death. In: Stover SL, DeLisa JA, Whiteneck GG, eds. Spinal Cord Injury: Clinical Outcomes from the Model Systems. Gaithersburg, MD: Aspen Publishers, 1995:289-316. DeVivo MJ, JS Krause and DP Lammertse. Recent trends in mortality and causes of death among persons with spinal cord injury. Arch Phys Med Rehabil 1999;80:1411-1419. Duckworth WC, Jallepalli P & Solomon SS. Glucose intolerance in spinal cord injury, Arch Phys Med Rehabil 1983; 64(3):107-10. Hadley MN. Nutritional support after spinal cord injury. Neurosurgery 2002; 50:S81-S84. Hirafuji M, Machida T, Hamaue N, Minami M. Cardiovascular protective effects of n-3 polyunsaturated fatty acids with special emphasis on docosahexaenoic acid. J Pharmacol Sci 2003;92:308-316. Holick, MF. Vitamin D: Important for prevention of osteoporosis, cardiovascular heart disease, type I diabetes, autoimmune diseases, and some cancers. Southern Medical Association 2005:1024-1027. Javierre C, J Vidal, R Segura, J Medina and E Garrido. Continual supplementation with n-3 fatty acids does not modify plasma lipid profile in spinal cord injury patients. Spinal Cord 2005;43:527-530.

Kendall RW, G Jacquemin, R Frost and SP Burns. Creatine supplementation for weak muscles in persons with chronic tetraplegia: a randomized double-blind placebo-controlled crossover trial. J Spinal Cord Med 2005;28:208-213. Kocina P. Body composition of spinal cord injured adults. Sports Medicine 1997;23(1):48-60. Krause RM, Deckelbaum RJ, Ernst N et al. Dietary guideline for health American adults: a statement for health professional from the Nutrition Committee, American Heart Association. Circulation. 1996; 94:1795-1800. Lynch AC, Palmer C, Lynch AC, Anthony A, Roake JA, Frye J, Frizelle FA. Nutritional and immune status following spinal cord injury: a case controlled study. Spinal Cord 2002;40:627-630. Mohr T, Dela F, Handberg A, Biering-Sorensen F, Galbo H, Kjaer M. Insulin action and longterm electrically induced training in individuals with spinal cord injuries. Med Sci Sports Exerc. 2001; 33(8):1247-1252. Monroe MB, Tataranni PA, Pratley R, Manore MM, Skinner JS, Ravussin E. Lower daily energy expenditure as measured by a respiratory chamber in subjects with spinal cord injury compared with control subjects. Am J Clin Nutr 1998;68:1223-1227. Moussavi RM, Garza HM, Eisele SG, Rodriguez G, Rintala DH. Serum levels of vitamins A, C and E in persons with chronic spinal cord injury living in the community. Arch Phys Med Rehabil 2003;84:1061-1067. Petchkrua W, Burns SP, Stiens SA, James JJ, Little JW. Prevalence of vitamin B12 deficiency in spinal cord injury. Arch Phys Med Rehabil. Vol 84, November 2003:1675-1679. Petchkrua W, Little JW, Burns SP, Stiens SA, James JJ. Vitamin B12 deficiency in spinal cord injury: a retrospective study. J Spinal Cord Med summer 2002;26(2):116-121. Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr 1999;70:560S-569S. Szlachcic Y, RH Adkins, T Adal, F Yee, W Bauman and RL Waters. The effect of dietary intervention on lipid profiles in individuals with spinal cord injury. J Spinal Cord Med 2001;24:26-29 Warden SJ, Bennell KL, Matthews B, Brown DJ, McMeeken JM and Wark JD. Efficacy of lowintensity pulsed ultrasound in the prevention of osteoporosis following spinal cord injury. Bone 2001;29(5):431-436. Weinsier RL, Bacon JA, Birch R. Time-calorie displacement diet for weight control: a prospective evaluation of its adequacy for maintaining normal nutritional status. Int J Obes 1983;7:539-548. Yekutiel M, Brooks ME, Ohry A, Yarmon J,& Carel R. The prevalence of hypertension, ischaemic heart disease and diabetes in traumatic spinal cord injured patients and amputees. Paraplegia, 1989; 27(1):58-62. Zemper ED, Tat DG, Roller S, Forchheimer M, Chiodo A, Nelson VS, Scelza W. Assessment of a holistic wellness program for persons with spinal cord injuries. Am J Phys Med Rehabil 2003;82:957-968. Zhou XJ, Vaziri ND, Segal JL, Winer RL, Eltorai I, Brunnemann BS. Effects of chronic spinal cord injury and pressure ulcer on 25(OH)-vitamin D levels. J Am Paraplegic Soc. 1992;16:913.

CHAPTER TWENTY
Pressure Ulcers Following Spinal Cord Injury
MaryAnn Regan, RN BSCN CNN(C) Robert W Teasell, MD FRCPC David Keast, MD FRCPC William B Mortenson, BScOT, MSc Jo-Anne Aubut, BA

Key Points Electrical stimulation may decrease ischial pressures. Electrical stimulation may increase blood flow to tissues. More research is needed to see if increasing blood flow to tissues will help prevent pressure ulcers post-SCI. The type and duration of pressure relief by position changing must be individualized post-SCI using pressure mapping or similar techniques. No one cushion is suitable for all individuals with SCI. Cushion selection should be based on a combination of pressure mapping results, individual characteristics and preference. Adding lumbar support to the wheelchairs of individuals with chronic SCI is unlikely to have a role in pressure ulcer prevention post-SCI. Research is needed to determine the role of behavioral contingencies in pressure ulcer prevention post-SCI. Research is needed to determine more fully why some individuals adhere to pressure ulcer prevention strategies and others do not. Telerehabilitations role in delivering prevention education and treatment to those individuals with SCI living in the community is not yet proven. Early attendance at specialized seating assessment clinics should be part of a comprehensive rehabilitation program. Electrical stimulation should be added to standard wound management to promote healing of Stage III/IV pressure ulcers post-SCI. Laser treatment does not improve pressure ulcer healing post-SCI. US/UVC should be considered as an added treatment when pressure ulcers are not healing with standard wound care post-SCI. Pulsed electromagnetic energy improves wound healing in Stage II and Stage III pressure ulcers post-SCI. Anabolic steroid agents may promote healing of serious pressure ulcers post -SCI.

Table of Contents
20.1 Introduction ................................................................................................................. 20-1 20.1.1 Impact of Pressure Ulcers...........................................................................................20-1 20.1.2 Incidence and Prevalence...........................................................................................20-1 20.1.3 Risk Factors ................................................................................................................20-2 20.1.4 Stages (I-IV) of Pressure Ulcers .................................................................................20-2 20.1.5 Prevention...................................................................................................................20-3 20.1.6 Treatment....................................................................................................................20-3 20.2 Prevention ................................................................................................................... 20-4 20.2.1 Effects of Electrical Stimulation on Reducing Ischial Pressure Post-SCI....................20-4 20.2.2 Electrical Stimulation for Promoting Tissue Health by Increasing Local Blood Flow to Tissues at Risk for Pressure Ulcer Formation Post-SCI .............................................20-5 20.2.3 Pressure Relief Practices on Pressure Ulcer Prevention Post-SCI ............................20-6 20.2.4 Wheelchair Cushion Selection and Pressure Ulcer Prevention in Post-SCI ...............20-8 20.2.5 Lumbar Support Thickness on Reducing Ischial Pressures Post-SCI ......................20-10 20.2.6 Effect of Behavioral Contingencies on Pressure Ulcer Prevention Post SCI ............20-11 20.2.7 Telerehabilitation and Pressure Ulcer Management Post SCI..................................20-12 20.2.8 The Effect of Specialized Seating Clinics on Pressure UlcerPrevention Post-SCI ...20-13 20.3 Treatment................................................................................................................... 20-15 20.3.1 Electrical Stimulation for Pressure Ulcer Healing Post-SCI ......................................20-15 20.3.2 Laser Treatment for Pressure Ulcer Healing Post-SCI .............................................20-17 20.3.3 Ultrasound/Ultraviolet C for Pressure ulcer healing Post-SCI...................................20-18 20.3.4 Effects of Non-Thermal Pulsed Electromagnetic Energy Treatment for Healing of Pressure Ulcers Post SCI .........................................................................................20-19 20.3.5 Anabolic Steroid Agents for Healing of Pressure Ulcers Post-SCI ...........................20-21 20.4 Summary.................................................................................................................... 20-21 References........................................................................................................................... 20-24

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Regan M, Teasell RW, Keast D, Mortenson WB, Aubut J. (2006). Pressure Ulcers Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 20.1-20.26. www.icord.org/scire

Pressure Ulcers Following Spinal Cord Injury

20.1 Introduction 20.1.1 Impact of Pressure Ulcers Traumatic spinal cord injury (SCI) has a major impact on affected individuals and their families. As well as dealing with the direct consequences of the SCI, individuals are also at risk for a number of secondary complications (Krause & Broderick, 2004). Pressure ulcers are a serious, lifelong secondary complication of SCI that have the potential to interfere with physical, psychological and social well being and to impact overall quality of life (Consortium for Spinal Cord Medicine 2000; p9). Although preventable in most situations, pressure ulcers may disrupt rehabilitation, prevent individuals with SCI from working or attending school and interfere with community reintegration (Fuhrer et al. 1993; Krause 1998; Consortium for Spinal Cord Medicine 2000; Jones et al. 2003). It has been estimated that pressure ulcers can account for approximately one-fourth of the cost of care for individuals with SCI. In the United States alone, it has been estimated that the cost of care for pressure ulcers is about 1.2-1.3 billion dollars annually while prevention could cost about one-tenth of this (Bogie et al. 2000; Jones et al. 2003). Because of the costs associated with treating pressure ulcers, Krause et al. (2001) state, they have received more attention among rehabilitation and public health professionals than any other type of secondary complications associated with SCI (p107). Despite the attention given to prevention strategies, pressure ulcers are common among individuals with SCI (Krause et al. 2001). 20.1.2 Incidence and Prevalence Pressure ulcers (term used in the current document), also known as pressure ulcers, decubitius ulcer, ischemic ulcer, bed sores or skin sores, have been defined as a lesion on any skin surface that results from pressure, friction or shear forces. (Crenshaw & Vistnes 1989; Salzberg et al. 1996; Richards et al. 2004). The primary cause of pressure ulcers is felt to be externally applied pressure for a prolonged period of time over bony prominences such as the sacrum and ischial tuberosities. This applied pressure leads to decreased blood supply to the overlying soft tissues; tissue ischemia and can ultimately lead to tissue necrosis (Lamid & Ghatit 1983; Crenshaw & Vistnes 1989; Bogie et al. 1995). DeLisa and Mikulic (1985) have noted that the visible ulcer represents only the tip of the iceberg or the apex of the lesion (p 210). Deeper tissues such as muscle are more sensitive than skin to ischemia caused by pressure (Consortium for Spinal Cord Medicine 2000). Different investigators have reported a wide range of incidence of pressure ulcers varying from 20 to 80% of the SCI population with many individuals having more than one (Richardson et al. 1981; Richards et al. 2004). Most SCI patients develop pressure ulcers within the first 5 years of sustaining their injury (Vidal & Sarrias 1991; Bryne et al. 1996). Fuhrer et al. (1993) noted that less extensive pressure ulcers, stages I & II, comprise about 75% of the total number of ulcers observed, leaving 25% as more severe or stage III and IV ulcers. When the pressure ulcer is severe and not treated aggressively it can lead to further disability such as decreased mobility and loss of independence, surgical interventions, fatal infections and even amputations (Krause 1998). It has been estimated that 7-8% of those who develop

20-1

pressure ulcers will die from related complications (Richards et al. 2004). Due to the increasing life expectancy for those who sustain an SCI, the risk of developing pressure ulcers is even greater; thus making prevention a priority and a daily concern for individuals with SCI and health care providers. 20.1.3 Risk Factors Prevention of pressure ulcers requires recognizing risk factors. The number of risk factors that have been associated with pressure ulcers post-SCI is numerous and yet there is limited evidence that with more understanding of these risk factors a decrease in pressure ulcer incidence will occur (Salzberg et al. 1996). Many risk assessment tools in existence were designed for the general population and for this reason their predictive value is imprecise in the SCI population and those that have been developed for use in the SCI population need more study (Consortium for Spinal Cord Medicine 2000). Risk factors that have been identified most often include: limitiation in activity and mobility, injury completeness, moisture from bowel and bladder incontinence, lack of sensation, muscle atrophy, nutritional status and being underweight (DeLisa & Mikulic 1985; Bryne et al. 1996; Krause et al. 2001). Studies have also found that those most likely to develop pressure ulcers are male, have lower levels of education, are unemployed and do not practice standing (Bryne et al. 1996; Schryvers 2000; Ash 2002; Richards et al. 2004). Other risk factors include: smoking (Lamid & Ghatit 1993; Salzberg et al. 1996; Niazi et al. 1997; Krause et al. 2001), the number of comorbidities especially renal, cardiovascular, pulmonary disease and diabetes (Salzberg et al. 1996; Niazi et al. 1997; Ash 2002); autonomic dysreflexia (Salzberg et al. 1996), anemia and hypoalbuminenia (Delisa & Mikulic 1985; Scivoletto et al. 2004); spasticity and a history of previous ulcers (Vidal & Sarrias 1991; Bryne et al. 1996). Identifying the significant risk factors associated with pressure ulcer development and being able to predict which individuals are most at risk are key elements of prevention for individuals with SCI. 20.1.4 Stages (I-IV) of Pressure Ulcers The assessment of an individual with a pressure ulcer is the basis for planning treatments, evaluating treatment effects and communicating with other caregivers (AHCPR, Executive Summary #15 p 3). One key piece of this assessment is the staging of the pressure ulcer to classify the degree of tissue damage observed by the clinician (AHCPR 1992). In 1989, the following staging system was recommended by the National Pressure Ulcer Advisory Panel (NPUAP). This staging system is widely used and supported (AHCPR 1992; Consortium of Spinal Cord Medicine 2000; RNAO 2002). Since 1989, the following staging system has been used consistently in the literature. However, authors of earlier studies have used numerous ways of documenting the severity of pressure ulcers making it challenging to draw parallels between studies. Stage 1: Observable pressure-related alteration of intact skin, which may include changes in skin temperature, tissue consistency and/or sensation. Stage 2: Partial thickness skin loss involving epidermis, dermis or both. The ulcer is usually superficial and presents clinically as an abrasion, blister or shallow crater. Stage 3: Full thickness skin loss involving damage to or necrosis of subcutaneous tissue that may extend down to, but not through, underlying fascia. The ulcer presents clinically as deep crater with or without undermining of adjacent tissue.

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Stage 4: Full thickness skin loss with extensive destruction, tissue necrosis or damage to muscle, bone or supporting structures e.g. tendon joint capsule. Undermining and sinus tracts also may be associated with stage 4 ulcers. (NPUAP-2003) Stage 1 pressure ulcers may be difficult to observe in darkly pigmented skin. It is also not possible to accurately determine the stage of a pressure ulcer with eschar present (AHCPR 1992). Another type of pressure ulcer which has been identified has been called a deep tissue injury (Ankrom et al. 2005). This is a pressure related injury to subcutaneous tissues under intact skin which initially looks like a bruise but may go on to develop a stage IIIIV pressure ulcer. Current staging systems do not address this issue making tracking difficult (Ankrom et al. 2005). 20.1.5 Prevention Preventing pressure ulcers is ultimately the best medicine. Lifelong prevention recommendations include: examining skin daily to allow for early detection of a pressure ulcer; shifting body weight in bed and wheelchair on a regular basis independently or with assistance; keeping moisture accumulation to a minimum and cleaning and drying skin promptly after soiling; having an individually prescribed wheelchair, pressure reducing cushion and power tilt mechanism if manual pressure relief is not possible; ensuring all equipment is maintained and functioning properly; decreasing or stopping smoking and limiting alcohol intake (Consortium for Spinal Cord Medicine 2000). Krause et al. (2001) notes that effective prevention strategies require the individual with SCI to take responsibility for his/her skin care. Whenever possible, individuals who are at risk for pressure ulcer development or who are being treated for a pressure ulcer should be referred to a registered dietician for assessment and intervention as necessary (Keast et al. 2006). Eating a well balanced, nutritionally complete diet with appropriate calories, proteins, micronutrients (vitamins and minerals) and fluids is essential and such a nutrition plan must be individualized based on the assessed needs (Consortium for Spinal Cord Medicine 2006; Keast et al. 2006). If a pressure ulcer were present, the plan would need to be optimized using foods, supplements and/or enteral nutrition if warranted (Keast et al. 2006). The individuals weight must be monitored as an undesirable weight trend has been identified as an early indicator of risk (Keast et al. 2006). Further information on nutrition can be found in the section on Nutrition and SCI. The following potential preventative techniques found in the SCI literature have been reviewed and discussed in the following section: effect of electrical stimulation on ischial pressures and blood flow, pressure relief practices, wheelchair cushion selection, effect of lumbar support thickness on ischial pressures, behavioral contingencies, telerehabilitation, and specialized seating clinics. 20.1.6 Treatment Once a pressure ulcer has begun it is important to prevent if from worsening and ultimately to have it heal quickly. As previously stated, severe pressure ulcers can lead to further disability, surgery, amputations and death (Krause 1998). According to Chen et al. (2005) pressure ulcers are among the leading cause of unplanned rehospitalization post-SCI and can contribute to longer length of stays and more costly treatment than other medical conditions. Once an individual has had an ulcer they are at increased risk for recurrence (Krause & Broderick 2004). Pressure ulcer treatment is more costly than prevention (Bogie et al. 2000; Jones et al. 2003).

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Research has looked at the effect of: electrical stimulation, laser, US/UVC, non-thermal pulsed electromagnetic energy and anabolic steroid therapy for healing of pressure ulcers post-SCI. Each of these treatments will be discussed in subsequent sections. 20.2 Prevention 20.2.1 Effects of Electrical Stimulation on Reducing Ischial Pressure Post-SCI Electrical stimulation has been used since the 1960s to enhance healing of various chronic wounds including pressure ulcers on both the able bodied and spinal cord injured individual (Kloth & Feeder 1988; Baker et al. 1996, Bogie et al. 2000). More recently electrical stimulation has been studied to assess its potential for pressure ulcer prevention post-SCI. Given that the primary cause of pressure ulcers is felt to be externally applied pressure over bony prominences such as ischial tuberosities (Bogie et al. 1995), researchers have studied the role of electrical stimulation in reducing ischial pressures and redistributing seating interface pressures both of which could assist with pressure ulcer prevention (Bogie et al. 2006). Prevention studies are focusing on skin vs muscle stimulation, dynamic vs long-term effects and surface vs implanted devices (Levine et al. 1990; Bogie et al. 1995; 2000; 2006). Table 20.1 Effects of Electrical Stimulation on Reducing Ischial Pressure Post-SCI
Author Year; Country Score Research Design Total Sample Size Bogie & Triolo 2003; USA Downs & Black score=13 Pre-post N=8 Ferguson et al. 1992; Scotland (UK) Downs & Black score=12 Case Series N=9 Methods Population: Gender: m=7, f=1; age at start of study: 27 to 47; SCI; ASIA score: 56.70 to 113.40 Treatment: The exercise regimen included 3 different stimulation patterns. Duration of exercise were varied over the 8 wk training period as the muscles became conditioned. Population: SCI ; Age:21-56, SCI Treatment: A 2-channel neuromuscular stimulator with surface electrodes was used to apply stimulation to the quadriceps 30 minutes/day for at least 5 days/week. 1. Outcome Overall, with chronic neuromuscular electrical stimulation (NMES), mean interface pressure showed no significant differences between baseline and post exercise levels. Mean ischial region interface pressure had a uniform tendency to decrease post exercise assessment, p<.01. The difference between resting and stimulated pressures at ischia were statistically significant (p<.001) for 8/9 patients. Mean pressure drop with stimulation was right (44mmHg) and left (27mmHg).

2. 1.

Discussion Two articles were found that examined the effects of electrical stimulation on ischial pressure (Ferguson et al. 1992; Bogie & Triolo 2003). Bogie and Triolo (2003) have studied changes in interface pressure distribution at the support/surface interface following 8 weeks of chronic electrical stimulation (NMES) delivered via an implanted neuroprosthesis. With chronic NMES, mean ischial regional interface pressure had a uniform tendency to decrease post exercise assessment, p<.01. Ferguson et al. (1992) applied dynamic functional electrical stimulation (FES) to the conditioned quadriceps muscles of 9 subjects. In 8/9 of these individuals, the difference between resting and stimulated pressures at the ischia were significant (p<.001). The mean pressure drop with stimulation was right (44mmHg), left (27mmHg). While it is difficult to compare these results because one study used chronic NMES versus dynamic FES, it does appear that electrical stimulation decreases ischial pressures. More

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research is needed to study the effect of electrical stimulation on reducing ischial pressures and whether this leads to prevention of pressure ulcers post SCI. Conclusion There is limited level 4 evidence that electrical stimulation decreases ischial pressures post SCI. Electrical stimulation may decrease ischial pressures.

20.2.2 Electrical Stimulation for Promoting Tissue Health by Increasing Local Blood Flow to Tissues at Risk for Pressure Ulcer Formation Post-SCI As was stated previously, researchers are focusing on the effects of electrical stimulation, which may have a role in pressure ulcer prevention post-SCI. One such effect under investigation is changes in blood flow to skin and muscle. Bogie et al. (2006) state that with increasing interface pressures over bony prominences, regional blood flow is adversely affected. It is believed that by increasing regional blood flow, tissue health would be enhanced assisting with pressure ulcer prevention (Levine et al. 1990; Bogie et al. 1995; 2000; 2006). Table 20.2 Electrical Stimulation for Increasing Tissue Blood Flow Post-SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=7, f=1; age at start of study: 27 to 47; Level of injury: C5/6 to T9; ASIA score: 56.70 to 113.40; Ht: 1.65 to 1.88 meters; Wt: 18.30 to 32.10. Treatment: Electrical stimulation delivered via an implanted neuroprosthesis, which included gluteal electrodes, 8 weeks of conditioning exercises followed. Outcome measures: Transcutaneous Oxygen Levels (PTCO2) Population: Age: range 18-57yrs; Site of ulcer= sacral n=7, heel n=2, other n=1; Ulcer grade: 1-4, SCI Treatment: Study was carried out on SCI pts lying on egg crate mattresses. Sensor was applied to the skin at approximately the second sacral segment along the midline using a two sided airtight seal. 2 electrodes and conductive sponges, measuring 4 cm in diameter were used for administering electrical stimulation. Outcome measures: PTCO2 1. Outcome Baseline mean unloaded tissue oxygen levels increased by 1-36% at post exercise assessment for 5/8 subjects. Differences between baseline and post exercise tissue oxygen levels did not show any statistical significance.

Bogie & Triolo 2003; USA Downs & Black score=13 Pre-post N=8

2.

1.

2. 3.

Mawson et al. 1993; USA Downs & Black score=10 Case Series N=29

4.

Experiment 1: Subsequent experiments were performed using 75 volts as no additional effect on trancutaneous oxygen tension (PTCO2 ) was seen when 100 volts was used. Experiment 3: No change in PTCO2 with simulated high voltage pulsed galvanic stimulation (HVPGS). Experiment 4: No significant differences were observed (p=0.66 in all comparisons) when experiment 2 and 4 results were compared. Experiment 4: Compared to final baseline PTCO2 reading (mean SD) of 4921mmHg, the level reached at the 30min period of HVPGS was 6618 mmHg -- 35% higher (p<0.00001).

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Author Year; Country Score Research Design Total Sample Size

Methods 5.

Outcome The level fell slightly following the first 15 minutes post stimulation period (p<0.00001).

Discussion Mawson et al. (1993) administered high voltage pulsed galvanic stimulation (HVPGS) to 29 SCI subjects lying supine. Baseline transcutaneous oxygen tension (PTCO2) levels were compared to levels reached at the end of 30 minutes of HVPGS. The authors found PTCO2 level at the end of stimulation was 6618 mmHg 35% higher (F=39.42, p<.00001). Bogie and Triolo (2003) administered 8 weeks of neuromuscular electrical stimulation (NMES) to 8 subjects using gluteal electrodes. They then assessed unloaded gluteal tissue blood flow through assessment of local transcutaneous oxygen levels (PTCO2). While the results did not reach statistical significance, baseline mean unloaded tissue oxygen levels increased by 1-36% in 5/8 subjects. Given the very limited evidence to date, more research is needed to determine the effect of various forms of electrical stimulation on increasing blood flow to tissue at risk for pressure ulcer development post-SCI. Conclusion There is level 4 evidence that electrical stimulation may increase blood flow at sacral and gluteal areas post-SCI. Electrical stimulation may increase blood flow to tissues. More research is needed to see if increasing blood flow to tissues will help prevent pressure ulcers post-SCI.

20.2.3 Pressure Relief Practices on Pressure Ulcer Prevention Post-SCI Teaching individuals with spinal cord injuries to shift their weight regularly is an important aspect of pressure sore prevention in rehabilitation. The absence of such health promoting behaviors places the person with SCI at higher risk for pressure ulcers (Krause 1998). Bogie et al. (1995) stated that pressure relief includes lifting the whole ischial region clear of the seating surface for about 30 seconds or leaning forward or side to side as far as possible for 1-2 minutes (p141). The techniques chosen depend on the physical and cognitive status of the individual. When a manual weight shift cannot be performed, an alternative is mechanical reclining or using a power tilt wheelchair. Pressure relief should be optimally performed every 15-30 minutes (Consortium for Spinal Cord Medicine 2000). Table 20.3 Pressure Relief Practices on Preventing Ulcers Post-SCI
Author Year; Country Score Research Design Total Sample Size Coggrave & Rose 2003; UK Methods Population: Gender: f=13, m=33; Age:20 to 83 1. Outcome Mean duration of pressure relief required to raise tissue oxygen to

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Author Year; Country Score Research Design Total Sample Size Downs & Black score=14 Case Series N=50

Methods Duration of injury: 5 wks-50yrs SCI, Frankel grade A-D Treatment: Retrospective chart review Outcome Measures: Effect of pressure relief TCPO2

Outcome unloaded levels was 1 min 51 sec (range 42 secs-3 mins). Leaning forward with elbows or chest on knees leaning from side to side and tilting back in wheelchair to > 65o were all effective for pressure relief (raising TCPO2 to unloaded levels) and more easily sustained for most individuals than a pressure lift. Resulted in a change in practice at the seating clinic. Average pressure in the resting seated position were 189mmHg for point pressure area and 114mmHg for the circumscribed area. o When patients were in the 65 backward tip position there was a 47% reduction in maximum point pressure and 36% for the circumscribed area pressure. (p<0.05). In the leaning forward position there was a 78% reduction in maximum point pressure and a 70% reduction in circumscribes area (p<0.05)

2.

3. Population: Gender: m=9, f=1; Age: 22 to 67; SCI Time since injury 1mth to 7yrs Treatment: Subjects sat upright in wheelchair in neutral position; tipped backward at 35o & 65o; assisted to lean forward (>45o from wheelchair backrest). Pressures were measured at ischial tuberosity (IT) (point pressure) and circumscribed area around IT. Outcome Measures: Pressure levels 1.

Henderson et al. 1994; USA Downs & Black score=12 Case Series N=10

2.

3.

Discussion There are very few studies that have researched which techniques provide adequate pressure relief and how long a weight shift must be performed to unload weight-bearing areas such as the ischia. Coggrave and Rose (2003), in a retrospective chart review of 46 SCI subjects seen in a seating clinic, assessed the duration of various pressure relief positions required for loaded transcutaneous oxygen tension (TCPO2) to recover to unloaded levels. Results indicated that it took approximately 2 minutes of pressure relief to raise tissue oxygen to unloaded levels for most subjects. This length of pressure relief was more easily sustained by the subjects leaning forward, side to side or having the wheelchair tipped back at > 65 compared to a pressure relief lift. Henderson et al. (1994) pressure mapped 10 SCI subjects and recorded pressures at the ischial tuberosity (IT) and a circumscribed area around the IT. The authors then pressure mapped the subjects with their wheelchairs tipped back at 35, 65 and after the subjects were assisted into a forward leaning position. Results showed that the wheelchairs tipped back at 65 and the subjects in a forward leaning position demonstrated statistically significant pressure reduction at the IT and circumscribed area (p<0.05) with the forward lean showing the greatest reduction (78% reduction at IT, 70% reduction circumscribed area). The two studies discussed, demonstrate through pressure mapping and the effect of pressure relief on tissue oxygen levels, that a forward leaning position and having the wheelchair tipped back at > 65 are effective pressure relief techniques if sustained for an appropriate time period, which varies from individual to individual. Coggrave and Rose (2003) showed leaning side to side, or doing a pressure relief lift is also effective if sustained for the appropriate length of time.

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The traditional pressure relief lift (15-30sec) was ineffective in reducing tissue oxygen levels to unloaded levels. Conclusion There is level 4 evidence to support the forward leaning position and the wheelchair tipped back position (> 65) as effective methods of pressure relief. The type and duration of pressure relief by position changing must be individualized post-SCI using pressure mapping or similar techniques.

20.2.4 Wheelchair Cushion Selection and Pressure Ulcer Prevention in Post-SCI Wheelchair cushion selection is important when an individual with SCI is prescribed a wheelchair. The purpose of the cushion is to relieve pressure along with other pressure relief practices while the individual is seated. Bogie et al. (1995) stated that 47% of pressure ulcers occur at the ischial tuberosities or sacrum and are therefore more likely to have been initiated while seated. There are numerous cushions on the market, each citing specific characteristics along with various amounts of pressure reduction that make that cushion superior. While pressure reduction can be objectively measured using techniques such as pressure mapping, clinical judgment and individual preference also have a role in a complete cushion evaluation; these are more difficult to measure. Many factors must be assessed and no single cushion is appropriate for every individual with SCI underscoring the need for individualized cushion prescriptions (Garber 1985; Seymour et al.1985; Brienza & Karg 1998). Table 20.4 Wheelchair Cushion Selection
Author Year; Country Score Research Design Total Sample Size Methods Population: Age: 21-52 yrs; BMI: 17-32.3 kg/m2: SCI Treatment: Assessed forces for 3 different surfaces (flat foam, the initial contour and final optimized contour) with the force sensing array (FAS) pad between the cushion and buttocks. Compared SCI to seniors group. Outcome Measures: Pressure mapping, BMI 1. 2. 3. 4. Outcome Depth values for the SCI group from 37.9 6.5 mm to 52.5 11.5 mm (p<0.001). A significant increase was also noted for the elderly group. The mean max depth of the final contour was deeper for the SCI group (p=0.016). Mean pressure values for initial and final cushions were significantly less than for flat cushions (p=0.006, p=0.003 respectively). BMI was significantly related to peak and mean pressure values. Greatest pressure was seen under the soft tissue areas of most subjects, no significant differences between the cases and controls Temperatures were lowest for gel, water and air cushions and highest for alternating pressure and foam cushions. SCI groupGreatest pressure under a bony area occurred most often with

Brienza & Karg 1998; USA Downs & Black score=14 Case Series N=12

5. Population: Age: 16-35yrs, wt: 40.672.5kg, 10 cases & 10 controls. Treatment: 7 commercially available cushions and 1 experimental cushion were evaluated for each subject. Outcome Measures: Temperature and pressure effects for each cushion. Subjects were asked to rate each cushion as to cosmesis, handling and suitability for purchase. 1.

Seymour et al. 1985; USA Downs & Black score=13 Case Control N=20

2.

3.

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Author Year; Country Score Research Design Total Sample Size

Methods

Outcome the Spenco cushion (90.10 8.75); controls- it occurred most often with the Tri-pad (89.20 11.40) indicating that these cushions did not compare favorably to others. 4. There was wide variability in pressure measurements in individual subjects (SD=12.21 mmHg) 5. Cosmesis (83%) and handling (73%) were related to purchase decisions No statistical results reported. 1. The air filled cushion (Roho which was 1 of 2 used) produced the greatest pressure reduction in 51% of the subjects. 2. A foam cushion (the stainless comfy hard cushion) was effective for only 18% of the subjects even though it was the second most frequently prescribed cushion. 3. More quadriplegic subjects received the Rohos than paraplegic subjects (55% vs 45%) while more paraplegic subjects were prescribed the Jay cushion (a combination of foam and floatation materials (19%vs7%).

Population: Gender: m=207, f=44; SCI Treatment: Assessment of pressure distribution for 7 cushions. Outcome Measures: Seated Pressure Garber 1985; USA Downs & Black score=8 Case Series N=251

Discussion Brienza and Karg (1998) had subjects sit on 3 different surfaces (flat foam, initial contour and final contour). Interface pressures were measured using a pressure-sensing pad. Results indicated that when SCI subjects were compared to the elderly subjects depth values increased and the mean maximum depth of the final contour was deeper for the SCI group, suggesting that pressure distributions for the SCI group are more sensitive to support surface characteristics than elderly subjects. Seymour et al. (1985) evaluated 8 cushions for pressure, temperature effects and subjective factors influencing cushion purchase. While data indicated a wide variability in pressure measurements in individual subjects, the air filled cushion had the best pressure readings. The alternating pressure and foam had consistently higher temperature reading across both groups. Garber (1985) evaluated 7 cushions based on amount of pressure reduction. The author also looked at how frequently each cushion was prescribed to subjects with quadriplegia and paraplegia. The roho cushion produced the greatest pressure reduction in the majority of subjects (51%) but was prescribed more often for subjects with quadriplegia vs paraplegia (55% vs 45%). All 3 studies looked at various indicators of wheelchair cushion suitability, which are thought to have a role in pressure ulcer formation. Collectively the results support the need for wheelchair cushion prescriptions to be based on objective findings such as pressure mapping but also clinical knowledge of the individuals and his or her subjective reports. Individualized cushion prescriptions will optimize pressure ulcer prevention characteristics and compliance with cushion usage.

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Conclusion There is level 4 evidence to support individualized wheelchair cushion prescriptions to optimize pressure ulcer prevention post-SCI. No one cushion is suitable for all individuals with SCI. Cushion selection should be based on a combination of pressure mapping results, individual characteristics and preference.

20.2.5 Lumbar Support Thickness on Reducing Ischial Pressures Post-SCI Shields and Cook (1992) discussed the role spinal deformities such as kyphosis, may play in the formation of pressure ulcers in individuals with chronic SCI. In previous research with nondisabled subjects, they had demonstrated that the addition of lumbar support reduced highest seated buttock pressure and was associated with a change in pelvic tilt. If those findings were to hold true in the SCI population, the authors noted this could lead to ways to monitor seated postures for optimal pressure distribution and augment electric wheelchair seating systems to assist with pressure shifts, aiding in pressure ulcer prevention. Table 20.5 Lumbar Support Thickness on Reducing Ischial Pressures Post-SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=20, f=16; Age: 21 to 52 yrs; SCI & non=SCI Treatment: All were seated onto a pressure sensing transducer incorporated into an adjustable chair. The output was calibrated so that eight pressure intervals were displayed. Outcome Measures: Pressure distribution 1. Outcome Significantly reduced pressures were seen with greater thickness of lumbar supports (2.57.5 cm) for controls but not those with SCI (p<0.0001). The highest-pressure areas were greater for SCI group (p<0.05) than control group for all lumbar support conditions. The mean area of lowest pressure for all support conditions was significantly less for SCI groups than control group. SCI group had significantly lower pelvifemoral angles than control groups in all lumbar support conditions (p<0.05).

2.

Shields & Cook; 1992 Downs & Black score=19 Case Control N=36

3. 4.

Discussion Shields and Cook (1992) studied 18 SCI and able-bodied subjects to test the effect of varying lumbar support thickness (0, 2.5, 5.0, 7.5 cm) on seated buttock pressures at the ischial tuberosities. With the SCI group a 2% decrease in mean high pressure was seen with the 7.5 cm lumbar support compared to a 90% reduction for the control group. With the 2.5 cm and the 5 cm lumbar support there was an increase in mean high pressure of 12% and 13% respectively compared to reductions in the control group of 25% and 80%, respectively. Surprisingly, the findings showed that the addition of lumbar support to wheelchairs had a minimal effect on reducing highest seated buttock pressure at the ischial tuberosities of subjects with chronic 3 years SCI. Given the minimal effect noted on reducing pressures at the IT, adding lumbar

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support to the wheelchair of those with chronic SCI is unlikely to have a role in prevention of pressure ulcers post-SCI. Conclusion There is level 3 evidence that adding lumbar support to the wheelchair of those with chronic SCI has a negligible effect on reducing seated buttock pressures at the ischial tuberosities. Adding lumbar support to the wheelchairs of individuals with chronic SCI is unlikely to have a role in pressure ulcer prevention post-SCI.

20.2.6 Effect of Behavioral Contingencies on Pressure Ulcer Prevention Post SCI Jones et al. (2003) documented that despite what we know about pressure ulcers and methods of prevention, the problem persists. Little is known about why some patients do not establish and maintain the health behaviors necessary for optimal skin care and pressure ulcer prevention (p. 796). The questions are, does rewarding positive prevention strategies reduce the severity of pressure ulcers and hopefully prevent them entirely, and are the results sustainable allowing the rewards to be withdrawn? Table 20.6 Effect of Behavioral Contingencies on Pressure Ulcer Prevention Post SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=6, f=2; Age: 2540yrs Paraplegia; Time since injury: 1220yrs. Interventions: Study 1-Behavioral Intervention: 3 primary components-health plan, clinic visits and financial rewards. Study 2- Behavioral intervention: 2 treatments components were implemented (Health plan and visits) during the initial phase. Phase 2 - which began after the patient began to experience skin problems (Included visits plus payment) Outcome Measures: Severity of pressure sores were recorded at each level; Ulcer severity- classified using PUSH tool Outcome Study 1: 1. Average Pressure Ulcer Scale for Healing (PUSH) decreased from baseline by an average of 10.5 points per participant (range 5.4-19.2). 2. 6 participants were hospitalized (not during the intervention) a total of 16 times during baseline for treatment of pressure ulcers. 3. Fewer hospitalizations were also noted during the post-intervention phase compared to the baseline phase. Average monthly cost of care decreased from $6262.00/participant to $235.00 (US) Study 2: 1. Mean PUSH scores decreased from baseline by 8.3 pts (visits only) and 11.4 pts (visits & payment phase) 2. Total number of hospitalization decreased from baseline to post intervention phase.

Jones et al. 2003; USA Downs & Black score=11 Pre-post Study 1: Initial N=8 Study 1: Final N=6 Study 2: Initial N=4 Study 2: Final N=3

Discussion Results of study 1 showed average Pressure Ulcer Scale for Healing (PUSH) scores were lower by 10.5 points from baseline; no hospitalizations were required and ultimately costs during the

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intervention phase went from $6263.00 (US) to $235.00 (US). In the post intervention phase, 3 subjects were able to maintain the lower PUSH scores and 3 were not. In study 2, the results were highly variable. There was a small drop in mean PUSH scores across the 3 subjects once payments were introduced. 2 out of 3 participants showed that the PUSH scores rose again during the post intervention phase. Although this was a very small study, the data from study 1indicates that when behavioral contingencies were introduced, positive behaviors resulted. For some participants results were sustainable once behavioral contingencies were withdrawn. More research is needed to determine the role of behavioral contingencies in pressure ulcer prevention post-SCI. Conclusion There is very limited level 4 evidence to suggest that the introduction of behavioral contingencies are associated with a reduction in pressure ulcer severity and decreased health care costs. Research is needed to determine the role of behavioral contingencies in pressure ulcer prevention post-SCI. Research is needed to determine more fully why some individuals adhere to pressure ulcer prevention strategies and others do not. 20.2.7 Telerehabilitation and Pressure Ulcer Management Post SCI Telerehabilitation is the use of telecommunication technology to deliver rehabilitation services at a distance (Vesmarovich et al. 1999; p 264). Telerehabilitation allows visual and verbal interaction between the individual with SCI and the health care provider. Impaired mobility and distance to specialized SCI centers often make follow up care difficult for individuals with SCI (Mathewson et al. 2000; Galea et al. 2006). Telerehabilation has the potential to deliver medical rehabilitation, nutritional and psychosocial elements of health care at a distance facilitating continuity of care. Pressure ulcer management is one area where telerehabilitation is being used (Galea et al. 2006). Table 20.7 Telerehabilitation and Pressure Ulcer Management Post SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Age: ~35 yrs Treatment: videoconferencing was used to assist patients in treating and monitoring pressure ulcers. Outcome Measures: number of pressure ulcers, emergency room (ER) visits, hospitalization, doctors visits annually and employment rate 1. Outcome Overall it was found that the video group reported the largest number of ulcers, followed by the standard care group and the telephone group. The standard care group reported the lowest number of ER visits, hospitalization, and health care provider visits. The numbers of visits were similar for the other two groups. Over half the members of each group had no hospitalizations during the study period. It was also noted that 26% of the subjects had returned to work 6 mths after injury.

2.

Phillips et al. 1999; USA Downs & Black score=12 Case Control Initial N=37; Final N=35

3. 4.

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Author Year; Country Score Research Design Total Sample Size

Methods Population: Gender: m=8; Age: 38-78yrs; SCI Treatment: The outpatient nurse using the Picasso Still Image Videophone conducted weekly telerehabiliatation visits. Subjects and family members received 30 min of education; equipment was sent home with subjects. Interviews were conducted to determine level of satisfaction

Outcome No statistical results reported 1. Subjects were seen approx 7 times (range 1-18 visits). 2. 7 wound sites healed completely, 2needed surgery. 3. Subjects and family were highly satisfied

Vesmarovich et al. 1999; USA Downs & Black score=10 Case Series N=8

Discussion Vesmarovich et al. (1999) described the use of telerehabilitation delivered via a videophone system that transmitted still images and audio to treat stage III/IV ulcers. While no statistical results were reported, 7 out of 12 ulcer sites healed. Philips et al. (1999) using the same videophone system divided SCI participants into 3 groups. The video group had the highest number of identified and or reported ulcers. The annualized data for emergency room (ER) visits, hospitalizations and health care visits were similar for the video and telephone groups while hospitalizations and visits were less in the standard care group. No differences were significant at p<0.05. Results of these two small studies fail to support the use of telerehabilitation in delivery of cost effective prevention strategies and early pressure ulcer identification and treatment. More research is needed to determine how telerehabilitation can be used to deliver and monitor compliance with pressure ulcer prevention strategies as well as its use in identification and treatment of pressure ulcers post SCI. Conclusion The data collected to date does not support a role for telerehabilitation in prevention and treatment of pressure ulcers post SCI. More research is needed to explore its usefulness. Telerehabilitations role in delivering prevention education and treatment to those individuals with SCI living in the community is not yet proven.

20.2.8 The Effect of Specialized Seating Clinics on Pressure Ulcer Prevention Post-SCI Developing the ability to maintain skin integrity and prevent pressure ulcer formation is an important component of any SCI rehabilitation program. Education for prevention includes an emphasis on taking personal responsibility for maintaining healthy skin through personal care, inspection of skin, pressure relief and correct use of prescribed equipment (Bogie et al. 1995). The incorporation of seating clinics into both the inpatient and outpatient rehabilitation program has been shown to reduce the incidence of pressure ulcers and readmission rates due to pressure ulcers (Dover et al. 1992). Seating clinics not only provide education but also make recommendations for appropriate seating systems based on interface pressures, thermography

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and assessment of tissue viability. Verbal and visual feedback is provided to the individual with SCI and active participation is encouraged (Dover et al. 1992; Coggrave & Rose 2003; Kennedy et al. 2003). Table 20.8 The Effect of Specialized Clinics on Pressure Ulcer Prevention
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=37, f=13; Age:1674 yrs , SCI, Treatment: Postural assessment took place while the individual adopted their usual posture in the wheelchair. Physical alignment was documented and correct positioning of adjustable parts of the chair was checked. Any abnormal posture was then checked for correct ability and the setup of the seating was adjusted where required. Outcome Measures: Skin management subscale of the Needs Assessment Checklist (NAC) to assess skin management rehab 1. 2. Outcome Significant differences were identified between group 1 & 3 at both NAC 1 (p<0.05) and NAC 2 (p<0.01). Skin management to be achieved scores were significantly lower for patients who had attended specialized seating assessment clinic (SSA) before their first NAC at both time points. Significant differences were also observed between the skin management to be achieved scores at the first & second NAC within all groups: Group 1 (p<0.0001), groups 2 (p<0.01) & group 3 (p<0.01)

Kennedy et al. 2003; UK Downs & Black score=18 Cohort N=50

3.

Discussion Kennedy et al. (2003) studied 50 individuals with SCI participating in a comprehensive rehabilitation program. The individuals were divided into 3 groups to determine if attendance at a specialized seating assessment clinic (SSA) would improve skin management ability as evidenced by lower to be achieved scores on the skin subscale of the Needs Assessment Checklist (NAC); optimal timing of attendance at the SSA was also studied. Results indicated significant differences between group 1 (attendance at SSA prior to NAC 1) and group 3 (no attendance at SSA) at both NAC 1 (p<0.05) and NAC 2 (P<0.01). Skin management to be achieved scores were significantly lower for individuals who attended SSA before their first NAC at both time points. Significant differences were also observed between to be achieved scores at first and second NAC within all groups: Group 1(p<0.0001), Group 2 (p<0.01) and Group 3 (p<0.01). Results indicate that attendance at a SSA did improve individuals skin management abilities and that early attendance was optimal. The results also indicate that attendance at SSA is an adjunct to the skin management abilities learned during a comprehensive rehabilitation program. More research is needed to determine if early attendance at an SSA translates into prevention of pressure ulcers over time. Conclusion There is Level 2 evidence showing that early attendance at specialized seating assessment clinics (SSA) increases the skin management abilities of individuals postSCI. More research is needed to determine if early attendance at an SSA results in pressure ulcer prevention over time. Early attendance at specialized seating assessment clinics should be part of a comprehensive rehabilitation program.

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20.3 Treatment

20.3.1 Electrical Stimulation for Pressure Ulcer Healing Post-SCI

The use of various forms of electrical current in augmenting tissue repair was reported as early as the 1600s when charged goldleaf was used to prevent scarring in smallpox survivors (Kloth & Feedar 1988). The therapeutic effects of electrical stimulation for wound healing has been well documented since the 1960s especially for wounds not responding to standard forms of treatment (Kloth & Feeder 1988; Baker et al. 1996; Bogie et al. 2000). One theory as to why electrical stimulation is effective in promoting wound healing includes the possibility that the electrical current promotes migration of cells such as epithelial, macrophages, neutrophils and fibroblasts-galvanotaxis (Feedar et al. 1991; Baker et al. 1996; Bogie et al. 2000). Under normal circumstances there is a flow of charged particles from an uninjured area to an injured area triggering a biological repair system. The belief is that application of exogenous electrical current should be able to enhance healing in non healing wounds by mimicing the bodys own healing system. (Carley & Wainapel 1985; Baker et al. 1996). A second theory believes that application of electric current activates cutaneous nerves and creates a centrally mediated increase in circulation to the wound thereby promoting healing (Baker et al. 1996). Despite the usage of electrical stimulation to promote wound healing, there remains a lack of clear understanding as to how it works to repair tissue (Bogie et al. 2000). Some of the effects of electrical stimulation on wound healing include decreased healing time, increased collagen synthesis, increased wound tensile strength, increased rate of wound epithelialization and bactericidal effects (Kloth & Feedar 1988). Electrical stimulation has also been shown to improve tissue perfusion and reduce edema formation indirectly stimulating healing by improving oxygen delivery to tissues (Houghton & Campbell 2001). The studies on electrical stimulation for wound healing have looked at low intensity direct current, high voltage pulsed direct current, and alternating current. The literature shows a high variability as to which protocols are the most effective for a specific patient or ulcer (Bogie et al. 2000). The use of electrical stimulation to promote closure of pressure ulcers when combined with standard wound interventions has been recommended in both the able bodied and spinal cord injured individual. Most studies discuss the role of electrical stimulation in pressure ulcers which have failed to respond to standard treatments and electrical stimulation is seen as an adjunctive modality to standard wound treatments (Consortium of Spinal Cord Medicine 2000; Keast et al. 2006; AHCPR1992). Table 20.9 Electrical Stimulation for Pressure Ulcer Healing Post-SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: age: 10 to 74yrs; duration of SCI: 4 to 1,820 wks; Ulcer duration: 1116wks; Treatment: Patients with pelvic (sacral/coccygeal or gluteal/ischial) ulcers received high voltage pulsed direct current (HVPC) or placebo HVPC for one hour a day for 20 consecutive days. All patients received equivalent dressing changes. Wounds were mechanically debrided as necessary. Efforts were made to relieve pressure, but this was not described. 1. Results Percentage of change decreased in the wound surface area (WSA) exhibited by the HVPC group was greater than placebo group at day 5 (p=.03), day 15 (p=.05) and day 20 (p=.05)

Griffin et al. 1991; USA PEDro=7 RCT N=20

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Author Year; Country Score Research Design Total Sample Size

Methods Outcome Measures: Pressure Ulcer Status Population: Age: 21 to 60 yrs; Ulcer surface area: approx 15.8mm ; Ulcer location: trochanter & sacrum; SCI Treatment: Stimulation with interrupted direct current (IDC) and nursing care or placebo IDC and nursing care; 3-45 minute treatments three times/week for 4 weeks. Outcome Measures: Surface area of pressure ulcers Population: Age: 17 to 76; Gender: m=66, f=14; SCI Complete, incomplete; Total number of wounds: 192. Treatment: Stimulation of A (asymmetric biphasic), vs B (symmetric biphasic) vs microcurrent (MC) group originally thought to incorporate stimulation below effective level became the 3rd treatment group when some early therapeutic effect was noted. All remained on their stimulation protocols until their ulcers healed, the MD intervened or subject withdrew from study. Control group received sham for 4 wks then were entered into either A or B groups. Electrical stimulation treatment for all subjects consisted of 1.5 hrs of stimulation 5/days/wk Outcome Measure: Pressure ulcer status

Results

1. 2.

Adegoke & Badmos 2001; Nigeria PEDro=6 RCT N=7

Surface area of pressure ulcers of IDC group decreased by 22.2% versus 2.6% in placebo IDC group. Most of the decrease in surface area occurred during the first two weeks of the study (IDC group 13.3 14.1, % change 15.8; placebo IDC group 15.1 3.6, % change 1.9) No statistical differences were noted between the initial or discharge ulcer areas or in the mean healing rates among the four treatment groups. Comparing the descriptive data by classifying them as good or poor healing responses failed to identify any statistically significant differences between the 2 groups. When looking at the good response group, the group A protocol was most effective as compared to the MC and C protocols (p<0.05). No significant differences were found between B protocol and other treatments. Those in the control group who had wounds healed by either protocol A or B showed that the healing rate was greater (43.3% 12.5% /week) than it was during the control period (9.7% 3.4% /week). The healing rate for the AC group (N = 42) was significantly better than the other two groups DC (N=12), CO (N=34) p=0.003, after excluding those with very deep, superficial or long term wounds.

1.

2.

Baker et al. 1996; USA PEDro=4 RCT N=80

3.

4.

Stefanovska et al. 1993; Slovenia Downs & Black=14 Prospective Controlled Trial N=150

Population: Not described Treatment: Currents were applied across the wounds by a pair of self-adhesive skin electrodes. Low density (DC) group (N=18) treated with low-density direct currents (600A) for two hours daily. AC group (N = 82) were treated with low frequency pulsed currents for two hours daily. CO group (N=50) received conventional treatment (not described) for the first month. Outcome Measures: Pressure Ulcer Status

1.

Discussion Griffin et al. (1991) showed the efficacy of high voltage pulsed direct current (HVPC) for the healing of pelvic pressure ulcers in subjects with SCI. When compared with the placebo group, the subjects healed with HVPC showed a greater percentage of change decrease in wound surface area (WSA) at day 5 (p=.03), day 15 (p=.05) and day 20 (p=.05). Several studies also reported similar finding (Stefanovska et al. 1993; Baker 1996; Adegoke & Badmos 2001). Stefanovska et al. (1993) showed that the healing rate for wounds treated with low frequency pulsed current (AC) was significantly better than the groups treated with direct current or conventional treatment alone (p=.003). Baker (1996) showed that for ulcers that responded to 20-16

any form of electrical simulation (good responses), asymmetric biphasic stimulation (group A) was most effective for enhanced wound healing. Wounds that were already showing healing in the control group, with the addition of either protocol A or B (symmetrical Biphasic) showed that healing rate was greater (43.3% 12.5% / week) when compared to control period (9.7% 3.4% / week). Adegoke and Badmos (2001) showed that the surface area of grade IV pelvic pressure ulcers treated with interrupted direct current (IDC) and nursing care decreased by 22.2% versus 2.6% in the placebo group. While there were differences in the type and duration of electric current applied in the 4 studies, they all demonstrated that when used in conjunction with standard wound management, electrical stimulation did accelerate the healing rate of pressure ulcers in patients with SCI. More research is needed to determine which type of electric current and application protocol will be most useful to enhance healing of pressure ulcers post-SCI. Conclusion There is level I evidence from 2 studies to support the use of electrical stimulation to accelerate the healing rate of stage III/IV pressure ulcers when combined with standard wound management. Electrical stimulation should be added to standard wound management to promote healing of Stage III/IV pressure ulcers post-SCI.

20.3.2 Laser Treatment for Pressure Ulcer Healing Post-SCI The Consortium for Spinal Cord Medicine (2000) reviewed the literature on adjunctive wound therapies including laser and did not find enough supporting evidence to recommend laser for the treatment of pressure ulcers in individuals with SCI. No controlled clinical trials involving pressure ulcers and laser were found and existing data specific to treatment of pressure ulcer with laser in the SCI population was minimal. The two studies presented in this document support the conclusion of the consortium. Table 20.10 Laser Treatment for Pressure Ulcer Healing Post-SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=27, f=8; Age: 8 to 65 yrs, Stage of ulcers: 55 stage 2, 8 stage 3, 3 stage 4 Treatment: Treatment for the experimental group consisted of multi-wavelength light therapy (gallium-aluminum arsenide laser source) in addition to conventional treatment. For the control group, the light therapy source was held over the ulcer after switching off the beam. 14 treatments were given, 1 every other day,3 X per week. Treatments ended when the ulcer healed or after the 14 treatment exposures Outcome measures: number of ulcers that healed. 1. Outcome Overall no significant differences were found between the control and treatment groups. 14 ulcers healed completely compared to 18 in the treatment group (p<0.802) The mean time taken to heal was 2.45 2.06 weeks in the treatment group and 1.78 2.13 in the control group (p<0.330). Multi-wavelength light therapy reduced the time taken by a small subgroup (N=4) of stage three and four ulcers to reach stage two, 2.25 0.5 weeks; control group (N=5) it took 4.33 1.53 weeks. (t=2.621, p=.047)

Taly et al. 2004; India PEDro=10 RCT N = 64 (ulcers) in 35 patients

2.

3.

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Author Year; Country Score Research Design Total Sample Size

Methods Population: Age: 15 to 61; Gender: m=16, f=2; SCI; Urinary tract infection: n=16 Treatment: Control group received standard wound care consisting of twice daily cleansing with Hygeol (1:20) and Jelonet dressing, and avoidance of pressure on existing ulcers; Laser group received standard wound care plus laser treatment 3x weekly; Ultrasound/Ultraviolet C (US/UVC) group received standard wound care with US and UVC treatments alternating over a 5 day period. Outcome measures: Pressure ulcer status 1.

Outcome US/UVC and laser treatment with US/UVC showing greater effect on wound healing than laser or control. Mean percentage of change per week in ulcer size (1 SD) from day 0 to complete healing for control (32.4%), US/UVC (53.5%), and laser (23.7%) Several subjects showed deterioration over the study. Ulcers increased in size; (laser=3, 62-167% change; control =1, 58% change; US/UVC=1, 1% change). All ulcers healed by end of study with last ulcer healed in laser group by week 20 as opposed to US/UVC group at week 6.

Nussbaum et al. 1994; Canada PEDro=6 RCT Initial N=20; Final N=16

2.

Discussion Taly et al. (2004) studied 35 subjects (64 ulcers) using multi-wavelength light therapy compared to standard wound care alone. Overall no significant differences were found between the two groups with regard to the number of ulcers healed and time taken to heal. Both of these studies demonstrated that laser treatment was no more effective in promoting wound healing than standard wound care alone post-SCI. Nussbaum et al. (1994) studied 16 patients and compared standard wound care alone to standard care combined with either laser or Ultrasound/Ultraviolet C (US/UVC). Results showed that laser treatment combined with standard wound care had the least effect on wound healing compared to the control group and US/UVC group. A significant difference was found between the US/UVC and laser group with the US/UVC treatment showing the greater effect on wound healing. Conclusion There is level 1 evidence (from two RCTs) to suggest that laser treatment has no added benefit in pressure ulcer healing post-SCI than standard wound care alone. Laser treatment does not improve pressure ulcer healing post-SCI.

20.3.3 Ultrasound/Ultraviolet C for Pressure ulcer healing Post-SCI Houghton and Campbell (2001) note that both ultrasound (US) and ultraviolet light C (UVC) have been used in the treatment of chronic wounds. Ultrasound acts mainly at the inflammatory stage of the wound healing cascade to stimulate the release of chemical mediators of cells which in turn produces changes in the amount and strength or integrity of the scar tissue (p464). The bactericidal effects of UVC suggest that it is indicated for the treatment of chronic infected wounds where there is much surface bacteria or where bacteria have become resistant to antibiotic therapy. The authors go on to say that there is research to support the positive effects of these two treatments for chronic wounds. The Consortium of

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Spinal Cord Medicine (2000) found minimal data specific to the use of US or UVC to treat pressure ulcers in SCI. One small RCT will be discussed that combined US/UVC and compared its effects to laser and standard wound care. Table 20.11 Ultrasound/Ultraviolet C for Pressure Ulcer Healing Post-SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Age: 15 to 61; Gender: m=16, f=2; SCI; Urinary tract infection: n=16 Treatment: Subjects were assigned into one of three groups: control group received standard wound care consisting of twice daily cleansing with Hygeol (1:20) and Jelonet dressing, and avoidance of pressure on existing ulcers; Laser group received standard wound care plus laser treatment 3x weekly; Ultrasound/Utraviolet C (US/UVC) group received standard wound care with US and UVC treatments alternating over a 5 day period. 1. 2. Outcome Healing rate was not equal under all treatment conditions Paired comparisons showed the significant difference was between US/UVC and laser treatment with US/UVC showing greater effect on wound healing. Mean percentage of change per week in ulcer size (1 SD) from day 0 to complete healing for control (32.4%), US/UVC (53.5%), and laser (23.7%) Several subjects showed deterioration over the study. Ulcers increased in size; (laser=3, 62-167% change; control =1, 58% change; US/UVC=1, 1% change). All ulcers healed by end of study with last ulcer healed in laser group by week 20 as opposed to US/UVC group at week 6.

Nussbaum et al. 1994; Canada PEDro=6 RCT N=16

3.

4.

Discussion In one small RCT (n=16) Nussbaum et al. (1994) demonstrated that when compared to standard wound care alone or laser combined with standard wound care, Ultrasound/Ultraviolet C (US/UVC) plus standard wound care showed a greater effect on wound healing in a shorter period of time. As US/UVC were alternated over 5 days and seen as one treatment, conclusions cannot be drawn as to the individual effects of US or UVC. More research is needed to study the effects of US and UVC (alone or in combination) on pressure ulcer healing post-SCI. Conclusion There is level 1 evidence, from 1 small RCT, to suggest that combining US/UVC with standard wound care decreases wound healing time of pressure ulcers post-SCI. US/UVC should be considered as an added treatment when pressure ulcers are not healing with standard wound care post-SCI.

20.3.4 Effects of Non-Thermal Pulsed Electromagnetic Energy Treatment for Healing of Pressure Ulcers Post SCI Keast et al. (2006) in updating best practices recommendations for the prevention and treatment of pressure ulcers, recommends considering electromagnetic fields as one adjunctive modality

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for stimulating closure of chronic non-healing pressure ulcers. Salzberg (1995) states that the effect of non-thermal pulsed electromagnetic energy (PEE) on wound healing has been studied though not in the spinal cord population hence the rationale for his study. Table 20.12 Non-Thermal Pulsed Electromagnetic Energy for Healing of Pressure Ulcers Post-SCI
Author Year; Country Score Research Design Total Sample Size Methods Population: Stage II group: age 24-69 yrs Treatment: A non-thermal pulsed high frequency, high peak power, electromagnetic energy (PEE), was delivered through a treatment head placed in light contact with the wound site and tuned to resonance in the area of the wound. Treatment was non-invasive and delivered through wound dressings for 30 minutes, twice daily for 12 weeks or until healed. The control group received 12 weeks of sham treatment. Outcome Measures: Pressure Ulcer Status 1. Outcome Stage II group:Treatment (N=10), control (N=10). After 1 week, the treatment group had a greater percentage of ulcer healed (84%) compared to the control group (40%), p=.01 and the median size of ulcer was also smaller at one week (2.7 versus 16.5 cm2, p=.015). For complete healing, the treatment group healed in a median of 13 days versus 31.5 days for the controls (p<.001). Given that there were more large ulcers (>60cm2) in the sham group, data was reanalyzed for 15 subjects with ulcers <60cm2 with similar results as found initially. Stage III group: Treatment N=5, control N=5. 3/5 healed with an average of 43 days of treatment. 0/5 healed in control group. Ulcer area decreased by average 70.6% versus 20.7% in control group.

2.

Salzberg 1995; USA PEDro=8 RCT N=30

3.

4.

Discussion One RCT was found that studied the effects of electromagnetic energy on pressure ulcer healing in patients with SCI. Salzberg (1995) evaluated the effects of non-thermal pulsed electromagnetic energy (PEE) for healing of stage II/III ulcers in patients with SCI. In the stage II treatment group (N=10), a greater proportion of ulcers healed (84%) after 1 week versus control (40%), p=.01. For complete healing, the treatment group healed in a median 13 days versus 31.5 days for controls (p<.001). Given that there were a larger number of ulcers with size >60cm2 in the sham group, the data was reanalyzed and results obtained were consistent with initial findings that the treatment group showed a greater proportion healed at one week (p=.002) and the number of days to fully healed was less (p=.007). In the stage III group, healing was also associated with PEE treatment. 3/5 healed on average within 43 days; while 0/5 healed in control group. Ulcer area decreased 70.6% versus 20.7% in control group. More research will be needed to further our understanding of the mechanism of action of PEE and its role in pressure ulcer healing in individuals post-SCI. Conclusion There is level I evidence from one RCT to support the efficacy of pulsed electromagnetic energy to accelerate healing of stage II/III pressure ulcers post-SCI.

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Pulsed electromagnetic energy improves wound healing in Stage II and Stage III pressure ulcers post-SCI. 20.3.5 Anabolic Steroid Agents for Healing of Pressure Ulcers Post-SCI Impaired nutritional status and decreased nutritional intake are significantly associated with development and healing of pressure ulcers (Consortium for Spinal Cord Medicine 2000). Spungen (2001) stated that use of anabolic steroids and increased protein intake have been associated with promoting anabolism, weight gain and in turn wound closure in burn patients. Since a hypermetabolic, potentially catabolic state also is associated with pressure ulcers (p 140), the use of an anabolic steroid agent may also promote closure of nonhealing, pressure ulcers in the SCI population. Table 20.13 Anabolic Steroid Agents for Healing of Pressure Ulcers Post-SCI
Author Year; Country Score Research Design Total Sample Size Spungen et al. 2001; USA Downs & Black score=15 Case Series N=9 Methods Population: Age: 24 to 73 yrs; SCI m=9; Total # of PU since SCI: 1 to 7. Treatment: subjects with stage III/IV pressure ulcers were treated with 20mg of oxandrolone daily with 20g of glutamine dissolved in orange juice. Pressure ulcer care and support surfaces remained consistent 1. Outcome After oxandrolone and glutamine treatment, 8/9 subjects were completely healed, the majority within 3-6 months. 2 subjects required 12 months of treatment for complete healing.

Discussion In a case series of nine subjects with stage III/IV pressure ulcers, Spungen et al. (2001) demonstrated complete healing in 8/9 subjects 3-12 months after administration of 20mg oxandrolone. Given that this is only one small case series, more research is needed to determine the role of anabolic steroid agents (oxandrolone) for promotion of healing of stage III/IV pressure ulcers post-SCI. Conclusion There is very limited level 4 evidence to support the use of anabolic steroid agents (oxandrolone) to promote healing of stage III/IV pressure ulcers post-SCI. Anabolic steroid agents may promote healing of serious pressure ulcers post -SCI.

20.4 Summary Numerous studies cited in this document have spoken to the fact that pressure ulcers, though largely preventable, are still a common, potentially serious lifelong secondary complication of SCI. Pressure ulcers have the potential to impact overall quality of life (Consortium for Spinal Cord Medicine 2000); disrupt rehabilitation, vocational and educational pursuits and community

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reintegration (Fuhrer et al. 1993; Krause 1998; Consortium for Spinal Cord Medicine 2000; Jones et al. 2003); and lead to increased hospital readmission rates with longer length of stays (Chen 2005). Pressure ulcer prevention is more cost effective than treatment (Bogie et al. 2000; Jones et al. 2003). Despite the attention given to prevention strategies, pressure ulcers are still occurring. Of the 21 articles found for this review only 7 are RCTS and those studies have all looked at ways to treat ulcers once they have occurred. This author has not found any level 1 or 2 evidence to support the prevention strategies discussed in this document, most of which are being recommended for use by individuals post SCI in rehabilitation and after discharge to the community. Given the human and economic costs of pressure ulcer formation post SCI, more quality research needs to be done on all aspects of pressure ulcer management, especially prevention so that solid evidence is available to individuals with SCI, their families and health care providers so they know what works and what does not work. Pressure ulcers are potentially preventable. There is limited level 4 evidence that electrical stimulation decreases ischial pressures post SCI. There is level 4 evidence that electrical stimulation may increase blood flow at sacral and gluteal areas post-SCI. There is level 4 evidence to support the forward leaning position and the wheelchair tipped back position (> 65) as effective methods of pressure relief. There is level 4 evidence to support individualized wheelchair cushion prescriptions to optimize pressure ulcer prevention post-SCI. There is level 3 evidence that adding lumbar support to the wheelchair of those with chronic SCI has a negligible effect on reducing seated buttock pressures at the ischial tuberosities. There is very limited level 4 evidence to suggest that the introduction of behavioral contingencies are associated with a reduction in pressure ulcer severity and decreased health care costs. The data collected to date does not support a role for telerehabilitation in prevention and treatment of pressure ulcers post SCI. More research is needed to explore its usefulness. There is Level 2 evidence showing that early attendance at specialized seating assessment clinics (SSA) increases the skin management abilities of individuals postSCI. More research is needed to determine if early attendance at an SSA results in pressure ulcer prevention over time. There is level I evidence from 2 studies to support the use of electrical stimulation to accelerate the healing rate of stage III/IV pressure ulcers when combined with standard wound management.

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There is level 1 evidence (from two RCTs) to suggest that laser treatment has no added benefit in pressure ulcer healing post-SCI than standard wound care alone. There is level 1 evidence, from 1 small RCT, to suggest that combining US/UVC with standard wound care decreases wound healing time of pressure ulcers post-SCI. There is level I evidence from one RCT to support the efficacy of pulsed electromagnetic energy to accelerate healing of stage II/III pressure ulcers post-SCI. There is very limited level 4 evidence to support the use of anabolic steroid agents (oxandrolone) to promote healing of stage III/IV pressure ulcers post-SCI.

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Fuhrer MJ, Garber SL, Rintala DH, Clearman R and Hart KA. Pressure ulcers in communityresident persons with spinal cord injury: Prevalence and risk factors. Arch Phys Med Rehabil. 1993;74:1172-1177. Galea M, Tumminia J and Garback LM. Telerehabiliation in spinal cord injury persons: A novel approach. Telemedicine and e-Health 2006;12(2):160-162. Garber SL. Wheelchair cushions for spinal cord injured individuals. Am J Occup Ther. 1985;39(11):722-5. Griffin JW, Tooms RE, Mendius RA, Clifft JK, Vander Zwang R et al. Efficacy of high voltage pulsed current for healing of pressure ulcers in patients with spinal cord injury. Physical Therapy 1991;71(6):433-444. Henderson JL, Price SH, Brandstater ME and Mandac BR. Efficacy of three measures to relieve pressure in seated persons with spinal cord injury. Arch Phys Med Rehabil 1994;75(5):535-539. Houghton PE and Campbell KE. Therapeutic Modalities in the treatment of chronic recalcitrant wounds. In: Chronic Wound Care: A clinical source book for health care professionals. 3rd edition, ED Krasner, Rodheaver, Sibbald. Health Management Publications Inc., Wayne, PA. April 2001. Jones ML. Mathewson CS, Adkins VL and Ayllon T. Use of behavioral contingencies to promote prevention of recurrent pressure ulcers. Arch Phys Med Rehabil 2003;84(6):796-802. Keast DH, Parslow N, Houghton PE, Norton L, Fraser C. Best practice recommendations for the prevention and treatment of pressure ulcers: Update 2006. Wound Care Canada 2006;2232. Kennedy P, Berry C, Coggrave M, Rose L and Hamilton L. The effect of a specialist seating assessment clinic on the skin management of individuals with spinal cord injury. J Tissue Viability 2003;13(3):122-125. Kloth LC and Feedar JA. Acceleration of wound healing with high voltage, monophasic, pulsed current. Physical Therapy 1988;68(4):503-508. Krause JS and Broderick L. Patterns of recurrent pressure ulcers after spinal cord injury: Identification of risk and protective factors 5 or more years after onset. Arch Phys Med Rehabil 2004;85:12571264. Krause JS, Vines CL, Farley TL, Sniezek J and Coker J. An exploratory study of pressure ulcers after spinal cord injury: relationship to protective behaviours and risk factors. Arch. Phys Med Rehabil. 2001;82(1):107-113. Krause JS. Skin sores after spinal cord injury: relationship to life adjustment. Spinal Cord 1998;36:51-56. Lamid S and El Ghatit AZ. Smoking, spasticity and pressure sores in spinal cord injured patients. Am J Phys Med. 1983;62(6):300-306. Levine SP, Kett RL, Cederna PS and Brooks SV. Electrical muscle stimulation for pressure sore prevention: tissue shape variation. Arch Phys Med Rehabil. 1990;71(3):210-5. Levine SP, Kett RL, Gross MD, Wilson BA, Cederna PS, and Juni JE. Blood flow in gluteus maximus of seated individuals during electrical muscle stimulation. Arch Phys Med Rehabil. 1990;71:682-686. Mathewson C, Adkins VK, and Jones ML. Initial experiences with telerehabiliation and contingency management programs for the prevention and management of pressure ulceration in patients wth Spinal Cord Injuries. JWOCN 2000;27(5):269-271. Mawson AR, Siggiqui FH, Connolly BJ, Sharp CJ Stewart GW et al. Effect of high voltage pulsed galvanic stimulation on sacral transcutaneous oxygen tension levels in the spinal cord injured. Paraplegis 1993;31(5):311-319. National Pressure Ulcer Advisory Panel (NPUAP): NPUAP staging report (2003). http://www.npuap.org/positn6.html

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Niazi ZB, Salzberg CA, Bryne DW and Viehbeck M. Recurrence of initial pressure ulcer in persons with spinal cord injuries. Adv Wound Care. 1997;10(3):38-42. Nursing Best Practice Guideline: Assessment and management of stage 1 to IV pressure ulcers. Toronto. RNAO 2002. www.rnao.org/bestpractices Nussbaum EL, Biemann I and Mustard B. Comparison of ultrasound/ultraviolet-C and laser for treatment of pressure ulcers in patients with spinal cord injury. Phys Ther 1994;74(9):812823. Phillips VL, Temkin A, Vesmarovich S, Burns R and Idleman L. Using telehealth interventions to prevent pressure ulcers in newly injured spinal cord injury patients post-disharge. Results from a pilot study. Int J Technol Assess Health Care. 1999;15(4):749-755. Richards JS, Waites K, Chen YY, Kogos S & Schmit MM. The epidemiology of secondary conditions following spinal cord injury. Topics in Spinal Cord Injury Rehabilitation 2004;10(1):15-29. Richardson RR and Meyer PR Jr. Prevalence and incidence of pressure sores in acute spinal cord injuries. Parplegia 1981;19(4):235-247. Salzberg CA, Byrene DW, Cayten CG, van Niewerburgh P, Murphy JG and Viehbeck M. A new pressure ulcer risk assessment scale for individuals with spinal cord injury. Am J Phys Med Rehabil. 1996;75(2):96-104. Salzberg CA, Cooper-Vastola SA. Perez F, Viehbeck MG and Byrne DW. The effects on nonthermal pulsed electromagnetic energy on wound healing of pressure ulcers in spinal cordinjured patients: a randomized double blind study. Ostomy Wound Management 1995;41(3):42-50 Schryvers OI,Stranc MF and Nance PW. Surgical treatment of pressure ulcers: 20-year experience. Arch Phys Med Rehabil. 2000;81(12):1556-1562. Scivoletto G. Fuoco U, Morganit B, Cosentino E and Molinarit M. Pressure sores and blood serum dysmetabolism in spinal cord injury patients. Spinal Cord 2004;42:473-476. Seymour RJ and Lacefield WE. Wheelchair cushion effect on pressure and skin temperature. Arch Phys Med Rehabil 1985;66(2):103-108. Shields RK and Cook TM. Lumbar support thickness: effect on seated buttock pressure in individuals with and without spinal cord injury. Physical Therapy 1992;72(3):218-26. Spungen Am, Koehler KM, Modest-Duncan R, Rasul M, et al. 9 clinical cases of nonhealing pressure ulcers in patients with spinal cord injury treated with an anabolic agent: a therapeutic trial. Adv Akin Wound Care 2001;14(3):139-144. Stefanovska A, Vodovnik L, Benko H, and Turk R. Treatment of chronic wounds by means of electric and electromagnetic fields. Part 2. Value of FES parameters for pressure sore treatment. Med Biol Eng Comput 1993;31(3):213-220. Taly AB, Sivaraman Nair KP, Murali T and John A. Efficacy of multiwavelength light therapy in the treatment of pressure ulcers in subjects with disorders of the spinal cord: a randomized double blind controlled trial. Arch Phys Med Rehabil 2004;85(10)1657-1661. Vesmarovich S, Walker T, Hauber RP, Temkin A. and Burns R. Use of telerehabilitation to manage pressure ulcers in persons with spinal cord injuries. Adv Wound Care 1999;12(5):264-269. Vidal J, and Sarrias M. An analysis of the diverse factors concerned with the development of pressure sores in spinal cord injured patients. Paraplegia 1991;29:261-267.

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CHAPTER TWENTY-ONE
Spasticity Following Spinal Cord Injury
Jane TC Hsieh, MSc Dalton L Wolfe, PhD Sandra Connolly, BHScOT(C), OT Reg (Ont.) Andrea F Townson, MD FRCPC Armin Curt, MD FRCPC Jeff Blackmer, MD FRCPC Keith Sequeira, MD FRCPC Jo-Anne Aubut, BA

Key Points Rhythmic passive movements may produce short-term reductions in spasticity. Prolonged standing or other methods of producing muscle stretch may result in reduced spasticity. Active exercise interventions such as hydrotherapy and (FES) functional electrical stimulation-assisted walking may produce short-term reductions in spasticity. Electrical stimulation applied to individual muscles may produce a short term decrease in spasticity. There is also some concern that long-term use of electrical stimulation may increase spasticity. Ongoing (TENS) transcutaneous electrical nerve stimulation programs result in shortterm reductions in spasticity which may last for up to 24 hours. Penile vibration and rectal probe stimulation may be effective at reducing lower limb muscle spasticity for several hours. Other forms of afferent stimulation including massage, cryotherapy, hippotherapy and helium-neon irradiation may result in immediate spasticity reduction but require more research to examine long-term effects. Spinal cord stimulation may provide spasticity relief over a few months but long-term effectiveness and cost-effectiveness is less certain. Dorsal longitudinal T-myelotomy may result in reduced spasticity. Oral baclofen reduces muscle spasticity in people with SCI. Bolus or long-term intrathecal Baclofen decreases spasticity and may improve functional outcomes with low complication rates and is a cost effective intervention. Tizanidine, Clonidine, Cyproheptadine and Gabapentin may be useful in treating SCI spasticity. The usefulness of Diazepam, Dantrolene, 4-Aminopyridine, L-Threonine and Cannabis in the treatment of SCI spasticity requires confirmation through additional well designed studies. Well designed studies should include effective outcome measures that meet minimum standards and that encompass the range of medical outcomes relevant to the treatment and the patients.

Table of Contents

21.1 Introduction ..................................................................................................................21-1 21.2 Non-Pharmacological Interventions for Spasticity...................................................21-1 21.2.2 Interventions Based on Active Movement (Including FES-assisted Movement).........21-5 21.2.3 Interventions Based on Direct Muscle Electrical Stimulation ......................................21-7 21.2.5 Interventions Based on Direct Spinal Cord Stimulation ............................................21-18 21.3 Neuro-Surgical Interventions....................................................................................21-20 21.4 Pharmacological Treatment of Spasticity ...............................................................21-22 21.4.1 Oral Baclofen ............................................................................................................21-22 21.4.2 Intrathecal Baclofen for Reducing Spasticity ............................................................21-25 21.4.3 Effect of Medications Other than Baclofen on Spasticity after SCI ...........................21-32 21.4.4 Neurolysis with Botulinum Neurotoxin ......................................................................21-42 21.5 Spasticity Outcome Measures..................................................................................21-45 21.6 Summary.....................................................................................................................21-47 References............................................................................................................................21-50

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Hsieh JTC, Wolfe DL, Connolly S, Townson AF, Curt A, Blackmer J, Sequeira K, Aubut J (2006). Spasticity Following Spinal Cord Injury. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 21.1-21.56. www.icord.org/scire

Spasticity Following Spinal Cord Injury

21.1 Introduction Spasticity has been described as being inclusive of velocity-dependent increases in tonic stretch reflexes, exaggerated phasic stretch reflexes, hyperactive cutaneous reflexes, increased autonomic reflexes, and abnormal postures that are the result of excessive involuntary motor activity reacting to excitatory stimuli (Young 1989; 1994). Pandyan et al. 2005 (adapted from Tardieau et al. 1954) has proposed a new definition of spasticity as follows: disordered sensori-motor control, resulting from an upper motor neurone lesion, presenting as intermittent or sustained involuntary activation of muscle. This definition is more inclusive of clinical signs and symptoms of spasticity but has yet to be validated for clinical relevance. It has been estimated that 53% (Walter et al. 2002) to 78% (Maynard et al. 1990; Levi et al. 1995) of individuals report spasticity secondary to SCI. Furthermore, approximately 41% (Levi et al. 1995) of these individuals with spasticity secondary to chronic SCI list it as one of the major medical obstacles to community and workplace re-integration (CPA WPNS 1996). Although a variety of management strategies are currently available for the treatment of spasticity in spinal cord injury, an assessment of treatment goals and costs is necessary initially. Often, increased spasticity is beneficial for transfers and mobility and the reduction of tone may negatively impact those activities of daily living. The goal should not be to modify the excitability and rigorousness of reflexes, but to overcome functional impairments related to spasticity (Dietz 2000). Therefore, the decision to treat spasticity should not only be based on the findings gained by the examination in a passive (lying bed, sitting in the wheelchair) but also in an active condition (like walking, doing transfer etc.). Incrementally applying the less invasive and cost efficient treatments will likely lead to a combination of treatments necessary to achieve the most successful outcome specific for each individual. Simultaneously with the completion of an assessment that clearly delineates the treatment goals, objective measures of spasticity are important to identify in order to confidently assess the success of treatment choice(s). Physical therapy, surgery, pharmacotherapy and neurolysis are among the most common treatment options currently employed to manage spasticity in SCI. Physical therapy is initiated during rehabilitation and usually continues post-discharge either formally or through patient education and caregiver administration. Pharmacotherapies are thought to be the most efficacious for treatment of the velocity-dependent increase in hyperexcitable tonic stretch reflexes, one component of the upper motor neuron syndrome defined by Lance (1980). Surgery and neurolysis may be necessary to treat focal spasticity. A combination treatment regimen can be individualized and appears to be a common approach in clinical practice. 21.2 Non-Pharmacological Interventions for Spasticity As noted above, there are a wide variety of approaches in treating spasticity. It is generally accepted practice to employ more conservative approaches initially and gradually administer more invasive treatments with the understanding that no one approach is likely to be universally successful for all individuals (Kirshblum 1999). However, some have contended that this stepwise approach is not necessarily the ideal. For example, Gormley Jr. et al. (1997) have asserted that in the hands of an experienced clinical team, it may be decided that aggressive

21-1

measures are needed early on based on the individual presentation and the many factors that may influence spasticity. Regardless, effective clinical management requires an individualized and often a combination approach, thereby necessitating a broad knowledge of the various options available. In the present section, non-pharmacological interventions are outlined - from the more conservative options such as passive and active movement-based interventions, to those based on forms of electrical and other types of stimulation and finally to more invasive neurosurgical interventions. For the purpose of this review we have classified the various non-pharmacological approaches into 6 general categories. These include interventions based on i) passive movement, ii) active movement, iii) direct muscle electrical stimulation, iv) various forms of afferent stimulation, v) direct spinal cord stimulation and vi) neuro-surgical approaches. It should be noted that although we have tried to be as specific as possible within these distinctions, there may be some overlap across the categories for specific modalities. For example, passive movements produce afferent outflow and may have also been classified as a form of afferent stimulation. Hydrotherapy, classified as an active movement-based intervention given the bouyancy and viscous properties of water in aiding active movement exercise (Kesiktas et al. 2004), often involve passive movements as well as the contributions of afferent stimulation associated with heated water. We have tried to categorize the approaches based on the primary intent of the authors in describing the various interventions. In addition, when considering final conclusions we have tried to be as specific as possible within each category, despite the obvious need to bring together evidence from different sources. 21.2.1 Interventions Based on Passive Movement or Stretching It has been reported that self-stretching, regular physiotherapy and physical activities affect spasticity and should be considered as a therapeutic approach prior to antispastic medication and surgical procedures (Merrit 1981). In particular, therapies based on physical interventions are advantageous as they generally have fewer related adverse events although they also typically have short-lasting effects. Movement therapies can be differentiated into passive or active maneuvers that are assumed to affect both spinal neuronal circuits and fibro-elastic properties of the muscles, thereby potentially reducing spasticity. An underlying physiologic paradigm that explains why passive movements have an influence on spasticity in patients with a lesion of the upper motor neuron is equivocal (Katz 1991). Passive movement may be accomplished by therapist or self-mediated limb movement focusing on muscle stretching or on preserving full range of motion over joints that may be immobilized. Alternatively, a mechanical device may be employed such as a motorized therapy table (Skold 2000) or exercise cycle (Kakebeeke et al. 2005; Kiser et al. 2005). These mechanical devices have the advantages for research purposes of producing repeatable movements over a specific range and also in standardizing other parameters (e.g., frequency, speed). Although it has been suggested by some that repetitive movements are deemed necessary for obtaining a clinical effect (Rosche et al. 1997), there have been several reports of reduced spasticity associated with engaging in regular periods of passive standing (Odeen & Knutsson 1981; Bohannon 1993; Kunkel et al. 1993; Dunn et al. 1998; Eng et al. 2001; Shields & DudleyJavoroski 2005). The majority of these are individual case reports (Bohannon 1993; Kunkel et al. 1993; Shields & Dudley-Javoroski 2005) or user satisfaction surveys (Dunn et al. 1998; Eng et al. 2001) and have not been included in Table 21.1 (i.e., other than Odeen & Knutsson, 1981) which outlines the specific investigations of effectiveness of these passive approaches. The individuals examined in all 3 case reports reported reductions in lower limb spasticity associated

21-2

with passive standing despite the fact that different procedures and devices were used across the reports including a tilt table (Bohannon 1993), a standing frame (Kunkel et al. 1993) and a stand-up wheelchair (Shields & Dudley-Javoroski 2005). In addition, a significant number of people have indicated they receive benefit with respect to reduced spasticity in response to surveys about prolonged standing programs. Specifically, Eng et al. (2001) reported that 24% and Dunn et al. (1998) reported that 42% of individuals engaged in this activity find it beneficial in reducing spasticity. However, it should be noted that in each of these studies some individuals also reported an increase in spasticity with this activity (13% and 3% respectively). Table 21.1 Studies of Passive Movement-based Approaches for Reducing Spasticity
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=39, f=6, age: 1747, time since injury: 3-26 years, ASIA: AD, cervical-thoracic injuries. (Passive stretches performed on n=12, thoracic ASIA C, D). Treatment: Repetitive passive movements of standardized range of motion in 3 different positions administered with motorized table, 10 minutes per position, 20-30 movements/minute, 2 sessions/week for 6 weeks. Outcome Measures: self-reported Visual Analogue Scale (VAS): "no spasticity" to "most imaginable spasticity", modified Ashworth scale (MAS), collected just prior and after each treatment session. Population: Gender m=9, f=1, Age 23 to 60 yrs, Injury level C6 to T12, ASIA: A & B, 1-25 years post-injury (median 2 years). Treatment: Passive cycling with motorized cycle for 30 minutes at 40 RPM (1 session) vs no cycling. Outcome Measures: Torque resistance to movement on isokinetic dynamometer, subjective subject assessment collected just prior and following cycling (or control). Population: Gender m=8, f=1, Age 21 to 67 yrs, > 3 years post-injury. Treatment: Standing in forced dorsiflexion or plantarflexion (i.e., load applied) vs stretch applied to plantarflexors while supine. 30 minute sessions Outcome Measures: Torque resistance and angular displacement to sinusoidal ankle movement as measured by strain gauge transducer and potentiometer respectively. EMG recorded for some subjects as well. All collected just prior and following treatment. 1. 2. Outcome Spasticity decreased after each intervention session as indicated by VAS (p<0.001) and MAS (p<0.001). Spasticity reductions were maintained in VAS values (albeit to a lesser degree) after treatment was discontinued for 4 days (p<0.018).

Skld 2000; Sweden Downs & Black score=15 Pre-post N=45 (Passive stretches peformed on n=12)

1.

Kakebeeke et al. 2005; Switzerland Downs & Black score=14 Pre-post N=10

2.

6/10 subjects estimated that their spasticity was less after cycling and 3/10 estimated it was less after no cycling. No effect on spasticity was noted as indicated by no differences with torque before and after cycling or before and after the control (no cycling) condition. Average reduction in resistance to passive movement at 1 cycle/s was 32%, 26% and 17 % for standing in dorsiflexion, standing in plantarflexion and supine dorsiflexion respectively. Greater reductions were seen at 1 cycle/s than at 0.25 cylce/s, although significant reductions were still seen for both conditions of dorsiflexion stretch (i.e., standing and supine) at the slower test speed.

1.

Odeen & Knutsson 1998; Sweden Downs & Black score=12 Pre-post N=9

2.

Discussion Kakebeeke et al. (2005) employed externally applied repetitive cycling movements to the lower limbs with a specifically adapted motorized exercise bicycle. This study employed an

21-3

experimental non-RCT design with each subject acting as his or her own control (i.e., cycling vs. no cycling 1 week apart). However, it involved only a single intervention session and no clinically relevant outcome measures were employed. In addition to a self-report measure of more, less or equal amounts of spasticity, a Cybex II isokinetic dynamometer was used to measure torque resistance to 2 different speeds of knee flexion/extension. The majority of subjects tested (i.e., 6 of 10) reported subjectively that their spasticity was reduced following cycling; however, some subjects (i.e., 3 of 10) also indicated it was reduced following the control (no cycling) condition. No changes were seen for either condition with the objective torque resistance response to movement. Given the mixed results of this study and uncertainty of the clinical relevance of the outcome measures the findings of this study are deemed equivocal. Although a weaker study design (i.e., Pre-Post Trial), Skld (2000) employed a more rigorous methodology with clinically relevant outcome measures (i.e., modified Ashworth and a selfreport visual analogue scale) and an intervention administered over 6 weeks. This intervention involved the evaluation of standardized, repetitive passive movements of prone and supine hip flexion/extension and lumbar lateral flexion elicited by a motorized table in a subset of subjects with ASIA C and D paraplegia. These subjects were drawn from a larger study examining selfvs. clinically rated spasticity fluctuations. Results of the study indicated that there was a significant reduction in the modified Ashworth Score and also a significant decrease in the selfreport measure of spasticity immediately following passive movement. In addition, it was reported that these reductions in spasticity were partially maintained when self-report assessments (but not clinical evaluations) were conducted 4 days following the discontinuation of the intervention. Odeen and Knutsson (1981) employed a tilt table and 9 subjects with spastic paraparesis due to spinal cord lesions to examine whether benefits of reduced spasticity with passive activity were due to increased muscle load or muscle stretch. These investigators examined the effect of various conditions on resistance to passive sinusoidal ankle movement by loading the tibialis anterior or gastrocnemius while standing by having the subject stand at an angle of 85 with the ankle dorsi- or plantarflexed by 10-15 or by applying stretch to the gastrocnemius muscles while supine. All procedures tested resulted in reduced resistance to passive movement (i.e., reduced tone or spasticity) with the most significant reductions noted for standing in forced dorsiflexion with load applied (i.e., stretch applied to calf muscles, p<0.001) (Odeen & Knutsson, 1981). Conclusion There is level 4 evidence that rhythmic, passive movements may result in a short-term reduction in spasticity. There is level 4 evidence that externally applied forces or passive muscle stretch as are applied in assisted standing programs may result in short-term reduction in spasticity. This is supported by individual case studies and anecdotal reports from survey-based research. Rhythmic passive movements may produce short-term reductions in spasticity. Prolonged standing or other methods of producing muscle stretch may result in reduced spasticity.

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21.2.2 Interventions Based on Active Movement (Including FES-assisted Movement) Physical therapy approaches are often advocated as the first treatment choices for reducing spasticity and are deemed as the foundation upon which other therapies are built (Merritt 1981; Kirshblum 1999; Rosche 2002). Despite these contentions, there is a relative paucity of literature addressing the efficacy of either the passive techniques noted in the previous section or approaches involving active movement. In practice, active movement approaches may be conducted using a variety of exercise forms that may also provide benefits beyond spasticity reduction (e.g., strength, endurance, gait re-training). The studies meeting the criteria for the present review involve exercises performed in a therapeutic pool (i.e., hydrotherapy) (Kesiktas et al. 2004) or those associated with locomotor training programs, whether assisted by FES (Granat et al. 1993; Mirbagheri et al. 2002) or a FES-powered orthosis (Thoumie et al. 1995). Table 21.2 Studies of Active Movement-based Approaches for Reducing Spasticity
Author Year; Country Score Research Design Total Sample Size Methods Population: gender m=20, f=1, age: 2053, level of injury: C8-T12, time post-injury: 4-72 months (mean 26 months). Treatment: Fitting of a Reciprocating Gait Orthosis II (RGO) hybrid (FES-assisted) system and subsequent locomotor training program of 2 1 hour sessions/week for 314 months. Outcome measures: Spasticity (Subjective self-report scale based on Ashworth scale), Cardiovascular function (HR, VO2, blood lactate), Constipation (Radiopaque markers transit). Osteoporosis (Bone mineral density) collected prior to and following the 3-14 month trial. Population: Groups: Hydrotherapy vs Control, gender m/f = 8/2 vs 7/3, age = 32.1 vs 33.1 years, level of injury: C5-6/T89 = 3/7 vs 3/7, ASIA: A/B-C/D = 3/3/4 vs 3/3/4, time post-injury = 7.7 vs 8.6 years. Treatment: 20 min of underwater exercises at 71F, 3 times/week for 10 weeks in addition to conventional rehabilitation (passive ROM exercises, oral baclofen, psychotherapy) vs conventional rehabilitation alone. Outcome Measures: Ashworth Scale, Penn Spasm Severity, FIM scores and oral baclofen intake were recorded weekly and evaluated at the beginning and end of the treatment period. Mirbagheri et al. 2002; Canada Downs & Black score=17 Pre-post (1 unplanned control, Population: gender m=5, f=4, age: 2548.9, level of injury: C5-L1, ASIA: C-D, time post-injury: 3.1-12.3 years. (1 unplanned control, dropout from training) Treatment: FES-assisted walking for as 1. Outcome No group analysis reported for spasticity measure No marked changes reported, decrease in spasticity for 7 subjects at 0.5-5 hours and increase in spasticity for 4 subjects at 0.5-1 hour. No long-term effects were observed.

Thoumie et al. 1995; France Downs & Black score=24 Pre-post N=21

1.

2.

Kesiktas et al. 2004; Turkey Downs & Black score=17 Experimental Non-RCT N=20

3. 4.

1.

Both groups showed a significant decrease in Ashworth scores (hydrotherapy = p<0.01 and control = p<0.02) with hydrotherapy having a larger reduction in spasticity but this difference was not significant. Spasticity was significantly reduced with hydrotherapy (p<0.001) and with Control (p<0.05) as indicated by Penn Spasm Severity. Post-treatment hydrotherapy scores were reduced vs Controls (p<0.02). Oral baclofen intake was significantly reduced for the hydrotherapy group but not for the control group (p<0.002). Both groups demonstrated significant increases in FIM scores (hydrotherapy = p<0.0001 and control = p<0.01), with a larger increase for the hydrotherapy group (p<0.001). Spasticity was reduced in those that did FES-assisted walking as indicated by reductions in decreased reflex (p<0.001) and intrinsic (p<0.001) stiffness.

21-5

Author Year; Country Score Research Design Total Sample Size dropout from training) Initial N=9; Final N=5

Methods much time as possible during daily living (~1-3 hours/day) for 16-18 months following 4 weeks of training. Outcome measures: Reflex and intrinsic stiffness (mathematical modelled responses of torque resistance to movement), modified Ashworth scale collected prior to and following the 16-18 month trial. Population: 6 incomplete SCI (3 males, 3 females), aged 20-40, 2-18 years post injury with lesion levels from C4 to L1, 3 Frankel C, 3 Frankel D. Treatment: FES-assisted locomotor training for at least half an hour each day for a minimum of 5 days/week for a minimum of 3 months. Outcome Measures: Spasticity (Ashworth Scale and Pendulum Test), Manual muscle tests using Oxford Scale (MMT), maximum voluntary contraction (MVC), Upright motor control, Gait Performance (Energy Cost), postural stability (Centre of Pressure) and modified Barthel Index. Spasticity tests were conducted at least 24 hours after FES use. 2.

Outcome Spasticity increased for the non-FES subject as indicated by increased reflex stiffness and no change in intrinsic stiffness. The modified Ashworth score either showed no change following the training period or was not collected (this was not clearly presented by the authors). Significant reductions in spasticity as indicated by increased relaxation index of pendulum test (p<0.05). No changes were evident with Ashworth scale. Gait and muscle strength changes are elaborated in Chapter entitled Lower Limb Rehabilitation.

3.

1. 2. 3.

Granat et al. 1993; Scotland Downs & Black score=5 Pre-post N=6

Discussion All studies demonstrated positive benefits for at least one outcome measure associated with spasticity. However, it should be noted that results between two spasticity-related outcome measures within some studies were not consistent and that there was also little uniformity across studies with respect to homogeneous outcome measure selection. Kesiktas et al. (2004) employed an experimental non-RCT design to test the effectiveness of a water-based exercise (i.e., hydrotherapy) program in reducing spasticity in a group of individuals (n=10) with complete and incomplete paraplegia and tetraplegia. Subjects were matched within a treatment group (i.e., hydrotherapy + conventional rehabilitation) vs. a control group (conventional rehabilitation only) on the basis of age, gender, time post-injury, injury level and severity, spasticity (Ashworth) and function (FIM). This study produced consistent results across all spasticity-related measures with spasticity reductions evident following the 10 week hydrotherapy treatment program for both Ashworth Scale scores and the Penn Spasm Severity scores. The control group also showed significant spasticity reductions relative to baseline with these measures but not to the same degree. In addition to these measures, dosages of oral baclofen were significantly reduced for those receiving hydrotherapy vs. conventional rehabilitation only (i.e., > 50%) and the hydrotherapy treated group made much greater FIM gains than did the control group. These latter results may reflect the deleterious effect that high baclofen doses can have on motor and cognitive function and also the benefits of reduced spasticity on motor function. Kesiktas et al. (2004) did not mention how soon after the final intervention the measures were taken so there is no indication of how long the beneficial effect might be maintained.

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The remaining studies using active movement-based approaches involved pre-post trial designs of FES-assisted walking with and without orthoses. Mirbagheri et al. (2002) calculated reflex and intrinsic stiffness of the ankle by employing a mathematical model of position vs torque resistance in response to perturbations as a means of assessing spasticity prior to and following a FES-assisted walking training program. This program involved 4 individuals with longstanding ASIA C or D SCI who participated a minimum of 16 months. Both reflex and intrinsic stiffness were reduced following training while another individual with SCI, but not actively involved in FES-assisted walking, demonstrated no reduction in spasticity. Although the modified Ashworth scale was noted as an outcome measure in the Methods the authors failed to report the final results associated with this clinical measure. Granat et al. (1993), in a similar trial of FES-assisted walking in people with Frankel C or D longstanding SCI, also found reductions in spasticity by employing a pendulum drop test but were unable to show any change pre- and post-training when considering Ashworth scale scores. Granat et al. (1993) performed the final spasticity assessment 24 hours after the final FES-assisted walking session; thereby ensuring the final outcomes would not be unduly influenced by the short-term effects of muscle stimulation. Thoumie et al. (1995) examined the effects of a FES-assisted Reciprocting Gait Orthosis II (RGO) on spasticity following a long-term program (i.e., 3-13 months) of gait training. No group results were reported for spasticity although it appeared that no systematic effects were obtained on a customized self-report version of the Ashworth scale. Some subjects (n=7) reported decreases in spasticity in the short-term, while others reported increased spasticity (n=4). Conclusions There is level 2 evidence that hydrotherapy is effective in producing a short-term reduction in spasticity. There is level 4 evidence that a program of FES-assisted walking acts to reduce ankle spasticity in the short-term (i.e., 24 hours). There is no evidence that describes the length and time course of the treatment effect related to spasticity for hydrotherapy or FES-assisted walking. Active exercise interventions such as hydrotherapy and (FES) functional electrical stimulationassisted walking may produce short-term reductions in spasticity. 21.2.3 Interventions Based on Direct Muscle Electrical Stimulation A variety of electrical stimulation methods have been employed to reduce spasticity including direct muscle stimulation, sometimes also termed patterned electrical stimulation (PES) or patterned neuromuscular stimulation (PNS), functional electrical stimulation (FES) and transcutaneous electrical nerve stimulation (TENS). In the present section, we will examine the effect of interventions based on direct muscle stimulation. The objective of direct muscle stimulation (or stimulation of the motor nerve) is to produce a muscle contraction and related therapies are focused on the beneficial effects of series of muscle contractions. Often this stimulation is cyclical in nature (patterned) so as to simulate natural physiologic conditions such

21-7

as might be seen in walking or cycling. With FES, the stimulation parameters are set to produce a coordinated contraction of several muscles with the intent of producing purposeful movement. This approach is often used to assist or simulate active exercise paradigms and therefore, the articles addressing FES have been summarized in the previous section on active movementbased approaches. TENS, on the other hand, is focused on stimulating large, low threshold afferent nerves so as to alter motor-neuron excitability and thereby reduce spasticity. Stimulation intensities are maintained subthreshold for eliciting muscle contraction when stimulating mixed motor and sensory nerves so that only lower threshold sensory nerves are selectively stimulated. For this reason articles concerning TENS will be included in the next section that is directed towards interventions based on afferent stimulation. Table 21.3 Studies of Direct Muscle Stimulation for Reducing Spasticity
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: m=8, f=2; age 21-42 yrs, level of injury: C3-T11, time since injury: 28-275 months, ASIA: 9 A and 1 C. Treatment: Electrical motor (agonist or antagonist) or afferent (S1 dermatomal) stimulation of the triceps surae or a placebo (application of electrodes but no current). 1 45 minute session of each type of stimulation. Intensity @ 3 x motor threshold for motor stimulation and 80% of motor threshold for afferent stimulation. Outcome measures: modified Ashworth scale (MAS), clonus score, H reflex, and H/M ratios. Measurements were conducted just prior to, immediately after, 1 hour after and 2 hours after the intervention for each of the 4 conditions. Population: Age 19-73yrs, gender: m=6, f=4, duration of injury 3-16yrs (n=5 SCI), 16 yrs (n=5 TBI). Treatment: 1, 20 minute session of electrical stimulation over the tibialis anterior measured in ipsilateral (treatment) and contralateral (control) leg vs a sham stimulation (control). Outcome Measures: Viscous and elastic ankle stiffness measured by frequencydependent torque resistance immediately post-stimulation (n=10/9), and 24 hours post-stimulation (n=9/8), and immediate post-stimulation subjective spasticity assessment (n=9). Population: Age 21-62yrs, 6 paraplegics / 6 quadriplegics, complete(6)/incomplete(6) Treatment: 1, 20 minute session of electrical stimulation of quadriceps with leg maintained at 60 flexion (isometric exercise). Outcome measures: Normalized relaxation index obtained during Pendulum test (R2n) collected prior and immediately after stimulation. 1. Outcome Only the agonist muscle stimulation differed significantly (46% reduction) from the placebo as indicated by reduced MAS (p<0.001) No significant carry-over effect (over 2 hours) although there was a trend of continued reductions for the MAS (p=0.113). No significant intervention effect was shown for the clonus score or the H/M ratio. The reflex-initiating angle showed a significant change for antagonist stimulation (n=8, p<0.015) but the carryover effect was not significant. Spasticity was reduced in 9/10 participants (p<0.05) (p<0.05 for SCI subjects only) and this was sustained for 24 hours over all subjects (p<0.01) but not for SCI subjects only. Spasticity was not reduced immediately or after 24 hours in the contralateral leg nor with sham stimulation. Subjective spasticity assessment immediately post-stim only recorded notable reductions for SCI subjects for up to 6 hours post-simulation. Decrease in spasticity was noted with pendulum test (average R2n increased in most cases) (p<0.005). The greatest reduction in spasticity after stimulation was noted for patients who were the most spastic before stimulation. No carry over effect of stimulation in spasticity measured 24 hours later.

2.

Van der Salm et al. 2006; Netherlands Downs & Black score=18 Prospective Controlled Trial N=10

3. 4.

1.

Seib et al. 1994; USA Downs & Black score=14 Prospective Controlled Trial N=10

2.

3.

1. 2.

Robinson et al. 1988; USA Downs & Black score=15 Pre-post N=12

3.

21-8

Author Year; Country Score Research Design Total Sample Size

Methods Population: Paraplegic (15)/quadriplegic (16), complete/incomplete injuries, time since injury: <1yr (15), >1yr (16). Treatment: 4-8 wk quad reconditioning program of twice daily 20-minute stimulation sessions of quadriceps, which were at least 4 hours apart, six days per week. Stimulus currents were set at 120160mA. Outcome Measures: R2n-index of spasticity (by means of pendulum drop test). Peak isometric quad torque in response to surface electrical stimulation. Biweekly tests of spasticity and torque at baseline, 4 and 8 weeks (1-3 evals performed each time). 1.

Outcome Most participants had increased spasticity after four weeks of reconditioning but not after eight weeks. Twice as many legs had R2n decreases (spasticity increases) as had increases or no change. Baseline vs 4wk left and right R2n yielded a significant within subject difference between baseline and 4wk values (p=0.008).

Robinson et al. 1988; USA Downs & Black score=14 Pre-post Initial N=31; Final N=8 4wk tx N=21, 8wk tx N=8

2. 3.

Discussion Van der Salm et al. (2006), Seib et al. (1994) and Robinson et al. (1988a) tested the effects of a single session of muscle stimulation on spasticity. Each employed slightly different stimulation parameters and a variety of outcome measures. Of note, Van der Salm et al. (2006) and Seib et al. (1994) each employed controlled trials of electrical stimulation and demonstrated immediate effects of reduced spasticity although these effects waned and were mostly absent by the next day. In particular, Van der Salm et al. (2006) examined 3 different stimulation methodologies vs. a placebo condition and assessed ankle plantar flexor spasticity with the modified Ashworth scale, a clonus score and via EMG responses (i.e., H-reflex and H/M ratio). The various stimulation methods examined consisted of stimulation over the triceps surae (agonist), the tibialis anterior (antagonist) and the S1 dermatome vs a control placebo condition of electrode application but no current being generated. Presumably, subjects were not aware of this because all subjects had no sensation in the stimulated areas. Significant spasticity reductions were only obtained with agonist muscle stimulation for the modified Ashworth scale (p<0.001) and not the clonus or EMG responses. This was not sustained for 2 hours post-stimulation although there was still a trend for reduced modified Ashworth scores at this time (p=0.113). Spasticity was also reduced (but not statistically significantly) with antagonist muscle stimulation but not for dermatomal or sham (placebo) stimulation Interestingly, Van der Salm et al. (2006) noted that if they had examined their data by employing t-tests to test for pre-post effects (i.e., univariate analysis) within a specific stimulation method, they also would have demonstrated a reduction in spasticity for antagonist muscle stimulation, thereby illustrating the potential of obtaining false positives in uncontrolled or poorly controlled studies. Robinson et al. (1988a) conducted a pre-post study design without control conditions and Seib et al. (1994) conducted an experimental non-RCT with appropriate control conditions but then inappropriately employed univariate analysis. Regardless, the results of these studies corroborate the finding of an immediate post-stimulation effect by Van der Salm et al. (2006). Seib et al. (1994) and Robinson et al. (1988a) employed stimulation of different muscles (tibialis anterior, i.e., ankle dorsiflexion and quadriceps, i.e., knee extension respectively) and each demonstrated short lasting reductions in spasticity. Similar to the findings of Van der Salm et al. (2006), Seib et al. (1994) reported the effect of reduced spasticity waned quickly but was still evident up to 6 hours post-stimulation (mean 4.4 hours) as indicated by subject self-report.

21-9

In the only study of the long-term effects of simulation, Robinson et al. (1988b) employed a similar stimulation protocol for the quadriceps as noted above over a period of 48 weeks with twice daily 20-minute sessions at least four hours apart, six days per week. Although 31 individuals initiated the study and 21 completed 4 weeks of the stimulation program, the study had severe subject retention issues with only 8 individuals continuing participation for the intended 8 weeks. Study results showed that most subjects actually had increased spasticity at four weeks but for the subjects who remained in the study for 8 weeks there was no significant difference. This null result begs further study of the long-term effects of muscle stimulation given the beneficial results obtained with short-term stimulation and in reports involving individuals with other etiologies (Chen et al. 2005; Ozer et al. 2006) The other aspect of these studies worth noting is the variability across even just these 4 studies with respect to outcome measure selection. Within these papers there were measures that were clinical, neurophysiological, biomechanical and subject self-report in nature. The study with the strongest design (i.e., Van der Salm et al. 2006) employed clinical and neurophysiological measures with the modified Ashworth scale, clonus score and H-reflex testing. Seib et al. (1994) employed a biomechanical approach by using a spasticity measurement system which monitored ankle viscoelastic stiffness through measurements of resistance torque to repetitive sinusoidal ankle movements. Robinson et al. (1988a;1988b) used a clinical/biomechanical approach in measuring the normalized relaxation index (R2n) obtained from the pendulum drop test. Others have noted that spasticity is a multi-faceted construct with individual components of spasticity weakly related to each other suggesting that while different tools may measure unique aspects of spasticity the overall construct is best measured with an appropriate battery of tests (Priebe et al. 1996). Conclusions There is level 2 evidence that a single bout of surface muscle stimulation reduces local muscle spasticity with agonist stimulation more effective than stimulation to the antagonist. There is conflicting evidence for how long the effects of a single bout of electrical stimulation on muscle spasticity persist, although they appear to be relatively short lasting (i.e., 6 hours). There is no evidence that a long-term program of muscle stimulation has an effect on reducing muscle spasticity and may even increase local muscle spasticity. Electrical stimulation applied to individual muscles may produce a short term decrease in spasticity. There is also some concern that long-term use of electrical stimulation may increase spasticity. 21.2.4 Interventions Based on Various Forms of Afferent Stimulation There are a variety of approaches that have been investigated which employ afferent (i.e., sensory) stimulation for the reduction of spasticity in people with SCI. As noted previously, electrical stimulation, in particular TENS, is one of the preferred methods for providing afferent stimulation. This technique differs from the approaches noted in the previous sections that involve stimulation to the motor system, whether via muscles or motor nerves. TENS may

21-10

involve the stimulation of large, low threshold afferent nerves (Goulet et al. 1996) or dermatomal stimulation which is directed towards cutaneous skin receptors supplying the skin in the dermatome of the muscle of interest (Bajd et al. 1985; van der Salm et al. 2006). These methods are aimed at altering motor-neuron excitability through sensory reflex arcs, thereby reducing spasticity. An alternate approach employing electrical stimulation involves rectal probe stimulation, developed originally to overcome anejaculation in males and heretofore a technique employed only within fertility clinics (Halstead & Seager 1991). In addition, a variety of methods of mechanical stimulation to various afferent systems have also been studied. These include therapeutic massage over the spastic muscle (Goldberg et al. 1994), penile vibration (Laessoe et al. 2004; Alaca et al. 2005;) and hippotherapy (Lechner et al. 2003). Although the specific mechanisms by which an antispastic effect may be achieved with hippotherapy is unkown, it is postulated that it may be brought about by the combination of the sensorimotor stimulation, psychomatic effects and the specific postural requirements and passive and active movements necessary for riding a horse (Lechner et al. 2003). Finally, other sensory stimulation examined for antispasticity properties include thermal stimulation, with the application of cold (i.e., cryotherapy) to reduce local muscle spasticity (Price et al. 1993) and also irradiation of the skin overlying sensory nerves with a helium-neon laser purported to induce photochemical reactions which may trigger neural activity (Walker, 1985). It should be noted that the article examining cryotherapy (i.e., Price et al. 1993) did not meet the review criteria of having 50% of subjects with SCI. Regardless, the article was included in the review as individual results were presented for all subjects with SCI (N=7), enabling discernment of the effects on SCI. Table 21.4 Studies of Various Forms of Afferent Stimulation for Reducing Spasticity
Author Year; Country Score Research Design Total Sample Size Methods Population: SCI (n=21), chronic, complete and incomplete, traumatic vs health controls (n=20) Treatment: Either oral baclofen (titrated up to 80 mg/day) for 8 weeks or Trancutaneous Electrical Nerve Stimulation (TENS) for 15 minutes/day for 15 days. Outcome measures: Penn Spasm Frequency Scale (SFS), Painful Spasm Scale, Ashworth Scale, various clinical (clonus, deep tendon reflexes, response to plantar stimulation) or electrophysiologic measures (H-reflex latency and amplitude, H/M ratio) of spasticity as well as measures of function (FIM and functional disability score (FDS)). Measures were taken preand post- first treatment (15 minutes after) and 15 minutes and 24 hours after the last TENS session. 1. Outcome For both treatment groups a significant improvement was noted immediately post treatment in the lower limb Ashworth score (p<0.011 baclofen group and p<0.020 TENS group), SFS (p<0.014 for both groups), deep tendon reflex score (p=0.025 for both groups) as well as in measures of disability (FIM - baclofen group p<0.005, TENS group p<0.003; FDS-baclofen group p=0.004, TENS group p=0.003. In comparison with baseline, TENS showed a trend for a reduced Ashworth immediately after the first treatment (p=0.059), a significant reduction immediately after the last treatment (p=0.006) and a significant but lesser reduction 24 hours after the last treatment (p=0.020). Similar findings were obtained for Deep Tendon Reflex scores. Plantar Stimulus Response scores were only significantly reduced immediately following the last treatment session (p=0.034) whereas clonus scores

Aydin et al. 2005; Turkey PEDro = 6 RCT N=41

2.

21-11

Author Year; Country Score Research Design Total Sample Size

Methods

Outcome were only significantly reduced immediately following the first treatment (p=0.046). There was a significant reduction in Hreflex maximal amplitude (p=0.032) 24 hours after the final session. This reduction was even more apparent when tested only 15 minutes after the last treatment (p=0.026). There were only small (statistically non-significant) changes in other electrophysiologic variables with either baclofen or TENS. There was a significant decrease in spasticty after penile stimulation as indicated by decreases in Modified Ashworth Scale (0<0.01). This was not sustained at 24 hours. There was a slight reduction in the Penn Spasm Frequency Scale 24 hours after penile stimulation but this was not significant. There was a significant reduction in EMG activity in the initial 3 hours after vibration, as compared to before vibration (p<0.05). This was not seen in the no-vibration condition. The largest reduction in EMG activity occurred in the first hour after vibration, after which the events gradually decreased until no significant effect was observed following the 3rd hour after vibration. No statistical comparisons reported. 40 s of laser irradiation and 1 hour of electrical stimulation similarly produce complete suppression of clonus lasting 30 and 60 minutes after cessation of stimulation. 20 s of laser irradiation and 45 min of electrical stimulation similarly only produce partial suppression of clonus. Distal nerve irradiation or electrical stimulation still produced clonus suppression but not when stimulation was applied to skin not overlying a peripheral nerve.

3.

Laessoe et al. 2004; Denmark PEDro=6 RCT N=9

Population: Gender: m=9, f=0, age: 27-67 yrs, time post-injury: 4 months - 50 yrs. Level of injury: C2-T8, ASIA A D. Treatment: Penile Vibratory stimulation for 5 minutes or to ejaculation. Outcome Measures: Modified Ashworth Scale, Penn Spasm Frequency Scale, 24 hour EMG recordings of quadriceps and tibialis anterior activity. All collected prestimulation and 24 hours post-stimulation. The Modified Ashworth was also collected immediately after stimulation.

1.

2.

3.

4.

Walker 1985; USA PEDro=4 RCT N=41

Van der Salm et al. 2006; The Netherlands Downs & Black score=18 Pre-post N=10

Population: Level of injury: T12-L2, time since injury: > 2 years. Treatment: Helium-neon laser irradiation to peripheral nerve sites (radial, median, saphenous nerves) for 20 or 40s to each site versus a variety of control conditions including sham irradiation (same probe but not emitting laser), irradiation to skin not innervated by peripheral nerves and electrical stimulation for 45 min or 1 hr over innervated and non-innervated areas. (N=5-7 in various experimental groups). Outcome Measures: Clonus count after brisk dorsiflexion of the foot by a blinded registered PT before treatment and at 30minute intervals up to 2 hours after irradiation. Population: Gender: m=8, f=2; age 21-42 yrs, level of injury: C3-T11, time since injury: 28-275 months, ASIA: 9 A and 1 C. Treatment: Electrical motor (agonist or antagonist) or afferent (S1 dermatomal) stimulation of the triceps surae or a placebo (application of electrodes but no current). 1 45 minute session of each

1. 2.

3. 4.

1.

2.

No significant difference was seen with S1 dermatomal stimulation. Only the agonist muscle stimulation differed significantly (46% reduction) from the placebo as indicated by reduced MAS (p<0.001) No significant carry-over effect (over 2 hours) although there was a trend of

21-12

Author Year; Country Score Research Design Total Sample Size

Methods type of stimulation. Intensity @ 3 x motor threshold for motor stimulation and 80% of motor threshold for afferent stimulation. Outcome measures: modified Ashworth scale (MAS), clonus score, H reflex, and H/M ratios. Measurements were conducted just prior to, immediately after, 1 hour after and 2 hours after the intervention for each of the 4 conditions. Population: Gender: m=6, f=3; age 2141yrs, time since injury: 0.5-15yrs, Frankel: A=4 or B=5, Level: Quad=6, Para=3. Treatment: At least 6 sessions of Rectal Probe Electrical Stimulation (RPES) 6 times spaced 1-4 weeks apart. Each session consisted of 7 or 15 stimulations of ~1 second duration and lasted 5-10 min. Three subjects underwent a placebo with probe insertion but no stimulation. Outcome Measures: Ashworth scale, Penn Spasm Frequency Scale, Deep Tendon Reflexes, Ankle Clonus, Subject self-report (5 point scale) on interference of spasticity on selected self-care activities. All were collected just prior to stimulation, within 1 hour after and 2-4 hours after. Subject self-report was collected every 2 hours up to 24 hours after stimulation. Pendulum tests were collected on 4 subjects and somatosensory evoked potentials (SSEPs) on 2 subjects pre and post. Population: Gender: m=10, f=0, age: 2235 yrs, time post-injury: 1.1-9 years, Level of injury: C8-L1, ASIA A. Treatment: Penile Vibratory stimulation for 6, 3 minute periods (separated by 1 minute) or to ejaculation. Outcome Measures: Ashworth Scale, Penn Spasm Frequency Scale and nominal scales of painful spasms, plantar stimulation response, deep tendon reflexes, clonus and effect on function. All collected pre-stimulation and 3, 6, 24 and 48 hours post-stimulation.

Outcome continued reductions for the MAS (p=0.113). No significant intervention effect was shown for the clonus score or the H/M ratio. The reflex-initiating angle showed a significant change for antagonist stimulation (n=8, p<0.015) but the carryover effect was not significant. Spasticity was reduced as indicated by reduced Ashworth scores assessed within 1 hour post-stimulation (p<0.01). Spasticity relief as indicated by selfreport was for 7.8/9.5 hours (quad/para mean values). No significant correlation of RPES effect on spasticity were seen with age, duration of injury, level of injury or completeness. In general, spasticity was reduced as indicated by the pendulum test in the 4 subjects assessed. SSEPs were abolished in the 2 subjects tested following stimulation. Probe size, number of stimuli, voltage and current did not reveal any significant correlation with the amount of relief provided.

3. 4.

1. 2. 3.

Halstead et al. 1993; USA Downs & Black score=17 Pre-post N=9

4. 5. 6.

1.

Alaca et al. 2005; Turkey Downs & Black score=16 Pre-post N=10

2.

3.

Goulet et al. 1996; Canada Downs & Black score=16 Pre-post N=14

Population: Gender: m=13, f=1; age 2154yrs, level of injury: C4-T12, time since injury: 2-194mths, ASIA: A-D. Treatment: TENS stimulation (i.e., low threshold afferent nerve stimulation) over the common peroneal nerve for 30 minutes. Outcome measures: modified Ashworth scale, Clonus score, Achilles tendon reflex score (ATR), H-reflex amplitude, and H-

1.

2.

There was a significant decrease in spasticty after penile stimulation as indicated by decreases in the Ashworth Scale (0<0.001). This was significantly lower than baseline at hour 3 (p=0.001) and 6 (p=0.03) with a trend lower at 24 hours (p=0.08). There were slight (nonsignificant) reductions in the Penn Spasm Frequency Scale and clonus scores at hour 3. There were no changes in painful spasms, plantar stimulation responses, deep tendon reflexes and effect on function scale scores with penile vibration. Significant decreases were seen in clinical measures of spasticity as seen by reductions in modified Ashworth (p=0.04), ATR (p=0.01), and global spasticity scores (p=0.01). A trend was seen with reduced clonus scores (p=0.11). No significant effects of TENS were seen with electrophysiological measures of spasticity as indicated by

21-13

Author Year; Country Score Research Design Total Sample Size

Methods reflex/M response ratio collected just prior to and after TENS. H-reflex and M responses were also collected during TENS. Population: Gender: m=9, f=1; age: 21-33 yrs, level of injury: C4-T10, time since injury: 3-11 months, ASIA: complete and incomplete. (Study 2). [Study 1 N=7 (healthy controls)] Treatment: One-handed petrissage (massage) applied to the belly of the triceps surae muscle group for 3 minutes. Outcome Measures: H-reflex peak amplitude, H-reflex latency (Study 2, SCI only), M-responses collected during massage plus 3 and 6 minutes prior and 3 and 6 minutes after massage (10 responses of each averaged). Population: Gender: m=28, f=4, age: 1672yrs (mean 37yrs), time since injury: 1mth to 6 yr, injury level: C4-T12, ASIA A-D. Treatment: Hippotherapy-K (HTK; Kuenzle 2000): An average of 11 sessions (5-24) each lasting 25-30 minutes. Sheepskin (no saddle) on Icelander horse. Outcome Measures: Ashworth scale of 8 limb movements bilaterally for a summed score of 16-80. Measures were taken pre and post each session and the proportion of scores with a +ive or ive change was recorded. Population: 25 subjects with stroke (9), head injury (9) and SCI (7); no information provided on subject details Treatment: Cryotherapy (water and ice placed on calf for 20 minutes).

Outcome H-reflex amplitudes (p=0.89) and H/M ratio (p=0.50). 1. Significant decrease in H-reflex amplitude during massage as compared to before and after (p=0.008). The response 3 minutes after massage is somewhat reduced but not to the same extent as during the massage. No difference between M-response amplitudes (p=0.13) or H-Reflex latencies (p=0.22) before, during or after massage. Study 1: Verified that H-reflex amplitude decreases seen in controls in supine position were also able to be obtained in prone position which was preferred position for SCI subjects. 93% of treatment sessions led to lower Ashworth scores immediately after sessions. Significant decrease in muscle tone as indicated by reduced Ashworth scores in the lower limbs (p<0.001). There was no carry-over effect from session to session as there was no longitudinal trend or trend of the before and after session differences. No significant difference between para/tetraplegic subjects (p=0.4).

Goldberg et al. 1994; Canada Downs & Black score=15 Pre-post N=17

2.

3.

1. 2. 3.

Lechner et al. 2003; Switzerland Downs & Black score=13 Pre-post N=32

4.

Price et al. 1993 ; USA Downs & Black score=12 Pre-post N=25

Outcome Measures: Elastic and viscous components of ankle stiffness represented by mathematical modelling of torque vs position in response to 5 sinusoidal ankle displacements at frequencies from 3 to 12 Hz. This resulted in measures of total path length associated mainly with passive spasticity of the ankle and elastic path length associated with viscous stiffness. Data was collected prior to, during and 1 hour after cryotherapy. Population: 6 in- and outpatients with SCI, age: 11-52 yrs, time postinjury: 5-48 months, level of injury: C5-T9, 4 complete, 2 incomplete. Treatment: TENS stimulation over L3, 4

SCI Results 1. Clinically significant reductions in spasticity as indicated by a reduction in total path length of 11Nm/rad or greater were seen in 5 of 7 subjects with SCI during cryotherapy and 5 of 7 one hour after. Overall Results 1. Reduction in spasticity as indicated by total (p=0.009) and elastic (p=0.006) path length resulted from cryotherapy compared to the baseline measures. 2. Significant differences between the baseline measure and 1 hour after treatment were noted in spasticity as indicated by elastic path length (p=0.0198) but only a trend was noted for total path length (p=0.058). 1. 2. Group statistical analysis was not conducted. In 3 patients, spasticity decreased markedly as indicated by increased relaxation index values immediately

Bajd et al. 1985; Yugoslavia Downs & Black score=10 Pre-post N= 6

21-14

Author Year; Country Score Research Design Total Sample Size

Methods dermatomes. Stimulation amplitude of up to 50mA was used and applied continuously for 20 mins. Outcome Measures: Pendulum test (relaxation index) performed just prior to and just after stimulation as well as 2 hours post-stimulation.

Outcome after the stimulation and returned to pre-stimulation values at 2 hours. The remaining 3 individuals showed no change.

Discussion Aydin et al. (2005) employed a RCT design to compare oral baclofen (N=10) and TENS (N=11) to the bilateral tibial nerves (i.e., innervating gastrocnemius muscle) in reducing lower limb spasticity. Most important, this is the only trial examining ongoing applications of TENS. Fifteen minute sessions of TENS were applied to the tibial nerve over 15 days demonstrating significantly reduced spasticity as indicated by reductions in the following measures assessed immediately after the last treatment session: Ashworth Scale, Spasm Frequency Scale, deep tendon reflex score, FIM and Functional Disability Scores and H-reflex amplitude. In addition, there were also some lasting effects over the next 24 hours as repeat testing the next day indicated continued spasticity reductions although to a lesser degree. It should also be noted that significant reductions were obtained on some measures (but not all) following a single session. However, the long-term effects were more profound than those obtained following a single session. Other researchers have examined the effects of TENS following a single session (Bajd et al. 1985; Goulet et al. 1996; van der Salm et al. 2006). Goulet et al. (1996) employed a single 30 minute bout of TENS over the common peroneal nerve in an attempt to reduce plantarflexor spasticity in 14 individuals with SCI. This study showed significant decreases in scores for the modified Ashworth scale and the Achilles tendon reflex but no significant changes were seen for H-reflex amplitude. A trend for decreased clonus scores was observed but this was not statistically significant. In this trial, TENS appears to be effective in reducing spinal spasticity following a single session. In contrast, van der Salm et al. (2006) and Bajd et al. (1985) each examined dermatomal TENS as opposed to direct nerve stimulation with conflicting results. Bajd et al. (1985), in a small prepost trial (n=6) reported reduced spasticity in 3 subjects as indicated by increased relaxation indexes associated with the pendulum test although provided no mean data or group statistical analysis. Van der Salm et al. (2006) conducted a more thorough analysis of the effect of a single 45 minute session of TENS to the L1 dermatome in 10 individuals with longstanding SCI (mostly ASIA A) and obtained no short- term effects, although as noted in the previous section obtained benefits with motor stimulation. A critical element within these investigations of singlesession effects is the precise time of assessment, relative to treatment, a detail not always precisely reported in the various studies, although it is clear that van der Salm et al. (2006) assessed individuals as close as possible to treatment end. Halstead et al. (1993) have evaluated another form of electrical stimulation, rectal electrostimulation, when they observed patients undergoing this procedure for the purpose of sperm retrieval reporting improved spasticity. These investigators conducted a prospective prepost trial examining the effects of a minimum of 6 sessions of rectal probe electrostimulation on various clinical measures of spasticity including the Ashworth scale, Penn Spasm Frequency 21-15

Scale, deep tendon reflexes and ankle clonus. Although they achieved good to excellent effects in more than half of the patients examined including significant reductions in the Ashworth scale (p<0.01) and with the effects outlasting the intervention by a mean of 8.2 hours according to patient self-report further therapeutic development of this approach has not continued. Afferent stimulation may also be produced via mechanical means. Goldberg et al. (1994) have employed therapeutic massage over the triceps surae muscle and assessed H-reflex amplitude to demonstrate that -motor neuron excitability is reduced significantly during a short 3 minute period of massage and somewhat reduced 3 minutes after but not 6 minutes after. Reductions in -motor neuron excitability are indicative of decreased spasticity. Penile vibration has also been investigated as a method of providing sensory stimulation to reduce spasticty (Laessoe et al. 2004; Alaca et al. 2005). In particular, Lssoe et al. (2004) employed an unblinded, crossover RCT design (N=9) in which male participants either received penile vibration or not followed by completed the opposite condition. The modified Ashworth scale and Penn Spasm Frequency Scale were conducted in addition to an EMG assessment in which ongoing muscle activity was recorded over a 24 hour period. Penile vibration was shown to be effective in reducing spasticity as indicated by reductions in modified Ashworth scale scores (p<0.01) and a slight trend for reduced Penn Spasm Frequency Scale Scores (p=0.26). These were not maintained over 24 hours. The EMG analysis showed that reduced muscle activity was most apparent in the first hour post-stimulation, and had returned to baseline by 3 hours suggesting the effect lasted no more than 3 hours. The authors attempted to include female subjects involving clitoral vibratory stimulation but were only able to recruit 2 subjects willing to submit to the procedure. Both women reported similar reductions in spasticity although evaluation of the effectiveness of the stimulation was more difficult (i.e., no ejaculation to guide). The results of Alaca et al. (2005) confirmed the overall study findings as penile vibratory stimulation in 10 males resulted in significant reductions in Ashworth Scale scores as assessed 3 hours after stimulation (p=0.001) and maintained at 6 hours (p=0.03) with a trend for reduced values still apparent at 24 hours (p=0.08). The longer carry over effect in this study may have been due to a prolonged stimulus period as Alaca et al. (2005) employed 6, 3 minute periods of stimulation (separated by 1 minute) whereas Lssoe et al. (2004) used a single 5 minute period. Lechner et al. (2003) evaluated the short term effect of hippotherapy on the spasticity of 32 patients. The results of the study indicated that hippotherapy had a short term effect on decreasing spasticity of the lower extremity, as demonstrated by significant decreases in muscle tone (i.e., reduced Ashworth scores, p<0.001). Ninety-three percent of treatment sessions led to lower Ashworth scores immediately after the session relative to the pre-session score, however there was no carry-over effect from session to session. As noted previously, it is difficult to know if afferent stimulation is the primary mechanism for this antispastic effect, although it is purported as one of the contributors to any putative benefits (Lechner et al. 2003). The short-term effect of cryotherapy was investigated by Price et al. (1993) who used a biomechanical approach similar to that described earlier (i.e., Seib et al.1994) to monitored ankle viscoelastic stiffness through measurements of resistance torque to repetitive sinusoidal ankle movements. Although the majority of subjects were individuals with stroke or head injury, 5 of 7 people with SCI showed a significant reduction in spasticity both immediately following cryotherapy and also at 1 hour after the cold stimulus was removed. Walker (1985) employed a helium-neon laser to irradiate the skin overlying sensory nerves and demonstrated a similar beneficial effect of suppressing clonus as seen with electrical stimulation of sensory nerves. This investigator employed a RCT design with a variety of small group 21-16

control conditions (N=5 to 7), but failed to report several important experimental details (i.e., method of concealment, method of analysis and statistical comparisons). This approach has not been investigated since this brief 1985 report. It should be noted that several of the modalities noted in this section have not been employed in regular clinical practice and may be deemed as more investigational in nature. For example, helium-neon laser irradiation has only been employed in one investigation and has not been considered as a viable therapeutic approach. Similarly, penile and rectal stimulation, first noted as delivering potential benefits within fertility clinic investigations, may not be acceptable forms of therapy to individuals from either a safety or a psychological perspective. Other therapies might simply be impractical to implement. For example, hippotherapy requires access to a suitable equine facility with appropriately trained individuals. Conclusions There is level 1 evidence that an ongoing program of TENS acts to reduce spasticity as demonstrated by clinical and electrophysiological measures. There is level 1 evidence that reductions in spasticity with ongoing programs of TENS may persist for up to 24 hours. There is level 1 evidence that a single bout of TENS acts to reduce spasticity but to a lesser degree than that seen with ongoing programs of TENS. This evidence is muted somewhat by conflicting results with a null result (level 2) compared with 2 positive results (level 4). There is level 4 evidence that several sessions of rectal probe stimulation reduces lower limb muscle spasticity for up to 8 hours. There is level 4 evidence that short periods of massage (e.g., 3 minutes) of the triceps surae results in reduced H-reflexes with the effect lasting no longer than a few minutes. There is level 1 evidence that a single bout of penile vibration acts to reduce spasticity lasting for at least 3 hours and possibly up to 6 hours. There is level 4 evidence that hippotherapy may reduce lower limb muscle spasticity immediately following an individual session. There is level 4 evidence that cryotherapy may reduce muscle spasticity for up to 1 hour after removal of the cold stimulus. There is level 2 evidence that helium-neon irradiation of sensory nerves may suppress ankle clonus for up to 60 minutes following 40 seconds of stimulation.

21-17

Ongoing (TENS) transcutaneous electrical nerve stimulation programs result in short-term reductions in spasticity which may last for up to 24 hours. Penile vibration and rectal probe stimulation may be effective at reducing lower limb muscle spasticity for several hours. Other forms of afferent stimulation including massage, cryotherapy, hippotherapy and helium-neon irradiation may result in immediate spasticity reduction but require more research to examine long-term effects. 21.2.5 Interventions Based on Direct Spinal Cord Stimulation Initial investigations of spinal cord stimulation were conducted in the early 1970s and were directed at individuals with multiple sclerosis (Cook & Weinstein 1973). Later studies have examined the effect of this approach in people with SCI to enhance bladder or bowel function and also for the relief of pain and spasticity (Richardson & McLone 1978; Illis et al. 1983; Dimitrijevic et al. 1986a; Barolat et al. 1988). Typically, these studies employ a surgically implanted electrode under either general or local anaesthesia placed over the dorsal columns of the spinal cord which supplies ongoing electrical stimulation. Pinter et al. (2000) noted a declining interest with this approach in the 1990s because of technical concerns and the realization that spinal cord stimulation was less effective in patients with severe spasms of the lower limbs (Dimitrijevic et al. 1986b; Barolat et al. 1995). Table 21.5 Studies of Spinal Cord Stimulation for Reducing Spasticity
Author Year; Country Score Research Design Total Sample Size Methods Population: Gender: 90% males, age: 1766 yrs, time post-injury: 6 545 months (mean 89.9 months), Level of injury: 67% cervical, 33% thoracic, 53% complete, 47% incomplete. Treatment: Spinal cord stimulation following surgical implantation of the Medtronic Resume electrode in the dorsal epidural space. Stimulus parameters determined in a training period 1-2 days after implantation typically resulted in a therapeutic window of stimulation between the motor and sensory threshold. Outcome measures: Average number of spasms, intensity of spasms and frequency of spasms. Severity score including both the intensity and frequency of the spasms. All were collected just prior and 3, 6, 12 and 24 months after implantation. 1. Outcome Of 48 initial subjects, 40 provided data at 3 months, 33 at 6 months, 31 at 1 year and 18 at 2 years. The remainder were discontinued due to lack of efficacy or lost to follow up. Average # of spasms/hour improved = 19.9 initially, 11.3 at 3 months, 9.2 at 6 months, 8.8 at 1 year and 12.9 at 2 years. A significantly greater proportion of subjects indicated reduced severity scores over time with significant differences at 6 months (p=0.0424), 1 year (p=0.0001and 2 years (p=0.0012) relative to baseline. Spasm intensity showed improvement over time with the proportion of individuals experiencing severe spasms being 83% initially,33% at 3 months, 45% at 6 months, 32% at 1 year and 28% at 2 years. Subjective rating of spasm relief also decreased with 68% of individuals experiencing good or excellent relief at 3 months, 69% at 6 months, 70% at 1 year and 79% at 2 years. Spasticity was reduced as indicated by reduced Ashworth scale scores

2.

3.

Barolat et al. 1995; USA Downs & Black score=15 Pre-post N=48

4.

5.

Pinter et al. 2000; Austria & USA

Population: Gender: m=4, f=4, age: 18-34 yrs, time post-injury: 19 94 months, Level

1.

21-18

Author Year; Country Score Research Design Total Sample Size Downs & Black score=10 Pre-post (Pilot study) N=8

Methods of injury: C5-T6, ASIA A C. Treatment: Epidural spinal cord stimulation over the upper lumbar cord. Final internal placement for surgical implantation determined following an 8 week trial period during which the stimulator was external. Outcome Measures: Ashworth scale, Clinical Rating Scale, Pendulum test, EMG activity in response to passive stretch. Data collection schedule was not described.

Outcome (p=0.0117). Pendulum test in 4 of 8 subjects showed reduced spasticity when stimulator was on for at least 1 hour vs off for > 12 hours. 6 subjects showed marked reductions and 2 subjects showed moderate reductions with the clinical rating scale. It was not described what this entailed. EMG responses to stretch in the presence of stimulation were significantly reduced for all muscles combined of the left (p=0.0040) and the right (p=0.0035). Antispastic medication discontinued in all but 1 patient when continuous stimulation started. This patient had baclofen dose reduced and tizanidine discontinued. At the time of the retrospective study, 1 of 17 patients reported that the epidural stimulator was producing symptomatic relief. The average length of time that all units produced symptomatic relief was 6 months (range 0-96 months). Fourteen units were removed within 3.4 years (5 days -7years); 9 implantations failed from the day of implantation. Total cost of initial implantation (not including follow-up) is $23,600 per unit.

2.

3.

4.

5.

Midha & Schmitt 1998; USA Downs & Black score=7 Case Series N=29

Population: Age: 29-63 years, time postinjury: 6 months 30 years, Level of injury: C4-T10, complete, incomplete. Treatment: Retrospective analysis of those having undergone implantation of an epidural stimulator between 1986-1988. Outcome Measures: Telephone follow-up (asked to quantify symptom relief on a scale from 0-10, 10=total symptom relief) and how long they had had the symptom relief since the time of the implantation.

1.

2. 3.

4.

Discussion Pinter et al. (2000) showed improvements following implantation with a variety of clinical measures including significant decreases in Ashworth scale scores (p=0.0117)), the pendulum test and muscle activity as indicated by reduced summed EMG activity collected during passive movements in both the left (p=0.0040) and the right (p=0.0035) lower limb. In addition, it was possible to discontinue anti-spastic medication in 7 of 8 subjects and reduce the dose in the remaining subject. These positive findings were achieved in a rather small population (N=8) and further studies from independent groups are required to further demonstrate the feasibility and efficacy of this approach. In particular, the long-term effectiveness of spinal cord stimulation is uncertain, as this study did not specify the specific time points when measures were collected, although they did state that spinal cord stimulation had been conducted for a mean of 14.38 months (Pinter et al. 2000). These authors asserted that better results were obtained with their approach as they were more careful in optimising location and other methodological aspects and outcomes could be further enhanced by improved stimulator design. Barolat et al. (1995) also reported beneficial reductions in spasticity with epidural spinal cord stimulation as assessed by subjective scales of spasm frequency and intensity. The spasm intensity and spasm frequency was reduced significantly over the follow-up period of 2 years 21-19

and a significantly greater proportion of subjects indicated reduced spasticity severity scores over time with significant differences at 6 months (p=0.0424), 1 year (p=0.0001and 2 years (p=0.0012) relative to baseline. It should be noted that the positive nature of the long-term findings are somewhat muted as subjects were increasingly dropped from the analysis over time when they were lost to follow-up or discontinued due to lack of efficacy. Of 48 initial subjects, 40 provided data at 3 months, 33 at 6 months, 31 at 1 year and 18 at 2 years (Barolat et al. 1995). In contrast to these more recent findings, (Midha & Schmitt 1998) conducted a telephone or inperson follow-up of individuals having epidural stimulators implanted between 1986 and 1988 to determine their long-term status (N=17). In only 1 of these individuals was the stimulator continuing to provide symptomatic relief although most felt it was initially effective with an average time of effectiveness of 6 months. The rate of stimulator failures was high with several removals and re-implantations of devices. At the time of follow-up only 10 individuals reported having an implanted stimulator. Conclusions There is Level 4 evidence that ongoing spinal cord stimulation may provide some relief from otherwise intractable spasticity for some time (i.e., months to years). There is level 4 evidence that the beneficial effects of spinal cord stimulation will subside for most initial users. This, combined with the potential for equipment failure and adverse events, suggests that spinal cord stimulation is not a cost-effective approach for managing spasticity. Spinal cord stimulation may provide spasticity relief over a few months but long-term effectiveness and cost-effectiveness is less certain.

21.3 Neuro-Surgical Interventions Surgical approaches have been considered as a treatment option for those individuals with severe spasticity which has been refractory to more conservative approaches and for which no useful or potential function exists below the level of the lesion (Livshits et al. 2002). There are few well-controlled neuro-surgical interventional studies that have examined the influence of this approach on spasticity as their main purpose. The primary and most commonly investigated technique is that of longitudinal myelotomy and this approach has also been applied to pain management and spasticty reduction in other etiologies, although spasticty in individuals with SCI is the most common application (Laitinen & Singounas 1971; Yamada et al. 1976; Fogel et al. 1985; Putty & Shapiro 1991). Table 21.6 Neurosurgical Interventions for Reducing Spasticity
Author Year; Country Score Research Design Total Sample Size Livshits et al. 2002; Israel PEDro=5 RCT Initial N=40; Final N=32 Methods Population: Groups: Pourpre vs Bischof II Surgical technique, Mean Age: 27.6 vs 27.1 years, Gender: 15m&5f vs 14m&6f, Time with spasticity: 2.75 vs 2.75 years, Level of injury: paraplegia only, complete 1. Outcome Authors states that good vs bad results with respect to spasticity were obtained with the Pourpre technique in 90% of subjects at 6 months, 75% at 5 years and 64.7% at 10 years. The

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Author Year; Country Score Research Design Total Sample Size and incomplete.

Methods

Outcome Bischof II technique was less effective in that good effects were seen in 65% of subjects at 6 months, 45% at 5 years and 40% at 10 years. The author did not specify what constituted a good vs a bad effect other than to say it was a return of spasticty. Ashworth scale scores and Penn Spasm Frequency scale scores were significantly reduced relative to presurgery values (p values unreported). People undergoing the Pourpre technique had significantly reduced Ashworth scale scores and Penn Spasm Frequency scale scores than those undergoing the Bischof II technique (p values unreported). Pain measures were relieved in all cases although there were successively increasing SFM, PPI and VAS scores at 6 months vs 5 years vs 10 years (p<0.0001 for all). Pain was relieved better (i.e., lower scores for all measures at all follow-up times) for the Pourpre technique vs Bischof II technique. No statistical results were reported. 9 of 10 patients with SCI had relief from spasms (1 died, unrelated to surgery).

Treatment: Longitudinal T-myelotomy by Pourpre vs Bischof II technique for the treatment of painful spasticity. Outcome Measures: Short form of McGill pain questionnaire (SFM), Present Pain Intensity (PPI), Visual analog score for pain (VAS), Ashworth scale, Penn Spasm Frequency scale. All collected prior to surgery and 6 months, 5 years and 10 years post-surgery. 2.

3.

4.

5.

Putty & Shapiro 1991; USA Downs & Black score=9 Case series Initial N=23; Final N=20

Population: 11 with SCI, 7 with MS, 2 others, Gender: male=12 female=8, Age: 22-69 years, time post-injury: 2 23 years, Level of injury: C5-T9, complete and incomplete. Treatment: Subjects underwent a modification of posterior T-myelotomy. Outcome Measures: subjective clinical impression.

1.

Discussion (Livshits et al. 2002) conducted a study comparing two approaches of dorsal longitudinal Tmyelotomy technique (i.e., Pourpre vs Bischof II) on the effectiveness of reducing pain and spasticity in people with SCI (N=40) with a follow-up period of up to 10 years. For the purpose of this review we have assessed this article as a low-quality RCT (i.e., Level 2 evidence, PEDro<6). The authors presented the article as a prospective trial with the two surgical techniques that were randomly applied as it was unknown which of the operations would prove to be more effective (Livshits et al. 2002). Unfortunately, the method of randomisation was not clearly stated and the explicit designation as a prospective trial was not noted. Regardless, it was demonstrated that good to excellent results were obtained with either of these surgical techniques with Ashworth scale scores and Penn Spasm Frequency scale scores significantly reduced relative to pre-surgery values (p values unreported). More individuals had positive results with the Pourpre technique vs the Bischof II technique in that 64.7% of subjects had maintained benefits at 10 years with the former as compared to 40% with the latter. These results are laudable considering these patients were originally refractory to more conservative treatment.

21-21

Putty and Shapiro (1991) in a retrospective review of 20 subjects (n=11 with SCI) employed a modified posterior T-myelotomy technique to reduce spasticity and improve nursing care. Although group results were not reported and no standardized measures of spasticity were employed, these authors concluded that this intervention achieved relief from spasms in almost all patients while the impact on nursing care and patient comfort was less specified. Conclusions There is Level 2 evidence that dorsal longitudinal T-myelotomy may result in reduced spasticity in those individuals initially refractory to more conservative approaches. These reductions may not always be maintained over the course of several years. There is Level 2 evidence that Pourpres technique for dorsal longitudinal T-myelotomy is more effective in maintaining reduced levels of spasticity than the Bischof II technique. Dorsal longitudinal T-myelotomy may result in reduced spasticity.

21.4 Pharmacological Treatment of Spasticity 21.4.1 Oral Baclofen Baclofen, a derivative of gamma aminobutyric acid (GABA), is widely used as the first line of pharmacological treatment for spasticity in people with SCI 1 (Kirshblum 1999; Taricco et al. 2006). Baclofen, also identified as Lioresal, CIBA Ba-34647 and -(parachlorophenyl) gamma aminobutyric acid, crosses the blood-brain barrier more readily than GABA itself and is believed to reduce spasticity by enhancing inhibitory influences on the spinal stretch reflex via increasing presynaptic inhibition (Kirshblum 1999). In typical practice, baclofen requires a careful dose titration period with a usual maximal recommended dose of 20 mg qid (Burchiel & Hsu 2001) which is also the dosage employed in the majority of studies involving people with SCI (Aydin et al. 2005; Nance 1994; Hinderer et al. 1990). Baclofen may be especially effective in reducing flexor spasms (Shahani & Young 1974; Duncan et al. 1976; Gracies et al. 1997) although these effects may also act to impair specific functional tasks such as walking or standing (Kirshblum 1999; Burchiel & Hsu 2001). A variety of adverse events may limit the use of baclofen including lowering of seizure threshold, sedatory effects (i.e., drowsiness), insomnia, dizziness, weakness, ataxia, anxiety and mental confusion (Hinderer 1990; Gracies et al. 1997; Kirshblum 1999; Burchiel & Hsu 2001). Sudden discontinuation or withdrawal of baclofen can result in seizures, confusion, hallucinations and rebound muscle overactivity with fever (Gracies et al. 1997). For the most part, tolerance with sustained use of baclofen is possible (Knutsson et al. 1974), but is not a major issue (Roussan et al. 1985; Gracies et al. 1997; Kirshblum 1999).

Once it has been demonstrated that additional measures are required after traditional conservative approaches such as removal of potential mitigating factors, stretching and other forms of physical therapy have been attempted (Kirshblum, 1999).

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Table 21.7 Oral Baclofen for Reducing Spasticity

Author Year; Country Score Research Design Total Sample Size Methods Population: SCI, chronic, complete and incomplete, traumatic, male. Treatment: Baseline placebo period of varying length (2.5-4.5 wks), followed by a 2 week dose titration period of baclofen at half target dose (40 mg/day), followed by 2.5-4.5 weeks of 80 mg/day. Outcome Measures: Viscous and elastic stiffness as assessed by measuring viscous and elastic torque responses to a sinusoidal ankle perturbation of 5 at 3 to 12 Hz. Testing occurred twice per week (Mon/Thu or Tue/Fri) over 9 weeks. Population: SCI (n=11), MS (n=11), 3 dropouts (etiology unknown). Treatment: Either oral baclofen (titrated up to 100 mg/day) for 4 weeks or identical looking placebo. Outcome Measures: Self-report of # of spasms, nocturnal awakenings (daily) and global impression of treatment (at end of each treatment period). Clinician also provided global impression (at end of treatment period) and also assessed resistance to movement and rated change on 5 point scale (weekly). Also rated clonus, impressions of pain, use of limbs and transfer activity (weekly). 1. Outcome No systematic effect of baclofen was noted. Of 300 total comparisons made, only 1 comparison reached significance, with an increased viscous stiffness apparent at a frequency of 4 cycles/sec when comparing placebo with initiation of baclofen at 40 mg per day (p<0.05). Visual inspection of the results for individual subjects showed no evidence for a therapeutic response of baclofen that might not have been demonstrated by group statistical analysis. Number of spasms was significantly reduced with baclofen vs placebo (p<.01) as was number of nocturnal awakenings (p<.01). 11 of 22 subjects demonstrated less resistance to passive movement by at least 2 grades on the initial 5 point scale with baclofen vs 1/22 with placebo and this was significant (p<.01). No improvement in gait was seen in any of those who could walk (n=8) nor were any improvements seen in tendon jerks, strength or voluntary movement. In 9 cases (41%) both patients and clinicians felt continued use of baclofen was warranted. 15 subjects identified mild side effects while on baclofen (4 on placebo). All were deemed insignificant. No group statistical results were provided. All 6 subjects had a reduced EMG/velocity ratio for any given speed tested with baclofen vs placebo (e.g., decreased to 37.5% (range 0%-67%) at a velocity of 200/s). All subjects displayed clinical effects with baclofen such as reduced stretch reflex responses. For both treatment groups a significant improvement was noted post treatment in the lower limb Ashworth score (p<0.011 baclofen group and p<0.020 TENS group), SFS (p<0.014 for both groups), deep tendon reflex score (p=0.025 for both groups) as well as in measures of disability (FIM baclofen group p<0.005, TENS group p<0.003; FDS--baclofen group p=0.004, TENS group p=0.003.

Hinderer et al. 1990; USA PEDro= 9 RCT (single subject design) N=5

2.

1.

2.

Duncan et al. 1976; USA PEDro = 8 RCT N=22

3.

4. 5.

Burke et al.1971; Australia PEDro=7 RCT N=6

Population: SCI (n=6), chronic, complete and incomplete, traumatic, quadriplegic. Treatment: Placebo or active drug (CIBA 34,647-Ba) was titrated to a maximum of 60 mg daily over a period of 2 weeks in a crossover, double-blind design. Outcome Measures: Surface slope of EMG (quadriceps) vs velocity relationship associated with passive flexion of the knee. Population: SCI (n=21), chronic, complete and incomplete, traumatic vs health controls (n=20)

1. 2.

3. 1.

Aydin et al. 2005; Turkey PEDro=6 RCT N=41

Treatment: Either oral baclofen (titrated up to 80 mg/day) for 8 weeks or Trancutaneous Electrical Nerve Stimulation (TENS) for 15 minutes/day for 15 days. Outcome Measures: Spasm Frequency Scale (SFS), Painful Spasm Scale,

21-23

Author Year; Country Score Research Design Total Sample Size

Methods Ashworth Scale, various clinical (clonus, deep tendon reflexes, response to plantar stimulation) or electrophysiologic measures (H-reflex latency and amplitude, H/M ratio) of spasticity as well as measures of function (FIM and functional disability score (FDS)). Measures were taken pre and post-treatment. Population: SCI (n=25), all male, complete and incomplete, tetraplegic and paraplegic Treatment: 1 wk up-titration, 1 wk target dose (0.05 mg bid clonidine; 4 mg qid cyproheptadine; 20 mg qid baclofen), 1 wk down-titration Outcome Measures: Ashworth Scale, Pendulum test, Vibratory Inhibition Index (VII) 2.

Outcome There were only small (statistically non-significant) changes in electrophysiologic variables with either baclofen or TENS, other than a significant reduction in H-reflex maximal amplitude (p=.032) 24 hours after the final session of TENS. This reduction was even more apparent when tested only 15 minutes after the last treatment (p=0.026). A significant reduction in spasticity was seen with baclofen in all 3 outcome measures - as with the other 2 drugs tested (p<0.0001). Generally, baclofen results were among the most improved as compared to the other 2 drugs although this was only significant for the pendulum test (p=0.06) and VII (p<0.0007 along w/ cyproheptadine).

1.

Nance 1994; Canada Downs & Black score=15 Pre-post N=25

2.

Discussion Despite the general acceptance and clinical experience of using oral baclofen to reduce spasticity in people with SCI, at least 2 systematic reviews have noted a relative paucity of high quality studies (i.e., RCTs) demonstrating specific or comparative efficacy (Chou et al. 2004; Taricco et al. 2006). Taricco et al. (2006) conducted a Cochrane Review of all pharmacological interventions for spasticity following SCI. Only one study examining the effect of oral baclofen (Burke et al. 1971) met the review inclusion criteria (i.e., RCT with at least 50% of participants with SCI published up to July 2004). The reviewers deemed this study to have been relatively poor quality with small n (6) so did not provide a positive assessment of the efficacy of oral baclofen. Since the latest report for the Cochrane Review, an additional RCT (Aydin et al. 2005) has been published (n=21) demonstrating a significant reduction in spasticity with oral baclofen on Ashworth Scale, Spasm Frequency Scale, deep tendon reflex score, FIM and Functional Disability Scores, but not for most electrophysiological measures. Another RCT (Duncan et al. 1976) demonstrated reduced spasticity on Ashworth Scale and Spasm Frequency Scale. Further support for the efficacy of oral baclofen was provided by a pre-post study by Nance (1994) in which baclofen was compared to clonidine and cyproheptadine in 25 subjects with SCI. In general, all three agents were shown to be effective in relieving spasticity with baclofen among the most effective for each of the measures. In contrast to these studies, a counter-therapeutic response to baclofen was found by Hinderer et al. (1990). In this single-subject randomized-controlled design study (n=5) the effect of baclofen on spasticity was studied by examining the viscous stiffness (resistance torque) following a 5 sinusoidal ankle perturbation at 3-12 Hz. No difference was noted between baclofen and placebo on this measure. No other outcome measures were assessed. This study illustrates one of the limitations in establishing the efficacy for any spasticity-relieving agent the heterogeneity of outcome measures used across studies (Chou et al. 2004; Taricco et al. 2006). Spasticity is multi-dimensional with a variety of clinical manifestations and much day-to-

21-24

day variation within an individual. A battery of measures is needed to obtain valid and reliable measurement of spasticity within a given trial (Priebe et al. 1996). The range of studies outlined in the present review demonstrates various physiological, clinical and functional measures, yet there is minimal consistency of outcome measure selection across trials. Conclusions Regarding the Effect of Oral Baclofen There is Level 1 evidence that oral baclofen improves muscle spasticity secondary to SCI. This conclusion is based on the results from 3 positive small-scale RCTs although is muted somewhat by a negative finding from a low n (5) single-subject design RCT and an overall lack of homogeneity in outcome measures and study participants. Additional uncontrolled cohort and case series studies also provide support for the use of oral baclofen in reducing spasticity. Oral baclofen reduces muscle spasticity in people with SCI.

21.4.2 Intrathecal Baclofen for Reducing Spasticity Programmable pumps can be implanted for the treatment of spasticity in spinal cord injury. The most commonly delivered drug is intrathecal baclofen. Many of the studies looking at intrathecal baclofen in spasticity combine different causes of spasticity such as spinal cord injury, multiple sclerosis and cerebral palsy making the results difficult to interpret. Outcome measures for intrathecal baclofen include direct spasticity measures such as Ashworth scale and spasm frequency scale, indirect measures such as functional outcome measures, complication rates and quality of life as well as cost-benefit analyses. Table 21.8 Intrathecal Baclofen for Reducing Spasticity
Author Year; Country Score Research Design Total Sample Size Methods Population: SCI (C5-T8, Frankel A-B) and MS (SCI n=5). Treatment: Test dose: A daily bolus of placebo or baclofen (12.5 to 100 mcg titrated dose). Long-term: Intrathecal baclofen pump implantation. Outcome Measures: Ashworth scale, spasm frequency score, Pendulum test, Hospital Cost Analysis, bladder and respiratory function, adverse events. 1. 2. Outcome Test dose: Intrathecal baclofen 50 mcg decreased the average Ashworth score. Long-term: A decrease in Ashworth score mean = 1.8 (p<0.005) and spasm frequency score mean =0.8 (p<0.005) and an improved leg swing in pendulum test. No change in bladder or respiratory function. Improvements in ADLs noted. N= 6 were included in the cost analysis. Overall savings of $153,120 were calculated based on a reduction in hospital related spasticity treatment following pump implantation. Follow-up ranged from 24 to 41 months. No statistical results were reported although all subjects showed an improvement in Ashworth. Muscle strength did not change.

Nance et al. 1995; Canada PEDro=9 RCT for test dose N=7

3.

4. Parke et al. 1989; USA PEDro=9 Pre-post N=8 Population: MS (n=4) and SCI (n=4) Treatment Intrathecal baclofen pump implantation. Outcome Measures: Ashworth scale, 1.

21-25

Author Year; Country Score Research Design Total Sample Size

Methods muscle strength and modified PECS scale. Population:: 10 MS and 10 SCI (C5-T9). Treatment Test dose: A 3 day infusion of saline or intrathecal baclofen (100 mcg/milliliter) via programmable pump. Long-term: An open label long-term observation of intrathecal baclofen. Outcome measures: Ashworth scale and spasm frequency scale, laboratory analysis of motor control (EMG) and patient impression 2. 1.

Outcome Improvements were also noted in the PECS scores. Follow-up was at least 6 months. Test dose: In both the SCI and MS groups, the period of baclofen administration could be identified from the saline administration period by the improvement in Ashworth and spasm frequency scores (p<0.01). Overall (all subjects combined), the Ashworth score decreased from 4.0 + 1.0 to 1.2 + 0.4 (p<0.0001) and the spasm frequency scale decreased from 3.3 + 1.2 to 0.4 + 0.8 (p<0.0005). Long-term: For all patients combined, the Ashworth scale and spasm frequency scale decreased. Follow-up ranged from 10-33 months (average 19). Test dose: 88 patients (94.6%) responded to the test dose with a decrease in Ashworth and spasm scale. No patients responded to placebo. Long-term: For the SCI group, the Ashworth score and spasm score decreased post-pump. Patients were followed for 5-41 months (mean 19 months). Test dose: All 66 patients responded positively to test bolus dose and none of the 9 randomized patients responded to placebo. Long-term: A decrease in Ashworth score and improvement in decreased from 4.3 pre-operatively to 1.4 (p<0.0005)at last follow-up, spasm frequency scale improved from 3.6 to 0.5 (p<0.0005) at last follow-up. An average reduction in 2.7 hospitalization days per patient was found for a cost savings of $2500 per day institutional costs (or $6700 per patient) with the cost of the treatment paid back in <2.5 years.

Penn et al. 1989; USA PEDro=9 Randomized double blind crossover study test dose; Open label observation long term study N=20

2. 3. Population: SCI, MS and other spinal pathology (SCI n=59) Treatment: Test dose: Randomized trial test injection baclofen versus placebo with up-titration from 50 mcg to 100 mcg. Long-term: Intrathecal baclofen pump implantation. Outcome Measures: Ashworth and spasm scales Population: MS, SCI and other causes of spinal spasticity (SCI n=27). Treatment: Test dose: N=9 patients were randomized to receive normal saline or test dose intrathecal baclofen. Subsequent test doses were not open label. Long-term: Intrathecal baclofen pump implantation. N=10 patients were studied for costs study comparing 1 year pre and post pump implantation. Outcome Measures: Ashworth scores, spasm frequency scale, drug tolerance, treatment complications, cost-benefit analysis. 1.

Coffey et al. 1993; USA PEDro=8 Randomized test dose; Before and After long term follow-up N=75

2. 3. 1.

Ordia et al. 1996; USA PEDro=6 RCT for trial dose N=9 Observational study for long-term N=66

2.

3.

21-26

Author Year; Country Score Research Design Total Sample Size

Methods Population: MS and SCI (C5-T11, Frankel A-D) (SCI n=12). Treatment Intrathecal baclofen pump implantation. Outcome Measures: Ashworth, spasm frequency score, FIM. 1.

Outcome Improvement in Ashworth score, spasm frequency score and At 6 months, Ashworth score was improved Z= -3.79 (p<0.001), spasm frequency score was improved Z= -3.78 (p<0.001). FIM. The most dramatic improvements were seen in the 12 patients with thoracic or low cervical lesions (FIM evolved from 50.99.7 to 76.314.5, Z=-3.06, p<0.01) . The following items gained 2 FIM scores: bathing, dressing lower body, and the 3 items related to transfers.. Follow-up ranged from 9-72 months (average 37.4) The SCI group demonstrated a lower Ashworth score (4.57 to 2.57, p=0.0134) and a decrease in spasm scale (3.71 to 1.28, p=0.00006) po post pump insertion. All patients reported improved function after surgery with an increase in Barthel Index Score increased as a result of the treatment in the SCI group (from 17.1 before to 50.7 after treatment, p<0.0073). Dressing and transfers were 2 activities that improved significantly (p=0.0465 and p=0.0016, respectively).The degree of improvement was different according to level of lesion. The self-assessment pain scale revealed a limited improvement in pain(p=0.0941). Follow-up ranged from 9-55 months (median 35 months). At final assessment average VAS satisfaction with the pump was 7.4. Ambulation status was unchanged in 85%. Improvements were noted in pain and sleep and Ashworth score decreased. Follow-up average 4 years Improvement in Ashworth score from baseline 2.82 to final assessment 0.91 (p<0.05) and spasm score from baseline 1.79 to final assessment 0.67 (p<0.05). Worsening in EDSS, AI and ISS (all p<0.05) compared with baseline (in progressive and non-progressive groups of patient disabilities). Worsening in level of disability (EDSS and ISS p<0.05) and the psychosocial aspect of the perceived health status scale (SIP) ( p<0.05) were seen when compared from baseline and at 26 weeks.

Azouvi et al. 1996; France Downs & Black score=25 Pre-post N=18

2. Population: MS and (n=7) SCI (C4 to T11). Treatment: Intrathecal baclofen pump implantation. Subjects were implanted with an infusion pump delivering a continuous flow at a fixed rate of bolus intrathecal baclofen. Boviatsis et al. 2005; Greece Downs & Black score=18 Case Series Initial N=22; Final N=21 Outcomes: Barthel index scale, Ashworth scale and Penn spasm scale, selfassessment pain scale 1.

2.

3. 4. Plassat et al. 2004; France Downs & Black score=16 Case series Initial N=41;Final N=37 Population: SCI, MS and cerebral spasticity (SCI= 17). Treatment: intrathecal baclofen pump placement Outcome Measures: VAS satisfaction score locomotion, pain, sleep, Ashworth. Population: MS and SCI and other spinal spasticity(SCI n=6). Treatment: Intrathecal baclofen pump implantation. Outcome measures: Ashworth scale, spasm score, Expanded disability status scale, ambulation index, Incapacity status scale, Sickness impact profile, Hopkins symptom check list. 1. 2.

3. 1.

Zahavi et al. 2004; Netherlands Downs & Black score=16 Observational (long-term) Initial N=38; Final N=21

2.

21-27

Author Year; Country Score Research Design Total Sample Size

Methods 3.

Outcome Follow-up ranged from 66 to 108 months with a mean of 84.9 months. Test dose: Decrease in Ashworth and spasm score. Long-term: Decrease in Ashworth scores Follow-up ranged from 2-34 months with average 16 months. Test dose: A decrease was seen in optimal reflex score (t=7.69, p<0.001) and the Ashworth score with baclofen. grade (t=6.05, p<0.001), between placebo and optimal reflex score a change was noted (t=3.68, p<0.01) and Ashworth grade (t=6.0, p<0.001) and between placebo and control Ashworth grade (t=2.95, p<0.02). At optimum intrathecal baclofen dosage, 8/9 patients benefited in functional evaluations. Long-term: Only 7 subjects participated. The Ashworth score and mean reflex score decreased from 3.79 + 0.69 to 2.00 + 0.96 (t=12.9, p<0.001). The mean reflex score decreased from 3.85 + 0.62 to 2.18 + 0.43 (t=6.76, P<0.001). Follow-up ranged from 3-22 months. Test dose: 64/66 patients responded to a test dose of intrathecal baclofen with a decrease in either Ashworth or spasm frequency scale. Long-term: 84% treated adequately for spasticity. Follow-up average 30 months (up to 81 months). Reduction in Ashworth and spasm frequency scale improvement in hyperreflexia, objective improvements in transfer activities and skilled acts, improved comfort, reduced H/M ratio and improved bladder function Mean follow-up 11 months.

Abel & Smith 1994; USA Downs & Black score=13 Observational N=23

Loubser et al. 1991; USA Downs & Black score=13 Randomized test dose; Before and After long term follow-up N=9

Population: MS and SCI (C4-T12 ASIA AD) (SCI n=17) Treatment: Intrathecal baclofen pump implantation. Outcome Measures: Ashworth score and spasm score. Population: Traumatic non-progressive SCI, all male, C2-T12 (n=9). Treatment: Test dose: 5 day infusion of varying doses of baclofen and a single 12 hour placebo infusion over a 5 day period to determine optimum intrathecal baclofen dosage. Long-term: Intrathecal baclofen pump implantation. Outcome Measures: Ashworth scale, neurological reflex scale, evaluation of functional abilities, evaluation of personal independence and global assessment scale.

1. 2. 3. 1.

2.

Penn 1992; USA Downs & Black score=13 Review N=66

Population: MS and SCI (SCI=32). Treatment: Intrathecal baclofen pump implantation. Outcome Measures: Ashworth score and spasm frequency scale.

3. 1.

2. 3.

Broseta et al. 1990; Spain Downs & Black score=11 Case series N=19

Population: SCI (T3-L1), MS and cerebral spasticity. (SCI n=5) Treatment: Implantation of programmable pump Outcome Measures: Ashworth, spasm frequency scale, reflex assessment, cystomanometry and perineal electromyography for assessment of neurological bladder dysfunction, electrophysiological H/M ratio, total dose. Population: SCI (n=12), all male. Treatment Intrathecal baclofen pump implantation. Outcome Measures: Ashworth scale and spasm frequency score.

1.

2.

1.

Korenkov et al. 2002; Germany Downs & Black score=10 Pre-post N=12

2.

3.

Significant post-operative reduction of muscle tone and spasm (P<0.05). Ashworth decreased from 4.2 to 2.2 in the lower limbs and from 2.2 to 1.0 in the UE. Decrease in Ashworth score. Self-care, nursing care, PT, transfers, sitting tolerance, muscle pain and sleeplessness were all reported as improved but no measures were reported. Follow-up was 12 months.

21-28

Author Year; Country Score Research Design Total Sample Size Ochs et al. 1989; Germany Downs & Black score=10 Prospective open design N=28

Methods Population: MS and SCI (SCI n=10) Treatment: Intrathecal baclofen pump implantation. Outcome Measures: Ashworth and spasm frequency scale, electrophysiological data. 1.

Outcome Improvement in Ashworth and spasm frequency scale. Intrathecal baclofen had an effect on electrophysiological data Follow-up up to 2 years.

2.

Discussion Spasticity Outcome There are 5 studies employing a randomized controlled trial design to evaluate the effects of test doses of intrathecal baclofen in SCI. Although these studies are small and combine different etiologies of spasticity, they do provide a limited body of level 1 evidence to support the use of intrathecal baclofen test doses to decrease spasticity in SCI as measured by Ashworth scale and spasm frequency score (Penn et al. 1989; Loubser et al. 1991; Coffey et al. 1993; Nance et al. 1995; Ordia et al. 1996). Table 21.9 Summary Intrathecal Baclofen RCTs for Reducing Spasticity Spasticity Outcome
Author Year; Total Sample Size Methods Test dose: Randomized trial test injection baclofen versus placebo with up-titration from 50 mcg to 100 mcg. Long-term: Intrathecal baclofen pump implantation. Outcome Test dose: 88 patients (94.6%) responded to the test dose with a decrease in Ashworth and spasm scale. No patients responded to placebo. Long-term: For the SCI group, the Ashworth score and spasm score decreased post-pump. Test dose: At optimum intrathecal baclofen dosage, 8/9 patients benefited in functional evaluations. Long-term: Only 7 subjects participated. The Ashworth score and mean reflex score decreased. Test dose & Long-term: Overall (all subjects combined), significant decreases for the Ashworth score and the spasm frequency scale decreased as a result of intrathecal Baclofen. Test dose: All 66 patients responded positively to test bolus dose and none of the 9 randomized patients responded to placebo. Long-term: A significant decrease in Ashworth score and spasm frequency scale at last follow-up Test dose: Intrathecal baclofen 50 mcg decreased the average Ashworth score. Long-term: A significant decrease in Ashworth score and spasm frequency score and an improved leg swing in pendulum test.

Coffey et al. 1993; N=75 (SCI =59)

Loubser et al. 1991; N=9 (SCI =9)

Test dose: 5 day infusion of varying doses of baclofen and a single 12 hour placebo infusion over a 5 day period to determine optimum intrathecal baclofen dosage. Long-term: Intrathecal baclofen pump implantation. Test dose: A 3 day infusion of saline or intrathecal baclofen (100 mcg/milliliter) via programmable pump. Long-term: An open label long-term observation of intrathecal baclofen. Test dose: N=9 patients were randomized to receive normal saline or test dose intrathecal baclofen. Subsequent test doses were not open label. Long-term: Intrathecal baclofen pump implantation. Test dose: A daily bolus of placebo or baclofen (12.5 to 100 mcg titrated dose). Long-term: Intrathecal baclofen pump implantation.

Penn et al. 1989; N=20 (SCI N= 10)

Ordia et al. 1996; Initial N=66; Final N=57 (SCI =27)

Nance et al. 1995; Initial N=7; Final N=6 (SCI =5)

21-29

It is unlikely that randomized controlled trials will be undertaken to look at the long-term effectiveness of intrathecal baclofen given the effectiveness of test doses. However, several level 4 studies support the long term use of intrathecal baclofen to decrease spasticity with the most frequently used outcomes measures being the Ashworth scale and spasm frequency scales (Ochs et al. 1989; Penn et al. 1989; Broseta et al. 1990; Loubser et al. 1991; Penn 1992; Coffey et al. 1993; Abel & Smith 1994; Nance et al. 1995; Ordia et al. 1996; Korenkov et al. 2002; Plassat et al. 2004; Boviatsis et al. 2005). The effects of intrathecal baclofen are more pronounced in the lower extremities than the upper extremities (Korenkov et al. 2002) Functional outcome The effects of intrathecal baclofen on functional outcomes are much harder to summarize. Most studies are observational, pre-post studies with small numbers of SCI patients grouped in combination with several other diagnoses (most often multiple sclerosis, MS). In addition, there is a lack of standardized outcome measures used to study functional outcomes. Finally, the majority of studies are not stratified by SCI level or ASIA impairment scale. There are several observational studies looking at the short-term and long-term complication rates seen with intrathecal baclofen. Overall, complication rates are low and can be categorized as medication related or pump related. However, complications can be severe and include death. (Loubser et al. 1991; Penn et al. 1992; Coffey et al. 1993; Abel & Smith 1994; Nance et al. 1995; Azouvi et al. 1996; Ordia et al. 1996; Stempien & Tsai 2000; Korenkov et al. 2002; Plassat et al. 2004) Tolerance to intrathecal baclofen has been observed (Ochs et al. 1989; Coffey et al. 1993; Abel 1994; Ordia et al. 1996) Overall, there is level 4 evidence to suggest that functional outcomes as measured by scales such as Barthel index scale and FIM improve with intrathecal baclofen (Parke et al. 1989; Broseta et al. 1990; Nance et al. 1995; Azouvi et al. 1996; Ordia et al. 1996; Plassat et al. 2004; Boviatsis et al. 2005). However, it is notable that Zahavi reports a small statistically significant deterioration in disability as measured by the expanded disability status scale, ambulation index and incapacity status scale. The article notes that this may not be a clinically significant deterioration (Zahavi et al. 2004). Loubser reports the potential for decreased functional outcomes especially with respect to ambulatory status in patients who may depend on their spasticity for ambulation (Loubser et al. 1991). Table 21.10 Summary Intrathecal Baclofen Observational Studies for Reducing Spasticity Functional Outcome
Author Year; Total Sample Size Boviatsis et al. 2005; N=22 (SCI =7) Parke et al. 1989; N=8 (SCI N=4) Ordia et al. 1996; N=66 (SCI =27) Azouvi et al. 1996; N=18 (SCI = 12) Methods Treatment: Intrathecal baclofen pump implantation. Subjects were implanted with an infusion pump delivering a continuous flow at a fixed rate of bolus intrathecal baclofen. Treatment: Intrathecal baclofen pump implantation. Long-term: Intrathecal baclofen pump implantation. Treatment: Intrathecal baclofen pump implantation. Outcome All patients reported improved function after surgery but the degree of improvement was different according to level of lesion. Improvements were noted in the PECS scores. Long-term: A decrease in Ashworth score and spasm frequency scale at last follow-up. Improvement in FIM at 6 months. - 2 FIM scores: bathing, dressing lower body, and

21-30

Author Year; Total Sample Size

Methods

Outcome the 3 items related to transfers. Most improvement in 12 patients with thoracic or low cervical lesions. Improvements in ADLs noted. Objective improvements in transfer activities and skilled acts, improved comfort, reduced H/M ratio and improved bladder function Improvements were noted in pain and sleep and Ashworth score decreased. Worsening in EDSS, AI and ISS and the psychosocial aspect of the perceived health status scale (SIP) were seen when compared from baseline and at 26 weeks. At optimum intrathecal baclofen dosage, 8/9 patients benefited in functional evaluations.

Nance et al. 1995; Initial N=7; Final N=6 (SCI =5) Broseta et al. 1990; N=19 (SCI =5) Plassat et al; 2004; N=41 (SCI= 17) Zahavi et al. 2004; N=38 (SCI =6)

Long-term: Intrathecal baclofen pump implantation. Treatment: Implantation of programmable pump. Treatment: intrathecal baclofen pump placement Treatment: Intrathecal baclofen pump implantation. Test dose: 5 day infusion of varying doses of baclofen and a single 12 hour placebo infusion over a 5 day period to determine optimum intrathecal baclofen dosage. Long-term: Intrathecal baclofen pump implantation.

Loubser et al. 1991; N=9 (SCI =9)

Cost-effectiveness There are 2 level 4 studies looking at cost-effectiveness with the usage of intrathecal baclofen (Nance et al. 1995; Ordia et al. 1996). Ordias study does not specify whether SCI or MS subjects were studied for cost-effectiveness, but does report gross cost savings with intrathecal baclofen due to an overall reduction in hospital days post pump implantation (Ordia et al. 1996) Table 21.11 Summary Intrathecal Baclofen for Reducing Spasticity Cost Analysis
Author Year; Total Sample Size Nance et al. 1995; Initial N=7; Final N=6 (SCI =5) Methods Long-term: Intrathecal baclofen pump implantation. Outcome N= 6 were included in the cost analysis. Overall savings of $153,120 were calculated based on a reduction in hospital related spasticity treatment following pump implantation. An average reduction in 2.7 hospitalization days per patient was found for a cost savings of $2500 per day institutional costs (or $6700 per patient) with the cost of the treatment paid back in <2.5 years.

Ordia et al. 1996; Initial N=66; Final N=57 (SCI =27)

Long-term: Intrathecal baclofen pump implantation. N=10 patients were studied for costs study comparing 1 year pre and post pump implantation.

Nances study also combines MS and SCI. In contrast to Ordia who looked at overall hospital days, Nance looked only at hospital days related to spasticity and found a net savings in costs related to pump implantation (Nance et al. 1995) Conclusions There is Level 1 evidence that bolus or test dose intrathecal baclofen decreases spasticity.

21-31

There is Level 4 evidence that the use of long-term intrathecal baclofen decreases spasticity. There is Level 4 evidence that intrathecal baclofen may improve functional outcomes. There is Level 4 evidence that complication rates with the long-term use of intrathecal baclofen are relatively low. There is Level 4 evidence that intrathecal baclofen is a cost-effective intervention. Bolus or long-term intrathecal Baclofen decreases spasticity and may improve functional outcomes with low complication rates and is a cost effective intervention. 21.4.3 Effect of Medications Other than Baclofen on Spasticity after SCI Although Baclofen is the most widely used drug for the treatment of spasticity in SCI, other drugs used as anti-spasmodics include tizanidine, cyproheptadine, diazepam, gabapentin, Lthreonine, cannibis, dantrolene, clonidine (oral, transdermal and intrathecal), 4-aminopyridine (intravenous, intrathecal, immediate and sustained release) and others that will each be discussed briefly. Table 21.12 Effect of Medications Other than Baclofen for Reducing Spasticity
Author Year; Country Score Research Design Total Sample Size Methods Tizanidine Population: SCI with moderate spasticity Treatment: Tizanidine Outcome Measures: Ashworth (hip adductors, knee flexors/extensors bilateral), Pendulum, modified Klein-Bell scale (ADL), Golabal evaluation of antispastic efficacy, Adverse Events. Outcome

1.

Nance et al. 1994; US & Canada PEDro=10 RCT (DB) N=118

2.

3. 4. 5. Population: SCI Treatment: Single-dose (8mg), tizanidine. Three pre-drug measurements 15 minutes apart after breakfast and 30 minute equilibration. Observations continued at 0.5, 1.0, 1.5, 2.0, 3, 4, 5, 6, 12, 24 hours. These measurements were repeated on a separate occasion (except measurements of sedation and blood collection) without drug administration. Outcome measures: Ashworth, Manual 1.

Mathias et al. 1989; United Kingdom Downs & Black score=14 Pre-post N=10

2. 3.

Ashworth: Tizanidine produced significantly (p<0.0001) greater decreases in muscle tone from baseline to end of titration (T3), end of plateau (P2) and end point (EP) as compared with placebo. Pendulum: Tizanidine produced significantly greater decreases in the swing parameters from based to T3 (p<0.0135), P2 (p<0.0401) and EP (p<0.0038) as compared to placebo. Modified Klein-Bell showed no change from baseline in their ADL score. Global changes were larger in Tizanidine vs Placebo but were not significant between groups. Adverse Events significantly greater in Tizanidine vs Placebo (P=0.002). Ashworth: peak reduction between 11.5 hrs (p<0.05 with spasticity returning to baseline by 4th hour; no rebound spasticity measured at 12 and 24 hours. Muscle power: no effects on impaired or unimpaired muscles at any stage of the study. No significant changes to vitals except with heart rate (decrease in HR; p<0.05 after 1.5hrs)

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Author Year; Country Score Research Design Total Sample Size

Methods muscle testing, vitals, sedation, pharmacokinetics (Pk), and adverse events. 4.

Outcome Sedation: Sedation in tetras>paras but increased in both with considerable variability. Peak within first hour with gradual waning to fully awake by 3rd hour. PK: Pk - Plasma levels rose at 0.5hrs and peaked by 1 hour. At 6 hrs, level was at 85% peak and still detectable but low levels at 12 and 24 hrs. Plasma half-life was 2.70.06hrs. Adverse Events: Sedation and dry mouth. 1/3 paretic patients had marked progression from non-ambulation to limited independent ambulation. The other 2 paretics who presented limited spasticity showed minimal changes while on clonidine. Spasticity -/+/0: VAS 6/1/2, Daily spasms 2/0/2, Daily clonus 4/0/1, Ankle TSR 5/2/2, Knee TSR 5/0/2, Evoked clonus 3/1/5. Side Effects in 8/9 patients during dose titration included dryness of eyes and mouth, lethargy, mild hypotension and constipation. The majority were transient or negligible while 2 patients experienced moderate to severe lethargy and constipation. VII significantly reduced by clonidine (p<0.001) but not the other interventions. Achilles reflex not affected by any intervention. Duration of clonus not affected by any intervention. Ashworth and Pendulum correlated well (r=0.88) in no-drug condition. Ashworth significantly reduced, significantly increased first swing amplitude, and increased VII in all three drug conditions (p<0.0001, all 3 outcome measures) with baclofen showing the most improvement (p=0.06). No difference between treatments (p=0.2618) for Ashworth and Pendulum. Cyproheptadine and Baclofen produced a greater reduction in the VII than Clonidine, p<0.01. 5/17 had clinically significant relief. 12/15 continued to use the medication. 10/15 were able to decrease or discontinue their current antispasticity

5.

6. Clonidine Population: Chronic, traumatic and nontraumatic SCI. Treatment: 2-week washout period between 4 weeks of randomly assigned Clonidine or Placebo treatment. Medication was administered orally 2 or 3 times per day. Initial dosage was 0.02mg/day and systematically increased to an optimal level (0.05-0.25mg/day) Outcome Measures: Body weight supported (BWS) treadmill assisted walking with surface EMG, footswitch and video recordings. Spasticity assessments: VAS subject self report, daily spasticity diary, tonic stretch reflex (TSR) assessment at the ankle/knee and assessment of ankle clonus), and Side Effects (AEs). Population: SCI Treatment: Clonidine, clonidine and desipramine, diazepam, placebo Outcome Measures: Vibratory inhibition index (VII) of the H-reflex; Achilles reflex; duration of clonus Population: Chronic complete and incomplete SCI with at least moderate spasticity Treatment: 1 wk up-titration, 1 wk target dose (0.05mg bid clonidine; 4mg qid cyproheptadine; 20 mg qid baclofen) , 1 wk down-titration Outcome Measures: Ashworth, Pendulum, Vibratory Inhibition Index (VII) 1.

2.

Stewart et al. 1991; Canada PEDro=8 RCT-DBPC N=12

3.

Nance et al. 1989; Canada Downs & Black=16 Non-randomized Controlled Trial (Single Blind) N=6

1. 2. 3. 1. 2.

Nance 1994; Canada Downs & Black score=15 Pre-post N =25

3. 4.

Weingarden & Belen 1992; USA Downs & Black score=13 Case Series

Population: SCI, traumatic. Treatment: Transdermal clonidine Outcome Measures: Clinically significant relief of spasticity; continuation of study

1. 2. 3.

21-33

drug after trial; discontinuation of other anti-spasticity medications Population: SCI, complete and incomplete, paraplegics and quadriplegics. Donovan et al. 1988; Treatment: Oral clonidine - 0.05mg bid USA and increased to 0.4mg bid if tolerated by Downs & Black score=13 the subject. Case Series Outcome Measures: Success of N=55 medication was defined as a decrease in hypertonicity. Population: Incomplete, paraplegic SCI. Treatment: Responders (walking capacity preserved) to a 60ug intrathecal test dose were scheduled for 3, 15-90ug doses of Remy-Neris et al. 1999; clonidine, and a placebo, by L2-3 puncture. France Non-responders were given 30 and 15ug Downs & Black clonidine and a placebo when possible. A score=11 minimum interval of 3 days separated each Non-randomized, injection. placebo controlled trial Outcome Measures: Ashworth scores N=11 (bilateral quadriceps), walking parameters, H-reflex, polysynaptic reflexes - recorded before and every hour for 4-6 hours after an i.t. injection of clonidine or placebo. Population: subacute, traumatic Cervical SCI. Yablon & Sipski 1993; Treatment: 0.1-0.3 mg/wk Transdermal USA Downs & Black score=10 Clonidine patch (Constant/continuous systemic delivery). Case Series Outcome measures: Change in spasticity Initial N=3; Final N=3 (no specific measure noted). Population: Incomplete SCI. Treatment: Intrathecal clonidine injection (30/60/90 ug). Outcome Measures: Amplitude and stimulation threshold of flexor reflex responses (FRR) in tibialis anterior after posterior tibial nerve stimulation; Ashworth score / pendulum test, and EMG latency / amplitude of quadriceps stretch reflex Remy-Neris et al. 2001; France Downs & Black score=6 Non-RCT N=15

Author Year; Country Score Research Design Total Sample Size N=17

Methods

Outcome medications. 1. 2. 3. 1. Results indicate that quadriplegics responded to the medication better than the paraplegics. (p<0.033). No significant difference based on complete vs incomplete lesions. 31/55 subjects responded to clonidine. Significant decrease in Ashworth spasticity score (p<0.0001) at all doses levels (30, 60, 90) with no consistent significant differences detected in reflexes. Statistically significant increase in the velocity at maximal overground speed (P-0.03) due to an increase in the stride amplitude (P=0.0009), without any significant decrease in the cycle duration (P=0.28). 90 and 120 ug doses did not produce significant improvement in 3 subjects able to walk after 60ug. Case 1: marked improvement noted in relief of flexor spasms; Case 2: Excellent improvement noted in both spastic hypertonia and flexor spasms; Case 3: Moderate improvement in spastic hypertonia and flexor spasms. FRR amplitude change significant (P<0.02) between 30 and 90 ug IT Clonidine but not significant between 30 and 50 ug between 30 and 90, NS for 30/60). FRR stimulation threshold significantly increased for each Clonidine dose compared to pre-injection. (P<0.05 for dose-dependent effect; no change in placebo effects showing no effect of lumbar puncture). Decrease in Ashworth score appeared a few minutes after injection, which lasted 4-6 hrs after a single 60ug dose. Latencies of the quadriceps stretch showed a significant increase in the latency after clonidine in all but 1 subject. Amplitudes of the quadriceps stretch showed a significant decrease in the latency after clonidine in all subjects. Parallel results seen in integrated rectified EMG observed with pendulum test.

2.

3. 1. 2. 3. 1.

2.

3.

4.

5. 6.

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Author Year; Country Score Research Design Total Sample Size

Methods 7. 4-Aminopyridine Population: chronic SCI Treatment: Subjects were randomized into one of two treatments and given either Fampridine-SR (12.5 mg bid to start with an increase to 17.5 mg bid) or placebo over a period of 2 weeks then following a washout period they were given the alternate treatment. Outcome Measures: motor index, sensory index, present pain intensity, spasm frequency, modified Ashworth scale, bowel and bladder scores, clinical interview questionnaire, global patient satisfaction questionnaire, seven point terrible delighted scale and FIM

Outcome Reported AEs include hypotension, feelings of negativism and depression, sedation

Potter et al. 1998; Canada & USA PEDro=10 RCT N=29

Donovan et al. 2000;USA PEDro=9 RCT N=12

Hayes et al. 1994; Canada & USA Downs & Black score=15 Case Series N=6

Population: SCI, complete and incomplete. Treatment: Drug or placebo was administered for 2 hours through an indwelling venous catheter attached to an infusion pump (4-AP reached doses of 30 to 80 ng/ml at the end of a 2 h) Outcome Measures: Patients were serially examined during and after infusion clinically for Pain (McGill questionnaire); Sensorimotor function (ASIA); Hypertonicity (Ashworth scale , Reflex scale); Electrophysiologic measurements (Brain motor control assessment); Blood and CSR sampling. Population: Chronic, traumatic SCI. Treatment: Under fasting conditions, patients received 24-25mg 4-AP IV. Monitoring for effect pre to 2 hours post and at 24 hours post drug administration Outcome Measures: Neurophysiological and standard neurological examination. Adverse Event monitoring.

Significant benefit of Fampridine-SR over placebo: 1. Motor scores (adjusted to only paretic segments; p1 < 0.01). 2. Sensory scores (p1 < 0.01), including both pin prick and light touch (p1 = 0.059 and 0.058). 3. Ashworth (p2 < 0.05). 4. Patient satisfaction and quality of life scores (McNemar's test, p2 < 0.01 and <0.05). 5. No statistical significance on measures of pain, bowel/ bladder/sexual function or FIM. 6. Side effects: lightheadedness and nausea transient/trivial relative to efficacy. 7. ~30% of patients reported a wish to continue to use. 1. No significant differences were noted pre-post infusion between 4-AP and the placebo. No differences between the motor incomplete and the motor complete groups. 2. The intravenous route may not be the best way to administer this drug as no short term benefits were observed.

1.

2.

3.

Potter et al. 1998; Canada & USA Downs & Black score=10

Population: Incomplete, traumatic, chronic, cervical SCI. Treatment: Day 1- single 10mg capsule of

1. 2.

Enhanced somatosensory evoked potentials (N=3), Improved motor evoked potentials (N=4), Increased voluntary EMG interference (N=2) Three of 6 patients reported neurological benefits of the drug (N=2 for reduced spasticity; N=1 for pain; N=1 for increased sensation; N=3 for increased limb movement and N=1 for restored bowel control. Adverse Events: aching IV site (N=6), transient lightheadedness (N=2), mild perioral paresthesia (N=1), +20mm Hg in systolic BP after 24 mg 4-AP (N=2), exacerbation of ankle phlebitis pain (N=1) and facial flushing after waking 1 day after the trial (N=1). A. Physical Exam: Improved bladder function (N=1), Improved spasticity (UE N=1, LE N=2),

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Author Year; Country Score Research Design Total Sample Size Case Series N=3

Methods 4-AP followed by physical and neurophysiological examination pre and post administration up to 24 hours. Day 4: 10mg bid to tid by Day 6, if tolerated. Tolerated dosing regimen continued for 4 months with prn intermittent assessments. Outcome Measures: A. Physical exam: ASIA motor and sensory classification; Modified Ashworth rating of spasticity. B. Neurophysiological exam: Motor evoked potentials (MEPs) following transcranial magnetic stimulation of motor cortex, quantitative assessment of ankle hypertonicity. C. Pharmacokinetics and Adverse Event monitoring. 3. 4. 5. 6. 7.

Outcome Reduced pain (N=1) Improved motor function (N=3) Improved gait (N=2) Improved sensory function (N=1), Improved penile tumescence (N=1) and a 8. Nonspecific but consistently "renewed vigour" (N=2). B. Neurophysiological results; 9. MEPs increased in amplitude (N=1). 10. Ankle hypertonicity reduced (N=1). C. Pharmacokinetics and Adverse Events: 11. Pk: 1-1.5 h Tmax; 75.05-121.27 ng/ml Cmax; 5.21-12.61L/h CL; 139.84306.84 /L Vss; 16.9-19.08h t1/2. 12. Wakefulness (1 case limited to bid rather than tid dosing) and transient light-headedness. Improvements in favour of Cyproheptadine vs placebo (descriptive statistics only; no pvalues provided): 1. Spasticity: all subjects reported a decrease in the severity and frequency of involuntary movements. 2. Walking pattern: A) Marked decrease in forward trunk flexion but no major changes for medial ham and TA EMG burst activity B) Maximum comfortable walking speed increased over control speed: decrease in cycle duration, percentage stance and associated decrease in the % double support duration.

Wainberg et al. 1990; Canada PEDro=7 RCT N=8

Barbeau et al. 1982 ; Canada Downs & Black score=12 Case series Pre-post N=6

Gruenthal et al. 1997; USA PEDro=7 RCT N=28

Cyproheptadine Population: Chronic, incomplete, traumatic, non-traumatic SCI. Treatment: One week washout between Cyproheptadine or placebo (identically appearing tablets) in random order dosetitrated over 3 weeks (1 week each at 2mg, 4mg and 8mg 5id). Four subjects also were tested after open-label long term Cyproheptadine (optimized dosing) of at least 6 months. Con meds and therapies were maintained for at least 3 months prior to the study. Outcome Measures: Treadmill walking without overhead harness BWS when possible, or 40% BWS - Temporal distance, surface EMG, Joint angular displacement, spasm severity in 2 positions, spasticity diary. Population: SCI and MS with spasticity of spinal origin. Treatment: Oral Cyproheptadine progressively increased from 6 mg to 24 mg per day over 4 to 24 months, including a placebo substitution period Outcome Measures: Muscle strength; EMG activity; patient log of clonus and spasms; ankle clonus Gabapentin Population: subacute to chronic SCI. Treatment: Eleven day washout between 2 day Gabapentin (400 mg total in 3 divided doses) or placebo with evaluations prior to, on second day within 5h of last dose and after washout for each treatment. Outcome Measures: Each evaluation: 1) U/LE Ashworth and 6 point Likert ratings of spasticity 2) muscle stretch reflexes, 3) presence or absence of ankle/wrist clonus

1. 2. 3. 4.

Muscle strength decreased in 4/6 patients. EMG activity decreased in 3/6. Patient log of clonus and spasms showed decreased spontaneous spasms in 5/6. Ankle clonus decreased in 6/6.

1.

2. 3. 4.

Gabapentin resulted in an 11% reduction in the median Ashworth Scale (z=2.011, P=0.044) and a 20% reduction in the median Likert Scale score (z=3.214, P=0.013) when compared to placebo. Other measures did not yield significant differences. No treatment order effect. No significant changes in any measure

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Author Year; Country Score Research Design Total Sample Size

Methods 4) reflex withdrawal to noxious stimuli in finger and foot. 5. L-Threonine Population: MS and traumatic and nontraumatic SCI with spasticity of spinal origin. Treatment: 6g/da y- 500mg L-Threonine or Placebo capsules taken 3x/day on empty stomach. Outcome Measures: Ashworth (bilat. hip adductors-flexors-extensors and knee flexors-extensors) - 6 highest summed for spasticity score, which was used throughout the study. Secondary outcome measures: Spasm frequency and severity score (spasm score was derived by multiplying two variables together over 2wk period using specially designed chart), Barthel Index, Kurtzke Disability Status Scale, Patient & Caregiver subjective responses, AEs, and glycine/thronine plasma concentrations. Measurements pre and post treatment. All measures conducted by a single investigator. Cannabis Hypothesis: To examine the perceived effects of cannabis on spasticity of spinal cord injured persons Treatment: No treatment Outcome Measures: In addition to demographic information (age range, sex, marital status, education, and range of time since injury), 8 other questions asked in 3 categories of questions: 1) choice of 5 categories of marijuana use - never, once or twice, 3-12 times, 12-24 times, >24 times, for the previous year and for the year prior to SCI 2) via Lickert-type scare, indicate how characteristic marijuana use is of the people they "admire and identify with" at present and before their injury and how similar they felt their ideas, beliefs, values, and the like" were to most other people in society, both at present and before their injury 3) via 5point scale ranging from not present to very severe, indicate the severity of spasticity they experienced when under and when not under the influence of marijuana 4) spasticity Change Index, describing the amount of change in spasticity, was computed by subtracting level of spasticity in the drug-state from level of spasticity in the non-drug-state.

Outcome seen when placebo compared to baseline. No Adverse Events.

Lee & Patterson 1993 USA & Ireland PEDro=8 RCT N=33

Modest but definite antispastic effect in favour of L-threonine vs placebo: 1. Mean spasm score reduced for both treatments - weak correlation between spasm score and spasticity reduction. 2. No change in BI or Kurtzke with either treatment. 3. Dramatic rise in plasma threonine during active treatment but no change in plasma glycine. 4. Weak correlation between plasma threonine and spasticity reduction. 5. Patient-carers subjective report6/2 threonine/placebo responders. 6. AEs included minor side effects during treatment (N=2) and Placebo (N=1). 7. Four dropouts - 2 for medical and 2 for non-medical reasons.

1. 2. 3.

Malec et al. 1982; USA Downs & Black score=12 Cohort N=43

SCI persons reported decreased spasticity with marijuana use; present use of marijuana correlated positively with past use; and the person's reference or peer group contributed significantly to current use. 53% reported using mj during last year with correlation to mj use prior to SCI (r=0.78, p<0.001, n=43; agrees with other studies). Also correlated with degree of mj use in present social reference group (r=0.32, p<0.05, n=38) and prior social reference group (r=0.30, p<0.05, n=37). Age was negatively correlated with current mj use (r=-0.56, p<0.001, n=43) Reduction in spasticity via mj use was reported in 88% (21/24) while 12% reported no change. No correlation between Spasticity Change Index and any variable (if significant correlation, then perhaps placebo effect) Education moderately correlated with reported change in spasticity (r=-0.65, p<0.001, n=23): lower education associated with greater reported change in Spasticity Change Index.

MJ use prevalent (53%, 23/43) among SCI surveyed and especially of SCI <30y (76%, 16/21) * Studies from 1980 to date, involving a spasticity intervention with 3 and 50% SCI have been included in this table.

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Discussion Tizanidine Table 21.13 Summary of Tizanidine Studies for Reducing Spasticity
Author Year; Total Sample Size Nance et al. 1994; Initial N=118; Final N=78 Mathias et al. 1989 N=10 Methods Treatment: Tizanidine vs Placebo Treatment: Single-dose (8mg), tizanidine. Three pre-drug measurements 15 minutes apart after breakfast and 30 minute equilibration. Observations continued at 0.5, 1.0, 1.5, 2.0, 3, 4, 5, 6, 12, 24 hours. 1. 1. Outcome Ashworth and Pendulum: significant change in favour of tizanidine. Ashworth: peak reduction between 11.5 hrs with spasticity returning to baseline by 4th hr; no rebound spasticity measured at 12-24 hrs. Muscle power: no effects.

2.

A randomized, placebo-controlled trial specifically conducted to elucidate the anti-spasmodic effect of tizanidine, an 2-adrenergic agonist, revealed significant spasticity improvements in favour of tizanidine over placebo where Ashworth and Pendulum were the primary measures used (p<0.0001 and p<0.002, respectively; Nance et al. 1994; N=118). Although this study represents level 1evidence, it is noteworthy to mention that 34% of subjects who received study treatment and discontinued prematurely due to adverse events, lack of efficacy and other reasons not specified, were not included in the study analysis. Another single dose, pre-test, post-test study (Mathias et al. 1989; N=10) presented evidence to corroborate the reduction in spasticity as measured by Ashworth and furthermore revealed that muscle power was not affected at any stage in the study. Clonidine Another commonly used anti-spasmodic is Clonidine, also an 2-adrenergic agonist (selective, central acting). Table 21.14 Summary of Clonidine Studies for Reducing Spasticity
Author Year; Total Sample Size Methods Treatment: Two week washout period between 4 weeks of randomly assigned Clonidine or Placebo treatment. Medication was administered orally 2 or 3 times per day. Initial dosage was 0.02mg/day and systematically increased to an optimal level (0.05-0.25mg/day) Treatment: Responders (walking capacity preserved) to a 60ug intrathecal test dose were scheduled for 3, 15-90ug doses of clonidine, and a placebo, by L2-3 puncture. Non-responders were given 30 and 15ug clonidine and a placebo when possible. A minimum interval of 3 days separated each injection. Treatment: 1 wk up-titration, 1 wk target dose (0.05mg bid clonidine; 4mg qid cyproheptadine; 20 mg qid baclofen) , 1 wk down-titration Treatment: Clonidine, clonidine and desipramine, diazepam, placebo 1. 2. Outcome 1/3 paretic patients had marked progression from non-ambulation to limited independent ambulation Spasticity -/+/0: Visual analogue scale (VAS) 6/1/2, Daily spasms 2/0/2, Daily clonus 4/0/1, Ankle Tendon Stretch Reflex (TSR) 5/2/2, Knee TSR 5/0/2, Evoked clonus 3/1/5. Significant decrease in Ashworth spasticity score at all doses levels Significant increase in the velocity at maximal overground speed due to an increase in the stride amplitude, without any significant decrease in the cycle duration. Significant Ashworth reduction, Pendulum first swing amplitude increase, and Vibratory Inhibition Index (VII) as a result of clonidine VII significantly reduced by Clonidine only.

Stewart et al. 1991; Initial N=12; Final N=9

1. 2.

Remy-Neris et al. 1999; Initial N=11; Final N=11

1.

Nance 1994; Initial N=25; Final N=25 Nance et al. 1989; Initial N=6; Final N=6

1.

21-38

Author Year; Total Sample Size Weingarden & Belen 1992; Initial N=17; Final N=17 Donovan et al. 1988; Initial N=55; Final N=55

Methods Treatment: Transdermal clonidine 1.

Outcome 15/17 had clinically significant relief and 12/15 continued use while 10/15 were able to decrease or discontinue their current antispasticity medications. 31/55 responded to Clonidine. Quadriplegics responded to the medication significantly better than the paraplegics but no difference between complete and incomplete Flexion Reflex Response (FRR) amplitude change significant between 30 and 90 ug IT Clonidine only. FRR stimulation threshold significantly increased for all Clonidine doses. Ashworth score decreased 4-6 hrs after a single 60ug dose. Quadriceps stretch reflex latency increased and amplitude decreased significantly Moderate to excellent improvement in spastic hypertonia and/or flexor spasms.

Treatment: Oral clonidine - 0.05mg bid and increased to 0.4mg bid if tolerated by the subject. Treatment: Intrathecal clonidine injection (30/60/90 ug)

1. 2.

1. 2.

Remy-Neris et al. 2001; N=15

3. 4. Treatment: 0.1-0.3 mg/wk Transdermal Clonidine patch (Constant/continuous systemic delivery). 1.

Yablon & Sipski 1993; Initial N=3; Final N=3

There are 2 placebo controlled trials (Stewart et al. 1991; N=12 and Remy-Neris et al. 1999; N=11) providing evidence for Clonidines effectiveness in reducing SCI spasticity. Stewart et al used oral Clonidine in a randomized trial but the spasticity outcome measures are not validated or well known clinically compared to the Ashworth measure used by Remy-Neris et als, intrathecal clonidine study. However the latter study was not randomized and therefore lacked somewhat in scientific rigor. Both studies had small sample sizes. Another non-randomized, placebo controlled study with a small sample size (Nance et al. 1989; N=6) concurred with Clonidines antispasmodic properties through the use of a non-validated Vibratory Inhibition Index (VII) which is not commonly known clinically. A subsequent pre-test post-test study by the same author (Nance 1994; N=25) using the Ashworth and Pendulum measures as well as the VII compared Clonidine with Cyproheptadine and Baclofen for their anti-spastic properties. Although all three treatments were significantly beneficial in reducing spasticity as measured by the Ashworth and Pendulum tests, Clonidine was significantly inferior to Baclofen and Cyproheptadine as measured by the VII. The remaining reports of antispastic effects of clonidine in various formulations (oral, transdermal and additional intrathecal studies) are derived from case series studies (Donovan et al. 1988, N=55; Weingarden & Belen 1992, N=17; Yablon & Sipski 1993, N=3; Remy-Neris et al. 2001, N=15). All presented results in favour of using Clonidine as an anti-spasmodic but all outcome measures chosen for each study were either not specified or unique to the study. 4-Aminopyridine Beginning in 1993, anecdotal reports emerged on the antispasmodic effects of a new class of K+ channel blocking drug, 4-aminopyridine (4-AP, immediate release oral and IV ; Hansebout et al. 1993; Hayes et al. 1994; Potter et al. 1998a; Segal et al. 1999). Table 21.15 Summary of 4-Aminopyridine Studies for Reducing Spasticity
Author Year; Total Sample Size Donovan et al. 2000; Initial N=12; Final N=12 Methods Treatment: Drug or placebo was administered for 2 hours through an 1. Outcome The intravenous route may not be the best way to administer this drug as no

21-39

Author Year; Total Sample Size

Methods indwelling venous catheter attached to an infusion pump (4-AP reached doses of 30 to 80 ng/ml at the end of a 2 h) Treatment: Fampridine-SR (12.5 mg to 17.5 mg bid) or placebo over a period of 2 weeks with a washout period between treatments. Treatment: 10mg id to tid 4AP capsules over 6 days with physical and neurophysiological examination pre and post administration up to 24 hrs . Tolerated regimen continued for 4 months with prn intermittent assessments. Treatment: 24-25mg 4-AP IV (fasting). Monitoring for effect pre to 2 hours post and at 24 hours post drug administration

Outcome short term benefits were observed. 1. Significant benefit of Fampridine-SR over placebo as measured by the Ashworth score. Improved spasticity (UE N=1, LE N=2), Ankle hypertonicity reduced (N=1).

Potter et al. 1998; Initial N=29; Final N=26

1. 2.

Potter et al. 1998; Initial N=3; Final N=3

Hayes et al. 1994; Initial N=6; Final N=6

1.

N=2 for reduced spasticity.

Two randomized, placebo-controlled trials for 4-Aminopyridine both employed the Ashworth measure of spasticity but neither study was specifically designed to study spasticity (Donovan et al. 2000 N=12; Potter et al. 1998 N=29). Only the latter study, using a sustained-release formulation of 4-AP (Fampridine-SR) reported a statistically significant reduction in spasticity as measured by the Ashworth (p<0.05, McNemars 2-tailed test). Intravenous administration was employed by Donovan et al and the study concluded that this mode of administration is not optimal based on the observation of no short term benefits. The remaining 2 case series studies, also not specifically designed to study spasticity alone, present only minimal evidence for the anti-spasmodic effects of 4-AP. Recent phase 3 clinical trial results of Fampridine-SR effects on spasticity in chronic SCI are yet to be published. Cyproheptadine Cyproheptadine is a non-selective serotonergic antagonist and antihistamine that has been reported to improve spasticity in SCI. Table 21.16 Summary of Cyproheptadine Studies for Reducing Spasticity
Author Year; Total Sample Size Methods Treatment: Cyproheptadine (1 week each at 2mg, 4mg and 8mg id) or placebo in random order dose-titrated over 3 weeks with 1 week washout between treatment arms. Open-label long-term study (N=4): Cyproheptadine (optimized dosing) of at least 6 months. Treatment: Oral Cyproheptadine - 6 mg to 24 mg per day over 4 to 24 months, including a placebo substitution period. Treatment: 1 wk up-titration, 1 wk target dose (0.05mg bid clonidine; 4mg qid cyproheptadine; 20 mg qid baclofen) , 1 wk down-titration Outcome Improvements in favour of Cyproheptadine vs. placebo (descriptive statistics only; no p-values provided): 1. Spasticity: all subjects reported a decrease in the severity and frequency of involuntary movements. Log of clonus and spasms showed decreased spontaneous spasms in 5/6. Ankle clonus decreased in 6/6. 1. Ashworth significantly reduced, significantly increased first swing amplitude, and increased Vibratory Inhibition Index (VII) in all three drug conditions with baclofen showing the most improvement 2. Cyproheptadine and Baclofen produced a greater reduction in the VII than Clonidine. 1.

Wainberg et al. 1990; Initial N=8; Final N=7

Barbeau et al. 1982; Initial N=6; Final N=6

Nance 1994; Initial N=25; Final N=25

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Cyproheptadine performed favourably versus placebo in improving spasticity and walking in a small sample of chronic SCI patients (Wainberg et al. 1990, N=8). Although the study design was randomized and placebo controlled, reductions in spasticity were only subjectively measured as subject reports of severity and frequency of involuntary movements. Similarly, Barbeau et al. (1982) in a case series study involving 6 subjects confirmed this antispasmodic effect of Cyproheptadine using subjective patient logs of clonus and spasms. Norman et al.* 1998 (N=12) corroborated the reduction in ankle clonus in a study of various drugs and gait in SCI. Validated outcome measures (i.e. Ashworth and Pendulum tests) were used by Nance 1994 (N=25) in a pre-test post-test study that provided statistically significant evidence supporting the use of Cyproheptadine in treating SCI spasticity. Gabapentin Limited level 1 evidence supports the use of Gabapentin for spasticity treatment. Gruenthal et al. 1997 (N=28) conducted a randomized, placebo-controlled trial and were able to reveal modest improvements as measured by Ashworth and Likert Scale scores (p=0.044 and 0.013, respectively). Despite the robust study design, no confidence intervals were reported and the sample size was relatively small. Other potential anti-spasmodics Other potential anti-spasmodics used in SCI include L-threonine, Diazepam, Dantrolene and Cannabis. A randomized, controlled study of L-threonine (Lee & Patterson 1993; N=33) only showed minimal effects on spasticity. Nance et al. 1989 in a study of Clonidine for SCI spasticity showed that effects of diazepam and placebo were not different from pre-treatment values. However, an earlier cross-over study (Corbett et al.* 1972, N=19) showed that Valium was more effective than Amytal and Placebo in reducing spasticity (p<0.02-0.05). No current studies (*1980 to date) were found that investigated the specific use of Dantrolene in the treatment of SCI spasticity. Cannabis has been rumoured to be effective in treating SCI spasticity and although scientifically robust studies investigating its use for this condition do not yet exist, a questionnaire study (no intervention) involving a sample of 43 subjects showed no consistent correlation between cannabis use and the Spasticity Change Index (i.e. spasticity level of drug state subtracted from spasticity level of non-drug state; Malec et al* 1982, N=43). Conclusions Although Level 1 evidence supports the use of tizanidine for the treatment of SCI spasticity, it is noteworthy to mention that 34% of subjects who received study treatment and discontinued prematurely due to adverse events, lack of efficacy and other reasons not specified, were not included in the study analysis. Level 1 evidence exists in favour of using Clonidine as a SCI anti-spasmodic. However, outcome measures chosen for each study included in this review were either not specified or unique to the study (i.e. invalidated). Currently there is conflicting evidence for the anti-spasmodic effects of 4-AP. Recent Phase 3 clinical trial results of Fampridine-SR effects on spasticity in chronic SCI are yet to be published.

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Limited Level 1 evidence (small sample size, N=7; and invalidated, subjective outcome measures) supports the use of Cyproheptadine in the treatment of spasticity in chronic SCI patients (Wainberg et al. 1990, N=8). However, level 4 evidence resulting from validated outcome measures collected from a larger sample (N=25) did corroborate the finding that Cyproheptadine is effective in treating chronic SCI patients with spasticity. A single RCT provided evidence towards modest improvements in spasticity with the use of Gabapentin (Gruenthal et al. 1997; N=28). Despite the robust study design and validated outcome measures, no confidence intervals were reported and the sample size was relatively small. Despite current use, very little evidence supports the use of other potential SCI antispasmodics such as Diazepam, Dantrolene and Cannabis. An RCT investigating Lthreonine for the treatment of SCI spasticity (Lee & Patterson 1973) showed only minimal effects on spasticity. Tizanidine, Clonidine, Cyproheptadine and Gabapentin may be useful in treating SCI spasticity. The usefulness of Diazepam, Dantrolene, 4-Aminopyridine, L-Threonine and Cannabis in the treatment of SCI spasticity requires confirmation through additional well-designed studies.

21.4.4 Neurolysis with Botulinum Neurotoxin Botulinum neurotoxins represent a variety of distinct immunologic serotypes (types A-G) synthesized by Clostridium botulinum (Yablon 2001). In particular, Type A (BTX-A) and Type B botulinum neurotoxins have been employed clinically to relieve focal muscle spasticity in a variety of etiologies, most notably cerebral palsy, multiple sclerosis, stroke and acquired brain injury. Across these various etiologies, several RCTs have been conducted which provide Type 1 level evidence for the efficacy of botulinum neurotoxin in ameliorating focal muscle spasticity (Snow et al. 1990; Simpson et al. 1996; Corry et al. 1997; Simpson 1997; Richardson et al. 2000; Smith et al. 2000; Hyman et al 2000; Bakheit et al. 2001; Wasiak et al. 2004). In addition, there are several treatment guidelines and other information available for assisting the clinician with dosing and medication administration decisions (Brin 1997a; Brin 1997b; Gormley Jr. et al. 1997; O'Brien 1997; Ward 2002; Francisco 2004). Clinicians and researchers have advocated the use of botulinum neurotoxin for relieving focal muscle spasticity in individuals with SCI (Brin 1997b; Kirshblum 1999; Fried & Fried 2003) and the Spasticity Study Group purport that the decision to use botulinum neurotoxin is independent of the etiology of the spasticity, depending rather on the presence of an increase in muscle tone that interferes with function (Brin 1997b). The advantages for its use have been outlined including the ability to achieve a focal response, a relative ease of administration and avoiding the sedation common with other pharmacological alternatives (Fried & Fried 2003). In spite of this information and the recognition that spasticity comprises a significant functional limitation for many people with SCI, (Maynard et al. 1990; Skold et al. 1996; 1999) there are relatively few studies directed specifically at this patient population. In fact, no studies have been identified which meet the criteria established for the present review (i.e., English language articles with

21-42

N=3 and at least half of the subjects having a SCI). 2 In lieu of these, we present the results of three studies which examined the effect of BTX-A on spasticity secondary to SCI but had either insufficient n (i.e, individual case studies) (Richardson et al. 1997; Al-Khodairy et al. 1998) or a subject pool comprised mainly of people having a stroke or acquired brain injury with only a small subset of subjects with spasticity secondary to SCI (Richardson et al. 2000). It should be noted that botulinum neurotoxin has also been employed successfully to overcome bladder detrusor-sphincter dyssynergia in people with SCI (Dykstra & Sidi 1990; Schurch et al. 1996; deSeze et al. 2002) and this will be addressed separately in the chapter dealing with bladder function. Table 21.17 Botulinum Neurotoxin for Reducing Spasticity
Author Year; Country Score Research Design Total Sample Size Methods Population: Stroke (23), Head Injury (12), SCI (6) and others with focal spasticity, details of SCI unknown Intervention: EMG guided injection of BTX-A with doses and specific muscles injected based on clinical judgment. Richardson et al. 2004; England PEDro=9 RCT N=52 (6 with SCI) Outcome Measures: modified Ashworth); passive ROM; Subjective rating of Problem Severity, 9-hole peg test (upper limb problems only), timed 10 m walk test (lower limb problems only), Goal Attainment Scale , Rivermead Motor Assessment Scale @ 3, 6, 9 & 12 weeks 2. 1. Outcome Spasticity was significantly reduced for active Tx vs placebo (as shown by modified Ashworth aggregate scores) (p<.02). The main reduction for both Tx and placebo groups occurred between baseline and week 3 with little further improvement thereafter. Tx group had more marked reduction than placebo group. Range of Motion was significantly improved for both groups but significantly more for Tx vs placebo group (p<.03). As with modified Ashworth most marked changes were between baselines - 3 weeks. In general, the various functional measures showed no systematic significant differences other than Subjective Rating of Problem Severity with aggregate outcome scores significantly better for active Tx vs placebo (p<.025). Spasticity was reduced (most Ashworth scores went from 3 to 1 finger flexors to 2 for all time periods after baseline) and range of motion was increased (70 to 90). These measures were maintained over testing period to 12 weeks. Grip strength was reduced initially but recovered close to baseline by 6 weeks. Jebsen hand function deteriorated on most tasks initially, then recovered on most but remained less agile at turning cards over and stacking draughts - yet improved on picking up objects.

3.

Population: 23 year old male, incomplete C5/6, 18 months post-injury Intervention: EMG guided injection of BTX-A (210 units total) (in various muscles of the hand) + wrist/thumb splint + hand exercise. Outcome Measures: Ashworth Scale, grip strength (Jamar dynamometer), passive ROM, Jebsen Hand Function Test, Rivermead Motor Assessment Scale @ 3, 6, 9 & 12 weeks

4. 1.

Richardson et al. 1997; England Downs & Black score=10 Case Study N=1

2. 3.

3 non-English language articles have been identified which examined the effects of botulinum neurotoxin on muscle spasticity in SCI (Oechsner, 2002; Keren et al., 2000; Takenaga et al., 1995).

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Author Year; Country Score Research Design Total Sample Size

Methods Population: 50 year old male, T12, ASIA A, 22 years post-injury 1.

Outcome Spasticity was reduced in that Ashworth scores went from 2-3 to 1+ and the Spasm Frequency Score went from 4 to 2. Pain Visual Analog Scale Scores went from 8 to 1. The subject also reported less difficulty with ADLs and better sitting tolerance. Unlike preceding treatments, the final treatment (8th over 2 year period) had no beneficial clinical effect with no explanation for what may have caused this phenomenon.

Al-Khodairy et al. 1998; Switzerland Downs & Black score=7 Case Study N=1

Intervention: 8 successive treatments of EMG-guided BTX-A (first in gastrocnemius, then other muscles as well) Outcome Measures: Modified Ashworth Scale, Spasm Frequency Score, Pain Visual Analogue Scale

2. 3. 4.

Discussion Individual case studies employing botulinum neurotoxin in individuals with SCI have been conducted by Richardson et al. (1997) and Al-Khodairy et al. (1998). Each of these reports employed EMG-guided BTX-A injections. Richardson et al. (1997) injected several wrist and hand muscles in a single chronic SCI subject. Spasticity was reduced as assessed by the Ashworth Scale and range of motion was increased with these measures maintained over the testing period to 12 weeks. Al-Khodairy et al. (1998) conducted a 2-year follow-up study of a chronic incomplete paraplegic male. Spasticity was reduced as determined by Ashworth Scale scores and the Spasm Frequency Score. In addition, pain due to spasticity was also markedly reduced and the subject reported less difficulty with activities of daily living, better sitting tolerance and fewer sleep disturbances. The final treatment delivered in this series (i.e., 8th over 2 year period) was without effect leaving the possibility of drug tolerance but this was not confirmed. Richardson et al. (2000) investigated the effects of BTX-A on impairment and focal disability in a group of 52 subjects with various etiologies using a prospective, randomized, double-blind, placebo-controlled, parallel group design. Subjects with stroke (23) and acquired brain injury (12) made up the majority of the sample with only 6 SCI subjects participating in addition to other individuals with spasticity due to other etiologies such as tumour (5), cerebral palsy (3) and anoxic brain damage (3). Subjects were not matched relative to their etiologies; rather they were randomized into separate treatment vs placebo groups depending on whether their identified problem with focal spasticity was in the upper vs the lower limb. BTX-A was injected via EMG-guided techniques in 1 or more muscles based on clinical judgment. Modified Ashworth scores demonstrated reduced spasticity across the appropriate joints when tested at 3, 6, 9 and 12 months with both active treatment and placebo although there was a significantly greater reduction with BTX-A (p<.02). Despite the randomized controlled trial utilizing a validated spasticity outcome measure, the conclusions must be cautiously interpreted with respect to BTX-A use in SCI, given that only 6/52 subjects had spasticity of confirmed spinal origin. Conclusions Regarding the Effect of Botulinum Neurotoxin Based on 2 case studies, there is Level 4 evidence that botulinum neurotoxin improves focal muscle spasticity secondary to SCI. This is cautiously supported by an RCT where only 6/52 subjects had spasticity of confirmed spinal origin.

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The effect of long-term administration of botulinum neurotoxin is based on the results of a single case study involving 8 treatments over 2 years (limited Level 4 evidence). Tolerance to BTX-A may occur with prolonged administration and requires further study. Botulinum neurotoxin appears to improve focal muscle spasticity in people with SCI.

21.5 Spasticity Outcome Measures The studies reviewed in this section involve a variety of outcome measures that have been summarized into 4 categories: 1) Known Clinical Measures; 2) Other Measures; 3) Electrophysiological Measures and 4) Quality of Life Measures. Among the known measures, some are validated and only a subset of those is used frequently by clinicians. The abundance of outcome measures in the other category are not well understood by the majority of clinicians and increases the difficulties encountered when comparing studies and treatments. Very few studies included measures addressing quality of life despite the need to ensure that treatments are well tolerated as well as functionally and practically effective for patients. Table 21.18 Summary of Outcome Measures used in Spasticity Intervention Studies
Known Clinical Measures 1. 2. Ambulation Index American Spinal Injury Assessment (ASIA; motor and sensory index) Ashworth (Original and Modified) Barthel Index Clonus (count or duration) Deep Tendon Reflexes (DTR) Expanded disability status scale (EDSS) Functional Independence Measure (FIM) Goal Attainment Scale Grip strength (Jamar dynamometer) Global Impression (Patient and/or Clinician) Incapacity Status Scale* Klein-Bell ADL scale Jebsen Hand Function Test Manual Muscle Testing Nine-hole peg test (upper limb problems only) Passive joint ROM Patient Evaluation and 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Other Measures Adverse Event monitoring Clinical interview questionnaire Clinical Rating Score (CRS) Clinically significant relief of spasticity Continuation of study drug after trial Cost effectiveness analysis. Cystomanometry Evaluation of functional abilities Decrease in hypertonicity Discontinuation of other antispasticity medications Evaluation of personal independence Five point scale (interference of spasticity on selected self care activities and weekly rate of resistance to movement) Functional disability score (FDS) Gait spasticity and transfer activity Electrophysiological Measures 1. Electrophysiologic testing 2. EMG/velocity ratio for any given speed stretch reflex response 3. Flexion reflex measurement Peak isometric quad torque in response to surface electrical stimulation 4. Gait analysis 5. H-Reflex and H/M ratio (latency and amplitude) 6. Joint angular displacement 7. Motor Evoked Potentials (MEP) 8. Polysynaptic reflex measurement 9. Quantitative assessment of ankle hypertonicity 10. Viscous and elastic stiffness to sinusoidal ankle perturbation of 5 at 3 to 12 Hz. Quality of Life Measures 1. 2. 3. Hopkins symptom check list (HSCL) Sickness Impact Profile (SIP) Global Impression (Patient and/or Clinician)

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.

13. 14.

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Known Clinical Measures Conference System (PECS) Pendulum test Plantar stimulation response Present Pain Intensity Rivermead Mobility Index (RMI) Seven point terribledelighted scale Six point Likert scale (spasticity) Spasm Frequency Scale (SFS) Spasm Severity Scale (SSS) Standard neurological examination Timed 10 m walk test (lower limb problems only) Visual Analogue Scale (VAS: Spasticity, Pain, Satisfaction)

Other Measures 15. Impression of pain 16. Neurological reflex scale 17. Outcome measure not specified. 18. Painful Spasm Scale 19. Patient Caregiver subjective responses 20. Patient/Clinician Global measure (4 point scale) 21. Patient Daily Diary or Log (spasticity, clonus, nocturnal awakenings related to spasms) 22. Subjective ratings (problem severity, spasticity assessment, pain) 23. Telephone questionnaire regarding decrease in symptoms 24. Use of limbs and transfer activity (weekly) 25. Vibratory Inhibition Index (VII)

Electrophysiological Measures

Quality of Life Measures

18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28.

The gold-standard for clinical testing is the double-blind, randomized, placebo-controlled study design, particularly for the measurement of short term treatment effects. However, the results of a well-designed trial are more easily interpreted if the outcome measures used follow outcome measure standards as outlined by Pierson 1997. In summary, effective outcome measures should be selected based on 1) understandability for administration/scoring/interpretation and validity/reliability; 2) relevancy to the clinical situation and population measured; 4) having a reasonable risk-benefit ratio; 5) requirement for strict adherence to test conditions and procedures; and 6) practicality in terms of personnel, time, equipment, cost, space and impact on the subject. No single outcome measure can capture the multi-dimensional nature of spasticity. Therefore, it is important, not only to choose an effective outcome measure but also to choose effective outcome measures to monitor the range of medical outcomes as suggested by Goldberg (1991): 1) technical outcome (i.e. reduction of spasm frequency); 2) functional outcome; 3) patient satisfaction and; 4) cost effectiveness. Some of the measures that have been tested for various aspects of spasticity and for validity and/or reliability include the Ashworth (Ashworth 1964) and Modified Ashworth (Bohannon & Smith 1987; Haas et al 1996) spasticity scale, Spasm Frequency scale (Penn 1988; Priebe 1996) and the Pendulum test (Nance 1994). Please refer to the chapter on outcome measures for a discussion of these measures. Well designed studies should include effective outcome measures that meet minimum standards and that encompass the range of medical outcomes relevant to the treatment and the patients.

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21.6 Summary There is level 4 evidence that rhythmic, passive movements may result in a short-term reduction in spasticity. There is level 4 evidence that externally applied forces or passive muscle stretch as are applied in assisted standing programs may result in short-term reduction in spasticity. This is supported by individual case studies and anecdotal reports from survey-based research. There is level 2 evidence that hydrotherapy is effective in producing a short-term reduction in spasticity. There is level 4 evidence that a program of FES-assisted walking acts to reduce ankle spasticity in the short-term (i.e., 24 hours). There is no evidence that describes the length and time course of the treatment effect related to spasticity for hydrotherapy or FES-assisted walking. There is level 2 evidence that a single bout of surface muscle stimulation reduces local muscle spasticity with agonist stimulation more effective than stimulation to the antagonist. There is conflicting evidence for how long the effects of a single bout of electrical stimulation on muscle spasticity persist, although they appear to be relatively short lasting (i.e., 6 hours). There is no evidence that a long-term program of muscle stimulation has an effect on reducing muscle spasticity and may even increase local muscle spasticity. There is level 1 evidence that an ongoing program of TENS acts to reduce spasticity as demonstrated by clinical and electrophysiological measures. There is level 1 evidence that reductions in spasticity with ongoing programs of TENS may persist for up to 24 hours. There is level 1 evidence that a single bout of TENS acts to reduce spasticity but to a lesser degree than that seen with ongoing programs of TENS. This evidence is muted somewhat by conflicting results with a null result (level 2) compared with 2 positive results (level 4). There is level 4 evidence that several sessions of rectal probe stimulation reduces lower limb muscle spasticity for up to 8 hours. There is level 4 evidence that short periods of massage (e.g., 3 minutes) of the triceps surae results in reduced H-reflexes with the effect lasting no longer than a few minutes. There is level 1 evidence that a single bout of penile vibration acts to reduce spasticity lasting for at least 3 hours and possibly up to 6 hours. There is level 4 evidence that hippotherapy may reduce lower limb muscle spasticity immediately following an individual session.

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There is level 4 evidence that cryotherapy may reduce muscle spasticity for up to 1 hour after removal of the cold stimulus. There is level 2 evidence that helium-neon irradiation of sensory nerves may suppress ankle clonus for up to 60 minutes following 40 seconds of stimulation. There is Level 4 evidence that ongoing spinal cord stimulation may provide some relief from otherwise intractable spasticity for some time (i.e., months to years). There is level 4 evidence that the beneficial effects of spinal cord stimulation will subside for most initial users. This, combined with the potential for equipment failure and adverse events, suggests that spinal cord stimulation is not a cost-effective approach for managing spasticity. There is Level 2 evidence that dorsal longitudinal T-myelotomy may result in reduced spasticity in those individuals initially refractory to more conservative approaches. These reductions may not always be maintained over the course of several years. There is Level 2 evidence that Pourpres technique for dorsal longitudinal T-myelotomy is more effective in maintaining reduced levels of spasticity than the Bischof II technique. There is Level 1 evidence that oral baclofen improves muscle spasticity secondary to SCI. This conclusion is based on the results from 4 positive small-scale RCTs although is muted somewhat by a negative finding from a low n (5) single-subject design RCT and an overall lack of homogeneity in outcome measures and study participants. Additional uncontrolled cohort and case series studies also provide support for the use of oral baclofen in reducing spasticity. There is Level 1 evidence that bolus or test dose intrathecal baclofen decreases spasticity. There is Level 4 evidence that the use of long-term intrathecal baclofen decreases spasticity. There is Level 4 evidence that intrathecal baclofen may improve functional outcomes. There is Level 4 evidence that complication rates with the long-term use of intrathecal baclofen are relatively low. There is Level 4 evidence that intrathecal baclofen is a cost-effective intervention. Although Level 1 evidence supports the use of tizanidine for the treatment of SCI spasticity, it is noteworthy to mention that 34% of subjects who received study treatment and discontinued prematurely due to adverse events, lack of efficacy and other reasons not specified, were not included in the study analysis. Level 1 evidence exists in favour of using Clonidine as a SCI anti-spasmodic. However, outcome measures chosen for each study included in this review were either not specified or unique to the study (i.e. invalidated). Currently there is conflicting evidence for the anti-spasmodic effects of 4-AP. Recent Phase 3 clinical trial results of Fampridine-SR effects on spasticity in chronic SCI are yet to be published.

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Limited Level 1 evidence (small sample size, N=7; and invalidated, subjective outcome measures) supports the use of Cyproheptadine in the treatment of spasticity in chronic SCI patients (Wainberg et al. 1990, N=8). However, level 4 evidence resulting from validated outcome measures collected from a larger sample (N=25) did corroborate the finding that Cyproheptadine is effective in treating chronic SCI patients with spasticity. A single RCT provided evidence towards modest improvements in spasticity with the use of Gabapentin (Gruenthal et al. 1997; N=28). Despite the robust study design and validated outcome measures, no confidence intervals were reported and the sample size was relatively small. Despite current use, very little evidence supports the use of other potential SCI antispasmodics such as Diazepam, Dantrolene and Cannabis. An RCT investigating Lthreonine for the treatment of SCI spasticity (Lee & Patterson, 1973) showed only minimal effects on spasticity. Based on 2 case studies, there is Level 4 evidence that botulinum neurotoxin improves focal muscle spasticity secondary to SCI. This is cautiously supported by an RCT where only 6/52 subjects had spasticity of confirmed spinal origin. The effect of long-term administration of botulinum neurotoxin is based on the results of a single case study involving 8 treatments over 2 years (limited Level 4 evidence). Tolerance to BTX-A may occur with prolonged administration and requires further study.

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Norman KE, Pepin A, Barbeau H. Effects of drugs on walking after spinal cord injury. Spinal Cord. 1998;36:699-715. O'Brien CF. Injection techniques for botulinum toxin using electromyography and electrical stimulation. Muscle Nerve Suppl 1997; 6:S176-S180. Ochs G, Struppler A, Meyerson BA, Linderoth B, Gybels J, Gardner BP, Teddy P, Jamous A, Weinmann P. Intrathecal baclofen for long-term treatment of spasticity: a multi-centre study. J Neurol Neurosurg Psychiatry 1989;52:933-939. Odeen I, Knutsson E. Evaluation of the effects of muscle stretch and weight load in patients with spastic paraplegia. Scand J Rehabil Med 1981;13:117-121. Oechsner M. Treatment of hip adductor spasticity with botulinum toxin type B. Nervenarzt 2002; 73:1179-1182. Ordia JI, Fischer E, Adamski E, Spatz EL. Chronic intrathecal delivery of baclofen by a programmable pump for the treatment of severe pasticity. J Neurosurg 1996;85:452-457. Ozer K, Chesher SP, Scheker LR. Neuromuscular electrical stimulation and dynamic bracing for the management of upper-extremity spasticity in children with cerebral palsy. Dev Med Child Neurol 2006;48:559-563. Pandyan AD, Gregoric M, Barnes MP, Wood D, Van Wijck F, Burridge J, Hermens H & GR Johnson. Spasticity: Clinical perceptions, neurological realities and meaningful measurement. Disability and Rehabilitation 2005;27: 2-6. Parke B, Penn RD, Savoy SM, Corcos D. Functional outcome after delivery of intrathecal baclofen. Arch Phys Med Rehabil 1989;70:30-32. Penn RD. Intrathecal baclofen for severe spasticity. Ann N Y Acad Sci 1988; 531:157-166. Penn RD. Intrathecal baclofen for spasticity of spinal origin: seven years of experience. J Neurosurg 1992;77:236-240. Penn RD, Savoy SM, Corcos D, Latash M, Gottlieb G, Parke B, Kroin JS. Intrathecal baclofen for severe spinal spasticity. N Engl J Med 1989;320:1517-1521. Pierson S. Spasticity: Etiology, Evaluation, management and the Role of Botulinum toxin Type A - Outcome Measures in Spasticity Management. Muscle Nerve 1997;20:536-560. Pinter MM, Gerstenbrand F, Dimitrijevic MR. Epidural electrical stimulation of posterior structures of the human lumbosacral cord: 3. Control Of spasticity. Spinal Cord 2000; 38:524-531. Plassat R, Perrouin Verbe B, Menei P, Menegalli D, Mathe JF, Richard I. Treatment of spasticity with intrathecal Baclofen administration: long-term follow-up, review of 40 patients. Spinal Cord 2004;42:686-693. Potter PJ, Hayes KC, Hsieh JT, Delaney GA, Segal JL. Sustained improvements in neurological function in spinal cord injured patients treated with oral 4-aminopyridine: three cases. Spinal Cord 1998;36:147-155. Potter PJ, Hayes KC, Segal JL, Hsieh JT, Brunnemann SR, Delaney GA, Tierney DS, Mason D. Randomized double-blind crossover trial of fampridine-SR (sustained release 4aminopyridine) in patients with incomplete spinal cord injury. J Neurotrauma 1998;15:837849. Price R, Lehmann JF, Boswell-Bessette S, Burleigh A, deLateur BJ. Influence of cryotherapy on spasticity at the human ankle. Arch Phys Med Rehabil 1993;74:300-304. Priebe MM, Sherwood AM, Thornby JI, Kharas NF, Markowski J. Clinical assessment of spasticity in spinal cord injury: a multidimensional problem. Arch Phys Med Rehabil 1996;77:713-716. Putty TK, Shapiro SA. Efficacy of dorsal longitudinal myelotomy in treating spinal spasticity: a review of 20 cases. J Neurosurg 1991;75:397-401. Remy-Neris O, Barbeau H, Daniel O, Boiteau F, Bussel B. Effects of ntrathecal clonidine injection on spinal reflexes and human locomotion in incomplete paraplegic subjects. Exp Brain Res 1999;129:433-440. 21-54

Remy-Neris O, Denys P, Bussel B. Intrathecal clonidine for controlling spastic hypertonia. Phys Med Rehabil Clin N Am 2001;12:939-951, ix. Richardson D, Edwards S, Sheean GL, Greenwood RJ, Thompson AJ. The effect of botulinum toxin on hand function after incomplete spinal cord injury at the level of C5/6: a case report. Clin Rehabil 1997;11:288-292. Richardson D, Sheean G, Werring D, Desai M, Edwards S, Greenwood R, Thompson A. Evaluating the role of botulinum toxin in the management of focal hypertonia in adults. J Neurol Neurosurg Psychiatry 2000;69:499-506. Richardson RR, McLone DG. Percutaneous epidural neurostimulation for paraplegic spasticity. Surg Neurol 1978;9:153-155. Robinson CJ, Kett NA, Bolam JM. Spasticity in spinal cord injured patients: 1. Short-term effects of surface electrical stimulation. Arch Phys Med Rehabil 1988;69:598-604. Robinson CJ, Kett NA, Bolam JM. Spasticity in spinal cord injured patients: 2. Initial measures and long-term effects of surface electrical stimulation. Arch Phys Med Rehabil 1988; 69:862868. Rosche J. Treatment of spasticity. Spinal Cord 2002; 40:261-262. Rosche J, Paulus C, Maisch U, Kaspar A, Mauch E, Kornhuber HH. The effects of therapy on spasticity utilizing a motorized exercise-cycle. Spinal Cord 1997;35:176-178. Roussan M, Terrence C, Fromm G. Baclofen versus diazepam for the treatment of spasticity and long-term follow-up of baclofen therapy. Pharmatherapeutica 1985;4:278-284. Schurch B, Hauri D, Rodic B, Curt A, Meyer M, Rossier AB. Botulinum-A toxin as a treatment of detrusor-sphincter dyssynergia: a prospective study in 24 spinal cord injury patients. J Urol 1996;155:1023-1029. Segal JL, Pathak MS. Optimal drug therapy and therapeutic drug monitoring after spinal cord injury: a population-specific approach. Am J Ther 2001;8:451-463. Segal JL, Pathak MS, Hernandez JP, Himber PL, Brunnemann SR, Charter RS. Safety and efficacy of 4-aminopyridine in humans with spinal cord injury: a long-term, controlled trial. Pharmacotherapy. 1999;19:713-723. Seib TP, Price R, Reyes MR, Lehmann JF. The quantitative measurement of spasticity: effect of cutaneous electrical stimulation. Arch Phys Med Rehabil 1994;75:746-750. Shahani BT, Young RR. Management of flexor spasms with Lioresal. Arch Phys Med Rehabil 1974;55:465-467. Shields RK, Dudley-Javoroski S. Monitoring standing wheelchair use after spinal cord injury: a case report. Disabil Rehabil 2005;27:142-146. Simpson DM. Clinical trials of botulinum toxin in the treatment of spasticity. Muscle Nerve Suppl 1997;6:S169-S175. Simpson DM, Alexander DN, O'Brien CF, Tagliati M, Aswad AS, Leon JM, Gibson J, Mordaunt JM, Monaghan EP. Botulinum toxin type A in the treatment of upper extremity spasticity: a randomized, double-blind, placebo-controlled trial. Neurology 1996;46:1306-1310. Skold C. Spasticity in spinal cord injury: self- and clinically rated intrinsic fluctuations and intervention-induced changes. Arch Phys Med Rehabil 2000; 81:144-149. Skld C, Harms-Ringdahl K, Hultling C, Levi R, Seiger A. Simultaneous Ashworth measurements and electromyographic recordings in tetraplegic patients. Arch Phys Med Rehabil 1998;79:959-965. Skold C, Levi R, Seiger A. Spasticity after traumatic spinal cord injury: nature, severity, and location. Arch Phys Med Rehabil 1999;80:1548-1557. Smith SJ, Ellis E, White S, Moore AP. A double-blind placebo-controlled study of botulinum toxin in upper limb spasticity after stroke or head injury. Clin Rehabil 2000;14:5-13. Snow BJ, Tsui JK, Bhatt MH, Varelas M, Hashimoto SA, Calne DB. Treatment of spasticity with botulinum toxin: a double-blind study. Ann Neurol 1990;28:512-515.

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Stempien L, Tsai T. Intrathecal baclofen pump use for spasticity: a clinical survey. Am J Phys Med Rehabil 2000;79:536-541. Stewart JE, Barbeau H, Gauthier S. Modulation of locomotor patterns and spasticity with clonidine in spinal cord injured patients. Can J Neurol Sci. 1991;18:321-332. Takenaga S, Kawahigashi Y, Sonoda Y, Horikiri T, Hirata K, Arimura K, Osame M. Treatment of spastic paraparesis with botulinum toxin with reference to beneficial effects, disease severity and long-term treatment. Rinsho Shinkeigaku 1995;35:251-255. Tardieu G, Shentoub S, Delarue R. A la recherch dune technique de measure de la spsticite. Revue de Neurologie (Paris) 1954;91:143-144. Taricco M, Pagliacci MC, Telaro E, Adone R. Pharmacological interventions for spasticity following spinal cord injury: results of a Cochrane systematic review. Eura Medicophys 2006;42:5-15. Thoumie P, Le CG, Beillot J, Dassonville J, Chevalier T, Perrouin-Verbe B, Bedoiseau M, Busnel M, Cormerais A, Courtillon A. Restoration of functional gait in paraplegic patients with the RGO-II hybrid orthosis. A multicenter controlled study. II: Physiological evaluation. Paraplegia 1995;33:654-659. van der Salm A, Veltink PH, Ijzerman MJ, Groothuis-Oudshoorn KC, Nene AV, Hermens HJ. Comparison of electric stimulation methods for reduction of triceps surae spasticity in spinal cord injury. Arch Phys Med Rehabil 2006;87:222-228. Wainberg M, Barbeau H, Gauthier S. The effects of cyproheptadine on locomotion and on spasticity in patients with spinal cord injuries. J Neurol Neurosurg Psychiatry 1990;53:754763. Walker JB. Temporary suppression of clonus in humans by brief photostimulation. Brain Res 1985;340:109-113. Walter JS, Sacks J, Othman R, Rankin AZ, Nemchausky B, Chintam R, Wheeler JS. A database of self-reported secondary medical problems among VA spinal cord injury patients: its role in clinical care and management. J Rehabil Res Dev 2002;39:53-61. Ward AB. A summary of spasticity management--a treatment algorithm. Eur J Neurol 2002;9 Suppl 1:48-52. Wasiak J, Hoare B, Wallen M. Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy. Cochrane Database Syst Rev 2004;4:CD003469. Weingarden SI, Belen JG. Clonidine transdermal system for treatment of spasticity in spinal cord injury. Arch Phys Med Rehabil 1992;73:876-877. Yablon SA. Botulinum neurotoxin intramuscular chemodenervation. Role in the management of spastic hypertonia and related motor disorders. Phys Med Rehabil Clin N Am 2001;12:833874. Yablon SA, Sipski ML. Effect of transdermal clonidine on spinal spasticity. A case series. Am J Phys Med Rehabil 1993;72:154-157. Yamada S, Perot PL, Jr., Ducker TB, Lockard I. Myelotomy for control of mass spasms in paraplegia. J Neurosurg 1976;45:683-691. Young RR. Treatment of spastic paresis (editorial) N Engl J Med 1989;320:1553-1555. Young RR. Spasticity: a review. Neurology 1994;44:S12-S20. Zahavi A, Geertzen JH, Middel B, Staal M, Rietman JS. Long term effect (more than five years) of intrathecal baclofen on impairment, disability, and quality of life in patients with severe spasticity of spinal origin. J Neurol Neurosurg Psychiatry 2004;75:1553-1557.

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CHAPTER TWENTY-TWO
Outcome Measures
William C Miller, PhD, OT Armin Curt, MD, FRCPC Stacy Elliott, MD Jane TC Hsieh, MSc William B Mortenson, MSc, BScOT Vanessa Noonan, MSc, BScPT Luc Noreau, PhD Steve Orenczuk, PhD Bonita Sawatzky, PhD John Steeves, PhD Shannon Wilkinson, BScOT Dalton L Wolfe, PhD

Table of Contents
22.1 Introduction ..................................................................................................................22-1 Introduction References...........................................................................................................22-9 22.2 Body Function / Structure .........................................................................................22-11 22.2.1.1 The CAGE Questionnaire ......................................................................................22-12 22.2.1.2 Center for Epidemiological Studies Depression Scale (CES-D) ............................22-13 22.2.1.3 Patient Health Questionnaire (PHQ-9)...................................................................22-14 22.2.1.4 Zung Self-Rating Depression Scale (SDS) ............................................................22-15 22.2.2.1 Classification System for Chronic Pain in SCI .......................................................22-16 22.2.2.2 Donovan SCI Pain Classification System ..............................................................22-17 22.2.2.3 Tunks Classification Scheme ................................................................................22-18 22.2.2.4 Wheelchair Users Shoulder Pain Index (WUSPI) ..................................................22-19 22.2.3.1 Wingate Anaerobic Testing (WAnT) ......................................................................22-20 22.2.4.1 The American Spinal Injury Association: International Standards for Neurological Classification of Spinal Cord Injury .......................................................................22-21 22.2.4.2 Ashworth and Modified Ashworth ..........................................................................22-22 22.2.4.3 Penn Spasm Frequency Scale (PSFS)..................................................................22-23 22.2.4.4 Surface Electromyography (sEMG) .......................................................................22-24 22.2.5.1 Braden Scale .........................................................................................................22-25 22.2.5.2 Gosnell Measure....................................................................................................22-26 22.2.5.3 Norton Measure .....................................................................................................22-27 22.2.5.4 Spinal Cord Injury Pressure Ulcer Scale (SCIPUS) Measure ................................22-28 22.2.5.5 Spinal Cord Injury Pressure Ulcer Scale - Acute(SCIPUS-A) ................................22-29 22.2.5.6 Waterlow Scale ......................................................................................................22-30 22.2.6.1 Emotional Quality of the Relationship Scale (EQR) ...............................................22-31 22.2.6.2 Knowledge, Comfort, Approach and Attitude towards Sexuality Scale (KCAASS)22-32 22.2.6.3 Sexual Attitude and Information Questionnaire .....................................................22-33 22.2.6.4 Sexual Behaviour Scale (SB).................................................................................22-34 22.2.6.5 Sexual Interest, Activity and Satisfaction (SIAS) / Sexual Activity and Satisfaction (SAS) Scales..........................................................................................................22-35 22.2.6.6 Sexual Interest and Satisfaction Scale (SIS) .........................................................22-36 Body Function / Structure References ...................................................................................22-37 22.3 Activity ..........................................................................................................................22-41 22.3.1.1 4 Functional Tests for Persons who Self-Propel a Manual Wheelchair (4FTPSMW) ......................................................................................................22-42 22.3.1.2 10 Meter Walking Test (10 MWT) ..........................................................................22-43 22.3.1.3 Functional Standing Test (FST) .............................................................................22-44 22.3.1.4 Modified Functional Reach Test (mFRT) ...............................................................22-45 22.3.1.5 Tetraplegia Hand Activity Questionnaire (THAQ) ..................................................22-46 22.3.1.6 Timed Motor Test (TMT) ........................................................................................22-47

Table of Contents (Cont.)

22.3.1.7 Timed Up and Go Test (TUG)................................................................................22-48 22.3.1.8 Walking Index for Spinal Cord Injury (WISCI) and WISCI II...................................22-49 22.3.1.9 Wheelchair Circuit (WC) ........................................................................................22-50 22.3.1.10 Wheelchair Skills Test............................................................................................22-51 22.3.2.1 The Barthel Index...................................................................................................22-52 22.3.2.2 Functional Indepedence Measure (FIM) ................................................................22-53 22.3.2.3 Quadriplegia Index of Function (QIF).....................................................................22-55 22.3.2.4 Self Care Assessment Tool (SCAT) ......................................................................22-56 22.3.2.5 Skin Management Needs Assessment Checklist (SMNAC) ..................................22-57 22.3.2.6 Spinal Cord Injury Lifestyle Scale (SCILS) ............................................................22-58 22.3.2.7 The Spinal Cord Independence Measure (SCIM) ..................................................22-59 Activity References ................................................................................................................22-60 22.4 Participation .................................................................................................................22-64 22.4.1 Assessment of Life Habits Scale (LIFE-H)................................................................22-67 22.4.2 Canadian Occupational Performance Measure (COPM) ..........................................22-68 22.4.3 The Craig Handicap Assessment & Reporting Technique (CHART) ........................22-69 22.4.4 Impact on Participation and Autonomy Questionnaire (IPAQ) ..................................22-70 22.4.5 Participation Survey/Mobility (PARTS/M...................................................................22-71 22.4.6 Perceived Handicap Questionnaire (PHQ) ...............................................................22-72 22.4.7 The Physical Activity Recall Assessment for People with Spinal Cord injury (PARA-SCI)...............................................................................................................22-73 22.4.8 Reintegration to Normal Living (RNL) Index ...............................................................22-74 Participation References........................................................................................................22-75 22.5 Quality of Life ...............................................................................................................22-77 22.5.1 Life Satisfaction Questionnaire (LISAT -9 -11) .........................................................22-79 22.5.2 Quality of Life Index (QLI, Ferrans & Powers) ..........................................................22-80 22.5.3 Quality of Life Profile for Adults with Physical Disabilities (QOLP-PD) .....................22-81 22.5.4 Quality of Well Being.................................................................................................22-82 22.5.5 Qualiveen..................................................................................................................22-83 22.5.6 Satisfaction with Life Scale (SWLS, Deiner Scale) ...................................................22-84 22.5.7 The Short Form 12 (SF-12) and Short Form 36 (SF-36) ..........................................22-85 22.5.8 The Sickness Impact Profile 68 (SIP 68) ..................................................................22-86 22.5.9 WHOQOL (BREF).....................................................................................................22-87 Quality of Life References......................................................................................................22-88

This review has been prepared based on the scientific and professional information available in 2005. The SCIRE information (print, CD or web site www.icord.org/scire) is provided for informational and educational purposes only. If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors, contributors and supporting partners shall not be liable for any damages, claims, liabilities, costs or obligations arising from the use or misuse of this material. Miller WC, Curt A, Elliott S, Hsieh JTC, Mortenson WB, Noonan V, Noreau L, Orenczuk S, Sawatzky B, Steeves J, Wilkinson S, Wolfe DL (2006). Outcome Measures. In: Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Aubut J, Abramson C, Hsieh JTC, Connolly S, editors. Spinal Cord Injury Rehabilitation Evidence. Vancouver, p 22.122.89. www.icord.org/scire

Outcome Measures
22.1 Introduction Good science and good clinical practice both depend on sound information which in turn relies on sound measurement. Measurement, the process of assigning numbers to represent quantities of a trait, attribute or characteristic (Nunnally & Bernstein 1995), enables health care professionals and researchers to describe, predict and evaluate in order to provide benchmarks and summarize change (Law 1987; Wade 2004) related to the condition and care of individuals with spinal cord injury. Despite past evidence that suggested clinicians in the rehabilitation field did not regularly use outcome measures (Cole et al. 1994; Deathe et al. 2002; Skinner et al. 2006), there is mounting evidence that now confirms more clinicians are now reporting their findings using some ordinal or quantifiable outcome tool (Kay et al. 2001; Skinner et al. 2006). Beyond the administrative push to use datasets to track patient outcomes in relation to health care costs, clinical investigators recognize that using an appropriate outcome tool, to determine the validity of a therapeutic intervention, is the key to establishing or changing the models of best practice (Cole et al. 1994). There is a sincere desire to move beyond minimal data collected through datasets such as the mandatory Canadian Institutes of Health Information (CIHI) Rehabilitation Minimum Data Set or the Functional Independence Measure (FIM). Nevertheless there is a lack of validated tools for many disciplines within rehabilitation research. There is also uncertainty as to the strength and limitations for each type of assessment. It is hoped that this book will help demystify the various tools and provide the reader with the necessary confidence to move their clinical practice and research forward on a more rigorous basis. The language used when discussing methods used (eg. screen, tool, instrument, measure, scale) is often misused leading to confusion (Wade 2004). For the purposes of this review the terms listed will be used interchangeably to indicate a method used to capture data in a standardized manner. Why assess tools with the SCI Population? Why is there a need to assess the psychometric or clinometric properties of an outcome measure in different clinical populations? This is a fair question. For example, there is a considerable body of research suggesting the Functional Independence Measure (FIM) is a valid and reliable measure. Do we really need to test it in different diagnostic populations? The short answer is absolutely. The long answer is a bit academic, but important all the same. The FIM was developed to assess the burden of care in the stroke population (Granger et al. 1986). There has been significant investment in the development of the FIM and it has become the gold standard for the assessment of basic function (e.g. transfers, mobility, dressing, grooming, bowel and bladder). In fact it is core to the minimum dataset used in many administrative databases such as the CIHI Rehabilitation Reporting System and the Uniform Data Set for Medical Rehabilitation Centers in the United States. Despite the popularity of FIM (now a proprietary entity) and its universal recognition, the attempts to use it across a broad range of disabling physical disorders, including SCI, has revealed deficiencies and inadequacies. In fact, Catz and colleagues (1997) created the Spinal Cord Independence

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Measure (SCIM) in response to frustrations related to using the FIM to categorize the functional changes associated with Activities of Daily Living (ADL) during SCI rehabilitation. The results demonstrate that the responsiveness, or the ability to detect change, is better in the SCIM than the FIM (Catz et al. 1997; 2006; Itzkovich et al. 2003). Another example is the Short Form-36 (Ware & Sherbourne 1992) and its lesser cousin the Short-Form-12. These extremely popular generic surveys of health related Quality of Life (QoL) include items which are oriented around activity limitation at the personal level, as well as participation or restriction at a societal level (e.g. can you lift and carry and object; can you climb stairs?). It seems obvious that a good proportion of the SCI population would not be able to complete many of these activities. This is why it is critical to assess that each survey item is first and foremost appropriate for the level of SCI being assessed, as unacceptable items can alter the individuals response (seriousness to answer) or confound the data from each study cohort. This stance does not mean that new tools should be created for every diagnosis, health condition or situation (Streiner & Norman 2004), but it does make sense that existing tools must be validated for each study population so they are both sufficiently accurate and sensitive to detect a meaningful difference in a functionally significant clinical endpoint between the experimental and control groups of the trial (Steeves et al. 2006).. If the above reasons are not compelling enough, Portney and Watkins (2000), in their discussion of generalizability theory (the concept of reliability theory in which measurement error is viewed as multidimensional) remind us that establishing the population-specific reliability is essential especially to clinical practice. The nuances of many factors such as pain, spasticity and deformity can alter the reliability of any obtained result. In short, while a lack of evidence does not mean evidence is lacking, we are obligated to demonstrate and document the reliability and validity of a test score in order to have faith in our results. Inclusion Criteria for Measurement Tools of Interest to SCI Initially the measures targeted for this review included any and all tools for which there was at minimum one study that examined psychometric properties (reliability, validity, responsiveness) using a spinal cord population. More specifically, only those peer-reviewed manuscripts that directly reported values for their sample of SCI individuals were included. A list of 168 tools was originally derived (approximately 10 were different formats of a similar tool). Given the vast number of tools inclusion criteria was further narrowed to select tools for review based on clinician familiarity and interest (N=50) as well as some tools (N=4) such as the Barthel Index that are commonly known and used internationally. A table identifying all tools was developed and clinicians (nurses, occupational therapists, physiatrists, physical therapists, psychologists, recreation therapists and social workers) from GF Strong Rehabilitation Centre (Vancouver, British Columbia) and Parkwood Hospital (London, Ontario) were surveyed. Tools were then selected for review based on receiving at least 5 tallies of interest and/or familiarity. Note, while we recognize that in many randomized controlled trials investigators assess the reliability between their raters. Most often these efforts are to ensure stability of the results within the research team and therefore the results are not to generalize to the larger pool of tool users. As a result the statistical model chosen to calculate the intra class correlation coefficient (ICC) for example is different given this purpose (Shrout & Fleiss 1979). Given the dearth of RCTs conducted in SCI research the number of studies lost is potentially very small.

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Searching the Literature The Pubmed, MedLine, CINHAL, Embase, HaPI, Psycinfo, and Sportdiscus electronic databases were searched (1986 to January 2006) in an effort to locate papers reporting on measures. Additional searching was conducted by archiving the references of papers obtained from the electronic search. The key word spinal cord injury was used across each of the databases while the following terms varied in combination with spinal cord injury depending on the database used: validation studies, instrument validation, external validity, internal validity, criterion-related validity, concurrent validity, discriminant validity, content validity, face validity, predictive validity, reliability, interrater reliability, intrarater reliability, test-retest reliability, reproducibility, responsiveness, sensitivity to change, evidence-based medicine, outcome measures, clinical assessment tools, scales and measures. A database file was established using RefWorks to organize potential articles of interest. After eliminating duplicate manuscripts data extractors reviewed titles and abstracts in order to retain relevant papers. At this point all of the articles were read and the relevant information (reliability, validity and responsiveness coefficients and descriptions) was extracted. See Appendix 1 on page 22-8 for a copy of the data extraction form. Classifying the Tools To assist with the process or organizing the tools we used a conceptual framework developed by the World Health Organization called the International Classification of Functioning, Disability and Health or ICF for short (WHO 2001). See Figure 22.1. The advantages of using this framework include: 1) it is well recognized and used by the international community; 2) it was created to provide standard language for use when discussing health and health-related domains; 3) other reviews of outcome measures have used the ICF for similar purposes (Salter et al. 2005). Figure 22.1 Overview of the International Classification of Function, Disability and Health
Health condition (disorder or disease)

Body Functions and Structures

Activities

Participation

Environmental Factors

Personal Factors

According to the clinical practice guidelines (Consortium for Spinal Cord Medicine 1999) the expected outcomes after SCI range from basic physiological function such as motor/sensory function to higher level outcomes such as functional independence and social integration. The

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ICF accounts for these within the 4 constructs of its Functioning and Disability component. The tools were classified according to the body function/structure, activity and participation constructs. Table 22.1 briefly outlines the definitions. Table 22.1 Definitions for Body Function/Structure, Activity and Participation
Functioning (positive aspect) Body function the physiological functions of the body systems including psychological functions. Body structure the anatomical parts of the body such as organs, limbs and their components. Activity the execution of a task or action by an individual Participation involvement in a life situation. Disability (negative aspect) Impairment problems with body function or structure.

Activity Limitation difficulties an individual might experience in completing a given activity. Participation Restriction problems an individual may experience with involvement in a life situation.

Quality of life (QoL) surveys are a newly emerging category of outcome measurements. To capture these assessment tools, we included an additional dimension in order to help classify QOL tools. While some clinical physiologists might question whether QOL is a true outcome tool, the Food and Drug Administration (FDA) asks that QoL assessments be included as part of any clinical trial protocol and program (often as a secondary outcome measure). Since the perceived benefit by the target market population of any therapeutic intervention is an important consideration we have included QoL in our review. Three classifiers knowledgeable to both outcome measures and the ICF independently categorized all of the tools (N=168). The classifiers later met to reconcile any disagreement about classification of the tools. When a multidimensional tool covered more than one construct (e.g. activity and participation) they placed it in the category where the tool had the most items. The tools were divided once again into sub-classifications based on the sub-domains within each of the body function/structure, activity and participation areas. Upon classification into the main domains, the tools were further categorized into appropriate subgroups based on the ICF definitions. See Table 22.2 which outlines these subcategories. Table 22.2 Subcategories used for classifying tools
Body Functions/Structures Mental functions & structures of the nervous system Sensory functions and pain & the eye, ear and related structures Functions & structures involved in voice and speech Functions & structures of the cardiovascular, haematological, immunological and respiratory systems Functions & structures of the digestive, metabolic and endocrine systems Functions & structures of the genitourinary and reproductive systems Neuromusculoskeletal and Activities Learning and applying knowledge General tasks and demands Communication Mobility Self-care Participation Domestic life Interpersonal interactions and relationships Major life areas Community, social and civic life Quality of Life Subjective Objective

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movement-related functions & structures Functions of the skin and related structures

Assessing the Tools The team of reviewers who assessed each tool consisted of clinicians and scientists who have long established expertise in a wide variety of relevant research areas. Combining their knowledge of SCI with the data on the properties of the outcome tools, allowed us to generate the summaries for this chapter. Countless numbers of books and manuscripts have been written classifying and discussing psychometric principles and standards for the selection or validation of clinical tools. It is not our intent to replicate this process, but instead refer the reader to a couple of key dispositions such as Streiner and Normans Health Measurement Scales (2003) and Portney and Watkins chapters (4, 5 and 6) on reliability and validity (2000). For an excellent overview that provides insightful tips for selecting tools directly related to rehabilitation, read Finch and colleagues Physical Rehabilitation Outcome Measures (1999). Data was extracted from manuscripts reporting findings about the psychometric properties and several pragmatic factors for each of the various tools. In accordance with similar projects designed to review outcome measures (Salter et al. 2005) we relied heavily on the work by Fitzpatrick and colleagues (1998) for the methods and standards related to data extraction. Our evaluation criteria as well as the standard for quantifying the rating where possible are presented in Table 22.3. For an example of the data extraction forms used for the project see Appendix 1 on page 22-8. Table 22.3 Criteria for Rating Outcome Measures
Criterion Reliability Definition - the reproducibility and internal consistency of the tool (synonyms include stability, repeatability, etc) - Reproducibility is the degree to which the score is free from random error. Test retest, inter/intra observer reliability are commonly evaluated using statistics including ICC, Pearsons or Spearmans coefficients and kappa coefficients (weighted or unweighted). - Internal consistency assesses the homogeneity of the scale items. It is generally examined using split-half reliability or Cronbachs alpha statistics. Item-to-item and item-to-scale correlations are also accepted methods. Does the instrument measure what it purports to measure? Forms of validity include face, content, construct and criterion. Concurrent, convergent or discriminative and predictive validity are all considered to be forms of criterion validity. However, concurrent, convergent and discriminative validity all depend on the existence of a gold standard to provide a basis for comparison. If no gold standard exists, they represent a form of Standard - Internal consistency ratings are: excellent (0.80), adequate (0.70-0.79), or poor (0.70) (Andresen 2000). - ICC and Kappa for inter/intra and test-retest ratings are: excellent (0.75), adequate (0.4-0.70), or poor (0.40). (Andresen 2000).

Validity

Construct/convergent and concurrent correlations: Excellent (0.60), Adequate (0.31-0.59), Poor (0.30) (Andresen 2000) ROC analysis AUC: Excellent (0.90), Adequate (0.70-0.89), Poor (<0.70) (McDowell & Newell 1996) There are no agreed on standards by which to judge sensitivity and specificity as a validity index. (Riddle & Stratford 1999)

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Responsiveness

construct validity in which the relationship to another measure is hypothesized (Finch et al. 2002) Sensitivity to changes within patients over time (which might be indicative of therapeutic effects). Responsiveness is most commonly evaluated through correlation with other changes scores, effect sizes, standardized response means, relative efficiency, sensitivity & specificity of change scores and ROC analysis. Assessment of possible floor and ceiling effects is included as they indicate limits to the range of detectable change beyond which no further improvement or deterioration can be noted.

Interpretability

Acceptability

Feasibility

Clinical Summary

How meaningful are the scores? Are there consistent definitions and classifications for results? Are there norms available for comparison? How acceptable the scale is in terms of completion by the patient does it represent a burden? Can the assessment be completed by proxy, if necessary? Are there different formats available? Extent of effort, burden, expense & disruption to staff/clinical care arising from the administration of the instrument. Availability of the tool or representative version of the tool. Cost of the tool. Will the tool prove useful in clinical situations? What SCI sub groups is it suitable to use with? What type of information is generated (descriptive, predictive, and evaluative)? Will it help with discharge planning? Is the tool used as a component of an administrative data base?

Sensitivity to change: Excellent: Evidence of change in expected direction using methods such as standardized effect sizes: Small (<0.50), Moderate (0.50-0.80), Large (0.80) Also, by the way of standardized response means, ROC analysis of change scores (area under the curve see above) or relative efficiency. Adequate: Evidence of moderate/less change than expected; conflicting evidence. Poor: Weak evidence based solely on p-values (statistical significance) (Andresen 2000). Floor/Ceiling Effects: Excellent: No floor or ceiling effects Adequate: Floor and ceiling affects 20% of patients who attain either the minimum (floor) or maximum (ceiling) score. Poor: >20%. (Hobart et al. 2001) Jutai & Teasell (2003) point out these practical issues should not be separated from consideration of the values that underscore the selection of outcome measures. A brief assessment of practicality will accompany each summary evaluation.

Review Rigor In order to summarize the quality of each assessment tool with respect to the reported reliability, validity and responsiveness, a summary table, similar to Table 22.4 below is presented at the end of each review. The standards for rigor were adapted from McDowell and Newells (1996), as well as Andersens (2000) recent overview of Criteria for Outcome Measures.

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Table 22.4 Definitions of Rigor used to Rate the Psychometric Properties of the Measures
Excellent (+++): at least 2 studies involving subjects with SCI that corroborate each others findings (e.g., 2 studies with inter-rater reliability of > 0.75). Adequate (++): a single study involving subjects with SCI which has adequate to excellent findings of reliability, validity and / or responsiveness Poor (+): a single study involving SCI subjects which has findings of reliability, validity and / or responsiveness and less than adequate findings of reliability, validity and or responsiveness. Not Available (N/A) (-): no information is available.

Assessments of rigor, using the above standards, are provided along with the evaluation ratings of the reliability, validity and responsiveness for each measure at the bottom of each summary. The information is presented in tabular format, as outlined below. Table 22.5 Psychometric Summary
Rigor Reliability Results Rigor Validity Results Rigor Responsiveness Results Floor/ceiling

Summary tables of the extracted data (coefficients) can be obtained by contacting Ms. Caroline Abramson at Caroline.Abramson@vch.ca.

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Appendix 1: Outcome Measure Data Extraction Form

Reviewer ID: ICF Level:

Type of Outcome Measure: Description:

Total articles:

Author ID

Year

Study Design

Setting

Population (sample size, age)

Group (i.e. trans-femoral amputee)

1. RELIABILITY Author ID Internal Consistency Test-retest Reliability Inter-rater reliability Reliability Statistics Coefficient

2. VALIDITY Author ID Content Validity Construct Validity (Divergent/convergent/ Known groups) Concurrent Criterion Validity Predictive Criterion Validity Classification sensitivity/specificity (Screening measures)

3. RESPONSIVENESS Author ID Floor/ceiling effects Responsiveness over time (p-values, SRM, ES etc.)

Other Formats Advantages Derived from evidence source

Derived from expert opinion

Limitations Derived from evidence source Summary Interpretability Acceptability Feasibility Recommendation Strongly Recommended (proceed to ICF)

Derived from expert opinion

Recommended (Proceed to ICF)

Do not Recommended

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Introduction References Andresen EM. Criteria for assessing the tools of disability outcomes research. Arch Phys Med Rehabil 2000:81:S15 S20. Catz A, Itzkovich M, Agranov E, Ring H, Tamir A. SCIM--spinal cord independence measure: a new disability scale for patients with spinal cord lesions. Spinal Cord 1997;35:850-856. Catz A, Itzkovich M, Tesio L, Biering-Sorensen F, Weeks C, Laramee MT, Craven BC, Tonack M, Hitzig SL, Glaser E, Zeilig G, Aito S, Scivoletto G, Mecci M, Chadwick RJ, El Masry WS, Osman A, Glass CA, Silva P, Soni BM, Gardner BP, Savic G, Bergstrom EM, Bluvshtein V, Ronen J. A multi-center international study on the spinal cord independence measure, version III: Rasch psychometric validation. Spinal Cord 2006;44:(in press). Cole B, Finch E, Gowland C, Mayo N. In: Basmajian J, editor. Physical rehabilitation outcome measures. Health and Welfare Canada and Canadian Physiotherapy Association, Toronto ON, 1994. Consortium for Spinal Cord Medicine. Outcomes following traumatic spinal cord injury: clinical practice guidelines for health care practitioners. PDF available at http://www.pva.org/site/PageServer?pagename=pubs_generalpubs 1999. Deathe AB, Miller WC, Speechley M. The status of outcome measurement in amputee rehabilitation in Canada. Arch Phys Med Rehabil 2002;83:912-918. Finch E, Brooks D, Stratford PW, Mayo NE. Physical Rehabilitations Outcome Measures. A Guide to Enhanced Clinical Decision-Making (2nd ed). Canadian Physiotherapy Association, Toronto ON, 2002. Fitzpatrick R, Davey C, Buxton MJ, Jones DR. Evaluation of patient-based outcome measures for use in clinical trials. Health Technol Assess 1998:2:1 74. Hobart JC, Lamping DL, Freeman JA, Langdon DW, McLellan DL, Greenwood RJ, Thompson AJ. Evidence-based measurement: which disability scale for neurologic rehabilitation. Neurology 2001;57:639-644. Itzkovich M, Tamir A, Philo O, Steinberg F, Ronen J, Spasser R, Gepstein R, Ring H, Catz A. 2003. Reliability of the Catz-Itzkovich Spinal Cord Independence Measure assessment by interview and comparison with observation. Am J Phys Med Rehabil 2003;82:267-272. Jutai J, Teasell R. The necessity and limitations of evidence-based practice in stroke rehabilitation. Top Stroke Rehabil 2003;10:71-78. Kay TM,Myers AM, Juijbregts MPJ. How far have we come since 1992? A comparative survey of physiotherapists use of outcome measures. Physiother Can 2001;53:268-275. Law M. Measurement in occupational therapy: Scienfific criteria for evaluation. Can J Occup Ther 1987;54:133-138. McDowell I, Newell C. Measuring Health. A Guide to Rating Scales and Questionnaires. Oxford University Press, New York NY, 1996. Nunnally JC, Bernstein IH. Psychometric theory (3rd ed). McGraw-Hill, Toronto ON, 1994. Portney LG, Watkins MP. Foundations of Clinical Research: Applications to Practice. Prentice Hall Health; Upper Saddle River, NJ: 2000. Riddle DL, Stratford PW. Interpreting validity indexes for diagnostic tests: An illustration using the Berg Balance Test. Phys Ther 1999;79:939-948. Salter K, Jutai J, Foley N, Teasel R. Evidenced-Based Review of Stroke Rehabilitation: Outcome Measures in Stroke Rehabilitation. (8th ed) [online]. 2005 [cited Aug 20, 2006]. Available from http://www.ebrsr.com/index_modules_sub4.html . Shrout PE, Fleiss JL. Intraclass correlations: Uses in assessing rater reliability. Psychol Bull 1979;86:420-428. Skinner A, Turner-Stokes L. The use of standardized outcome measures in rehabilitation centres in the UK. Clin Rehabil 2006;20:609-615.

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Steeves JD, Lammertse D, Curt A, Fawcett JW, Tuszynski MH, et al. Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP Panel: Clinical trial outcome measures. Spinal Cord 2006;44:(in press). Streiner DL, Norman GR. Health Measurement Scales: A Practical Guide to Their Development and Use. (3rd ed). Oxford University Press, New York NY, 2004. Wade D. Assessment, measurement and data collection tools. Clin Rehabil 2004;18:233-237. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473-483. WHO International classification of functioning, disability and health. Geneva: World Health Organization 2001.

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22.2 Body Function / Structure We start our review with outcome measures that represent the areas of body function and structure as they can be considered the foundational for any personal activity, quality of life, and societal participation. The majority of outcome measures used in clinical rehabilitation come from the Body Function and Body Structure components of ICF (Dahl 2002). While the components covered under this dimension are still mechanistically complex and by and large unresolved in terms of clinical treatment (e.g. motor function, spasticity, autonomic nervous system activity, or pain), when compared to the complexity or validity of the tools used to assess activity or activity limitation at the personal or societal level (e.g. self-care, community function, and quality of life), these measures of SCI function are perhaps more straight forward. Of course, this really underscores the complexity of valid SCI outcome assessments! The outcome measures reviewed under this category include: 22.2 Body Function / Structure .............................................................................................22-11 22.2.1.1 The CAGE Questionnaire ......................................................................................22-12 22.2.1.2 Center for Epidemiological Studies Depression Scale (CES-D) ............................22-13 22.2.1.3 Patient Health Questionnaire (PHQ-9)...................................................................22-14 22.2.1.4 Zung Self-Rating Depression Scale (SDS) ............................................................22-15 22.2.2.1 Classification System for Chronic Pain in SCI .......................................................22-16 22.2.2.2 Donovan SCI Pain Classification System ..............................................................22-17 22.2.2.3 Tunks Classification Scheme ................................................................................22-18 22.2.2.4 Wheelchair Users Shoulder Pain Index (WUSPI) ..................................................22-19 22.2.3.1 Wingate Anaerobic Testing (WAnT) ......................................................................22-20 22.2.4.1 The American Spinal Injury Association: International Standards for Neurological Classification of Spinal Cord Injury .......................................................................22-21 22.2.4.2 Ashworth and Modified Ashworth ..........................................................................22-22 22.2.4.3 Penn Spasm Frequency Scale (PSFS)..................................................................22-23 22.2.4.4 Surface Electromyography (sEMG) .......................................................................22-24 22.2.5.1 Braden Scale .........................................................................................................22-25 22.2.5.2 Gosnell Measure....................................................................................................22-26 22.2.5.3 Norton Measure .....................................................................................................22-27 22.2.5.4 Spinal Cord Injury Pressure Ulcer Scale (SCIPUS) Measure ................................22-28 22.2.5.5 Spinal Cord Injury Pressure Ulcer Scale - Acute(SCIPUS-A) ................................22-29 22.2.5.6 Waterlow Scale ......................................................................................................22-30 22.2.6.1 Emotional Quality of the Relationship Scale (EQR) ...............................................22-31 22.2.6.2 Knowledge, Comfort, Approach and Attitude towards Sexuality Scale (KCAASS)22-32 22.2.6.3 Sexual Attitude and Information Questionnaire .....................................................22-33 22.2.6.4 Sexual Behaviour Scale (SB).................................................................................22-34 22.2.6.5 Sexual Interest, Activity and Satisfaction (SIAS) / Sexual Activity and Satisfaction (SAS) Scales..........................................................................................................22-35 22.2.6.6 Sexual Interest and Satisfaction Scale (SIS) .........................................................22-36

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22.2.1 Mental Functions & Structures of the Nervous System 22.2.1.1 The CAGE Questionnaire The CAGE is a 4 item screening questionnaire used to identify those individuals for whom more extensive evaluation of alcohol use is recommended. Initially developed by J. A. Ewing (1984), it is the oldest and likely most extensively used questionnaire across a variety of clinical and research settings. Originally developed for use with adults, it has been used in elderly populations as well. Procedure: A self report pen/paper or interview format. Responses of yes/no to the following: Have you ever felt you should Cut down on your drinking? Have people Annoyed you by criticizing your drinking? Have you ever felt bad or Guilty about drinking? Have you ever taken a drink first thing in the morning (Eye opener) to steady your nerves or get rid of a hangover?

Advantages: Brief, extensively used in variety of settings. Limitations: Susceptible to underreporting. Minimum age 16 years. Not recommended for use with adolescents. Not to be used as a diagnostic instrument (with increasing scores implying a continuum of increasing risk for alcohol use) but rather a screening index to cue for further evaluation. Acceptability: Less than 5 minutes to complete. Feasibility: Easy to administer and score. Flesch-Kincaid grade level of 5.1. A PDF version is available at http://www.lifewisewa.com/pdfs/012695.pdf. Interpretability: Typically, two or more of the questions answered affirmatively are considered to be CAGE positive, though some suggest a positive response to a single item warrants more in-depth investigation of consumption. In non-SCI populations, the CAGE test (scores >=2) has a sensitivity of 93% and a specificity of 76% for the identification of problem drinkers (Bernadt et al. 1982). Clinical Summary: Score correlates positively with pre-SCI consumption patterns and a greater incidence of medical complications (Tate 2003). Important that questions refer to whole life history rather than a particular period. As such, it does not discriminate between active and inactive drinkers. Used in combination with information regarding usual consumption patterns (e.g., frequency/quantity/heaviest consumption). In some populations, such inquiry can inhibit responses to CAGE questions, if it precedes them. Psychometric Summary
Reliability Validity Rigor Results Rigor Results Rigor N/A N/A ++ Construct ++ N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information Responsiveness Results Floor/ceiling N/A N/A

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22.2.1 Mental Functions & Structures of the Nervous System 22.2.1.2 Center for Epidemiological Studies Depression Scale (CES-D) This 20 item screening measure was developed by the National Institute of Mental Health to identify current depressive symptomatology related to major or clinical depression in the general population (adults and adolescents). The items were generated from other previously validated scales (Radloff 1977). The items include depressed mood, feelings of guilt, worthlessness and helplessness, psychomotor retardation, loss of appetite and sleep difficulties. It has an emphasis upon affective symptoms. It has been extensively used in large studies and norms are available. Since 1980, the CES-D has been cited in approximately 50 articles involving adjustment to SCI. Responses are based on the frequency of occurrence during the past week. Uses a 4-point ordinal scale: Rarely or none of the time (less than 1 day) Some or a little of the time (1-2 days) Occasionally or a moderate amount of the time (3-4 days) Most or all of the time (5-7 days) Procedure: Self report using pen/paper or interview. A summary score is calculated - 4 items are rated in positive direction to avoid response set. Advantages: 5 10 minutes to complete. Several translations are available (Dutch, Spanish, Thai, Chinese, Italian) Limitations: Not a diagnostic tool - a screening measure to help identify individuals at risk for depression. Created for the general population. Two psychometric studies with SCI populations one of which studies the Thai version of the CES-D (Kuptniratsaikul et al. 2002). Sensitivity and specificity adequate for Thai version but not for English version (small n for latter). Acceptability: Easy to complete. Flesch-Kincaid Grade Level 4.1. Shorter versions such as the 10, 8 and 4 item are available but have not been assessed in the SCI population. Feasibility: Easy to administer and score. Copyright Center for Epidemiological Studies, National Institute of Mental Health; West Publishing Company. PDF version available at http://www.chcr.brown.edu/pcoc/cesdscale.pdf Interpretability: The range of scores on the CES-D is 0-60 with higher scores indicating greater symptoms. A cutoff score of 16 is indicative of significant or mild depressive symptomatology. It is equivalent to experiencing six symptoms for most of the previous week or a majority of symptoms on one or two days. Scores of 22 or greater consistent with probable major depression. Some suggest increasing the cutting score in primary care settings to reduce the number of false positives. For example, the Thai version (Kuptniratsaikul et al. 2002) used a cutoff score of 19 to identify depression in the SCI sample. Has been used in sample of adolescents and young adults (Radloff 1991) and more recently in studies of older adults. Clinical Summary: Radloff (1977) cautions that the instrument should not be used for clinical diagnoses nor should individual scores be interpreted. It may fail to separate depression from generalized anxiety or from depression secondary to other diagnoses. In some clinical applications, the Beck Depression Inventory (second edition) or the PHQ-9 may be preferable as these survey a two week period consistent with DSMIV criteria for major depression. Further, they both include an item specific to suicidal ideation. Psychometric Summary:
Validity Responsiveness Results Rigor Results Floor/ceiling Predictive ++ N/A N/A N/A SS ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency; SS=Sensitivity/Specificity Rigor ++ Rigor ++ Reliability Results IC +++

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22.2.1 Mental Functions & Structures of the Nervous System 22.2.1.3 Patient Health Questionnaire (PHQ-9) The PHQ-9 is a 9 item screening measure devised to identify probable major depressive disorder (MDD) among adult primary care patients (Bombardier et al. 2004). The items parallel the diagnostic criteria of major depression, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). It was developed for use with medical patients to establish validity in populations with high rates of nonspecific physical symptoms that can confound a diagnosis of major depression. Assessment of symptoms and functional impairment indicating a diagnosis, and a severity score can be derived to help monitor treatment effects (Bombardier et al. 2004). Items are rated in terms of how persistent the symptoms have been in the past 2 weeks: 0 not at all, 1 several days, 2 more than half of the days, 3 nearly every day Procedure: Self report pen/paper or interview format. Symptomatology and severity scores can be derived based on the inclusion of specific items or by summing response categories. Advantages: Easy to understand and complete. Corresponds with nosological criteria (DSMIV). Limitations: One study of SCI patients assessed at one year post injury. Acceptability: Takes 5 minutes to complete. Items easy to understand. Appears acceptable to non-psychiatric samples. English and Spanish versions available. Feasibility: Easy to administer and score. Measure available online in PDF format Copyright Pfizer Inc. after agreeing to several conditions including use for research, in clinical programs or physician education (http://www.pfizer.com/pfizer/phq-9/index.jsp) or http://www.depressionprimarycare.org/clinicians/toolkits/materials/forms/phq9/ (includes scoring guide). Interpretability: Symptomatology and functional impairment for making a diagnosis of MDD requires a positive response to at least one of feelings of depression OR anhedonia for more than half the days in the past 2 weeks AND at least somewhat difficult functioning at work/home or getting alone with others. Severity scores are derived by adding the response options with scores ranging from 0-27. Scores of > 20 indicate major depression (severe), 15-19 major depression (moderately severe), 10-14 moderate and 5-9 mild depressive symptomatology. Clinical Summary: While having demonstrated good internal consistency, construct validity, sensitivity and specificity in a group of SCI survivors 1 year post injury, the PHQ-9 requires additional comparison with a criterion standard. Further, diagnostic specificity of somatic symptoms during inpatient acute rehabilitation is yet to be established. Available findings support that somatic symptoms are not simply nonspecific symptoms of SCI, but rather, are also predictive of MDD and should be included in arriving at a diagnosis in post-acute SCI sample (Bombardier et al. 2004). Psychometric Summary:
Validity Responsiveness Results Rigor Results Floor/ceiling Construct ++ N/A N/A N/A SS +++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency; SS=Sensitivity/Specificity Rigor ++ Rigor ++ Reliability Results IC +++

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22.2.1 Mental Functions & Structures of the Nervous System 22.2.1.4 Zung Self-Rating Depression Scale (SDS) The Zung Self-Rating Depression Scale (SDS) is a well-established (Zung 1965) screening measure of adult depression severity that has been used in a variety of mental health areas including primary care, psychiatric, drug trials, and related clinical, institutional, and research settings. The 20-item instrument identifies various symptoms of depression related to: Affective (e.g., feeling downhearted and blue, crying spells) Psychological (e.g., hopeless, irritable, suicidal ideation) Somatic (e.g., agitation; retardation) Symptoms over the past several days are rated according to a 4-point (1 to 4) ordinal scale. Half the items are worded positively and half are worded negatively (total possible of 80 points) 1 - Little or none of the time 2 - Some of the time 3 - A large part of the time 4 - Most or all of the time Procedure: Self-report pen and pencil or interview format. Advantages: Can be used to measure intervention outcomes over time. Useful for clinical and research purposes. Limitations: Limited information regarding use in SCI population (Tate et al. 1993). Items are similar to, but do not exactly match DSM-IV criterion for major depressive disorder. Has been criticized due to its focus upon symptom frequency rather than severity, though its intent was to assess the latter. Acceptability: Quick to complete (<10 minutes). The positive and negative item wording may be confusing for some individuals. Available in English, Chinese, Russian, Thai, Czech, Farsi, Indonesian, Lithuanian. Appears acceptable to non-psychiatric samples. Feasibility: Easy to administer and score. Has been translated into many languages. Copyright American Medical Association. Measure widely available in PDF versions (with scoring key) at: http://healthnet.umassmed.edu/mhealth/ZungSelfRatedDepressionScale.pdf. An online version is available at: http://www.afraidtoask.com/depression/depressionzung.htm. Other language versions available at: www.who.int/substance_abuse/research_tools/zungdepressionscale/en/index.html. Interpretability: Scores range from 20 to 80 with higher scores indicating increased depressive symptoms. Scores over 50 suggest depression with scores over 69 indicating severe depression. Sensitivity to correctly identify when depression is present using clinician ratings as the gold standard was 86% in the SCI population (Tate et al. 2003). Clinical Summary: The Zung provides information that enables description and evaluation of patients/subjects. Since 1980, has been cited in approximately 25 investigations of adjustment to SCI. In some clinical applications however, the Beck Depression Inventory (second edition) or the PHQ-9 may be preferable as they survey a two week period consistent with DSMIV criteria for major depression. Further, they include an item specific to suicidal ideation. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ IC +++ ++ Construct ++ N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency

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22.2.2 Sensory Functions and Pain & the Eye, Ear and Related Structures 22.2.2.1 Classification System for Chronic Pain in SCI This tool proposes a pain classification scheme with 2 major categories: neuropathic and musculoskeletal. Neuropathic pain is divided into 4 subcategories: SCI pain, transition zone pain, radicular pain and visceral pain. Musculoskeletal pain is divided into mechanical spine pain and over use pain. This scheme is design to help with the standardization of pain terminology used in the SCI population (Cardenas et al. 2002). Pain is categorized by pain location and distribution, as related to level of spinal injury (e.g. above level, at level or below level). This information is combined with a classification of the subjects SCI pain. Procedure: A 188 item questionnaire is administered by a clinician but could also be completed by the patient. The person identifies the worst pain problem on a body diagram and indicates whether pain worsens with activity, position or change of position or light touch. This procedure is repeated for second worse pain etc. Categorization is outlined in the table below.
Pain Category (major) Neurologic Pain Category (Specific) SCI Pain Transition zone pain Radicular Pain Visceral Musculoskeletal Mechanical spine pain Overuse pain Location Below injury in area without normal sensation At level of injury, bilateral At any dermatome level, usually unilateral, usually radiates In abdomen In back or neck, often bilateral Often above injury in areas of normal sensation in an incomplete, can be below Related to activity + _ + _ + + Affected by position _ _ + _ + + _ Worse with light touch + + _ _

+ yes, - no, + maybe

Advantages: This tool has the best reliability (within (=0.68) and between (=0.66) raters), standardized system for classifying pain in people with SCI using well defined terminology. Limitations: There is no information about validity or responsiveness and reliability results are based on a single study. Time taken to complete is considerable. Interpretability: This pain classification provides a nice summary table that makes it easy for clinicians to identify key problem areas that the patient has expressed. Acceptability: The initial patient burden is high however follow up session will require less time. Interview format improves utility for those with limited hand function. Feasibility: Considerable time (estimate not available) is required to complete the questions. No special equipment or training is necessary however expertise understanding pain would be an asset. See article for a copy of the tool (Cardenas et al. 2002). Clinical Summary: This tool has considerable promise but it requires additional study. This chronic pain classification scheme may be useful for individuals with complex pain conditions in order to map and monitor a patients progress related to pain management, as well as be used to compare intervention protocols across patient groups. This table can also be compared quickly with follow-up visits to determine improvement or deterioration in an area. Psychometric Summary:
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling Inter O ++ N/A N/A N/A N/A N/A Intra O ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; Inter O=Interobserver; Intra O=intraobserver Rigor ++

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22.2.2 Sensory Functions and Pain & the Eye, Ear and Related Structures 22.2.2.2 Donovan SCI Pain Classification System The Donovan Pain Classification system proposes 5 pain types, including segmental nerve and cauda equina, spinal cord, visceral, mechanical and psychogenic. This system combines both mechanistic (eg. slow fibre conduction from skin) and descriptive factors such as time to onset post-injury, characteristics of pain (eg. Burning, stabbing, dull aching, etc), pain duration, and factors that make it worse or better (Donovan et al. 1982). Procedure: This information is obtained through a semi-structured interview. Advantages: The patient describes not only the location and degree of pain they are having but also the type of pain and factors that make it worse or improved. It is an open ended style of assessment with less chance to lead the patient towards any specific pain statements. Limitations: Since the classification system does not follow a systematic method for acquiring the data from the patients, it is possible for some sites to be overlooked. This accounts for the relatively poor reliability with a inter rater consistency of only 50-62% (Richards et al. 2002) and modest retest reliability (Putzke et al. 2003). Interpretability: One may put the information into a tabular format for charting or research purposes may be very helpful for interpretation and clarity using the following table.
Pain Type Segmental nerve Cauda Equina Spinal Cord Visceral Mechanical Psychic Time of Onset Post Injury Days to weeks Weeks to months Weeks to months Weeks to months Variable Character Burning Stabbing Tingling Numbness Burning Dull Aching Variable Duration Seconds Constant Constant Variable Variable Aggravating factors Rest Activity Variable Activity Variable Diminishing factors Activity Rest Variable Rest Variable Possible causative factors Slow fibre conduction from skin All fibre conduction within cord Slow fibre conduction from viscera Slow fibre conducton from muscles or ligaments Preoccupation with unpleasant environmental stimuli

Acceptability: This may be a time consuming method for collecting this type of data but some clinicians may really find this type of approach more suitable for the more difficult cases to clarify the problems. This method allows the patients to explain their pain in their own language rather than being forced to pick specific descriptors for their pain. Feasibility: This is an inexpensive pen and paper method, but time consuming method to collect pain data for individuals with complex pain issues. Clinicians may not have time to do this for all SCI pain, which would take about 20-40 minutes, depending upon the number of sites and intensity of pain an individual may have. Clinical Summary: This may be a useful tool to help delineate what type of pain an individual is experiencing and the possible mechanism for that particular pain. Often individuals with SCI have pain in multiple sites with different origins. This break down of pain into the 5 categories would help clinicians work through the problems more methodologically via a semi-structured interview. Psychometric Summary:
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling TR++ N/A N/A N/A N/A N/A Inter O ++ Intra O ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; Inter O=interobserver; Intra O=intraobserver Rigor ++

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22.2.2 Sensory Functions and Pain & the Eye, Ear and Related Structures 22.2.2.3 Tunks Classification Scheme Classifying the type and location of pain enables better diagnostic and intervention results. The Tunks model identifies 11 types of pain for those with spinal cord injury according to the lesion level (Tunks 1986).
Above the lesion level 1) Myofacial 2) Syringomyelia 3) Non spinal cord At the lesion level 4) Radicular 5) Hyperalgesic border reaction 6) Fracture 7) Myofacial (incomplete lesion) Below the lesion level 8) Diffuse burning 9) Phantom 10) Visceral 11) Myofacial (incomplete lesion)

Procedure: This information is obtained through a semi-structured interview. Advantages: This pain classification allows the clinician to describe the general location and whether the pain differentiates between several types of pain. Limitations: Since the classification system does not follow a systematic method for acquiring the data from the patients, thus making consistency difficult from one time to another or between individuals very difficult. This system is very clinician dependent as it requires considerable knowledge about the various origins of pain to be able to interpret the patients comments into the defined classification scheme. This makes it a very inconsistent measure. The interrater reliability of the Tunks scheme is considered poor (Putzke et al. 2003). Interpretability: This system requires considerable knowledge from the clinician classifying the pain as well as other health care professionals who may be using the information to help with pain management, as it may be difficult to interpret what the classification system means for management of pain. Acceptability: Although this system has merit for giving more categories for which to describe the various types of pain an individual may have, it most likely would be useful for more complex pain cases where more time is allocated towards understanding the origins of the individuals pain. Feasibility: The interview takes 15-20 minutes. No formal training is required but knowledge about neuro anatomy and physiology specifically sensation and theories of pain is an asset. Clinical Summary: This may be a useful tool to help break down of pain into the 11 categories in an open and relatively quick way. However, for the more complex patients, it may take substantially more time than is indicated. It would be an intermediary point for clinicians to identify qualitative elements of pain but it should be augmented using a battery of other tools that would address pain duration, location and intensity in order to provide a complete picture of pain involvement. The disappointing reliability results suggest that identifying two broad types of pain, mechanical and neuropathic may be the best approach until specific diagnostic tools can be developed for each of the purported subtypes of SCI pain (Putzke et al. 2003). Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling + Inter O + N/A N/A N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; Inter O=interobserver

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22.2.2 Sensory Functions and Pain & the Eye, Ear and Related Structures 22.2.2.4 Wheelchair Users Shoulder Pain Index (WUSPI) The WUSPI score is a 15 item questionnaire designed to measure shoulder pain that limits function in individuals who use wheelchairs (Curtis et al. 1995). The scale was modeled on the Shoulder Pain and Disability Index (Roach et al. 1991; Curtis et al. 1995). Modifications made in the creation of the WUSPI included inclusion of common activities performed by the wheelchair user. Content validity was developed by having long term wheelchair users verify important items. It targets activity limitation resulting from shoulder pain on a 10 cm visual analogue scale. It covers 4 subsections which include transfers (4 items), wheelchair mobility (2 items), self-care (5 items), and general activities (4 items). The anchors for the items range from 0 no interference due to pain to 10 completely interferes due to shoulder pain. Procedure: A self report pen and paper format is used. A total score is derived by adding the individual item scores. Total scores range from 0 (no pain) to 150 (extreme pain). Subscale scores can be derived although there is minimal research supporting the use of these. Advantages: The WUSPI is a simple and effective joint specific method of quickly determining the degree of interference due to pain when doing typical tasks of daily living. Limitations: This tool is specific to shoulder pain. It does not obtain information about the type or frequency of pain experienced during the activities. No strategies are suggested to assist with scoring if a person indicates they do not do certain activities (e.g./ load their chair into a car) although it may be possible to use a percentage score out of 150 max rather than using an absolute score to compare between individuals or groups (Sawatzky et al. 2005). No psychometric evidence is available for responsiveness and the majority of research for reliability and validity has been conducted using a mixed sample (not just SCI). The excellent total score and inter items retest ICCs are likely related to baseline and reassessment occurring during the same day. It seems plausible that floor effects are possible for new wheelchair users. Interpretability: Higher scores indicate more limitation due to pain. No information is available regarding norms or meaningful cut scores. Acceptability: The items selected reflect common activities performed by the general population of wheelchairs users across diagnostic classification. The very high internal consistency (alpha =.98) suggests there may be overlap in the items and therefore a shorter scale may be feasible. The WUSPI takes about 5 minutes to complete. Feasibility: The WUSPI requires approximately 10 minutes to score the VAS for each item with a ruler. No special training is required to administer or score the questionnaire. A copy can be obtained from K.A. Curtis the tool developer. Clinical Summary: The WUSPI presents the functional cost of shoulder pain in wheelchair users. It provides unique information that may enable clinicians to consider more detailed assessment based on specific items to explore strategies or equipment may be useful to decrease activity specific pain. Responsiveness data is required prior to recommending the index for clinical evaluation of interventions. Psychometric Summary:
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling TR +++ ++ Concurrent ++ N/A N/A N/A IC +++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; IC=Internal Consistency Rigor ++

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22.2.3 Functions & Structures of the Cardiovascular, Haematological, Immunological and Respiratory Systems 22.2.3.1 Wingate Anaerobic Testing (WAnT) The WAnT is a method of assessing muscle power. It involves a 30 second maximal effort trial on a leg or arm ergometer. It was first validated in able bodied individuals to use as a predictor of physical performance of anaerobic activities (Ayalon et al. 1974; Bar-Or et al. 1977). Leg WAnT was closely associated with 40 m running (r=0.84) and running speed (r=0.85) (Bar-Or & Inbar 1978). Arm and leg WAnT correlated with swimming performance (Hawley & Williams 1992). Arm WAnT has also been used in persons with paraplegia to compare to performance of upper limb anaerobic tasks such as transferring in and out of the car (r=0.81) and 26m wheelchair sprints (r=0.70) (Bar-Or et al. 1976). Procedure: The WAnT requires the use of an arm ergometer or an adapted leg ergometer suitable for arm use that allows for consistent resistance to be applied. The ergometer system is typically linked to a computer with specific software to calculate peak power based on resistance and speed (the highest average power output at any given 5 sec period) and mean power (average power output over a 30 sec trial). The individual typically free wheels with no resistance for 3-5 minutes, after which they increase the cadence to 100 rev/min. The resistance load is then applied (3.5% body weight) and the subject pedals as fast as they can for 30 seconds, followed by a 1-2 minute cool down without resistance. Advantages: Without a test like this, there is no standardized test, device or protocol to monitor upper extremity strength and power. Most assessments look at aerobic function rather than anaerobic tasks. This test has been shown to be valid and reliable across a wide range of able bodied and disabled individuals, including those with paraplegia (Jacobs et al. 2003). Limitations: This test requires significant financial investment (ergometer, computer and software). Interpretability: The outcome measures (peak and mean power) are easily interpreted as the higher the output, the greater strength the individual exhibits. Norms for non-disabled individuals (adults & children) are available for comparison (Jacobs et al. 2003; 2005). Acceptability: Since the test is quick (max. 8 minutes, including free wheeling) and the number of repetitions are relatively low, it generally does not contribute to overuse injuries in the wrist or shoulder. If the person already experiences symptoms of these injuries, this test may trigger pain. Feasibility: It is a relatively easy and inexpensive test to administer with appropriate equipment available; however, initial expenditure is significant. It does not require a highly trained individual to implement the test. Clinical Summary: The WAnT is a good measure of upper extremity strength and power that does link to other functional tasks such as transferring in and out of the car or wheeling up ramps/hills. It is also a well established protocol that has been used in many populations, and thus, comparisons are possible. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ TR +++ ++ Content +++ N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test

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22.2.4 Neuromusculoskeletal and Movement-Related Functions & Structures 22.2.4.1 The American Spinal Injury Association: International Standards for Neurological Classification of Spinal Cord Injury The International Standards for Neurological Classification of SCI (ASIA 2002) is a multidimensional approach to categorize motor and sensory impairment in individuals with SCI. Currently in its 6th edition, it identifies sensory and motor levels indicative of the most rostral spinal levels demonstrating unimpaired function. Twenty-eight dermatomes are assessed bilaterally using pinprick and light touch sensation and 10 key muscles are assessed bilaterally with manual muscle testing. The results are summed to produce overall sensory and motor scores and are used in combination with evaluation of anal sensory and motor function as a basis for the determination of the ASIA Impairment Scale (AIS). Procedure: A clinical examination is conducted to test whether sensation is 0=absent, 1=impaired or 2=normal. Muscle function is rated from 0=total paralysis to 5=(normal), i.e. active movement, full ROM against significant resistance. The presence of anal sensation and voluntary anal contraction are assessed as a yes/no. Bilateral motor and sensory levels and the AIS are based on the results of these examinations. A more accurate representation of motor function has been demonstrated when overall ASIA motor scores are divided into separate upper and lower limb scores (Marino & Graves 2004; Graves et al. 2006). Advantages: This is an internationally recognized standard which is widely used for research and clinical purposes. Its historical development and continued evolution are well grounded in expert clinical consensus thereby ensuring high content validity (Cohen et al. 1996). In addition, there is evidence that ASIA motor scores collected relatively early following injury have some predictive validity in explaining functional outcomes (Lazar et al. 1989; Blaustein et al. 1993). Limitations: ASIA scores have been assessed as having only moderate inter-rater reliability (Priebe & Waring 1991; Jonsson et al. 2000) with even poorer results following sensory examinations or associated with specific cases of incomplete SCI (Priebe and Waring 1991; Cohen et al. 1996). Inter-rater reliability for assignment of motor and sensory levels and AIS classifications is less than optimal. Enhanced training methods and materials have been recommended to improve inter-rater reliability (Priebe & Waring 1991; Cohen et al. 1998; Jonsson et al. 2000) Interpretability: The AIS scores are clearly defined and understood by most clinicians. The AIS (5 point ordinal scale), based on the Frankel scale (Frankel et al. 1969), classifies individuals from A (complete SCI) to E (normal sensory and motor function). Preservation of function in the sacral segments (S4-S5) is key for determining the AIS. Acceptability: The assessment is generally well tolerated although sensory testing can be problem with severe hypersensitivity and testing for voluntary anal contraction can result in the stimulation of a bowel movement. Feasibility: Takes approximately 20 minutes to conduct/score. Training is mandatory and no specialized equipment is required. For a copy see www.asiaspinalinjury.org/publications/2001_Classif_worksheet.pdf#search=%22ASia%20motor %20score%22 Clinical Summary: ASIA scores are considered essential when classifying persons with SCI as to their neurological status. ASIA scores are routinely collected in administrative data bases such the Model Systems and CIHI National Rehabilitation Reporting System. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling +++ TR ++ ++ Construct +++ N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test

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22.2.4 Neuromusculoskeletal and Movement-Related Functions & Structures 22.2.4.2 Ashworth and Modified Ashworth The Ashworth measure of spasticity was developed as a simple clinical classification to assess the anti-spastic effects of carisoprodol in multiple sclerosis (Ashworth 1964). It is a 5-point nominal scale using subjective clinical assessment of tone ranging from 0 no increases in tone to 4 limb rigid in flexion or extension [abduction/adduction]. An additional grade was added (1+) for the Modified Ashworth (MAS) to enhance sensitivity and accommodate hemiplegic patients who typically graded at the lower end of the scale (Bohannon & Smith 1986). These measures have been adopted for measuring spasticity in a variety of other indications including spinal cord injury (Haas et al. 1996), although some have noted that there are differences in the characteristics of spasticity with different etiologies (Noth 1991; Lechner et al. 2006). Procedure: A clinical examination performed on a relaxed supine patient. The muscle is assessed by rating the resistance to passive range of motion (ROM) about a single joint. Advantages: Both measures have been used for clinical and research purposes. The MAS correlates well with a self-rating visual analogue scale of spasticity (Skold 2000) and the Ashworth correlates strongly with the patellar tendon tap and the adductor tap (Priebe et al. 1996). The Ashworth correlates well with the Spinal Cord Assessment Tool for Spastic Reflexes (Benz et al. 1995) which measures different types and severity of spastic reflexes in SCI. Limitations: These measures assess single-joint resistance to passive ROM or a velocity dependent stretch reflex. They do not address spasm frequency or severity, nor do they differentiate between phasic and tonic components of spasticity (Priebe et al. 1996). The observation of resistance is subjective and requires experienced clinical judgment. Reliability varies muscle to muscle ( reliable in plantar flexors, reliable in adductors; Haas et al. 1996). Interpretability: The Ashworth scale is easily interpretable with discrete categories that reflect clinical experience. The MAS adds an additional grade at the lower end of spasticity. Acceptability: Well accepted and tolerated by patients as the procedures consist of range of motion movements similar to non-assessment ROM movements. Feasibility: These measures are easily administered during routine clinic visits. No specialized equipment is required. Clinical experience increases inter-rater reliability (Bohannon & Smith 1987; Haas et al. 1996). Standardization of speed of movement in the assessment is required since spasticity is velocity dependent (eg. use of metronome is helpful). Some consider the Ashworth to be of limited use in the assessment of spasticity in the lower limb of patients with SCI without this standardization (Haas 1996). Clinical Summary: These measures are the clinical gold standard for assessing spasticity in people with SCI. However, it should be noted that spasticity is a multi-faceted construct with individual components of spasticity weakly related to each other suggesting that different clinical scales measure unique aspects of spasticity (Priebe et al. 1996). Therefore, the overall construct is best measured with an appropriate battery of tests including the Ashworth Scale. Psychometric Summary
Rigor +++ Reliability Results TR+++ Overall TR++ adductors TR+ plantar flexor Rigor +++ Validity Results Ashworth Construct ++ Rigor +++ Responsiveness Results Floor/ceiling + N/A

MAS TR+ Overall TR+++ +++ Construct ++ +++ + With velocity standardization TR++ adductors TR+ plantar flexor Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test +++

N/A

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22.2.4 Neuromusculoskeletal and Movement-Related Functions & Structures 22.2.4.3 Penn Spasm Frequency Scale (PSFS) The Penn Spasm Frequency Scale (PSFS) is self report measure of the frequency or reported muscle spasms (Penn et al. 1989; Priebe et al. 1996) which is commonly used to quantify spasticity (Benz et al. 2006). The PSFS is a 2 component self-report scale developed to augment clinical ratings of spasticity and provide a more comprehensive understanding of an individuals spasticity status. The first component is a 5 point scale assessing the frequency with which spasms occur ranging from 0 = No spasms to 4 = Spontaneous spasms occurring more than ten times per hour. The second component is a 3 point scale assessing the severity of spasms ranging from 1 = Mild to 3 = Severe. The second component is not answered if the person indicates they have no spasms in part 1. Procedure: Patients report their perceptions of spasticity with regards to frequency and severity. Advantages: This measure is simple and appropriate to the clinical setting and does not require specialized equipment to perform. Validity has been partially established with adequate correlations with other clinical tools such as the Ashworth scale and the Spinal Cord Assessment Tool for Spastic Reflexes (SCATS) (Benz et al. 2005). Although not directly tested, responsiveness has been demonstrated in several studies employing this measure within a test battery to assess spasticity (Gianino et al. 1998; Aydin et al. 2005; Boviatsis et al. 2005). Limitations: The scale is subject to concomitant subclinical conditions such as fullness of the bladder, development of a symptomatic urinary tract infection, anxiety level, room temperature, subject comfort, and many other conditions. Although not directly tested, test-retest reliability and repeatability has been reported as highly variable (Priebe et al. 1996) since test administration timing is not standardized and subtle changes in underlying conditions affecting spasticity may not be considered at the time of test administration. Interpretability: The specific grades simple to interpret although no standardization of time frame is specified for test administration (i.e. within the last hour, day, week, etc.) and specific grades for spasm severity may mean different things to different people. Acceptability: The PSFS presents minimal patient burden and is easy for them to understand. Feasibility: The test is quick to administer and score. No training is required however understanding and experience of spacticity likely improves its utility. . Clinical Summary: These self-report measures of spasticity correlate only moderately with clinical examination suggesting that the elements of spasticity evaluated in the physical examination do not represent what is important to persons with SCI spasticity (Priebe et al. 1996). To more fully understand spasticity as experienced by the client, self-report spasticity measures are an important adjunct to other clinical measures of spasticity. However, the PSFS is suggested to have only modest repeatability and test-retest reliability (Priebe et al. 1996) and requires further investigation taking into consideration the slight changes in the patients concomitant subclinical condition(s) and the standardization of test administration timing. In addition, the PSFS was found to correlate highest with the SCATS clonus measure as compared to the flexor and extensor spasm components of SCATS suggesting that the role of clonus most represents the clients perception of spasticity (Benz et al. 2005). This measure is easily administered during routine clinic visits. Psychometric Summary:
Reliability Validity Rigor Results Rigor Results Rigor N/A N/A ++ Construct ++ N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information Responsiveness Results Floor/ceiling N/A N/A

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22.2.4 Neuromusculoskeletal and Movement-Related Functions & Structures 22.2.4.4 Surface Electromyography (sEMG) Surface electromyography (sEMG) is a noninvasive technique used to measure muscle activity (both voluntary and involuntary) in individuals with neuromuscular diseases (Pullman et al. 2000). Procedure: Surface electrodes are placed on the skin overlying the muscles of interest. Patients are instructed to voluntarily activate lower limb muscles to provide either maximal muscle strength or to perform simple movements (eg/ ankle flexion/extension). Advantages: These measures are simple to apply and complementary to the clinical evaluation by providing objective and quantifiable non-ordinal measures. Calancie et al. (2001) showed reasonable validity by analyzing the correlations between the sEMG recordings and MMT both for the upper and lower limb muscles in patients with acute and subacute SCI. Interestingly the correlation coefficients were lower in the acute than subacute stage of SCI. The studies performed by Lim et al. (2005) and Lim & Sherwood (2005) revealed high correlation coefficients to the clinical motor testing using the ASIA motor score for face validity and demonstrated good to very good retest reliability using Intra-class correlation (ICC) analysis based on same day and 1 week retest. Limitations: The extrapolation of sEMG values to absolute forces and the comparison between subjects is limited and does not allow direct comparisons. While the individual follow up of motor recovery can be performed the measures are of limited value to precisely diagnose motor impairments. The measures are not specific to the kind and timing of neurogenic lesion (no distinction between the affect on the central or peripheral nervous system and acute versus chronic). The control of the movement performance either due to motivation and the desired kinematics is difficult to achieve and other confounding factors as pain or non-neuronal complications (muscle tendon joint effects) have to be carefully excluded. Interpretability: The data can be quantified however the interpretation is not standardized. No normative values exist. Acceptability: Minimal burden for patients. The technique is tolerated well by patients and is much less intrusive than the gold standard (needle EMG). Feasibility: An EMG study takes approximately 15-20 minutes to complete however times vary based on the number and complexity of the muscle groups studied. An EMG can range in cost from several hundred to over a thousand dollars depending on features. Special training is mandatory to conduct and interpret the results. Clinical Summary: sEMG recordings can complement the clinical examination specifically by providing objective and quantifiable measures of muscle activity. They have been shown to be valid in comparison to the clinical testing of motor strength and might be of highest value to monitor motor recovery in incomplete SCI. As these measures need special training and equipment they will be most suitable in the frame of clinical studies rather than for clinical day to day routine. The proven re-test reliability and validation makes them a valuable asset to the clinical examination by providing more objective and statistically applicable data. So far sEMG has only been applied by a few specialized research groups and independent replications and confirmations of clinical usefulness need to be done. Psychometric Summary:
Validity Responsiveness Results Rigor Results Floor/ceiling Construct ++ N/A N/A N/A Concurrent +++ SS +++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test retest reliability; SS=Sensitivity/Specificity Rigor ++ Rigor ++ Reliability Results TR ++

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22.2.5 Functions of the Skin and Related Structures 22.2.5.1 Braden Scale The Braden Scale is an assessment tool for determining a patients risk level for incurring skin breakdown. It has been tested in acute care and long-term-care settings (Bergstrom et al. 1987). Items were developed based on expert consensus and predictive validity has been studied in several acute care settings with good sensitivity and specificity demonstrated (Bergstrom et al. 1987). The scale was developed based on a conceptual schema of pressure sore development which identified a variety of pressure and tissue tolerance issues that predispose individuals to develop pressure ulcers. A patient is evaluated in six domains (one item per domain): (1) sensory perception, (2) moisture, (3) activity, (4) mobility, (5) nutrition, and (6) friction and shear and receives a score between 1-3 or 4 point ordinal scale for each domain. Procedure: Raters indicate client status in the five domains (which could be based on personal experience or chart review). Each domain is given a rating of 1-3 or 4 based on an ordinal scale based on descriptive criteria provided on the scoring sheet, which are summed for a total of between 6 (worst prognosis) to 23 (best prognosis). Advantages: A commonly used tool, which has been used extensively in research. Familiarity with the scale facilitates communication of findings. The test is quick to administer, readily available and alternative cut-off scores have suggested depending on the population. Limitations: The scale omits items that Salzburg et al. (1999) found to be important predictors of pressure ulcer development for people with SCI and includes three factors (sensory perception, mobility and nutritional variables) that were not significantly related to pressure ulcer development for individuals with SCI. The reliability of the scale has been demonstrated in a variety of settings (Bergstrom et al. 1987), but not specifically with individuals with SCI. Cut-off scores have been shown to fluctuate between populations, and so the original cut off scores between groups do not seem appropriate for individual with SCI (Salzberg et al. 1999). Wellard & Lo (2000) found that Spearmans correlations comparing ulcer severity scores and scores on the Braden were not significant. Interpretability: Although a cut off score of 16 was originally suggested as indicative of those who develop a pressure sore (100% sensitivity and 64% sensitivity) (Bergstrom et al. 1987), 11 or less has been suggested for an ICU trauma population and less than or equal to 10 has been suggested for individuals with SCI (74.7% sensitivity and 56.6% specificity) (Salzberg et al. 1999). Scoring instructions are relatively detailed. Free pressure ulcer prevention protocols are available, based on Braden Scale scores (www.Bradenscale.com). Acceptability: There is minimal examiner and no respondent burden as the patient is not asked to perform any special activities. The scale has been translated into many languages. Feasibility: The scale takes 5-10 minutes and no formal training is required. The scale, scoring information (free) and a video tape manual ($150 US) are available at <www.bradenscale.com>. Clinical Summary: The Braden scale is quick and easy to use, although there may be issues with interpretation of the scores. The scale provides predictive information and evidence of validity is adequate, but there has been no reliability or responsiveness testing with these individuals with SCI. The Agency for Health Care Policy and Research (AHCPR) (1992) recommended the use of either the Braden or the Norton scales for the prevention of pressure ulcers for best practice. Pressure ulcer prevention protocols, which describe appropriate interventions based a patients Braden scale score are also available. These include suggestions about how to manage nutrition and deal with potential friction or shear problems. Psychometric Summary:
Validity Responsiveness Results Rigor Results Floor/ceiling Construct + N/A N/A N/A Predictive ++ SS ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; SS=Sensitivity/Specificity Rigor + Rigor ++ Reliability Results +++

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22.2.5 Functions of the Skin and Related Structures 22.2.5.2 Gosnell Measure The Gosnell scale was developed to identify individuals living in extended care and over the age of 65 who were at risk for developing a pressure ulcer (Gosnell 1973). Items were identified based on research by Norton which examined indicators of pressure ulcer development. It therefore includes four of the five domains/items included in the Norton scale, but omits general physical condition. Every patient is evaluated on five domains: 1) mental status, 2) continence, 3) mobility (the amount and control of movement of one's body), 4) activity (ability to ambulate) and 5) nutrition ( the process of food intake). In addition the evaluation includes recording of: vital signs (which includes temperature pulse respirations and blood pressure), skin condition (which includes appearance, skin tone and sensation) and medications but these are not scored. Items from the 5 domains are scored on domain specific ordinal scales from 1 to 4 based on the descriptors provided. Procedure: Raters indicate client status on each of the items (which could be based on personal experience or chart review). Scales are scored based on descriptive criteria provided on the scoring sheet. This produces a summary score from between 5 (worst prognosis) to 20 (best prognosis). Advantages: The test is quick to administer, readily available and is commonly used. Limitations: The scale omits items such as pulmonary disease, serum creatinine > 1.0, extent of paralysis, albumim < 3.4 or T, protein < 6.4, autonomic dysreflexia or severe spacticity, age, tobacco use/smoking, disease, cardiac disease or glucose > 110 mg/dl, renal disease, living in a nursing home or hospital, and hematorcrit <36.0% that Salzburg et al. (1996 & 1999) found to be important predictors of pressure ulcer development for people with SCI in acute and rehabilitation settings. No information on the reliability of the scale with any population could be located. Interpretability: There are issues with the interpretability of the measure given lack of detail in how to evaluate additional findings. Using a retrospective logistic regression anlaysis of hospital data from 226 patients, Salzberg (1999) found that the Gosnell had 18.4% sensitivity and 90.4% specificity for predicting the development of pressure ulcers in individuals with SCI within the first 30 days of admission. Salzberg did not indicate what cut-off score was used to achieve this level. Salzberg found correlations between scores on the Gosnell and stage of first pressure ulcer and number of pressure ulcers of r= 0.241 and 0.297 respectively. Acceptability: The score is easy for a health care provider to calculate, but additional items such as the assessment of skin condition may require additional patient assessment. Items on the scale would not represent a burden to either patients or researchers, if this data was already collected as part of the normal plan of care. However, if these items needed to be performed as additional procedures, however, it would represent considerable rater burden and some respondent burden. No different formats or translation in languages other than English could be located. Feasibility: Scoring takes 5-10 minutes and no special training is required. The scale is readily available from the original article and electronically. Clinical Summary: The Gosnell scale is a quick and easy to use, but validity evidence is poor with persons with SCI, and there has been no reliability or responsiveness testing. In light of these findings other generic scales (such as the Braden) or SCI specific scales such as the SCIPUS or SCIPUS-A would be recommended. Psychometric Summary:
Validity Responsiveness Results Rigor Results Floor/ceiling Predictive + N/A N/A N/A SS ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; SS=Sensitivity/Specificity Rigor N/A Rigor + Reliability Results N/A

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22.2.5 Functions of the Skin and Related Structures 22.2.5.3 Norton Measure The 5 item Norton scale was the first pressure ulcer risk assessment that was developed and was intended for use with a geriatric hospital population (Norton et al. 1962). The measure was developed based on the researchers clinical expertise. Five domains relevant to skin condition are considered: (1) physical condition, (2) mental condition, (3) activity, (4) mobility and (5) incontinence. They are measured on an ordinal scale from 1 to 4. Procedure: Raters indicate client status based on personal observation or chart review. Scales are scored on a domain specific ordinal scale from 1 to 4. Each item comes with standardized descriptive criteria recorded on the score sheet. A summary score ranging from 5 (worst prognosis) to 20 (best prognosis) is calculated. Advantages: The test is quick to administer, readily available. Ash (2002) indicated the Waterloo, Braden, Norton and SCIPUS-A all had similar moderate predictive power. The Norton is a commonly used scale with a variety of populations. Limitations: The scale omits items that Salzburg et al. (1996; 1999) found to be important predictors of pressure ulcer development for people with SCI such as pulmonary disease, serum creatinine > 1.0, extent of paralysis, albumim < 3.4 or T, protein < 6.4, autonomic dysreflexia or severe spacticity, age, tobacco use/smoking, disease, cardiac disease or glucose > 110 mg/dl, renal disease, living in a nursing home or hospital, and hematorcrit <36.0%. The reliability of the scale has not been demonstrated with a SCI population. Descriptors for item scoring are very brief (Wellard & Lo 2000). Salzberg (1999) found that the Norton was the worst measure for predicting stage and number of pressure ulcers in individuals with SCI during the first 30 days of admission compared to the SCIPUS, SCUIPUS-A, Braden, Gosnell and Abruzzese. Salzberg (1999) found correlations between scores on the Norton and stage of first pressure ulcer and number of pressure ulcers of r= -0.192 and -0.197 respectively. Interpretability: A cut-off score of 14 was suggested as a cut off score to identify individuals at risk for developing pressure sores, however, no evidence to support the use of this value (no sensitivity / specificity data) was provided (Norton et al. 1962). Because scoring descriptors are minimal, they may be subject to misinterpretation. Acceptability: Scoring and administration is easy. There is no patient burden. No alternative formats or version in languages other than English could be located. Feasibility: The Norton scale takes 5-10 minutes to administer and score. No training is required however knowledge of the area of wound care may is readily available for free on line or from the original publication. Clinical Summary: The Norton scale is a quick and easy to use, although there may be issues with interpretation of the scores. Validity evidence is poor and there has been no reliability or responsiveness testing with these individuals with SCI. Use of the Norton Scale is recommended by the Agency for Health Care Policy and Research (1992) but In light of the above findings other generic scales (such as the Braden) or SCI specific scales such as the SCIPUS or SCIPUS-A would be recommended. Psychometric Summary:
Validity Responsiveness Results Rigor Results Floor/ceiling Predictive + N/A N/A N/A Construct ++ SS ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; SS=Sensitivity/Specificity Rigor N/A Rigor ++ Reliability Results N/A

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22.2.5 Functions of the Skin and Related Structures 22.2.5.4 Spinal Cord Injury Pressure Ulcer Scale (SCIPUS) Measure The SCIPUS scale was developed as a measure of the risk for pressure ulcer development for individuals with spinal cord injury who are in a rehabilitation centre (Salzberg et al. 1996). Items for the scale were identified based on statistical analysis of data from 176 individuals with SCI, which compared development of pressure ulcers with demographic variables and potential pressure ulcer risk factors. Every patient is evaluated in fifteen domains (one item per domain): 1) level of activity, 2) mobility, 3) complete SCI, 4) urine incontinence or constantly moist, 5) autonomic dysreflexia or sever spacticity, 6) age, 7) tobacco use/smoking, 8) pulmonary disease, 9) cardiac disease or glucose > 110 mg/dl, 11) renal disease, 12) impaired cognitive function, 13) in a nursing home or hospital, 14) albumim < 3.4 or T, protein < 6.4 and 15) hematorcrit <36.0%. Most items are scored dichotomously as either present or absent, but 4 items have three response options. Procedure: Raters indicate client status based on personal knowledge of the of the client or chart review. Dichotomous items are given a weighted score of 0 when absent and 1 or 2 when present and non dichotomous items are given a weighted score based on the descriptive criteria provided on the scoring sheet. For example, the presence of pulmonary disease (ICD codes 450, 460-519 & 796.0) = a score of 2. By adding domain scores together a summary score is calculated which ranges from 0 = best prognosis to 25 = worst prognosis. Advantages: The content validity for the tool is likely the best for SCI as each of the items were identified based on data from individuals with spinal cord injury and needed to 1) demonstrate a significant statistical association with pressure ulcer development, 2) improve prediction, 3) be supported by the literature and 4) be biologically plausible. Correlations between scores on the SCIPUS and stage of first pressure ulcer and number of pressure ulcers are r= 0.343 and r= 0.339 respectively for individual with SCI in the first 30 days of admission. Limitations: Although the SCIPUS is reported to be the best measure for this population (Salzberg et al. 1996), the factors were identified with the same retrospective data that was used to determine the measures sensitivity and specificity, which may artificially inflate these numbers. The reliability of the scale has not been demonstrated with a SCI population. The scale was developed specifically for use in rehabilitation centers and has not been tested in community dwelling populations. The rationale for item scores is not well described. For example, the authors do not indicate why the presence of pulmonary disease receives a score of 2, whereas impaired renal function receives a score of 1. Interpretability: A cut off score of 6 has a sensitivity of 75.6% and a specificity of 74.4%. (Salzberg et al.1996). Response category scoring descriptors are operationalized in detail as noted in the level of activity example above. Acceptability: There is minimal burden related to administering or scoring the scale if tests for diabetes, albumin and hemocrit are already part of the patients medical record. Otherwise the blood tests required would be invasive and create respondent burden. No different formats or alternate language versions could be found. Feasibility: The SCIPUS takes 10-15 minutes to administer as long as laboratory data is already available otherwise additional time and burden is required. No special training is required to administer or score. The scale and its operational scoring definitions are available in the article that describes its development and testing (Salzberg et al. 1996). Clinical Summary: The SCIPUS scale is a quick and easy to use measure (if laboratory data is already available) that provides predictive information about risk of pressure sore. Despite the good content validity, other validity evidence is only adequate, and there has been no reliability or responsiveness testing. Additional reliability and responsiveness data is necessary. Psychometric Summary:
Reliability Validity Rigor Results Rigor Results Rigor N/A N/A ++ Predictive ++ N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information Responsiveness Results Floor/ceiling N/A N/A

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22.2.5 Functions of the Skin and Related Structures 22.2.5.5 Spinal Cord Injury Pressure Ulcer Scale Acute (SCIPUS-A) The SCIPUS-A scale was developed as a measure of the risk for pressure ulcer development for individuals with spinal cord injury who are in the acute phase of injury (within 30 days of admission) (Salzberg et al. 1999). Items for the scale were identified based on statistical analysis of data from 226 individuals with SCI, which compared development of pressure ulcers with demographic variables and 50 potential pressure ulcer risk factors. It consists of 8 items evaluating eight domains which include: 1) extent of paralysis, 2) moisture, 3) serum creatinine, 4) incontinence, 5) albumin, 6) mobility, 7) pulmonary disease, and 8) level of activity. Response categories are either dichotomous (present/ absent (score = 1 to 2 or 0, respectively) or have 3 to 5 options. For example, for extent of paralysis, none (ie. no paralysis) is awarded a score of 0, paraparesis =1, quadriparesis =4, paraplegia = 8 and quadriplegia = 10. Procedure: Raters indicate client function status based on personal experience or chart review. Scales are scored based on descriptive criteria provided on the scoring sheet. As noted above, responses to each item are awarded a value between 0 to 1-10 and these are added together to create a summary score of 0 = best prognosis to 25 = worst prognosis. Advantages: The content validity for the tool is high as it was designed for individuals with SCI. Domains were identified from data analysis from 226 individuals with spinal cord injury and needed to 1) demonstrate a statistical significant association with pressure ulcer development, 2) improve prediction, 3) be supported by the literature and 4) be biologically plausible. Weighting for factors was identified based on their regression coefficients. The SCIPUS-A had the highest correlations, for construct validity, compared to the SCIPUS, Braden, Gosnell, Abruzzese & Norton with this population (Salzburg et al. 1999). Limitations: Although the SCIPUS-A is reported to be the best measure for this population (Salzberg et al. 1999), the same retrospective data was used to determine the measures sensitivity and specificity and identify the domains used, which likely contributed to the higher values compared to other measures. As well, Ash (2002) indicated the Waterloo, Braden, Norton and SCIPUS-A all had similar moderate predictive power (however, the SCIPUS would have been more appropriate given the population he studied). Salzberg et al. (1999) indicated for individuals with SCI and a cut-off score of 10 the Braden scale had a 74.7% sensitivity and 56.6% specificity, which is only marginally worse than that of the SCIPUS-A (see below). Interpretability: Sensitivity and specificity percentages are provided at a variety of cut-off scores. A cut-off score of 18 has a sensitivity of 88.5% and a specificity of 59.0% for example. Response category descriptors are operationalized in detail as noted in the extent of paralysis example above. Acceptability: There is minimal burden related to administering or scoring the scale if tests for albumin and serum creatinine are already part of the patients medical record. Otherwise the blood tests required would be invasive and create respondent burden. No different formats or alternate language versions could be found. Feasibility: The SCIPUS takes 5-10 minutes to administer as long as laboratory data is already available otherwise additional time and burden is required. No special training is required to administer or score. The scale and its operational scoring definitions is available in the article that describes its development and testing (Salzberg et al. 1999). Clinical Summary: The SCIPUS-A scale is a quick and easy to use measure (if laboratory data is readily available) that provides predictive information about risk of pressure sore development. Despite the good content validity, other validity evidence is only adequate, and there has been no reliability or responsiveness testing with these individuals with SCI. Additional reliability and responsive data is necessary for this tool. Psychometric Summary:
Reliability Validity Rigor Results Rigor Results Rigor N/A N/A ++ Predictive ++ N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information Responsiveness Results Floor/ceiling N/A N/A

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22.2.5 Functions of the Skin and Related Structures 22.2.5.6 Waterlow Scale The Waterlow scale (Waterlow 1985) is a risk for pressure ulcer development assessment tool that was created to provide better sensitivity and specificity than the Norton by increasing the number of items used (Wellard & Lo 2000). Every patient is evaluated on eight domains(using 8 items): 1 ) age, 2) sex, 3) body build, 4)appetite, 5) continence of urine and feces, 6) mobility, 7) skin appearance in risk areas and (8) special risks (disorders associated with tissue malnutrition, neurological deficits, medication, recent surgery or trauma). Procedure: Raters indicate client status based on personal knowledge of the client or chart review. Items are scored as either dichotomous (yes/no) or on domain specific scales that range from 0-1 to 3-5. Domains are scored based on descriptive criteria provided on the scoring sheet (for example, for body build, average=0, above average =1, obese = 2 below average = 3) and totaled to produce a summary score from between 3 (best prognosis) to 45 (worst prognosis). Advantages: The test is quick to administer and readily available. Ash (2002) indicated the Waterlow (area under the curve (AUC) = 76% with a 68-84% confidence interval), Braden, Norton and SCIPUS-A all had similar moderate predictive power for patients with SCI. Limitations: Scoring for some scale items is poorly operationalized as noted in the example above. The weighting of items is not explained, but does make some intuitive sense as it frequently reflects weightings from other measures. The scale omits items that Salzburg et al. (1996; 1999) found to be important predictors of pressure ulcer development for people with SCI in acute and rehabilitation settings. The reliability of the scale has not been demonstrated with a SCI population, but poor inter-rater reliability has been reported in other populations (Kelly 2005). A revised version of the scale has been published but no research has been conducted regarding its psychometric properties. Interpretability: Interpreting scores is difficult given lack of detail in item descriptions. Scores of 10+ denote risk of developing a pressure ulcer, 15+ high risk and 20+ very high risk. No rationale is provided for how these numbers were determined. Acceptability: Easy to score and administrate with no patient burden. No other versions/formats or translation into other languages could be located. Feasibility: The scale takes 5-10 minutes to administer and no training is required. The original scale can be found at http://www.aelseating.com/pdfs/waterlow.pdf#search=%22Waterlow%20scale%22. The revised scale is available for free over the internet http://www.judywaterlow.co.uk/downloads/Waterlow%20Score%20Card.pdf. The Waterlow Pressure Ulcer Prevention Manual is available for 6.95 from http://www.judy-waterlow.co.uk/the-waterlowmanual.htm. Clinical Summary: The Waterlow scale is quick and easy to use screen that provides predictive information about the risk of developing a pressure sore. Validity evidence is adequate, but there has been no reliability or responsiveness testing with individuals with SCI. Although it is the most common measure used in the United Kingdom (Wellard & Lo 2000; Kelly 2005), reliability issues with the original scale in non SCI populations and lack of psychometric testing with the revised scale, suggest that other generic measures (such as the Braden) or SCI specific measures, such as the SCIPUS or SCIPUS-A should be considered for use. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling + Inter O + ++ AUC ++ N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; Inter O=interobserver; AUC=area under curve

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22.2.6 Functions of the Reproductive System 22.2.6.1 Emotional Quality of the Relationship Scale (EQR) The EQR scale measures feelings of affection and intimacy, ability to solve problems within the relationship, ability to communicate about sex with the partner and satisfaction with these areas and the relationship as a whole (Kreuter et al. 1994a). The 7 item EQR covers these topics as follows: affection and problem-solving (1 item each), communication (2 items) and satisfaction (3 items). Responses are scored on a four-point ordinal scale ranging from 4 (very great) to 1 (very poor) (Kreuter et al. 1996). Procedure: The EQR is a self-report instrument. Scores are summed resulting in a composite score that ranges from a maximum value of 28 to a minimum of 7. A higher score indicates that the emotional quality of the relationship is stronger. Advantages: The EQR is useful in looking at aspects of relationships experienced by individuals with spinal cord injuries. No other similar measures of these characteristics exist. Limitations: There is insufficient information provided that adequately describes the EQR. This tool has only been utilized in 3 studies referenced (Kreuter et al. 1994a; 1994b; 1996), but it was only one of a battery of questionnaires and was not used on its own. The lack of responsiveness limits the utility of the scale to measure changes after intervention. Interpretability: A greater summary score demonstrates better emotional quality of a relationship. There are no definitions and classifications of the results provided. Kreuter et al. (1994a; 1994b; 1996) reported mean values for SCI patients ranging from 21.65.0 to 23.93.9. Acceptability: The EQR questions are easily understood and the time participants take to complete the questionnaire is minimal. Kreuter et al. (1994a) found 33% and Kreuter et al. (1994b) found 40% of the subjects thought the questions talking about sex difficult to answer. It is currently only available in English. Feasibility: Staff burden is limited given the self-report nature of the scale and the estimated time for completion is 2-5minutes. No special equipment or training is required, however, the items may illicit an emotional response in the subject that requires professional attention. Copies of the tool can be obtained from the article referenced (Kreuter et al. 1996). Clinical Summary: Further investigation of tool is required before useful recommendations can be made. The tool could feasibly be used with both individuals with tetraplegia and paraplegia. Due to the lack of current literature using this tool, other more mainstream methods such as client interview should be used in conjunction with this scale. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ IC +++ +++ Construct ++ N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency

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22.2.6 Functions of the Reproductive System 22.2.6.2 Knowledge, Comfort, Approach and Attitude towards Sexuality Scale (KCAASS) The 45 item Knowledge, Comfort, Approach and Attitude towards Sexuality Scale was developed to assess the training needs and professional skills of staff working in sexuality rehabilitation with spinal cord injury patients (Kendall et al. 2003). Four subscales are found within the questionnaire: knowledge (14 items), comfort (21 items), approach (5 items), and attitudes (5 items). A four-point Likert scale is used for all subscales, where 1=no knowledge/no discomfort/strongly disagree (for both approach and attitudes subscales) and 4=excellent knowledge/high discomfort/strongly agree (for both approach and attitudes subscales). Procedure: The KCAASS is administered by interview. Summary scores for each of the four aspects of sexuality are calculated (knowledge (/56); comfort (/104); approach (/20); attitude (/20)) with higher scores representing greater knowledge and skills. The subscales comfort, approach and attitude are reverse scored (Kendall et al. 2003). A maximum composite score of 200 is obtained by summing up the subscales. Advantages: The KCAASS is an SCI specific tool that identifies the individual training needs of staff working in sexual rehabilitation and aids in the development of educational programs. Principal components factor analysis confirmed the presence of 5 individual factors (knowledge, comfort, attitudes, approach and appropriateness), which accounted for 66% of the overall variance. The alpha coefficients for the subscales are all high (>.80) suggesting the items are internally consistent. Fronek et al. (2005) evaluated the change in each subscale using treatment and control groups, and discovered significant improvement across all subscales demonstrating the effectiveness of such a program. The scale was developed specifically for use within the spinal cord population. Limitations: There was weak item-total correlation between the composite score and attitude and the approach subscales illustrating these subscales should be considered separately. This is not a concern as the utility of having a composite score for developing an educational program is questionable. Interpretability: Scores for each scale provide an assessment of where education time should be allocated when creating a sexual education program. There are no classifications for the results as the purpose of the scale is to assess where the greatest need for education lies. Mean values for comparison are available in the Kendall et al. (2003) and Fronek et al. (2005) articles in case comparisons with other users need to be made. Acceptability: The scale items were developed based on literature review and are SCI specific. The scale appears to be comprehensive in nature. The tool is available in English and Dutch. Feasibility: The KCAASS is easy to administer and score. Approximately 10-15 minutes is required to complete the scale although interviewing different learners may be time-consuming and may not assist in course development for a group. If the KCAASS is self-administered then staff burden and timing issues are reduced. Copies of the questionnaire can be accessed by obtaining the paper by Kendall et al. 2003. Clinical Summary: The KCAASS addresses a broad range of potential topics which helps identify specific areas that should be focused on when developing sexual education programs for staff working within the spinal cord population. Information elicited from this tool could enhance the quality and comfort of sexual education for both the staff and client. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ IC +++ ++ Content ++ ++ + N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency

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22.2.6 Functions of the Reproductive System 22.2.6.3 Sexual Attitude and Information Questionnaire The SAIQ was developed to evaluate the impact of counseling programs and sexual education for persons with SCI and their partners (Brockway et al. 1978). The original SAIQ (number of items not stated) consists of four scales while the revised 39-item SAIQ includes more items within each scale and a single rating of overall concern for ones ability to have a satisfactory sexual relationship. The revisions to the original SAIQ were made to enhance reliability and validity (Brockway & Steger 1980). The SAIQ-revised is broken down as follows: scale I, sexual information (18 multiple-choice questions), scale II, sexual behavior acceptability (6 items), scale III, sexual concerns (8 items), and scale IV, non-sexual concerns (6 items). Scales II and III and the overall rating of sexual concern are scored using a 6-point Likert-scale (from 1= totally disagree/extremely concerned to 6=totally agree/not concerned) and scale IV also uses a 6-point scale, but scores are inversed (1=not concerned to 6=extremely concerned). Procedure: SAIQ is a self-report questionnaire. The subscales are scored independently of one another. Scale I is scored according to the number of items answered correctly. The scale scores for scales II, III and IV are found by summing ratings across items. Advantages: SAIQ considers not only sexual behavior but also sexual and non-sexual concerns, illustrating a more client-centered questionnaire. A lack of change in ratings for nonsexual functioning demonstrates that sexual education and counseling programs are specific in emphasizing change of attitude towards sexuality and not other non-sexual concerns (Brockway et al. 1978). Limitations: Responsiveness data may be questionable, as control groups were not used and learning effects may be responsible for the changes seen (Brockway et al. 1978). The questionnaire may require up-dating, as there has been a considerable increase in public awareness and understanding of issues such as erectile dysfunction since its publication in 1980. Interpretability: Each subscale presents separate information: higher scores for scale I suggest individuals are knowledgeable about physiological aspects of sexual functioning, higher scores on scale II represents acceptance of sexual behaviors, higher scores on scale III indicates little concern about sexual functioning, and higher scores on scale IV suggests considerable concern about non-sexual functioning (Brockway & Steger 1980). Acceptability: The SAIQ is easy to complete and the phasing is clear and not misleading; however, the content may be culturally sensitive. Some sex specific issues are considered (e.g. issues related to the menstrual cycle). The SAIQ is currently only available in English. Feasibility: Administration and scoring of the tool takes 10-15 minutes. No special equipment is required. If used as part of a counseling or training program then staff training is required. Contact the author at brockja@u.washington.edu to obtain a copy of the scale. Clinical Summary: The SAIQ may prove to be a useful tool to evaluate the effectiveness of sexual counseling and education programs designed for individuals with tetraplegia and/or paraplegia. Also, the tool may be useful for identifying individuals who would benefit from such a program. Psychometric Summary
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling IC +++ ++ Construct + ++ + N/A TR +++ Concurrent ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; IC=internal consistency Rigor +++

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22.2.6 Functions of the Reproductive System 22.2.6.4 Sexual Behaviour Scale (SB) The SB scale measures the sexual expressions used by couples. There are seven items that cover touching, kissing, manual and oral stimulation of genital and other erogenous zones, and sexual intercourse (Kreuter et al. 1996). Procedure: The SB is a self-report instrument. Items are summed resulting in a composite score that ranges from a maximum value of 49 to a minimum value of 7. Advantages: There is high internal consistency (alpha=.96) suggesting the stability of the items is good and the high factor loadings of the items using principle components suggest the scale is measuring a single dimension (behaviour). Limitations: There is no description of the response categories used with this scale. The scale has only been used as part of a larger battery of questionnaires and not on its own. Additional study of the psychometrics such as test-retest reliability is required. Interpretability: There are no definitions or classifications, important cut point or norms provided to assist with interpreting the scores. No descriptions of scores are given, other than the higher the score the better. Acceptability: The time taken to complete the SB is less than 5 minutes. Feasibility: Staff burden is minimal. No special equipment or training is required. Contact the author at margareta.kreuter@fhs.gu.se to obtain a copy of the scale. Clinical Summary: The SB allows a couple to gain insight into the type and degree of sexual expression they experience together. The information obtained from this tool might be useful in assisting couples with issues related to sexual intimacy. There is limited information found on the SB and further study is required before recommending this tool for clinical use. Psychometric Summary
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ IC ++ ++ FA ++ N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency; FA=factor analysis

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22.2.6 Functions of the Reproductive System 22.2.6.5 Sexual Interest, Activity and Satisfaction (SIAS) / Sexual Activity and Satisfaction (SAS) Scales The SAIS (Kreuter et al. 1994a; 1994b) and SAS (Kreuter et al. 1996) are tools used to investigate the sexual activity and satisfaction of individuals with SCI. The SAIS consists of 6 items covering the following areas: sexual desire (1 item; scale from 1, very often, to 4, never), sexual activity (1 item; scale from 1, never, to 8, every other day), and sexual satisfaction (4 items; differing scales from a 3-point to 5-point response; see tool). Based on research by the developers (Kreuter et al. 1994; 1996), the 3-item SAS was created by removing the sexual desire item and two sexual satisfaction items from the SAIS, thus leaving the sexual activity item (same scale as above) and two sexual satisfaction items (scale from 1, not at all, to 4, very much). Procedure: The SAIS and SAS are self-report questionnaires. The response items can be summed without weights or standardization. The composite score ranges from 28 to 6 for SAIS and 16 to 3 for SAS. A higher score indicates greater sexual activity and satisfaction. Advantages: This tool is one of the better researched measures within the area of sexual interest and satisfaction. There is strong psychometric support for the scales with alpha values between .8 and .9. Validity is supported by principle components analysis which demonstrates strong uni-dimensionality (the scale consists of a single dimension) with both SCI and general population samples. Support for construct validity exists based on hypothesis testing. Limitations: Detailed explanation of the purpose of the scale modification is not provided in the literature. Independent replication of the psychometrics and additional studies of test-retest reliability and responsiveness is require if the scale is to be used for evaluating the effect of interventions. Interpretability: There are no consistent definitions or classifications for the results detailed within the paper that developed SAS (Kreuter et al. 1996). For mean values for normative comparisons consult Kreuter et al. (1994a; 1994b) for the SAIS and Kreuter et al. (1996) for the SAS. Acceptability: These scales take between 1-2 minutes to complete. The items may contain content that is culturally sensitive. These tools are only available in English. The tool may be administered in interview format if required. Feasibility: There is relatively no staff burden due to the short length of this measure. No special training is required to score or administer the SAS. The articles referenced contain the tools (Kreuter et al. 1994;1996). Clinical Summary: Both of these tools may be clinically useful to assist in understanding, describing and quantifying the sexual activity and satisfaction of individuals with SCI (both tetra and paraplegia). The tools may provide a platform from which to explore issues of sexuality. Upon further study, the tool may also be effective in evaluating the effectiveness of sex specific interventions. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling +++ IC +++ +++ Construct ++ N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; IC=internal consistency

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22.2.6 Functions of the Reproductive System 22.2.6.6 Sexual Interest and Satisfaction Scale (SIS) The 7-item SIS scale measures sexual adjustment after SCI. The tool was designed to assess different aspects of sexuality before and after injury. Four items determine the impact SCI had on sexuality and sexual function using a 4-point response scale (increased=3, unchanged=2, decreased=1, and absent=0). The remaining 3 questions assess general satisfaction before and after injury, using a modified visual analogue scale with 7 marked intervals and end point descriptors of very dissatisfied (1) to very satisfied (7) (Siosteen et al. 1990). Procedure: The SIS is self-administered then checked by personal interview. The scores for the 3 satisfaction items are rescaled to a range of 0 to 3 in order to enable calculation of a composite score. The composite score is a sum of 6 items (satisfaction pre-injury is not used) and has a maximum value of 18 and a minimum value of 0. Advantages: The SIS was developed for use in the spinal cord population. It provides a quick review of the individuals sexual experiences, while factoring in their pre-injury state. The internal consistency (alpha=.96) is extremely high and the factor analysis indicates this tool represents a single dimension, despite the tool name. Furthermore, it has strong construct validity, for example, frequency of sexual intercourse predicts 56% of the variance in the SIS. Limitations: The type of spinal cord injury needs to be taken into consideration when interpreting the results. Sexual adjustment for those with incomplete injuries may differ considerably when compared to complete injuries. Lack of depth and breadth of the SIS items may limit the usefulness to clinicians. Furthermore, description of the SIS is inconsistent within the literature. Independent assessment of the reliability and validity and investigation of the testretest reliability and responsiveness of the tool is warranted. Interpretability: Achieving a high score on the SIS illustrates greater sexual adjustment while a lower scorer demonstrates poor sexual adjustments after spinal cord injury. There are no known cut points or norms to assist with interpretation. Acceptability: Patient burden in completing the SIS is minimal due to the small number of questions. Items should be acceptable to both males and females. Question items may seem personal and embarrassing to some. This tool is available only in English. Feasibility: Administration and scoring requires approximately 5 minutes. No special training is required to administer or score this tool and it can be found in Siosteen et al. (1990). Clinical Summary: Sexual satisfaction and interest is an area of serious concern for the SCI population. The SIS provides a reasonably well defined spinal cord specific measure that may be useful in eliciting information regarding a sensitive area. Although it has not been widely used and psychometric properties have been reported by only one study, it is one of few sexuality scales that have been used within the SCI population. When comparing pre and post injury results in those with tetraplegia, one must consider the time since injury, as this variable affects sexual function and satisfaction. Psychometric Summary
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ IC +++ ++ Content ++ N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency

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Body Function / Structure References Agency for Health Care Policy and Research (AHCPR). Panel on the prediction and prevention of pressure ulcers in adults. Pressure Ulcers in Adults: Prediction and Prevention. In Clinical Practice Guideline No. 3. AHCPR Publication No. 92-0047. Rockville MD: AHCPR; 1992. American Spinal Injury Association: International Standards for Neurological Classification of Spinal Cord Injury, revised 2002. 2002. Chicago, IL, American Spinal Injury Association. Ash D. An exploration of the occurrence of pressure ulcers in a British spinal injuries unit. J Clin Nurs 2002;11:470-478. Ashworth B. Preliminary trial of carisoprodol in multiple sclerosis. Practitioner 1964;192:540542. Ayalon A, Inbar O, Bar-Or O. Relationships among measurements of explosive strength and anaerobic power. In: Nelson RC, Morehouse CA. (ed). International Series on Sport Science 1: Biomechannics IV. University park press, Baltimore, MD, 1974, p 527-532. Aydin G, Tomruk S, Keles I, Demir SO, Orkun S. Transcutaneous electrical nerve stimulation versus baclofen in spasticity: clinical and electrophysiologic comparison. Am J Phys Med Rehabil 2005;84:584-592. Bar-Or O, Inbar O, Dotan R. Proficiency, speed and endurance test for the wheelchair-bound. In: Simri U. (ed). Motor Learning in Physical Education and Sports. Wingate Institute, Natanya, Israel,1976: p 310-318. Bar-Or O, Dotan R, Inbar O. A 30 second all out ergometric test its reliability and validity for anaerobic capacity. Isreali J Med Sci 1977;13:326. Bar-Or, Inbar O. Relationships among anaerobic capacity, sprint and middle distance running of school children. In: Shephard RJ, Lavelle H. (ed). Physical Fitness Assessment. Charles C Thomas, Springfield, IL,1978: p 142-147. Benz EN, Hornby TG, Bode RK, Scheidt RA, Schmit BD. A physiologically based clinical measure for spastic reflexes in spinal cord injury. Arch Phys Med Rehabil 2005;86:52-59. Bergstrom N, Braden BJ, Laguzza A, Holman V. The Braden Scale for Predicting Pressure Sore Risk. Nurs Res 1987;36:205-210. Bernadt MW, Mumford J, Taylor C, Smith B, Murray RM. Comparison of questionnaire and laboratory tests in the detection of excessive drinking and alcoholism. Lancet 1982;1:325 328. Blaustein DM, Zafonte R, Thomas D, Herbison GJ, Ditunno JF. Predicting recovery of motor complete quadriplegic patients. 24 hour v 72 hour motor index scores. Am J Phys Med Rehabil 1993;72:306-311. Bombardier CH, Richards JS, Krause J, Tulsky D, Tate D. Symptoms of Major Depression in People With Spinal Cord Injury: Implications for Screening. Arch Phys Med Rehabil 2004;85:1749-1756. Booth S, Kendall M, Fronek P, Miller D, Geraght T. Training the interdisciplinary team in sexuality rehabilitation following spinal cord injury: A needs assessment. Sex Disabil 2003;21:249-261. Boviatsis EJ, Kouyialis AT, Korfias S, Sakas DE. Functional outcome of intrathecal baclofen administration for severe spasticity. Clin Neurol Neurosurg 2005;107:289-295. Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 1987;67:206-207. Brockway JA, Steger JC. Sexual attitude and information questionnaire: Reliability and validity in a spinal cord injured population. Sex Disabil 1981;4:49-60. Brockway JA, Steger JC, Berni R, Ost V, Williamson-Kirkland TE, Peck CL. Effectiveness of a sex education and counseling program for spinal cord injured patients. Sex Disabil 1978;1:127-136.

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Calancie B, Molano MR, Broton JG, Bean JA, Alexeeva N. Relationship between EMG and muscle force after spinal cord injury. J Spinal Cord Med 2001;24:19-25. Cardenas D, Turner J, Warms C, Marshall H. Classification of chronic pain associated with spinal cord injuries. Arch Phys Med Rehabil 2002;83:1708-1714. Cohen ME, Ditunno JF, Jr., Donovan WH, Maynard FM, Jr. A test of the 1992 International Standards for Neurological and Functional Classification of Spinal Cord Injury. Spinal Cord 1998;36:554-560. Cohen ME, Sheehan TP, Herbison GJ. Content validity and reliability of the International Standards for Neurological Classification of Spinal Cord Injury. Top Spinal Cord Inj Rehabil 1996;1:15-31. Curtis KA, Roach KE, Applegate EB, Amar T, Benbow CS, Genecco TD, Gualano J. Development of the Wheelchair User's Shoulder Pain Index (WUSPI). Paraplegia 1995;33:290-293. Curtis KA, Roach KE, Applegate EB, Amar T, Benbow CS, Genecco TD, Gualano J. Reliability and validity of the Wheelchair User's Shoulder Pain Index (WUSPI). Paraplegia 1995;33:595-601. Curtis KA, Drysdale GA, Lanza RD, Kolber M, Vitolo RS, West R. Shoulder pain in wheelchair users with tetraplegia and paraplegia. Arch Phys Med Rehabil 1999;80:453-457. Dahl TH. International classification of functioning, disability and health: An introduction and discussion of its potential impact on rehabilitation services and research. J Rehabil Med 2002;34:201-204. Donovan W, Dimitrijevic M, Dahm L, Dimitrijevic M. Neurophysiological approaches to chronic pain following spinal cord injury. Paraplegia 1982;20:135-146. Ewing JA. Detecting Alcoholism: The CAGE Questionnaire. JAMA 1984; 252:1905-1907. Frankel HL, Hancock DO, Hyslop G, Melzak J, Michaelis LS, Ungar GH, Vernon JD, Walsh JJ. The value of postural reduction in the initial management of closed injuries of the spine with paraplegia and tetraplegia. Paraplegia 1969;7:179-192. Fronek P, Booth S, Kendall M, Miller D, Geraght T. The effectiveness of a sexuality training program for the interdisciplinary spinal cord injury rehabilitation team. Sex Disabil 2005;23:51-63. Gianino JM, York MM, Paice JA, Shott S. Quality of life: effect of reduced spasticity from intrathecal baclofen. J Neurosci Nurs 1998;30:47-54. Gosnell DJ. An assessment tool to identify pressure sores. Nurs Res 1973;22:55-59. Graves DE, Frankiewicz RG, Donovan WH. Construct validity and dimensional structure of the ASIA motor scale. J Spinal Cord Med 2006;29:39-45. Haas BM, Bergstrom E, Jamous A, Bennie A. The inter rater reliability of the original and of the modified Ashworth scale for the assessment of spasticity in patients with spinal cord injury. Spinal Cord 1996;34:560-564. Hawley JA, Williams MM, Vickovic MM, Handcock PJ. Muscle power predicts freestyle swimming performance. Br J Sports Med 1992;26:151-155. Hayes KC, Wolfe DL, Hsieh JT, Potter PJ, Krassioukov A, Durham CE. Clinical and electrophysiologic correlates of quantitative sensory testing in patients with incomplete spinal cord injury. Arch Phys Med Rehabil 2002;83:1612-1619. Jacobs P, Mahoney E, Johnson B. Reliability of wingate anaerobic testing in persons with complete paraplegia. J Spinal Cord Med 2003;26:141-144. Jacobs PL, Johnson B, Somarriba GA, Carter AB. Reliability of upper extremity anaerobic power assessment in persons with tetraplegia. J Spinal Cord Med 2005;28:109-113. Jonsson M, Tollback A, Gonzales H, Borg J. Inter-rater reliability of the 1992 international standards for neurological and functional classification of incomplete spinal cord injury. Spinal Cord 2000;38:675-679.

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Kelly J. Inter-rater reliability and Waterlows pressure ulcer risk assessment tool. Nursing Standard 2005;19:86-87,90-92. Kendall M, Booth S, Fronek P, Miller D, Geraghty T. The development of a scale to assess the training needs of professionals in providing sexuality rehabilitation following spinal cord injury. Sex Disabil 2003;21:49-64. Krassioukov A, Wolfe DL, Hsieh JT, Hayes KC, Durham CE. Quantitative sensory testing in patients with incomplete spinal cord injury. Arch Phys Med Rehabil 1999;80:1258-1263. Kreuter M, Sullivan M, Siosteen A. Sexual adjustment and quality of relationships in spinal paraplegia: A controlled study. Arch Phys Med Rehabil 1996;77:541-548. Kreuter M, Sullivan M, Siosteen A. Sexual adjustment after spinal cord injury (SCI) focusing on partner experiences. Paraplegia 1994; 32:225-235. Kreuter M, Sullivan M, Siosteen A. Sexual adjustment after spinal cord injury (SCI) -comparison of partner experiences in pre- and postinjury relationships. Paraplegia 1994;32:759-770. Kuptniratsaikul V, Chulakadabba S, Ratanavijitrasil S. An instrument for Assessment of Depression among Spinal Cord Injury Patients: Comparison between the CES-D and the TDI. J Med Assoc Thai 2002; 85:978-982 LaChapelle D, Alfano D. Revised neurobehavioral scales of the MMPI: Sensitivity and specificity in traumatic brain injury. Appl Neuropsychol 2005;12:143-150. Lazar RB, Yarkony GM, Ortolano D, Heinemann AW, Perlow E, Lovell L, Meyer PR. Prediction of functional outcome by motor capability after spinal cord injury. Arch Phys Med Rehabil 1989;70:819-822. Lechner HE, Frotzler A, Eser P. Relationship between self- and clinically rated spasticity in spinal cord injury. Arch Phys Med Rehabil 2006;87:15-19. Lim HK, Lee DC, McKay WB, Priebe MM, Holmes SA, Sherwood AM. Neurophysiological assessment of lower-limb voluntary control in incomplete spinal cord injury. Spinal Cord 2005;43:283-290. Lim HK, Sherwood AM. Reliability of surface electromyographic measurements from subjects with spinal cord injury during voluntary motor tasks. Journal of Rehabilitation Research & Development 2005;42:413-421. Marino RJ, Graves DE. Metric properties of the ASIA motor score: subscales improve correlation with functional activities. Arch Phys Med Rehabil 2004;85:1804-1810. Measurement Excellence and Training Resources Information Center. Critical Review of CAGE Questionnaire. Available fromURL: http://www.measurementexperts.org//instrument/instrument _reviews.asp?detail=46 Norton D, McLaren R, Exton-Smith AN. An Investigation of Geriatric Nursing Problems in Hospitals. London: National Corporation for the Care of Old People;1962. Noth J. Trends in the pathophysiology and pharmacotherapy of spasticity. J Neurol 1991;238:131-139. Penn RD. Intrathecal baclofen for severe spasticity. Ann N Y Acad Sci 1988;531:157-166. Priebe MM, Sherwood AM, Thornby JI, Kharas NF, Markowski J. Clinical assessment of spasticity in spinal cord injury: a multidimensional problem. Arch Phys Med Rehabil 1996; 77:713-716. Priebe MM, Waring WP. The interobserver reliability of the revised American Spinal Injury Association standards for neurological classification of spinal injury patients. Am J Phys Med Rehabil 1991;70:268-270. Pullman SL, Goodin DS, Marquinez AI, Tabbal S, Rubin M. Clinical utility of surface EMG: report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology. Neurology 2000;55:171-177. Putzke JD, Richards JS, Ness T, Kezar L. Test-retest reliability of the Donovan spinal cord injury pain classification scheme. Spinal Cord 2003;41:239-241.

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Putzke JD, Richards JS, Ness T, Kezar L. Interrater reliability of the International Association for the Study of Pain and Tunks' spinal cord injury pain classification schemes. Am J Phys Med Rehabil 2003;82:437-440. Radloff LS. CES-D scale: A self report depression scale for research in the general populations. Applied Psychological Measurement 1977;1:385-401. Radloff LS. The Use of the Center for Epidemiological Studies of Depression Scale in Adolescents and Young Adults. J Youth Adoles 1991;20:149-166. Richards JS, Hicken BL, Putzke JD, Ness T, Kezar L. Reliability characteristics of the Donovan spinal cord injury pain classification system. Arch Phys Med Rehabil 2002;83:1290-1294. Salzberg CA, Byrne DW, Kabir R, van Niewerburg P, Cayten CG. Predicting pressure ulcers during initial hospitalization for acute spinal cord injury. Wounds 1999;11:45-57. Salzberg C A, Byrne DW, Cayten CG, van Niewerburgh P, Murphy JG, Viehbeck M. A new pressure ulcer risk assessment scale for individuals with spinal cord injury. Am J Phys Med Rehabil 1996;75:96-104. Sawatzky BJ, Slobogean GP, Reilly CW, Chambers CT, Hol AT. Prevalence of shoulder pain in adult- versus childhood-onset wheelchair users: a pilot study. J Rehabil Res Dev 2005;42:18. Siosteen A, Lundqvist C, Blomstrand C, Sullivan L, Sullivan M. Sexual ability, activity, attitudes and satisfaction as part of adjustment in spinal cord-injured subjects. Paraplegia 1990;8:285-295. Skold C. Spasticity in spinal cord injury: self- and clinically rated intrinsic fluctuations and intervention-induced changes. Arch Phys Med Rehabil 2000;81:144-149. Spitzer RL, Kroenke K, Williams J. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA 1999;282:1737-1744. Tate D. Alcohol Use Among Spinal Cord Injured Patients. Am J Phys Med Rehabil 1993;72:175183. Tate DG, Forcheimer M, Maynard F, Davidoff G, Dijkers M. Comparing Two Measures of Depression in Spinal Cord Injury. Rehabil Psychol 1993;38:53-61. Tunks E. Pain in spinal cord injured patients. In: Bloch R, Basbaum M (ed). Management of Spinal Cord Injuries. Williams and Wilkins, Baltimore, MD, 1986: p 180-211. Waterlow JJ. Pressure sores: a risk assessment card. Nurs Times1985;81:49-55. Wellard S, Lo SK. Comparing Norton, Braden and Waterlow risk assessment scales for pressure ulcers in spinal cord injuries. Contemp Nurse 2000;9:155-160. Zung WWK. A self-rating depression scale. Arch Gen Psychiatry 1965;12:63-70.

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22.3 Activity Activity as defined for use in the International Classification of Function, Health and Disability (WHO 2001) is the execution of a task or action. As such activity can be considered to occur at a person level rather than a systems level such as body function. A debate exists regarding the segregation of activity and participation as separate components or in our case classifications and even the (WHO 2001) acknowledges this difficulty and therefore presents the domains as a single list. Recently Jette et al. (2003) tested the hypothesis that activity and participation were distinct dimensions within physical function. They concluded that distinct concepts were indeed identifiable for mobility and daily activities and social/participation. As such we present tools mobility and self care (daily) activity tools in the following section. The reader is reminded that several tools cross not only domains (mobility, daily activity) but also components (activity, participation). In this case we have classified the tool in the area most clearly represented by measure. For example in a self report questionnaire this would be reflected by the area with the most questions (items). The outcome measures reviewed under this category include. 22.3.1 Mobility......................................................................................................................22-42 22.3.1.1 4 Functional Tests for Persons who Self-Propel a Manual Wheelchair (4FTPSMW) ........................................................................................................22-42 22.3.1.2 10 Meter Walking Test (10 MWT) ..........................................................................22-43 22.3.1.3 Functional Standing Test (FST) .............................................................................22-44 22.3.1.4 Modified Functional Reach Test (mFRT) ...............................................................22-45 22.3.1.5 Tetraplegia Hand Activity Questionnaire (THAQ) ..................................................22-46 22.3.1.6 Timed Motor Test (TMT) ........................................................................................22-47 22.3.1.7 Timed Up and Go Test (TUG)................................................................................22-48 22.3.1.8 Walking Index for Spinal Cord Injury (WISCI) and WISCI II...................................22-49 22.3.1.9 Wheelchair Circuit (WC) ........................................................................................22-50 22.3.1.10 Wheelchair Skills Test..........................................................................................22-51 22.3.2 Self-care....................................................................................................................22-52 22.3.2.1 The Barthel Index...................................................................................................22-52 22.3.2.2 Functional Indepedence Measure (FIM) ................................................................22-53 22.3.2.3 Quadriplegia Index of Function (QIF).....................................................................22-55 22.3.2.4 Self Care Assessment Tool (SCAT) ......................................................................22-56 22.3.2.5 Skin Management Needs Assessment Checklist (SMNAC) ..................................22-57 22.3.2.6 Spinal Cord Injury Lifestyle Scale (SCILS) ............................................................22-58 22.3.2.7 The Spinal Cord Independence Measure (SCIM) ..................................................22-59

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22.3.1 Mobility 22.3.1.1 4 Functional Tests for Persons who Self-Propel a Manual Wheelchair (4FTPSMW) The 4 Functional Tests for Persons who Self-Propel a Manual Wheelchair (4FTPSMW) was developed to assist clinicians in assessing the effect of different postural supports (e.g. back support and seat cushions) (May et al. 2003). The assessment of postural supports is important because they can influence sitting comfort, postural alignment, buttock pressure and functional abilities (May et al. 2003). Existing tests assessing wheelchair skills such as the Wheelchair Skills Test are not ideal due to the crude nature of the scoring schema (i.e. pass/fail). A test assessing sitting balance, such as the modified Functional Reach Test, are not well suited to assessing postural supports since the individual reaches forward and removes contact with their back support. The test was developed by an experienced group of physiotherapists. A literature review was conducted and input from individuals with SCI and researchers were obtained. The test includes 4 tasks: 1) timed forward wheeling; 2) ramp ascent (forward wheeling); 3) forward vertical reach distance; and 4) one-stroke push replaced ramp decline. Five minute rest breaks were provided between tasks to limit fatigue. Procedure: The tasks in the 4FTPSMW are scored as follows: 1) timed forward wheeling (seconds); 2) ramp ascent (forwards wheeling) (seconds); 3) forward vertical reach distance (cm); and 4) one-stroke push (cm). Advantages: The 4FTPSMW was conceptually well developed to be a functional test suited for the clinical setting (May et al. 2003). For example the timed forward wheeling task is based on a distance of 23 meters (plus length of the wheelbase), which is the average length of a crosswalk in a 4 lane intersection. Limitations: The 4FTPSMW is a relatively new test and has not been widely tested. To date, the test has not included female subjects and limited information was available on the types of SCI included in the initial study (i.e. no information was available on the ASIA impairment grade, level or completeness of injury). It is only relevant to individual who use a manual wheelchair (i.e. not suited to individuals who use an electric wheelchair). Interpretability: The 4FTPSMW assesses the capacity of an individual to complete functional tasks wheelchair task which will enable postural supports to be compared. The scoring system is useful since it is objective and has ratio level properties. No normative data is available. Acceptability: The tasks included in the 4FTPSMW were tolerated well by participants, only the ramp ascend task was difficult for an individual with C6 SCI at 4 months post injury. Feasibility: The 4FTPSMW is well suited to be administered in the clinical setting. The tasks have been well described which allows the test to be administered in a standardized manner. The equipment required for the test includes: 23 m corridor, 1 m measuring stick, ramp (10.3 m and 1:13 grade), carpeted surface (1.5 cm pile), and a stop watch. The test takes between 30 45 minutes to complete 2 trials of the 4 functional tasks including rest breaks (note: 2 trials were required for test re-test reliability rather than to eliminate the practice effect). Clinical Summary: The 4FTPSMW appears to be a useful test to assess postural support in individuals with SCI, however data to validate that it can discriminate between different postural supports has not been provided (May et al. 2003). Future research should compare tests such as the 4FTPSMW with the modified Functional Reach Test and the Wheelchair Skills Test to assist clinicians in determining what information is provided by each test and the test(s) needed to prescribe wheelchairs, cushions, back supports and to assess wheelchair skills. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ TR +++ N/A N/A N/A N/A N/A ++ Inter O +++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; Inter O=interobserver

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22.3.1 Mobility 22.3.1.2 10 Meter Walking Test (10 MWT) The 10 Meter Walk Test (10 MWT) assesses short duration walking speed (m/sec). It has been used in various patient populations including stroke, Parkinsons disease, patients with general neurologic movement disorders and only recently has been assessed in individuals with SCI (van Hedel et al. 2005; 2006). The 10 MWT measures the measures the time (seconds) for an individual to walk 10 meters. It is performed using a flying start, patient walks 14 meters and the time is measured for the intermediate 10 meters. The individual walks at their preferred walking speed. Individuals can use an assistive device and must wear shoes. Procedure: The time (seconds) is reported and can also calculate a walking speed m/sec. Advantages: The 10 MWT is easy to administer in the clinical setting or in the community. The equipment required is available in the clinical setting and includes a 14 m corridor and a stopwatch. Responsiveness has been assessed in patients with incomplete SCI at 1, 3, 6 and 12 months after SCI and was reported to be superior to measures with an interval scale (i.e. WISCI II) (van Hedel et al. 2006). Limitations: The 10 MWT only assesses walking ability and does not consider the amount of physical assistance required, devices or endurance. The test is also conducted in a controlled environment (i.e. lab setting) and so results can not be directly translated to the environment (i.e. crossing a busy street). The 10 MWT also requires an individual to ambulate a minimum of 14 m. There have been reports in the literature that the distance is not always standardized (i.e. 10 m versus 14 m). Interpretability: The information obtained from the 10 MWT can be reported as a time (seconds) or a walking speed. Results of the 10 MWT have been reported in the literature for individuals with incomplete SCI. An average 10 MWT was 30+28 seconds (van Hedel et al. 2005) with a walking speed of 4.5 km h-1 (1.25 m s-1). Normative values are available for walking speed (i.e. reported to be 4.7 km h-1 [1.31 m s-1]). It is also possible to compare results for various patient populations. Acceptability: The 10 MWT is a short test taking approximately 30 sec and is suitable for individuals who can at a minimum, ambulate in household settings (i.e. > 14 m). Feasibility: The 10 MWT is quick and easy to administer in the clinical setting, does not require any special equipment, and does not require advanced training. Clinical Summary: The 10 MWT assesses short distance capacity in ambulation and other measures are required to assess balance, physical assistance required and endurance. It appears to be a useful measure in the SCI population for both research and clinical practice. The scale properties (time in sec or m/sec) of the 10 MWT make it a responsive test well suited to evaluating clinical interventions. Psychometric Summary:
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling Inter O +++ ++ Construct +++** + +++* N/A Intra O +++ Concurrent ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; Inter O=interobserver; Intra O=intraobserver; varied (re. floor/ceiling effects; mixed results). * Responsiveness assessed using the Freidmans test. ** For construct validity, the results with other walking tests (i.e. TUG & 6 MWT) were considered stronger evidence to support validity compared to LEMS based on ASIA. Rigor +

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22.3.1 Mobility 22.3.1.3 Functional Standing Test (FST) The Functional Standing Test (FST) is designed to assess an individuals ability to perform one handed reaching tasks while standing (Triolo et al. 1994). This test was originally developed using able-bodied individuals and has been modified for individuals with SCI. The FST is unique because it defines standing as a stable upright posture that frees at least one upper extremity to manipulate objects, while other standing tests focus on specific factors such as balance, endurance, coordination etc. The FST consists of 21 tasks, 6 of which are the same as in the Jebson Test of Hand Function. Tasks involve gross to fine motor skills, crossing midline, lifting and lowering light and heavy objects to and from a set of shelves which is intended to simulate a kitchen cabinet. Examples of tasks include: lifting light objects down from the lowest shelf; stacking checkers on the counter top at the midline; lifting heavy objects up to the top shelf. The tasks are done as quickly as possible and the individual is allowed to use assistive devices such as knee-ankle-foot-orthoses (KAFO) or functional neuromuscular stimulation. A practice test is not required based on the data from able-bodied individuals. Procedure: The time in minutes/seconds to complete each of the 21 tasks is recorded. Advantages: It evaluates the functional ability of standing while using technology. The tasks simulate skills required to work in a kitchen environment but theses skills are easily transferred to other environments (e.g. shopping). The tasks cover a broad range of difficulty. Limitations: There has been limited testing of the FST in individuals with SCI and it has been done in individuals with T3-6. Some tasks were not reliable in individuals with SCI (i.e. total standing time, lifting heavy objects down from low shelves, pulling objects from the nondominant side and pouring). Caution must be used when comparing to able-bodied data since only half of the tasks were equally reliable between groups (i.e. SCI and able-bodied) (Triolo et al. 1994). Interpretability: The FST could be used to assess which types of technology maximize standing balance. Information from the FST provides a measure of an individuals skill/capacity to perform various tasks while standing. The FST was originally developed and tested on 69 able-bodied adolescents, so some data is available to compare to able-bodied individuals. Acceptability: The FST was tested in individuals who were one year post injury and who received therapy using assistive devices (i.e. KAFOs). The time to complete the entire test (i.e. total standing time) was 15.58 + 2.99 minutes. Time required for each task ranged from 1.86 to 13.70 seconds for individuals with SCI. Feasibility: Equipment is required to conduct the FST and includes the standard Jebson Test board and a set of shelves mounted on a counter top 36 inches high in order to simulate a kitchen cabinet. This type of equipment may not be available in most clinical or research settings. Training is required to administer the test. Clinical Summary: The FST has been used to assess functional tasks while standing in individuals requiring technological assistance (i.e. KAFOs or functional neuromuscular stimulation). It is a potentially useful measure for individuals with SCI but more research is needed to assess modifying the test (removing the unreliable items) and assessing the validity and responsiveness. The specialized equipment may limit its usefulness in some clinical/research settings. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ Inter O +* + SS + N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; Inter O=interobserver; SS=Sensitivity/Specificity * Note: the ICC values for the IO reliability ranged from 0.13 0.98. If the tasks that were identified as being unreliable in the SCI group were eliminated, then the results for reliability would be assessed as ++.

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22.3.1 Mobility 22.3.1.4 Modified Functional Reach Test (mFRT) The Functional Reach Test (FRT) was originally designed as a simple reach test designed to assess standing balance. Lynch et al. (1998) modified the FRT to assess sitting balance in individuals with SCI (i.e. modified FRT), since no suitable measures existed at the time this paper was published. Sitting balance was defined in the study as the ability to maintain control over upright posture during forward reach without stabilization (Lynch et al. 1998). The individual is seated on a bench and the maximum distance forward they could reach was measured with the upper extremity flexed to 90 degrees. The anatomical landmark was the ulnar styloid process since individuals with tetraplegia could not make a fist. No weight bearing was allowed through the non reaching arm. The individual is allowed two practice trials and then the following three trials are recorded. Procedure: A clinician administers the test. The average of the three trials is reported in either cm or inches. Advantages: The mFRT is a very functional activity that is required in daily living. It can distinguish between individuals who have abdominal and back extensors (i.e. high tetraplegia/high paraplegia versus low paraplegia) but not between individuals with high lesions. Information from the mFRT may be assist clinicians in prescribing equipment (e.g. cushions and wheelchairs) to maximize sitting balance (Lynch et al. 1998). Limitations: The mFRT requires an individual to have 90 degrees of shoulder flexion and it is therefore not suitable for individuals with limited range of motion or musculoskeletal deformity. More data on the psychometric properties of the test is required since the only data published in on the test re-test reliability with just one rater using a small sample of men (Lynch et al. 1998). Interpretability: No normative data exists for the mFRT for any health care condition at this time. Lynch et al. (1998) reported that the maximal reach for C5-6 group was 14.7+ 7.6 cm (3.3-27.4); T1-4 was 15.5 + 4.3 cm (7.6 -21.3); and T10-12 was 22.9 + 5.6 cm (14.7-29.2). Acceptability: The mFRT has been developed specifically for individuals with SCI. As long as an individual has 90 degrees of shoulder flexion, then it is possible to complete the test. Feasibility: The equipment required should be available in a rehabilitation setting. It includes: a meterstick/yardstick (attached horizontally to the wall); seat (mat or bench approximately 61 cm in width); and a backboard (at an angle of 80 degrees). Clinical Summary: The mFRT can be used to assess sitting balance in individuals with SCI. It may prove to be a useful tool to assist clinicians in prescribing equipment and to evaluate the effects of rehabilitation therapy. More research is required to establish its psychometric properties before it should be used to evaluate clinical interventions (Lynch et al. 1998). Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ TR +++ N/A N/A N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test

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22.3.1 Mobility 22.3.1.5 Tetraplegia Hand Activity Questionnaire (THAQ) The Tetraplegia Hand Activity Questionnaire (THAQ) is a disease specific measure (Land et al. 2004) of arm and hand function of individuals with tetraplegia. The scale was designed to provide information on the body function, activity and participation levels of the WHOs International Classification of Function. It consists of 153 items within 9 subclasses: self-care (22 items), dressing (15 items), continence (15 items), mobility (14 items), eating and drinking (25 items), work/admin/telecom (17 items), leisure (10 items), household (13 items) and miscellaneous (22 items). Items are scored based on 3 dimensions Performance or Doing (0= without difficulty to 3=help from others); Use of an aid (0=never and 3=always); Importance of performing activity independently (0=not important to 2 very important). Procedure: Information is collected using an interview format Advantages: The THAQ was designed to be sensitive to treatment effects of interventions of the arm and hand for tetraplegics who traditionally score poorly on other measures that are designed for paraplegics. Conceptually well founded and well developed using items identified as important by expert clinicians and clients. The THAQ focuses on the activities that individuals do versus what they can do in a treatment setting. Limitations: Information on psychometric properties is not yet published. Currently there are no studies using this tool in the literature. It is not clear at what point the THAQ should be administered (acute/chronic, inpatient, outpatient, after community reintegration). Interpretability: No information regarding interpretability of the scores (eg/ norms). Acceptability: Specific to the tetraplegic population; individual items identified by client population. At present the THAQ is available in English but no other language. Feasibility: No special training is required to administer the THAQ although experience is likely an asset. It takes 30-45 minutes to complete. Contact Land et al. (2004) for a copy of the tool. Clinical Summary: The THAQ is a SCI specific questionnaire used to assess performance, use of an aid and importance in completing actual activities. It has relevant application for individuals with tetraplegia who have completed in-patient rehabilitation. The test may not be useful when the individual is an in-patient as exposure to out of facility activities related to community living, work, leisure, which are not typically addressed in early phases of in patient rehabilitation. The THAQ could potentially be used as a method of goal identification for intervention and/or as a test to measure change after intervention. However, while the THAQ is promising considerable additional development and psychometric assessment is required before recommendations can be made to use the scale clinically. Psychometric Summary:
Reliability Validity Rigor Results Rigor Results Rigor N/A N/A N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information Responsiveness Results Floor/ceiling N/A N/A

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22.3.1 Mobility 22.3.1.6 Timed Motor Test (TMT) The Timed Motor Test (TMT) is a performance test assessing function for children with SCI who use a manual wheelchair. It was developed because existing functional measures for children either measure burden of care/assistance required (i.e. Wee FIM) or are not appropriate for children requiring a wheelchair (i.e. Pediatric Outcomes Data Collection Instrument or the Pediatric Quality of Life Inventory include walking related tasks/questions)(Chafetz et al. 2004). The TMT includes 6 tasks: donning a shirt; donning sweat pants; performance of even transfers; performance of uneven transfers (4 inch height difference); wheelchair propulsion on even surfaces; and wheelchair performance up a ramp. The individual completes each task 5 times, except for wheelchair skills which is only done 3 times. They are instructed to complete the task quickly but safely. If they are unsuccessful in completing the task, they can re-try it and if they are not able to complete all 5 trials then no time was reported. If the individual requires more than 20 seconds to complete the task then it is considered incomplete. Procedure: A clinician records the time (seconds) to complete each task. Based on the results of the reliability data it was decided to use the fastest 3 trials for scoring each task. Advantages: The TMT includes common ADL tasks for children with SCI. This test can be used to assess the impact of wearing a brace such as a TLSO on everyday function (Chafetz et al. 2004). An objective scale such as time (seconds) is useful to detect change. The necessary equipment for the TMT is usually available in the rehabilitation setting and includes: adjustable mat; an 80 foot (24.3 m) corridor; and a 45 foot (13.72 m) ramp with an 8 degree angle. Limitations: Only reliability data has been reported and there is a need to conduct more research to assess the validity and responsiveness of the TMT. It may be tiring for some children to complete each task 5 times. There is no information regarding how the TMT compares to other manual wheelchair tests. Interpretability: The TMT is designed to assess the capacity to perform ADL in children with SCI (Chafetz et al. 2004). This tool is still in the early stages of development and more research is required to determine how to score it (i.e. confirm that the 3 fastest trials should be averaged). No norms are available and the results for the 3 fastest trials for each task were not reported. Acceptability: All individuals were able to complete 5 trials of the TMT (except 3 trials of the wheelchair skills) without a brace (i.e. TLSO) but some of the tasks (i.e. donning pants and propelling the wheelchair on flat surfaces and a ramp) were more difficult with a brace. Feasibility: It takes between 6090 minutes to complete. No special training is required. Clinical Summary: The TMT is potentially useful measure for in-patient or out-patient rehabilitation settings to assess the impact of interventions (e.g. surgery or braces) on function for children requiring manual wheelchairs. More research is needed to assess the psychometric properties (i.e. reliability, validity and responsiveness). Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ TR ++* ++ Construct ++** N/A N/A N/A ++ Inter O +++ ++ Intra O +++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; Inter O=interobserver; Intra O=intraobserver * TR values for each of the 6 tasks were >0.75 for 4 tasks, 0.67 for one task and 0.30 for one task. An overall value of adequate (++) was selected to best represent the range of values. ** There is support for construct validity by using the data comparing known groups (TLSO versus no brace). F values were reported and 5 out of 6 tasks demonstrated that the TLSO times were significantly (p<0.05) compared to no brace.

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22.3.1 Mobility 22.3.1.7 Timed Up and Go Test (TUG) The Timed Up and Go Test (TUG) is a timed walking test designed to measure gait performance and balance. It was originally developed as a clinical measure of balance in elderly individuals (Mathias et al. 1986). The individual is instructed to stand up from an arm chair, walk 3 meters, return to the chair and sit down at their preferred walking speed. Assistive devices can be used. A practice test is recommended to improve the reliability of the test. Procedure: The individual is timed and a score is reported in seconds. Advantages: The TUG is a quick and easy test to administer and can be done in any setting (i.e. clinical setting or community). The task is very functional and incorporates mobility, balance and lower extremity leg strength. Limitations: The distance walked in the TUG is only 3 meters and so it is not a good test of endurance. The test has also not been reported to be reliable in individuals who require longer than 40 seconds to complete the test. To date the TUG has not been widely used in the SCI patient population. In order to complete the TUG an individual is required to be able to stand up from sitting and walk 3 meters and so it may not be suitable for some individuals with SCI who are not able to do both of these skills. Interpretability: Results from the TUG provide an objective measure of time required to complete functional task. Results from the study by van Hedel et al. (2005) reported that the time required to complete the TUG ranged between 8 and 156 seconds, with a mean of 36+27 seconds. Since the TUG has been used in other patient populations (e.g. elderly, stroke etc.) it is possible to compare results, but it will not be possible to determine if an assistive device was used. Acceptability: The TUG appears acceptable to individuals (i.e. all individuals completed the test). Feasibility: The TUG is easy to administer in the clinical setting and does not require any special training to administer. The equipment required is commonly found in most clinical settings and includes an armchair, stopwatch, and 3m corridor. It is difficult to obtain information on how to standardize the test as it has been used in various patient populations and the details of how it was administer are not always clearly stated (e.g. can an individual turn to their right or left, height of the arm chair, number of practice tests, what is a preferred walking speed, etc.). Clinical Summary: The TUG appears to be a very useful measure for individuals with incomplete SCI who have lower extremity function and provides some information on a basic mobility task. The TUG may be useful to assist in the clinical assessment of whether an individual should ambulate or use a wheelchair in a home environment. More research is required to assess the psychometric properties, especially responsiveness in individuals with SCI before it should be used to assess clinical interventions. Psychometric Summary:
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling TR< 40 sec +++ ++ Construct +++ N/A N/A N/A TR>40 sec + Inter O<40 sec +++ Inter O>40 sec ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; InterO=interobserver Rigor ++

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22.3.1 Mobility 22.3.1.8 Walking Index for Spinal Cord Injury (WISCI) and WISCI II The WISCI a measure of ambulation was developed for specifically for SCI clinical trials using a modified Delphi technique (Ditunno et al. 2000). Existing measures of function (e.g. FIM, Barthel Index, Rivermead Mobility Index) do not adequately measure walking ability due to the limited scale responses (i.e. not sufficient incremental differences between levels). The WISCI evaluates the amount of physical assistance, braces or devices required to walk at 10 m. The original WISCI incorporated 19 levels, including increasing levels of physical assistance and devices (arm devices for using parallel bars, walkers, crutches and canes as well as leg braces) required for walking. Level 0 was patient is unable to stand and/or participate in walking to level 19 ambulates with no devices, no braces and physical assistance, 10m. The WISCI II contains an additional item ambulates with no devices, with brace and no assistance (Ditunno & Ditunno 2001; Ditunno et al. 2005; Morganti et al. 2005). Ten meter distance selected as it represents household ambulation and it represents the international metric. Procedure: The clinician observes and rates the level which the person is considered safe. For the WISCI II, a score from 0 to 20 is assigned. It is not clear if practice tests are allowed. Advantages: The WISCI II is an SCI specific test. It covers the entire range of walking ability. Unlike other tests such as the Timed Up and Go, the WISCI II scoring includes the type of assistance or device required. A score is possible even if the individual cannot walk 10 m. Limitations: The WISCI II does not consider walking speed or energy consumption required for walking or an indication of endurance since the distance covered is only 10m. Because the furthest walk distance is 10m, it would not be suitable for individuals with minor impairments. In one study, 17% (42/249) of individuals had a score of 20 (i.e. ceiling effect) (Morganti et al. 2005). Comparisons with timed tests (e.g. 6 Minute Walk Test, 10 Meter Walk Test) indicated that the WISCI II is not as responsive. Morganti et al. (2005) and van Hedel et al. (2005) suggest walking speed data would improve responsiveness and decrease the ceiling effect. Interpretability: No normative data or cut scores are available but the WISCI II is gaining popularity and comparisons can be made with existing studies. Scores are self evident. Acceptability: The WISCI levels are relevant to individuals with SCI. There is no additional burden is as the test falls into typical clinical practice parameters. Feasibility: Equipment required is typically available in the clinical setting and includes: 5 meter parallel bars and walking devices (e.g. braces, cane, walker). Administration time is client dependent. Special training beyond knowledge of ambulation is not required. Scoring definitions provided are clear. Information regarding specific instructions (eg/ practice attempts) is lacking. Copies of WISCI I & II are available in the Ditunno et al. 2000 and Ditunno & Ditunno 2001 articles. Clinical Summary: The WISCI II is a SCI specific measure developed to assess functional walking capacity, including the amount of physical assistance and/or braces required. It would be a useful to incorporate the WISCI II in clinical practice and to evaluate new SCI therapies. Additional tests may be necessary to assess endurance (e.g. 6MWT) and/or walking speed (10MWT), especially for individuals with greater walking capacity. Psychometric Summary:
Validity Responsiveness Results Rigor Results Floor/ceiling Construct WISCI II ++ ++ ++ a) ++* (at 1 month ) +* (at 3,6, 12 months) b) +++** Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; Inter O=interobserver; varied (re. floor/ceiling effects; mixed results). * Compared to timed walking tests ** Compared to functional measures (e.g. FIM, SCIM, BI). Note: for the tables the Morganti paper used the WISCI II, but results were classified as WISCI I. Rigor +++ Rigor +++ Reliability Results Inter O +++ WISCI I/II

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22.3.1 Mobility 22.3.1.9 Wheelchair Circuit (WC) The WC assesses manual wheelchair mobility (i.e. skill and performance). This test was developed to overcome limitations in existing observational tests such as the Functional Independence Measure which assess wheelchair mobility but do not provide information on physical strain and are not able to detect change (Kilkens et al. 2002). Other wheelchair tests have limitations such as not being clinically feasible or are not comprehensive enough to assess functional wheelchair skills. The WC was adapted based on tasks from existing measures (Janssen et al. 1996; Harvey et al. 1998; Dallmeijer et al. 1999). It consists of 8 tasks and 3 aspects of mobility: 1) tempo; 2) technical skill; and 3) physical capacity. Tasks assessing tempo include figure-of-8 shape and sprint; tasks assessing skill include crossing a doorstep, mounting a platform, and transferring; and tasks assessing physical capacity include wheelchair driving and ascending slopes. An original an item on walking has been removed. Procedure: Three scores can be obtained from this performance based test including: 1) Ability score (primary score of the measure) provides information about the ability of the individual to perform each of the 8 test items within the allotted time. Assigned scores range from 1 (anchor such as individual can perform the task) to 0 (anchor if not). Three items also can receive a partial (i.e. point) score. Total scores range from 0-8 on an ordinal scale. 2) Performance time score is the sum of the performance times on the figure-of-8 and the 15 m sprint. Scores are reported in seconds. 3) Physical strain score consists of the strain experience in performing the 3% and 6% slope items. Scores are reported as either the mean peak heart rate (beats/min) reached for the 2 tasks or as mean the peak heart rates reached during the 2 slope items (% heart rate reserve). Advantages: The WC includes functional tasks developed specifically for the SCI population. It was designed and tested on individuals with ASIA A-D and individuals with tetra and paraplegia. Limitations: To date, this test has been primarily used in in-patient rehab settings in the Netherlands for research (Kilkens et al. 2002; 2004). The tasks are only relevant to manual wheelchair users. The ability and performance time score could be obtained in the clinical setting if the equipment is available but the strain score requires a formula using HR values. Interpretability: No normative data is available however the results can be compared to published data. Separate scores for ability (ordinal scale); performance time (seconds); and physical strain (formula using HR data) are calculated. The performance time and physical strain are useful to monitor progress once the individual achieves a maximal score on the ability score or if they have not demonstrated any change over repeated administrations. Acceptability: Some tasks may be too difficult / not suitable if individuals have medical complications or are older. Meaningfulness of time taken is questionable. Practice test is recommended. Feasibility: Space and equipment are required for the WC and include: an adjustable mat; treadmill (with 3% and 6% grade); HR monitor; stop watch; 0.10 m platform on floor; wood doorstep height 0.4 m; open space; and 15 m corridor. There was no mention of time required to administer the test. Clinicians require specialized training to perform exercise testing. A copy of the tool is available in the Kilkens et al. 2004 article. Clinical Summary: The WC is a promising test for individuals with SCI as preliminary results support its validity, reliability and responsiveness. It is primarily useful as a research measure and the equipment required for exercise testing may limit its usefulness in the clinical setting. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ Inter O +++ ++ Construct ++ ++ +++ ++** ++ Intra O +++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IntraO=intraobserver; InterO=interobserver; varied (re. floor/ceiling effects; mixed results).

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22.3.1 Mobility 22.3.1.10 Wheelchair Skills Test The Wheelchair Skills Test (WST) is a comprehensive measure used to objectively evaluate manual wheelchair skills (Kirby et al. 2002). Existing wheelchair tests (Harvey et al. 1998) do not include the level of wheelchair skills required for daily functioning. Version 1.0 of the WST includes 33 skills of varying difficulty (e.g. using the brakes, performing a wheelie) and the revised WST 2.4 (Kirby et al. 2004) includes 50 skills in 10 areas (brakes, armrests, footrests, rolling, turning, reaching, transfers, fold/open, obstacles, and wheelie). The individual is required to use a manual wheelchair and two attempts, with a rest, are permitted to complete the task. Procedure: Scoring is on a pass-fail basis (pass=1, fail=0, N/A=not applicable) with an additional goal attainment score (GAS), for which the clinician indicates whether or not the skill is a reasonable goal for the individual case (N/G=not a goal). The following scores are reported: 1) total score, 2) total percentage (total score/total score possible [excluding N/A items] * 100), 3) asymmetry ratio (L:R) for skills with L and R scores, and 4) GAS ((total score #N/G)/(total score possible #N/G) * 100). Advantages: The tasks cover a wide range of difficulty while remaining functional. It is a generic tool that can be used for several populations (e.g. SCI, amputees, stroke, musculoskeletal disorders, able-bodied) and it was developed using both inpatient and community dwelling samples. Limitations: To date, there has been insufficient testing with SCI populations (n=34) and more extensive research in community and long-term care settings is advisable. Interpretability: The total WST score for individuals with SCI was 68.4+15.1%, indicating that these individuals were able to complete approximately 70% of the tasks deemed suitable (Kirby et al. 2004). Since the WST is still being piloted and revised it is difficult to compare results and another version of the test is expected (i.e. WST 3.0). Acceptability: Although no adverse events occurred during testing and feedback was mainly positive, frustrations were noted for certain tasks. Clinicians rated the usefulness of the tool as 56.225.0% (range 2-93%), in which 0=not useful at all and 100=extremely useful. Translation into French version is in progress. Feasibility: The WST 2.4 was designed to require a minimal amount of equipment, set-up time and space. On average, it took 27.0+9.3mins (range 1270mins) to complete and therefore, it can be conducted in one session. The clinician requires test familiarization and a spotter is mandatory. The user manual and tool is available in pdf format on line at http://www.wheelchairskillsprogram.ca. Clinical Summary: The WST is a promising new measure to assess manual wheelchair mobility that can be used in both the clinical and research setting. Information on responsiveness is required before it should be used to evaluate interventions. Based on patient and clinician feedback, there likely will be content changes and version WST 3.0 is expected in the near future. Psychometric Summary:
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling WST 2.4 WST 2.4 N/A N/A WST 2.4 TR +++ ++ Construct +++ ++ Inter O +++ Intra O +++ ++ Criterion ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; Inter O=interobserver; Intra O=intraobserver; varied (re. floor/ceiling effects; mixed results). Rigor ++

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22.3.2 Self-Care 22.3.2.1 The Barthel Index The 10 item Barthel Index (BI) is one of the oldest developed measures of activities of daily living (ADL). It was developed to assess the severity of disability or independence in personal care and mobility in stroke patients (Mahoney & Barthel 1965). Scoring of the 10 items reflects the burden on nursing care and social acceptability of the activity and are weighted to give a maximum score of 100 (Mahoney & Barthel 1965).
Item Bathing Grooming Feeding Dressing Toilet use Ascend/descend stairs Bowel management Bladder management Bed/wheelchair transfer Mobility (level surface) Scoring 0=dependent; 5=independent 0=dependent; 5=needs help; 10=independent

0=dependent; 5=occasional accident; 10=independent 0=unable, 5=major help needed; 10= minor help; 15=independent 0=unable; 5=wheelchair >50yards; 10=walks >50 yards; 15=independent

Procedure: Scores are obtained using direct observation, self-report, or responses from family or friends. Scores based on information from the past 24-48 hours preferred. Total scores are calculated by adding the items 0 (dependence) to 100 (independence). Advantages: One of the best researched ADL tools. It has been used with a number of diagnoses including: amputation, burns, cardiac problems, stroke and MS. Use of adaptive aids are permitted with a score of independent. Limitations: While research on responsiveness has been done for other populations only the modified BI has published properties for the SCI population. Floor (tetraplegics) and ceiling (paraplegics) effects makes the scale less useful for the SCI population. Interpretability: Cut scores to categorize dependency of patients have been established on the stroke population and are not necessarily representative for the SCI population. These scores range from 0 (dependence) to 100 (independence). Scores of 0-20 indicate total dependence; 21-60 as severe dependence; 61-90 moderate dependence and 91-99 slight dependence (Granger et al. 1977; 1979). Acceptability: Minimum patient burden unless the entire is scored by observation. Several modified versions exist including a 15 item (Granger et al. 1979) and a 17 item version (McGinnis et al. 1986) designed to increase the sensitivity. The BI exists in English, Japanese and a Turkish which has been assessed on the SCI population (Kucukdeveci et al. 2000). Only the 10 item English version has been assessed for the SCI population. Items are deemed important to society but may not reflect activities that are of importance to individuals with SCI. Feasibility: The BI requires 2-10 minutes to complete (more if by observation) and it is easy to score. No specific equipment or training is required although clinical experience and practice will benefit the user. The scale is public domain. An online version of the BI can be obtained at: http://www.strokecenter.org/trials/scales/barthel.pdf#search=%22barthel%20index%22. Clinical Summary: The BI covers very basic functional abilities and while a score of 100 suggests independence assistance may still be required with other higher order tasks such as cooking and cleaning and therefore other measures would be needed to assess these areas. The floor and ceiling effects suggest that the sensitivity to detect subtle but important changes for individuals with very high and low lesion levels may not be good. Therefore the BI may provide valuable descriptive level. The BI is not a clinically useful tool for clients with SCI. Psychometric Summary
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling IC +++ +++ Concurrent +++ ++ +++ Floor ++ TR +++ Construct ++ Ceiling + Inter O ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; IC=internal consistency; Inter O=interobserver Rigor ++

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22.3.2 Self-Care 22.3.2.2 Functional Independence Measure (FIM) The Functional Independence Measure (FIM) was developed in 1983 as part of the Uniform Data System for Medical Rehabilitation for the assessment of burden of care and functional impairment (Granger et al. 1986). Consensus for the items was arrived by a national advisory committee (McDowell & Newell 1996). The FIM assesses physical and cognitive disability. It consists of 18 items with two subscales; motor and socio-cognitive. The motor subscale includes 13 items: eating, grooming bathing, dressing upper extremity, dressing lower extremity, bowel management, bladder management, transfers to bed, chair or wheelchair, transfer to tub, toilet and shower, walking or wheelchair propulsion and stair climbing. The socio-cognitive subscale includes 5 items: comprehension, expression, social interaction, problem solving and memory. Each item is scored on a 7 point ordinal scale ranging from 1 (total dependence) to a score of 7 (total independence). The scoring considers the use of adaptive equipment and/or the extent of personal assistance or supervision required to complete the task. Procedure: The tool is completed by trained health professionals who observe patient performance. FIM Motor, cognitive and/or total scores can be derived by summing items. Advantages: The FIM is internationally known/accepted measure that has been used for clinical and research purposes. Substantial evidence supports its use. Reliability and validity are well established (Dodds et al. 1993; Hamilton et al. 1994). Motor scores reflect the functional status of individuals with spinal cord injuries (SCI) (Hall et al. 1999). It predicts the amount of assistance needed indicating the cost of living in the community with SCI (Hamilton et al. 1999). Limitations: The FIM is not SCI specific. It has limitations in sensitivity to component abilities within tasks for people with SCI. The FIM is not able to discriminate between the subtle, yet important changes in functional skills between paraplegics and tetraplegics (Dodds et al. 1993). There is a ceiling effect with the socio-cognitive subscale for individuals with SCI (Davidoff et al. 1990) and it does not measure the social, psychological or vocational impact of disability (Dodds et al. 1993) or the quality of life or patient satisfaction of living with SCI. Interpretability: Total FIM scores range from 18 (totally dependent) to 126 (totally independent) motor scores range from 13 (total dependence) to 91 (total independence) and cognitive scores range from 5 (total dependence) to 35 (total independence). Higher scores reflect fewer care hours required upon discharge (Heinemann et al. 1997; Hamilton et al. 1999). The FIM motor score is a better predictor of discharge functional ability than the cognitive score with a SCI population (Graves 2005). Individuals with a diagnosis of ASIA A or B upon admission, have the most change in Motor scores from admission to discharge. Total scores are misleading for SCI due to ceiling effects of the cognitive subscale (Hall et al. 1999). Acceptability: Requires approximately 45 minutes to complete. The items are not necessarily SCI specific. It has been translated into 10 languages (Ottenbacher et al. 1996). There is a WeeFIM exists for children (McCabe et al. 1990). Short and phone versions also exist. Feasibility: Certification for FIM administration is required. Information on training can be obtained from http://www.udsmr.org/. See McDowell & Newell (1996) for a copy of the FIM. Clinical Summary: The FIM is often considered the gold standard for assessing activities of daily living. It is routinely used to collect data for administrative purposes in databases such as the Canadian Institute for Health Information National Rehabilitation Reporting System and the Uniform Data Set for Medical Rehabilitation. It is the best researched measure of function but it is not thorough in its evaluation and is not sensitive to the subtle important changes in function for SCI individuals. The cognitive subscale should only be used as a screen due to ceiling effects. Despite its limitations, the FIM, has well established psychometric properties and is accepted by fee users as a predictor of function and potential care hours required for discharge.

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22.3.2 Self-Care Psychometric Summary:

Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling IC ++ +++ Construct +++ +++ + Floor ++*, +** TR +++ Concurrent ++ Ceiling +, ++** Inter O +++ Predictive +++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; IC=internal consistency *Hall et al. (1999) reports poor floor scores on motor scales with high tetraplegics. ** Hall et al. (1999) reports adequate floor /ceiling scores on motor scales with low tetraplegics. Rigor +++

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22.3.2 Self-Care 22.3.2.3 Quadriplegia Index of Function (QIF) The QIF was developed in 1980 to provide a functional assessment that would be useful in documenting the small but clinically significant gains made by quadriplegics throughout inpatient rehabilitation (Gresham et al. 1986). This index is comprised of 10 areas including: transfers, grooming, bathing, feeding, dressing, wheelchair mobility, bed activities, bowel program, bladder program and understanding of personal care. The first 9 areas represent functional performance activities and the final area consists of a questionnaire designed to assess the clients understanding of skin care, nutrition, equipment medications and infections. The functional performance categories are scored on a 5 point scale from 0 (dependent) to 4 (independent). Procedure: Information is collected in an interview format. Scores are provided to give credit for being able to complete a portion of the task rather than the entire task. Each category of functional performance is calculated according to weighted scores. Functional performance categories: /180 Understanding of personal care: /20 Total: 200 /2 = /100 Advantages: The QIF was designed for SCI population, specifically for those individuals with tetraplegia. It measures improvement from admission to discharge for the in-patient rehabilitation population. Studies have shown that the ASIA motor scores are strongly correlated to performance improvement on QIF scores (Yavuz et al. 1998) and the scores are not dependent on age or length of stay in rehabilitation facility. Studies of the responsiveness or sensitivity to change indicate that the QIF reflects was better at detecting small gains in function than the Barthel Index or the Kenny Self-care Evaluation (Gresham et al. 1986). Limitations: The scoring criteria is highly specific due to the weighted calculations. Not all activities are relevant to all individuals and not all items are relevant or applicable to the inpatient rehabilitation setting. Given this it remains unclear how to score items that are not missed. There is some redundancy within the QIF. Interpretability: The scores represent functional performance in activities rather than performance in component parts. No information regarding interpretability of the scores (eg: norms or cut points) is provided. Acceptability: Tested on a total of 59 SCI subjects in two separate studies (Gresham et al. 1986; Yavuz et al. 1998). These studies reported good client co-operation and lack of expressed concern by the raters. Feasibility: Takes less than 30 minutes to administer when the assessor is familiar with the measure. It is easy to administer, requiring no special equipment or training. It is difficult to score due to the weighted scale of the functional performance activities. Copies of the scale and scoring instructions are available by contacting the authors of the Gresham et al. (1986) article. Clinical Summary: The QIF is a functional measure designed specifically for clients with spinal cord injury. It is sensitive to change, representing small gains in functional performance, which is important for both clinicians and clients. It provides a meaningful assessment of participation of functional self-care activities. This tool would be particularly useful for evaluating change and assessing rehab effectiveness for the tetraplegic population. Psychometric Summary
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling +++ Inter O ++ +++ Construct +++ + + N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; Inter O=interobserver

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22.3.2 Self-Care 22.3.2.4 Self Care Assessment Tool (SCAT) The Self Care Assessment Tool (SCAT) was developed by experienced clinicians to assess cognitive and functional skills required by individuals with an SCI below C7 to perform self-care (McFarland et al. 1992). C7 and below was selected because the individuals have the required skills to perform self-care activities. When this article was published, none of the existing measures were pertinent to the specific needs of individuals with SCI. It contains 81 items: 41 cognitive and 40 functional. Cognitive and functional skills are measured in eight self-care areas: bathing/grooming; nutritional management; medications; mobility/transfers/safety; skin management; bladder management; and bowel management. For each area the clinician assesses the cognitive and functional skills. The items in the SCAT consider the use of physical assistance as well as assistive devices. The scale for each item is yes/no/not applicable. Procedure: The SCAT is an interviewer administered test. A cognitive and a functional subscale score can be calculated as well as an overall score, although no details are provided on how to calculate the scores. Advantages: The SCAT was developed specifically for the SCI patient population whereas many self-care measures such as FIM have been developed for a broad range of health conditions. It assesses both cognitive and functional skill, which may be important as the incidence of SCI increases in older individuals. The items assess performance rather than what they are capable of doing. It has been used in both the rehabilitation and community setting. Some preliminary results indicate that results at 6 weeks prior to discharge from rehabilitation can predict self care performance at 6 months post discharge (McFarland et al. 1992). Limitations: The SCAT is designed for individuals with SCI below C7 and it is likely that high functioning individuals with thoracic and lumbar lesions may obtain a ceiling effect, but this needs to be confirmed in future research studies. The ordinal scale may not make the test suitable for assessing change. Since publication of the SCAT in 1992, the SCIM is now commonly used to assess self care for individuals with SCI and it would be important to compare these tests in future studies (McFarland et al. 1992). Interpretability: The SCAT provides information on the functional and cognitive skills required to perform self-care. The SCAT does not appear to be widely used in either the clinical setting or in research. No standardized norms are available and no results were reported so it is difficult to make any comparisons. Acceptability: The content of the SCAT appears to be clinically relevant based on the sample questions provided in the article. The test is designed for individuals with SCI lesion below C7. Feasibility: There is no information is available on the time it takes to complete the SCAT. However, considering it contains 81 items, it may not be feasible to administer in the clinical setting. It does not require special training and the test developers produced a manual. For a copy of the tool contact the authors of the McFarland et al. (1992) article. Clinical Summary: The SCAT was designed to assess the cognitive and functional skills required to perform self-care for individuals with a motor level below C7. It is relevant for individuals who require assistance or devices for self-care but more information is required to determine if it would be feasible to use it in the clinical setting. Psychometric Summary:
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling TR ++* ++ Predictive +++** N/A N/A N/A Inter O +++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; Inter O=interobserver * TR was assessed using Pearson correlation coefficients ** Validity was predictive validity (construct as no gold standard exists) and it was assessed by comparing predischarge score with 6 months post discharge score. Rigor ++

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22.3.2 Self-Care 22.3.2.5 Skin Management Needs Assessment Checklist (SMNAC) The Skin Management Needs Assessment Checklist (SMNAC) (Berry et al. 2004) was extracted from the Needs Assessment Checklist (Kennedy & Hamilton 1999), and was developed as a post discharge measure to assess client knowledge and ability to perform skin checks, pressure relief and prevention of skin breakdown. It is based on the individuals perception his/her ability to independently perform skin management activities. The checklist was developed in accordance with Treatment Theory (identifying the need for assessments that measure the processes between input and output, define issues for specific populations and outline the required step to produce the expected outcome (Keith & Lipsey 1993). Each item on the SMNAC receives a score ranging from 0-3 (0-complete dependence; 1-mostly dependent; 2-moderately dependent; 3-complete independence) or N/A (not applicable, representing no rehabilitation need or goal to be identified). Procedure: The self-report measure requires individuals to demonstrate or, for an individual with a high lesion, instruct their personal care attendant to perform the activities. The items are summed to generate a total score out of 36. The value reported is a proportion (client score/36). Higher scores reflect greater independence. Advantages: In addition to measuring physical and/or verbal independence, it considers specific attributes such as clients attitudinal and behavioural factors towards skin management. As a result, the SMNAC identifies the complex variables which impact an individuals actual performance in skin protection activities. The test includes a measure of verbal abilities for individuals with a high lesion SCI, enabling it to be sensitive to the subtle, yet significant gains for these individuals and encourages independence and control over skin protection activities. Data from the study suggest there is strong internal consistency ( = 0.85) and responsiveness. Limitations: Most raters tend to score in either category 0 or 3 leading to floor/ceiling effects. The ambiguity with the middle scores may reflect bias in interpreting or poorly defined categories for the other scores. There is limited research using this tool. Interpretability: No risk specific scores or normative data is available at this time. Acceptability: There is minimal patient burden however some embarrassment may be evident. Item wording and scoring options provided do not clearly correspond in all cases. This may lead to rater ambiguity for the middle response categories. For example, when asking Are you aware of the danger of zips, seams, calipers, etc? the response categories may cause the patient confusion, who may want to answer yes or no rather than rate their independence. Feasibility: It requires approximately 20 minutes to administer and score. No special equipment or training is required, however, experience with wound care may enhance tool use. A copy can be obtained from the author. Clinical Summary: The SMNAC provides SCI specific information related to skin management needs. The SMNAC score may be used to identify the problems for individuals living in the community to establish priorities and goal setting or to inform community health care professionals about a clients ability to manage skin management activities. In addition, the tool could be used preventatively at discharge, to identify individuals at risk for skin breakdown, enabling education prior to discharge. Additional research, particularly responsive and validity in general, is necessary before recommending the use of the SMNAC to evaluate the effectiveness of interventions targeting maintenance of skin integrity. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ IC +++ ++ SS + ++ + N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency; SS=sensitivity/specificity

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22.3.2 Self-Care 22.3.2.6 Spinal Cord Injury Lifestyle Scale (SCILS) The 25 item Spinal Cord Injury Lifestyle Scale (SCILS) is a self-report measure of the frequency of health-related behaviour performance in individuals with spinal cord injury (SCI). The tool was designed to enable examination of the effectiveness of clinical and educational efforts for health maintenance and prevention of secondary impairments (Pruitt et al. 1998). The items were developed from a review of the literature on secondary impairments related to SCI. In addition, expert clinicians (physician assistants, nurses and physiotherapists) generated items describing health related behaviours. Each item describes different health behaviours. The 5 subscales include: cardiovascular (4 items), genitourinary (4 items), neuromuscular (8 items), skin (6 items) and psychosocial (2 items). Its purpose is to evaluate the effectiveness of clinical and educational efforts for health maintenance and the prevention of secondary impairments following SCI. The frequency with which each behaviour has been performed over the past 3 months is rated using an ordinal scale where 4=almost always, 3=frequently, 2=sometimes, 1=rarely and 0=never. One item (genitourinary) is reverse scored. Procedure: Data can be collected by pen and paper or through interview if the individual is unable to write. A score is generated for each scale by totaling scores of each item using a 0-4 point scale. A total score is calculated by summing the 5 scale scores. Sub-scale scores may be used to identify/address specific areas of concern. Advantages: This is an SCI specific tool designed to address the concerns surrounding secondary conditions that they experience. Data from the study suggest that the SCILS has strong internal consistency (alpha=0.81) for the total score however the subsections range from alpha=.31 to .86 indicating some item revision may be useful (Pruitt et al. 1998). Limitations: Due to the nature of the small sample size (N=49) and the fact that the sample consisted of males only, the generalizability of the results is limited. Current research is for young adults (19-50 years old). Although the authors identified a comprehensive list of secondary impairments, only some of these impairments have been included in the tool. For example, items missed include autonomic dysreflexia, deep vein thrombosis, pressure relief in bed, adjustment to disability, to mention a few. The evidence did not identify an association between the SCILS and a decrease in secondary health impairments. The SCILS requires retrospective recall and personal diagnoses, which is not as accurate as a health record review or clinical assessment. Studies on responsiveness are not available. Interpretability: Higher total scores are intended to indicate better performance of behaviours which in turn promote health in individuals with SCI. The scores could be used for each subscale or as a tool for general overall health. There are no norms or reported cut scores. Acceptability: Individuals with SCI participated in item elimination during tool development therefore the included items should resonate with the population. Feasibility: Administration and scoring takes 10-15 minutes for each.The SCILS is not available in any other languages. A copy is available from the authors. Clinical Summary: The SCILS requires further testing and development of the measure before recommending it for clinical use. Specifically responsiveness studies are required if the tools is to be used to evaluate clinical or education interventions. At present there is no evidence to suggest that it is able to predict and therefore prevent secondary impairment. Studies of the utility of the SCILS with women and retest reliability are necessary. Psychometric Summary:
Validity Responsiveness Results Rigor Results Floor/ceiling Construct + N/A N/A N/A Concurrent + Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency Rigor ++ Rigor ++ Reliability Results IC ++

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22.3.2 Self-Care 22.3.2.7 The Spinal Cord Independence Measure (SCIM) The SCIM is a new disability scale developed (Catz et al. 1997) that specifically addresses patients with spinal cord lesions (SCL) in order to describe their ability to accomplish activities of daily living. Actually 3 versions of the SCIM (I-III) have been consecutively developed (Catz et al. 1997; 2001a; 2006). The SCIM scores 16 items in three subscales; 1) self-care (feeding, grooming, bathing, and dressing); 2) respiration and sphincter management and 3) mobility (bed and transfers and indoor/outdoor). The item scores are weighted related to the assumed clinical relevance. Procedure: Clinical staff scores the items based on the activities the patient is performing during the regular daily activities or as the patient reports in an interview. Scores are derived by adding up the items producing a total score (0 to 100) and/or subscale scores (self care 0-20; respiration and sphincter management 0-40; mobility 0-40). Higher scores reflect higher levels of independence. Advantages: This is an SCI specific measure of basic functional independence. Validity (face and construct) is supported by several studies including a recent multicentre (13 centers in 6 countries). The results suggest strong validity and reliability (Catz et al. 2006) and better sensitivity to change compared to the Functional Independence Measure (Catz et al. 1997). The SCIM is quickly becoming one of the best research tools within the SCI population (Catz et al. 1997; 2001a; 2001b; 2002; 2004; 2004; 2006; Grijalva et al. 2003; Itzkovich et al. 2002; 2003; 2006; Jackson et al. 2004; McKinley et al. 2001; Popovic et al. 2006; Ronen et al. 2004; Scivoletto et al. 2003; Morganti et al. 2005). The SCIM III, the most recent version, has been revised based on statistical analyses using Rasch analysis (Catz et al. in submission). Limitations: The weighting of the items may require revision to account for the assumed clinical relevance. Interpretability: The scores have shown to be of clinical relevance and are able to monitor improvements of independence during rehabilitation and represent typical rehabilitation goals. The SCIM has been found to be more sensitive to chance in SCI rehabilitation than the FIM. Acceptability: The items reflect basic areas of patient concern. There is minimal patient burden. The multicentre study showed no difficulties related to languages. Feasibility: The SCIM takes 30-45 minutes conduct and score. Minimal additional staff burden is required as the variables collected are important to patient care. No special equipment is necessary however knowledge of areas of function is beneficial and experience using the test is likely an asset. A copy of the tool can be obtained from the article by Catz et al. (1997). Clinical Summary: The SCIM has high clinical relevance for the rehabilitation for individuals with either traumatic/non-traumatic and complete/incomplete SCI. Research supporting the use of the tool is accumulating and the results suggest the SCIM is reliable and valid and may become the gold standard of basic function. Ceiling and floor effects (especially floor) may be an issue for individuals at either who have very high or low level lesions. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling +++ Inter O +++ +++ Construct+++ ++ ++ ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; Inter O=interobserver

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Activity References Berry C, Kennedy P, Hindson L. Internal consistency and responsiveness of the skin management needs assessment checklist post spinal cord injury. J Spinal Cord Med 2004;27:63-71. Catz A, Itzkovich M, Agranov E, Ring H, Tamir A. SCIM--spinal cord independence measure: a new disability scale for patients with spinal cord lesions. Spinal Cord 1997;35:850-856. Catz A, Itzkovich M, Agranov E, Ring H, Tamir A. The spinal cord independence measure (SCIM): sensitivity to functional changes in subgroups of spinal cord lesion patients. Spinal Cord 2001a;39:97-100. Catz A, Itzkovich M, Steinberg F, Philo O, Ring H, Ronen J, Spasser R, Gepstein R, Tamir A. The Catz-Itzkovich SCIM: a revised version of the Spinal Cord Independence Measure. Disabil Rehabil 2001b;23:263-268. Catz A, Itzkovich M, Steinberg F, Philo O, Ring H, Ronen J, Spasser R, Gepstein R, Tamir A. Disability assessment by a single rater or a team: a comparative study with the CatzItzkovich spinal cord independence measure. J Rehabil Med 2002;34:226-230. Catz A, Goldin D, Fishel B, Ronen J, Bluvshtein V, Gelernter I. Recovery of neurologic function following nontraumatic spinal cord lesions in Israel. Spine 2004;29:2278-2282. Catz A, Greenberg E, Itzkovich M, Bluvshtein V, Ronen J, Gelernter I. A new instrument for outcome assessment in rehabilitation medicine: Spinal cord injury ability realization measurement index. Arch Phys Med Rehabil 2004;85:399-404. Catz A, Itzkovich M, Tesio L, Biering-Srensen F, Weeks C, Laramee M, Craven BC, Tonack M, Hitzig SL, Glazer E, Zeilig G, Aito S, Scivoletto G, Mecci M, Chadwick RJ, El Masry WS, Osman A, Glass CA, Silva P, Soni BM, Gardner BP, Savic G, Bergstrom EM, Bluvshtein V, Ronen J. A multi-center International Study on the Spinal Cord Independence Measure, Version III: Rasch psychometric validation. Spinal Cord Resubmission requested 2006. Chafetz R, McDonald C, Mulcahey MJ, Betz R, Anderson C, Vogel L, Gaughan JP, Martin S, O'Dell MA, Flanagan A. Timed motor test for wheelchair users: initial development and application in children with spinal cord injury. J SCI Med 2004;27:S38-43. Dallmeijer AJ, van der Woude LH, Hollander AP, van As HH. Physical performance during rehabilitation in persons with spinal cord injuries. Med Sci Sports Exerc 1999;31:1330-1335. Davidoff GN, Roth EJ, Haughton JS, Ardner MS. Cognitive dysfunction in spinal cord injury patients: sensitivity of the Functional Independence Measure subscales vs neuropsychologic assessment. Arch Phys Med Rehabil 1990;71:326-329. Dijkers MP. Correlates of life satisfaction among persons with spinal cord injury. Arch Phys Med Rehabil 1999;80:867-876. Dijkers MP. A computer adaptive testing simulation applied to the FIM instrument motor component. Arch Phys Med Rehabil 2003;84:384-393. Dijkers MP, Yavuzer G. Short versions of the telephone motor Functional Independence Measure for use with persons with spinal cord injury. Arch Phys Med Rehabil 1999;80:14771484. Ditunno JF, Ditunno PL, Graziani V, Scivoletto G, Bernardi M, Castellano V, Marchetti M, Barbeau H Frankel HL D'Andrea Greve JM, Ko HY, Marshall R, Nance P. Walking index for spinal cord injury (WISCI): an international multicenter validity and reliability study. Spinal Cord. 2000;38:234-243. Dittuno PL Dittuno JF. Walking index for spinal cord injury (WISCI II): scale revision. Spinal Cord 2001;39:654-656. Ditunno JF, Burns AS, Marino RJ. 2005. Neurological and functional capacity outcome measures: essential to spinal cord injury clinical trials. J Rehab Res Dev 2005;42(Suppl 1): 35-41.

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Dodds TA, Martin DP, Stolov WC, Deyo RA. A validation of the functional independence measurement and its performance among rehabilitation inpatients Arch Phys Med Rehabil, 1993; 74: 531-536. Granger CV, Sherwood CC, Greer DS. Functional status measures in a comprehensive stroke care program. Arch Phys Med Rehabil 1977;58:555-561. Granger CV, Albrecht GL, Hamilton BB. Outcome of comprehensive medical rehabilitation: measurement by PULSES profile and the Barthel Index. Arch Phys Med Rehabil 1979;60:145-154. Granger CV, Hamilton BB, Keith RA et al. Advances in functional assessment for medical rehabilitation. Top Geriatr Rehabil 1986;1:59-74. Graves D. The construct validity and explanatory power of the AISA Motor Score and the FIM: implications for theoretical models of spinal cord injury Top Spinal Cord Inj Rehabil 2005;10:65-74. Gresham GE, Labi ML, Dittmar SS, Hicks JT, Joyce SZ, Stehlik MA. The Quadriplegia Index of Function (QIF): sensitivity and reliability demonstrated in a study of thirty quadriplegic patients. Paraplegia 1986;24:38-44. Grijalva I, Guizar-Sahagun G, Castaneda-Hernandez G, Mino D, Maldonado-Julian H, VidalCantu G, Ibarra A, Serra O, Salgado-Ceballos H, Arenas-Hernandez R. Efficacy and safety of 4-aminopyridine in patients with long-term spinal cord injury: a randomized, double-blind, placebo-controlled trial. Pharmacotherapy 2003;23:823-834. Hall KM, Cohen ME, Wright J, Call M, Werner P. Characteristics of the Functional Independence Measure in traumatic spinal cord injury. Arch Phys Med Rehabil 1999;80:1471-1476. Hamilton BB, Laughlin JA, Fiedler RC, Granger CV. Interrater reliability of the 7-level functional independence measure (FIM). Scand J Rehab Med 1994;26:115-119. Hamilton BB, Deutsch A, Russell C, Fiedler RC, Granger CV. Relation of disability costs to function: spinal cord injury. Arch Phys Med Rehabil 1999;80:385-391. Harvey LA, Batty J, Fahey A. Reliability of tool for assessing mobility in wheelchair-dependent paraplegics. Spinal Cord 1998;36:427-431. Heinemann AW, Kirk P, Hastie BA Semik,P, Hamilton BB, Linacre JM, Wright BD, Granger C. Relationships between disability measures and nursing effort during medical rehabilitation for patients with traumatic brain and spinal cord injury. Arch Phys Med Rehabil 1997;78:143149. Itzkovich M, Tripolski M, Zeilig G, Ring H, Rosentul N, Ronen J, Spasser R, Gepstein R, Catz A. Rasch analysis of the Catz-Itzkovich spinal cord independence measure. Spinal Cord 2002;40:396-407. Itzkovich M, Tamir A, Philo O, Steinberg F, Ronen J, Spasser R, Gepstein R, Ring H, Catz A. Reliability of the Catz-Itzkovich Spinal Cord Independence Measure assessment by interview and comparison with observation. Am J Phys Med Rehabil 2003;82:267-272. Itzkovich M, Catz A, Biering-Srensen F. SCIM III Reliability And Validity: A Multi-Center International Study. ISCoS Meeting Oct 2005 Munich, Germany Abs 34/8 http://www.iscos.org.uk/index.html Accessed May 2, 2006 Jackson AB, Dijkers M, DeVivo MJ, Poczatek RB. A demographic profile of new traumatic spinal cord injuries: change and stability over 30 years. Arch Phys Med Rehabil 2004;85:17401748. Janssen TW, van Oers CA, van der Woude LH, Hollander AP. Reliability of heart rate response to non-steady-state activities of daily living in men with spinal cord injuries. Scand J Rehabil Med 1994;26:71-78. Jette AM, Haley SM, Kooyoomjian JT. Are the ICF Activity and Participation dimensions distinct? J Rehabil Med 2003;35:145-149.

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Keith RA, Lipsey MW. The role of theory in rehabilitation assessment, treatment and outcomes. In: Glueckauf RL, Sechrest LB, Bond GR, McDonel EC. (ed). Improving Assessment in Rehabilitation and Health. Sage Publications, Newbury Park, CA, 1993, p 33-60. Kennedy P, Hamilton LR. The needs assessment checklist: a clinical approach to measuring outcome. Spinal Cord 1999;37:136-139. Kilkens OJ, Dallmeijer AJ, De Witte LP, Van Der Woude LH, Post MW. The Wheelchair Circuit: Construct validity and responsiveness of a test to assess manual wheelchair mobility in persons with spinal cord injury. Arch Phys Med Rehabil 2004;85:424-431. Kilkens OJ, Post MW, van der Woude LH, Dallmeijer AJ, van den Heuvel WJ. The Wheelchair Circuit: reliability of a test to assess mobility in persons with spinal cord injuries. Arch Phys Med Rehabil 2002;83:1783-1788. Kirby RL, Dupuis DJ, Macphee AH, Coolen AL, Smith C, Best KL, Newton AM, Mountain AD, Macleod DA, Bonaparte JP. The Wheelchair Skills Test (Version 2.4): measurement properties. Arch Phys Med Rehabil 2004;85:794-804. Kirby RL, Swuste J, Dupuis DJ, MacLeod DA, Monroe R. The Wheelchair Skills Test: a pilot study of a new outcome measure. Arch Phys Med Rehabil 2002;83:10-18. Kucukdeveci AA, Yavuzer G, Tennant A, Suldur N, Sonel B, Arasil T. Adaptation of the modified Barthel Index for use in physical medicine and rehabilitation in Turkey. Scand J Rehabil Med 2000;32:87-92. Land NE, Odding E, Duivenvoorden HJ, Bergen MP, Stam HJ. Tetraplegia Hand Activity Questionnaire (THAQ): the development, assessment of arm-hand function-related activities in tetraplegic patients with a spinal cord injury. Spinal Cord 2004;42:294-301. Lynch SM, Leahy P, Barker SP. Reliability of measurements obtained with a modified functional reach test in subjects with spinal cord injury. Phys Ther 1998;78:128-133. Mahoney FI, Barthel DW. Functional Evaluation: The Barthel Index. Md State Med J 1965;14:61-65. Marino RJ, Goin JE. Development of a short-form Quadriplegia Index of Function scale. Spinal Cord 1999;37:289-296. Marino RJ, Huang M, Knight P, Herbison GJ, Ditunno JF,Jr, Segal M. Assessing selfcare status in quadriplegia: comparison of the quadriplegia index of function (QIF) and the functional independence measure (FIM). Paraplegia 1993;31:225-233. Masedo AI, Hanley M, Jensen MP, Ehde D, Cardenas DD. Reliability and validity of a self-report FIM (FIM-SR) in persons with amputation or spinal cord injury and chronic pain. Am J Phys Med Rehabil 2005;84:167-176. Mathias S, Nayak US, Isaacs B. Balance in elderly patients: the get-up and go test. Arch Phys Med Rehabil. 1986;67:387-389. May LA, Butt C, Minor L, Kolbinson K, Tulloch K. Measurement reliability of functional tasks for person who self-propel a manual wheelchair. Arch Phys Med Rehabil 2003;84:578-83. McCabe MA, Granger CV. Content validity of a pediatric Functional Independence Measure. Appl Nurs Res 1990;3:120-122. McDowell I, Newell C. Measuring Health. A Guide to Rating Scales and Questionnaires. Oxford University Press, New York NY, 1996. McFarland SM, Sasser L, Boss BJ, Dickerson JL, Stelling JD. Self-care assessment tool for spinal cord injured persons. SCI Nursing 1992;9:111-116. McKinley WO, Seel RT, Gadi RK, Tewksbury MA. Nontraumatic vs. traumatic spinal cord injury: a rehabilitation outcome comparison. Am J Phys Med Rehabil 2001;80:693-699. Morganti B, Scivoletto G, Ditunno P, Ditunno JF, Molinari M. Walking Index for spinal cord injury (WISCI): criterion validation. Spinal Cord 2005;43:27-33. O'Connor RJ, Cano SJ, Thompson AJ, Hobart JC. Exploring rating scale responsiveness: does the total score reflect the sum of its parts? Neurology 2004;62:1842-1844.

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Ottenbacher KJ, Hsu Y, Granger CV, Fiedler RC. The reliability of the functional independence measure: a quantitative review. Arch Phys Med Rehabil 1996;77:1226-1232. Popovic MR, Thrasher TA, Adams ME, Takes V, Zivanovic V, Tonack MI. Functional electrical therapy: retraining grasping in spinal cord injury. Spinal Cord 2006;44:143-151. Pruitt SD, Wahlgren DR, Epping-Jordan JE, Rossi AL. Health behavior in persons with spinal cord injury: development and initial validation of an outcome measure. Spinal Cord 1998;36:724-731 Ronen J, Itzkovich M, Bluvshtein V, Thaleisnik M, Goldin D, Gelernter I, David R, Gepstein R, Catz A. Length of stay in hospital following spinal cord lesions in Israel. Spinal Cord 2004;42:353-358. Sander RA. Measurement of functional status in the spinal cord injured patient. Saint Louis University; 2004. Scivoletto G, Morganti B, Ditunno P, Ditunno JF, Molinari M. Effects on age on spinal cord lesion patients' rehabilitation. Spinal Cord 2003;41:457-464. Triolo RJ, Bevelheimer T, Eisenhower G, Wormser D. Inter-rater reliability of a clinical test of standing function. J Spinal Cord Med. 1994;18:14-22. van Hedel HJA, Wirz M, Curt A. Improving walking assessment in subjects with incomplete spinal cord injury: responsiveness. Spinal Cord 2006;44:352-356. van Hedel HJA Wirz M, Dietz V. Assessing walking ability in subjects with spinal cord injury: validity and reliability of 3 walking tests. Arch Phys Med Rehabil 2005;86:190-196. World Health Organization. International Classification of Functioning, Disability and Health. Geneva, Switzerland: World Health Organization, 2001. Yavuz N, Tezyurek M, Akyuz M. A comparison of two functional tests in quadriplegia: the quadriplegia index of function and the functional independence measure. Spinal Cord 1998;36:832-837.

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22.4 Participation Conceptualization and Definition of Participation: There has been tremendous progress in understanding how individuals resume participating in life activities following a health condition. In 2001, when International Classification of Functioning, Disability and Health (ICF) (Gray & Hendershot 2000) replaced the International Classification of Impairments, Disability and Handicap (ICIDH) there was a change from concept handicap to participation. Participation is defined in the ICF as involvement in a life situation and participation restriction is defined as problems an individual may experience while involved in life situations (World Health Organization 2001). This is a significant shift because handicap focused on the disadvantages for an individual in life roles considered normal (i.e. based on age, sex, and social and cultural factors), which was also referred to as a societal perspective. It is important to note that the World Health Organizations ICIDH and ICF models are just one way to conceptualize measuring life roles/activities. Other disciplines have proposed measuring similar concepts but have used alternate terms, which are conceptually quite similar, and include: social health; social adjustment; social or community re-integration; independent living; instrumental activities of daily living; and quality of life (Dijkers et al. 2000). Since the concept of measuring involvement in life situations is very broad, there will likely never be consensus, as to what life dimensions should be included and what construct should be addressed (Dijkers et al. 2000). In the ICF, activity and participation domains are listed together and the user of the model decides which ones to consider activity versus participation. Jette et al. (2003) analyzed items based on the ICF concepts activity and participation and demonstrated that they are distinct concepts, with the former assessing basic tasks (e.g. the ability to climb stairs) and the latter assessing more complex life tasks (e.g. preparing meals). It has been recommended that in future revisions of the ICF that these two concepts are better defined (Dijkers et al. 2000; Whiteneck 2006). The perspective of how to assess participation has also evolved over time. Measures of handicap primarily captured observable information, such as the frequency which an individual performed roles (e.g. hours of paid work) and in this review are called measures assessing objective participation. However, measures of objective participation do not capture the individuals perspective about the impact of the health condition and the problems they experience when carrying out everyday activities or fulfilling social roles. As a result, developers incorporated the perspective of participation as perceived by the individual which has been termed subjective or person-perceived participation (i.e. cognitive, emotional and motivational aspects of participation) (Noreau et al. 2005). Although the ICF model does not explicitly include a subjective dimension, the replacement of the term handicap with the term participation and the inclusion of a broader range of life roles provide the opportunity to capture subjective information. In this review, the term objective participation will be used to describe handicap and the term subjective participation will describe person perceived participation. Recommendations: For the purpose of this review, the measures included in this section had questions related to most ICF dimensions of participation, particularly, interpersonal relations/interactions/relationships, major life areas (e.g. education, employment), and/or community/ social/civic life. All of the measures have been tested, to varying degrees on individuals with SCI. The measurement of participation has been termed the most meaningful outcome of rehabilitation (Cicerone 2004); however, it is probably also the most challenging to measure 22-64

since there are many things that contribute to a persons level of participation. It is important not to select an outcome measure just because it is commonly used, but rather consider whether it provides information about the outcome of interest (Backman 2005). In this review consideration was given to the domains (i.e. content) which is frequently determined from the conceptual model, the perspective (i.e. objective versus subjective participation) of a particular measure, the psychometric properties as well as logistical issues (e.g. number of questions, patient burden etc.). The measures included in this review were based on various conceptual models. Some of the measures have been developed based on the ICIDH model (i.e. CHART, PHQ) or the ICF model (IPAQ, PARTS/M). While other measures have used other models such as the occupational performance model (COPM) and the Disability Creation Process model (Life-H). The RNL and the PARA-SCI did not use a specific model, but were developed based on the concepts re-integration and physical activity, respectively. All of the measures included multiple domains (i.e. are generic) with the exception of the PARA-SCI, which just focused on physical activity. The domains included vary depending on how participation was defined. Most measures (except PARA-SCI) included some items on self-care, mobility, family/social relations and work/education a few measures included details on items such as parenting, attending religious services or conducting economic transactions. The COPM is the only participation measure that has been used in an in-patient rehabilitation setting for individuals with SCI, which is likely due to its individualized approach thereby allowing the individual to select relevant goals that will ultimately result in them being able to participate in the community. The content and the measurement properties of the other participation measures are designed to be used in the community setting. The participation perspective varies among the measures. Some measures primarily assess objective participation (CHART, PARA-SCI) while other assess subjective participation (IPAQ, Life-H, RNL, PHQ, COPM); one measure (PARTS/M) included both. Objective participation measures such as the CHART are primarily useful for research purposes to describe from a societal point of view, how individuals with SCI differ from other patient populations and healthy controls. The CHART is probably the most widely used participation measure for individuals with SCI. However, information provided in the CHART does not include the individuals perspective and so information about how the person performs the tasks as well as what tasks are important to them is not captured, which is a significant limitation. In contrast, the subjective measures of participation (IPAQ, PARTS/M, Life-H, RNL, PHQ, COPM) offer tremendous potential to clinicians and researches working in the area of SCI. Most of the participation measures have established some aspects of reliability and validity. The IPAQ and the PARTS/M are relatively new measures and so not much has been published specifically on individuals with SCI. To date, very little has been published on responsiveness for any of the measures, with the exception of the IPAQ. In terms of logistical issues, the time required to complete the measures will vary, the PHQ has only 5 questions and the PARTS/M is the most comprehensive, containing 135 questions and this will likely be a contributing factor in which measure to select. In Canada, data using the RNL in individuals with SCI will become available since it is part of the NRS, although little work has been done to establish its psychometric properties in this population. Finally, measures such as the LIFE-H, the COPM and the PARTS/M include information on satisfaction with participation and clinicians and researchers can use this information to identify areas or target interventions to those life activities that are most important to the individual.

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Conclusion: Participation measures, particularly ones that measure subjective participation, provide important information for individuals working in the field of rehabilitation since they assess how the individual is doing in the community, which some would argue is the ultimate rehabilitation outcome. Future work establishing the psychometric properties of participation instruments will be essential to ensure the measures are reliable, valid and responsive for assessing participation in individuals with SCI thereby enabling clinicians and researchers to select appropriate measures. The outcome measures reviewed under this category include. 22.4.1 Assessment of Life Habits Scale (LIFE-H)................................................................22-67 22.4.2 Canadian Occupational Performance Measure (COPM) ..........................................22-68 22.4.3 The Craig Handicap Assessment & Reporting Technique (CHART) ........................22-69 22.4.4 Impact on Participation and Autonomy Questionnaire (IPAQ) ..................................22-70 22.4.5 Participation Survey/Mobility (PARTS/M...................................................................22-71 22.4.6 Perceived Handicap Questionnaire (PHQ) ...............................................................22-72 22.4.7 The Physical Activity Recall Assessment for People with Spinal Cord injury (PARA-SCI) ...............................................................................................................................................22-73 22.4.8 Reintegration to Normal Living (RNL) Index .............................................................22-74

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22.4 Participation 22.4.1 Assessment of Life Habits Scale (LIFE-H) The LIFE-H was developed using the Disability Creation Process Model (DCP) to assess life habits and handicap situations, which are concepts related to social participation (Noreau et al. 2002; Dumont et al. 2003). Life habits are defined as those habits that ensure the survival and development of a person in society throughout his or her life and they include activities ranging from ADLs to social roles (Fougeyrollas et al. 1998). A handicap situation is a disruption in the accomplishment of a persons life habits, taking into account age, sex and socio-cultural identity, resulting from impairments, disabilities or environmental factors (Fougeyrollas et al. 1998). The LIFE-H includes 12 categories: nutrition, fitness, personal care, communication, housing, mobility, responsibilities, interpersonal relationships, community life, education, employment, and recreation. The long form (Version 3.0, June 2003) contains 240 items, whereas the short form contains 77 items (Version 3.1, June 2003) (Noreau et al. 2002). The long form can be used as a whole or as sub-sections and the short form is a general measure of handicap. The response categories consider the level of difficulty (5 point ordinal scale) and the type of assistance (4 point ordinal scale) required to do each life habit. Satisfaction for each item is reported using a 5-point scale (1=very dissatisfied to 5=very satisfied). Procedure: Self- or therapist-administered. The level of difficulty and the types of assistance are combined and weighted to derive an accomplishment score: ( Scores x 10)/(number of applicable life habits x 9). Total scores for each life habit category range from 0-10. Advantages: The LIFE-H is a conceptually strong tool that incorporates the interaction of the individual and their environment, and thus, overlaps with the ICF (Fougeyrollas et al. 1998; Noreau et al. 1998; 2000). Input was obtained from rehabilitation experts and individuals with SCI (children and adults). Participation is based on the individuals perspective of performance rather than describing it from a societal perspective. Rasch modeling applied to the short form support its measurement model (Dumont et al. 2003). Limitations: Satisfaction data is not incorporated into the accomplishment score and it is unclear if this information was used in the cited research. There is no responsiveness data. Interpretability: Information from the accomplishment score describes an individuals performance for each life habit (i.e. social participation). Satisfaction information may guide clinical interventions. There are no published norms; however, data from various SCI studies provide some basis for comparison (Fougeyrollas et al. 1998; Noreau et al. 2000). Acceptability: The long form requires 20 to 120 minutes to complete (depending on which sections are used) and the short form takes between 30 to 60 minutes. Feasibility: No special training is required to administer or score the LIFE-H. It was originally developed in French and translated into English. Clinical Summary: Social participation is a meaningful rehabilitation outcome. Performance and satisfaction measures provide relevant community based information which can be used to guide clinical interventions. Psychometric Summary:
Rigor ++ Reliability Results *Adults: (S) TR +++ (L) TR ++ Rigor +++ Validity Results Convergent ++** Rigor N/A Responsiveness Results Floor/ceiling N/A N/A

*Children: (S) TR ++ (L) TR ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; S=Short Version; L=Long Version *: TR values were based on the overall values for the short and long version of the LIFE-H for adults. **: Note the LIFE-H was compared to the CHART and the CIQ which assess objective handicap/participation and so a high correlation is not expected.

++

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22.4 Participation 22.4.2 Canadian Occupational Performance Measure (COPM) The Canadian Occupational Performance Measure (COPM 1991) is a client-centered individualized measure of function (Donnelly et al. 2004). It was developed to measure change in an individuals self-perception of occupational performance, where occupational performance is defined as activities an individual performs in the areas of self-care, productivity and leisure, in the context of their environment (Pollock 1993). The individual identifies areas of difficulties, rates the importance of the issues (0 to 10, where 10 is the most important) and chooses up to 5 problems that they would like to make goals of their treatment. They rate their current level of performance and satisfaction with their performance for each of the 5 goals on a scale of 0 to 10 (1= with great difficulty or not satisfied and 10=no difficulty or completely satisfied). Upon reassessment, the goals initially defined are reviewed and the individuals performance and satisfaction are compared to the first assessment (Donnelly et al. 2004). Procedure: Information is administered in a semi-structured interview. Mean scores (range 110) are calculated for satisfaction and performance, along with change scores (i.e. posttreatment score initial score). Advantages: The COPM provides a unique perspective on occupational performance areas as identified and rated by the individual. It is frequently used by occupational therapists for clinical practice and research purposes. The areas covered are relevant for all patient populations. Limitations: There is no evidence to support the reliability and responsiveness of the COPM in individuals with SCI. The study by Donnelly et al. (2004) had a small sample (n=41) including mostly males (n=29) from one centre. Furthermore, there is no information for differing SCI groups (e.g. levels and severities of injury). It has been suggested (Donnelly et al. 2004) that a mid-point evaluation using the COPM would be useful to determine if there are any new problems identified during the rehabilitation process. Interpretability: The COPM provides a self-assessment of occupational performance. A change score of 2 has been demonstrated to be a meaningful difference, but it has not been confirmed for the SCI patient population. No published norms are available for the COPM since it is an individualized assessment. It is possible to compare results from the literature for other patient populations. Donnelly et al. (2004) reported that the most common goals in the SCI sample were self-care (79%), productivity (12%), and leisure (9%) and the most common problems were functional mobility, dressing, and grooming. Acceptability: The COPM is not suitable for very young children (under age of 8 years) or individuals with cognitive deficits. It can be completed by the individual or by a family member/care giver. The COPM has been demonstrated to work well in most cultures; however, there may be difficulties in cultures in which the health care professional is expected to set the individuals rehabilitation goals. Feasibility: The COPM takes approximately 20 to 40 minutes to administer. Further information is located on the Canadian Association of Occupational Therapists website: http://www.caot.ca/copm/. The cost the DVD kit is $225.45, which provides information on administering and scoring the COPM. In addition, a summary of the research conducted on the COPM is available for $63.86. The COPM is copyrighted. Clinical Summary: The COPM provides important client-centered information that is not captured in other standardized measures and is well suited to be used as part of clinical practice. Initial research findings suggest that the COPM may be a very useful measure for individuals with SCI. Future research studies should test the COPM with larger samples of individuals with SCI to further establish its psychometric properties. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling N/A N/A ++ Construct ++* N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information * - the COPM was compared to the FIM and so high correlations between the scales are not expected since the COPM is an individualized test and the FIM is a standardized performance test.

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22.4 Participation 22.4.3 The Craig Handicap Assessment & Reporting Technique (CHART) CHART was designed to measure the level of handicap in a community setting and was modeled on the ICIDH-1 (WHO 1980). The handicap dimension assessed initially the degree of disadvantage in 5 out of 6 handicap dimensions (physical independence, mobility, occupation, social integration, economic self-sufficiency) of people living in the community (Hall et al. 1998). Basically, CHART collects information on the degree to which the respondent fulfills the roles typically expected from people without disabilities. The original CHART consisted of 27 questions, 2 to 7 questions per subscale (Whiteneck et al. 1992). In 1995, some items were added to the instrument to cover the domain of cognitive independence (5 additional questions) (Cusick et al. 2001). A short form (CHART-SF) has been developed (19 questions) (Whiteneck et al. 1992). Procedure: The questions can be answered in a quantifiable, behavioral terms (e.g.: hours of physical assistance, how much time is someone with you to assist you, how many relatives do you visit, etc.). For each CHART dimension, a scoring procedure allows to compute a score from 0 to 100 points, the latter being the maximum attainable corresponding to a role fulfillment equivalent to that of most individuals without disabilities Advantages: - Relatively simple procedures, wording with few ambiguity and a development based on strong methodological studies that showed a good level of reliability and validity. - Has been tested with proxies (Cusick et al. 2001) Limitations: - Potential ceiling effects in thoracic lesions for physical and cognitive independence, mobility and social integration (Hall et al. 1998). - Its conceptual base differs from the new approach of participation as defined by the International Classification of Functioning (WHO 2001) - Given its quantitative base, one should be cautious in assessing the quality of social participation with CHART. For instance, counting the number of people contacted by the respondent is not necessarily an indicator of the quality of social relationships (social integration dimension), and fewer positive relationships is probably a more valuable asset for any individual than numerous negative relationships (Whiteneck et al. 1992). Interpretability: Total score is potentially a misleading assessment of handicap and the use of subscales is recommended. Norms and profiles of handicap have been widely published. Acceptability: Wording and clarity of questions make CHART easy to complete. Questions on cognitive independence might be seen as irrelevant in SCI population. Feasibility: No specific training is required to administer the CHART. An online pdf version of the CHART can be obtained from http://www.tbims.org/combi/chart/CHART.pdf. Clinical Summary: The CHART provides useful information mostly for research purposes to establish profile in SCI population. It is widely used and particularly in the U.S. National Spinal Cord Injury Database. Clinical utility remains to be demonstrated as no report informs on clinical use of the CHART. Psychometric Summary
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling TR +++ ++ Discriminant ++ N/A N/A N/A IR +++ PR +++, except SI (+, ++) Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; IR: Inter-rater reliability; PR= Proxy-subject reliability; SI= Social integration Rigor ++

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22.4 Participation 22.4.4 Impact on Participation and Autonomy Questionnaire (IPAQ) The Impact on Participation and Autonomy Questionnaire (IPAQ) is a self-administered questionnaire developed using the ICF model of human functioning and disability (Cardol et al. 1999). It was developed after a review of the literature revealed that there were no instruments available which obtained information about participation from the perspective of the individual. The IPAQ assesses autonomy and participation as perceived by the individual. It was developed using input from experienced clinicians and individuals attending an out-patient rehabilitation unit (e.g. stroke, SCI, rheumatoid arthritis, and neuromuscular conditions) (Cardol et al. 1999; 2001; 2002a; 2002b). The IPAQ measures two different aspects of participation: 1) perceived participation and 2) the experience of problems for each aspect of participation. The participation domains include: autonomy outdoors (e.g. visiting friends, leisure time); autonomy indoors (e.g. self-care); family role (e.g. housework); social relations; paid work; and education. The perceived participation scale consists of 31 items which are assessed using a 5 point rating scale (1=very good and 5=very poor). The problem scale contains 8 items which are assessed using a 3 point rating scale (0=no problem and 2=severe problem). Procedure: The questionnaire is completed by self-report or by interviewer. A participation score and a problem score are produced by summing items in each scale. The participation score range from 30-155 (higher score = lower participation) and a problem score ranges from 0-16 (higher score = more problems). Advantages: The IPAQ is a relatively short questionnaire that has been used in various patient populations (e.g. stroke, SCI, fibromyalgia, etc.). Limitations: The IPAQ is a relatively new measure and as a result there has been limited information on its psychometric properties for individuals with SCI. Interpretability: The IPAQ provides a measure of the individuals perceived autonomy and problems in life activities (i.e. participation). Although no normative data exists, published data is available to compare results for individuals with SCI. A study published by Larsson Lund et al. (2005) reported that approximately 50% of individuals with SCI did not complete the questions on work and education stating that it was not applicable to them. Acceptability: The IPAQ appears to be easy to understand and takes approximately 20 minutes to complete. Feasibility: The IPAQ questions are included in the published articles. It does not require any special training to administer or score. The IPAQ was originally published in Dutch and has been translated into English and Swedish. Clinical Summary: The IPAQ is a new generic measure which assesses participation from the perspective of the individual. It conceptually compatible with the WHOs ICF model. The IPAQ can be used to discriminate between individuals with different health conditions. More research assessing the responsiveness of the IPAQ will determine if it can be used to evaluate community interventions targeted at improving participation in life activities. Psychometric Summary:
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling TR domains +* Convergent ++ +* +++ N/A +++ TR items ++ IC +++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; IC=internal consistency; IO=interobserver; varied (re. floor/ceiling effects; mixed results). Note: * no SCI specific data reported and sample included a mix of individuals receiving out-patient rehabilitation. Rigor +*

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22.4 Participation 22.4.5 Participation Survey/Mobility (PARTS/M) PARTS/M has been designed to assess the concept of participation as defined by the International Classification of Functioning (Gray et al. 2006). It addresses 20 major life activities that are grouped into 6 domains (activity/participation) of the ICF: self-care, mobility, domestic life interpersonal interactions and relationships, major life areas, community, social and civic life. Its measurement scales focus on 6 components of participation: Frequency of the involvement, health-related limitations, importance, choice, satisfaction, use of assistive technology or personal assistance that are operationalised by 7 questions. Procedure: PARTS/M has been tested by a mail survey and in-home interview. The 20 life activities (and the 7 questions) can generate 135 different scores that can be grouped into more global scores: 24 scores for the 6 participation domains and each of the 4 participation components (temporal, evaluative, health-related, and supportive); 6 scores if only 1 score is generated for each participation domains. Finally an overall participation score can be generated. Advantages: PARTS/M addressed concepts that are fully compatible with the construct of participation as defined by the ICF. It can provide a guide for changes in participation based on ones aspiration without comparing him/her with normal (non-disabled) people (Gray et al. 2006). Limitations: PARTS/M might be seen a lengthy instrument. It might take as many as 60-90 minutes to complete the instrument. So far the scoring system has not been fully described in publications and more information is available from the developer (David Gray). Interpretability: The information provided by PARTS/M is compatible with the construct of person-perceived participation and fits into the participation construct of ICF. However, the scoring system has to be described more in-depth before we can comment on its usefulness. (Gray et al. 2006). Acceptability / Feasibility: No complaint was received from respondents but the amount of time needed to complete the instrument (WEB-based version 25-40 minutes; hard copy version 60-90 minutes) might be prohibitive in some settings. No special equipment or training seems to be required to administer PARTS/M. The scoring procedure is available via the developer (David Gray, see contact information below) Clinical Summary: PARTS/M is a promising instrument to be used after rehabilitation discharge but need more testing. It has the ability of providing information that can be used by clinicians to propose interventions (on the person or his/her environment) based on the persons importance or satisfaction regarding a specific participation activity. Psychometric Summary:
Rigor ++ Reliability Results IC Part-D = +++ IC Part-I = ++ IC Part-C = +++ Rigor ++ Validity Results Convergent +++ Rigor N/A Responsiveness Results Floor/ceiling N/A N/A

TR Part-D = +++ TR Part-I = +++ TR Part-C = +++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency; Part-D= participation domains; Part-I= Participation items; Part-C = Participation Component; TR=Test re-test; Contact information: David B. Gray, Washington University School of Medicine, Campus Box 8505, 4444 Forest Park, St. Louis, MO 63108 USA. E-mail: grayda@msnotes.wustl.edu

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22.4 Participation 22.4.6 Perceived Handicap Questionnaire (PHQ) The Perceived Handicap Questionnaire (PHQ) was developed using Whitenecks proposed model of quality of life based on an expanded version of the WHOs ICIDH model of disability. This model includes: impairment, disability and handicap as well as perceived outcomes (perceived impairments, perceived disability, perceived handicap), which affect subjective well being (i.e. contribute to quality of life). At the time this questionnaire was developed most of the research assessed objective measures of handicap/participation (i.e. CHART which asked about hours of paid employment, number of friends contacted monthly, etc.) but very little work had been done to measure perceived handicap, which assesses subjective handicap that considers value judgments of the individual. The PHQ contains 5 subscales (same as CHART): physical independence; mobility; occupation; social integration; and economic self-sufficiency. The individual rates their ability in each domain on a scale of 1 (low ability) to 5 (completely in control). The PHQ was developed and tested using the SCI patient population (Whiteneck et al. 1994). Procedure: The questionnaire is administered by interviewer but is also well-suited to being self-administered. A score of 1 to 5 for each of the 5 domains can be calculated as well as an aggregate score for the 5 domains (ranging from 5 to 25) to measure overall perception of handicap. Advantages: The PHQ measures a unique perspective of handicap that is not captured in the CHART. Research indicates that information obtained in the PHQ account for more of an individuals rating of their life satisfaction compared to objective measures of handicap such as the CHART (Hansen et al. 1998). Limitations: Since the publication of this questionnaire the ICIDH has been replaced by the ICF and the concept handicap has been replaced by the concept participation and so it may be preferable to use a measure assessing subjective participation rather than subjective handicap. There was evidence of floor/ceiling effects based on the range of scores reported in the article (note: actual percentages of floor/ceiling were not reported). The psychometric evidence is limited and more work is needed. Interpretability: Results from the PHQ provide an assessment of an individuals perception of their handicap. No norms are available for comparison. The questionnaire does not appear to be widely used and so it would be difficult to compare results. The PHQ would be a useful as a sister questionnaire to the CHART and is suited for understanding how handicap changes over time once an individual is living in the community and what factors are associated with a persons perceived handicap. Acceptability: The questions in the PHQ appears to be appropriate and easily understood. Feasibility: The PHQ is short (5 items total) and the items are listed in the article. Clinical Summary: The PHQ is a potentially useful measure of subjective handicap that can be used in conjunction with the CHART to assess community re-integration, but more research is required on its psychometric properties. Due to the change from the ICIDH to the ICF model it may be preferable to use a measure of subjective participation rather than assessing subjective handicap. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling N/A N/A ++ Construct +++* N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information * For validity the PHQ was compared to subscales of the CHART, but difficulty in interpreting this result since it is expected that they would assess different constructs.

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22.4 Participation 22.4.7 The Physical Activity Recall Assessment for People with Spinal Cord injury (PARA-SCI) The PARA-SCI has been designed to capture information on the type, frequency, duration and intensity of physical activity carried out by people with SCI using a wheelchair as their primary mode of mobility (Martin Ginis et al. 2005; Latimer et al. 2006). Interview protocol: An interview format was developed to capture activities performed over the last 3 days which are divided into 8 periods from morning routine to evening routine. The 2 routine periods are subdivided to capture activity related to daily living (transfer, bowel and bladder management, dressing, etc.). The interviewer asks the respondent about general activities performed during each period. The number of minutes spent on each specific activity is recorded and the activity is coded into 2 dimensions: Leisure-time physical activity or lifestyle activity (Martin Ginis et al. 2005). Intensity Classification system: This system was developed from empirical data collected during maximal exercise testing (VO2max and 1RM muscle workload for chest press and bicep curl). From a list of adjectives, participants of the experiment identified words that described how they felt during exercise. Based on their responses, definitions were created for mild, moderate and heavy intensity exercise (Martin Ginis et al. 2005). Procedure: Data are reported as an average number of minutes of activity per day (mild, moderate, heavy, total) for the two dimensions (Leisure-time physical activity or lifestyle activity) and a cumulative index. Advantages: - Provide a quantitative measure of physical activity that takes into account the intensity of exercise. - Specifically developed for SCI population and takes into account the activities of daily living. Limitations: - The 3 days recall period (capture the activities that are actually performed) enhanced the accuracy of the data but might lead to an underestimation of the overall physical activity if leisure-time activities are not performed on a regular basis (3-4x /week). - Construct validity has been only partially demonstrated and has to be proven by comparing the measure with another measure of physical activity (Latimer et al. 2006). Interpretability: A relatively new instrument but the design seems to be consistent with the usual dimension of physical activity. Acceptability: On average, the interview can be completed within 20-30 minutes. Feasibility: No specific training is required to administer the PARA-SCI. Flowcharts are used to guide the interviewer and provides prompts to help respondents recall the different types of physical activities. Clinical Summary: PARA-SCI is a promising instrument that provides information on the intensity-based type of physical activities. It has to be used more extensively before a final assessment is completed. Psychometric Summary:
Validity Responsiveness Results Rigor Results Floor/ceiling Concurrent ++ N/A N/A N/A Convergent + Construct + Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test Rigor ++ Rigor + Reliability Results TR ++, +++

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22.4 Participation 22.4.8 Reintegration to Normal Living (RNL) Index The Reintegration to Normal Living (RNL) Index is a self-report questionnaire that assesses an individuals satisfaction with performance in life activities (May & Warren 2002). The RNL assesses mobility, self-care, daily activity, recreational activity, and family roles. It was developed based on interviews with clinicians, patients and other their significant others. It contains 11 items and each one is scored using a 10 cm visual analogue scale anchored with phrases (0=no reintegration and 10=complete reintegration). Wheelchairs or other assistive/adaptive aids may be used when considering how to answer the questions. The CIHI National Rehabilitation Reporting System (NRS) uses a 3 point ordinal scale (0=does not describe my situation; 1=partially describes my situation; and 3=fully describes my situation). Procedure: The questionnaire is completed by self-report or by interviewer. The total score = sum (points all 11 items) and the adjusted score = (total score)/110 * 100. A minimum adjusted score is 0 and a maximum adjusted score is 100. No information was obtained on how the CIHI NRS scores the RNL. Advantages: The RNL is a short measure of participation that has been used in various patient populations. It is currently part of the CIHI NRS and is collected at the time of follow-up. Since the RNL is widely used with various patient populations it is possible to compare results. Limitations: Although the RNL is commonly used as part of the NRS for individuals with SCI, there has been very little research conducted on the psychometric properties for this patient population. In the literature the concepts of participation and quality of life are not always clearly defined and the RNL has been classified as a proxy measure of quality of life which may cause some confusion regarding the construct being measured (May & Warren 2002). Interpretability: The RNL provides a measure of the individuals perceived re-integration to life activities. Data is available on the CIHI website for individuals with SCI. Results can also be compared to other research studies. Acceptability: The RNL is easy to understand and does not take long to complete (i.e. 11 items). Feasibility: A copy of the RNL is available at no cost and can be found on the internet. It does not require any special training to administer or score. Clinical Summary: The RNL evaluates the overall function of individuals who have received rehabilitation by assessing the degree to which they are able to return to a normal life. The RNL is currently part of the NRS and is being administered at follow-up to various patient populations, including SCI. Psychometric Summary:
Reliability Validity Rigor Results Rigor Results Rigor N/A N/A ++ Construct ++ N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information Responsiveness Results Floor/ceiling N/A N/A

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Participation References Backman CL. Outcomes and outcome measures: measuring what matters is in the eye of the beholder. Can J Occup Ther 2005;72:259-264. Cardol M, Beelen A, van den Bos GA, de Jong BA, de Groot IJ, de Haan RJ. Responsiveness of the Impact on Participation and Autonomy Questionnaire. Arch Phys Med Rehabil 2002; 83:1524-1529. Cardol M, de Haan RJ, van den Bos GA, de Jong BA, de Groot IJ. The development of a handicap assessment questionnaire: the Impact on Participation and Autonomy (IPA). Clin Rehabil 1999;13:411-419. Cardol M, de Haan RJ, de Jong BA, van den Bos GA, de Groot IJ. Psychometric properties of the Impact on Participation and Autonomy Questionnaire. Arch Phys Med Rehabil 2001; 82:210-216. Cardol M, de Jong BA, van den Bos GA, Beelem A, de Groot IJ, de Haan RJ. Beyond disability: perceived participation in people with a chronic disabling condition. Clin Rehabil 2002;16:2735. Cicerone KD. Participation as an outcome of traumatic brain injury rehabilitation. J Head Trauma Rehabil 2004;19:494-501. Cusick C, Brook C, Whiteneck G. The Use of Proxies in Community Integration Research. Arch Phys Med Rehabil 2001;82:1018-1024. Dijkers MP, Whiteneck G, El Jaroudi R. Measures of social outcomes in disability research. Arch Phys Med Rehabil 2000;81:S63-S80. Donnelly,C., Eng,J.J., Hall,J., Alford,L., Giachino,R., Norton,K., Kerr,D.S. Client-centred assessment and the identification of meaningful treatment goals for individuals with a spinal cord injury. Spinal Cord 2004; 42:302-307. Dumont C, Bertrand R, Fougeyrollas P, Gervais M. Rasch modeling and the measurement of social participation. J Appl Meas 2003;4:309-325. Fougeyrollas P, Noreau L, Bergeron H, Cloutier R, Dion SA, St-Michel G. Social consequences of long term impairments and disabilities: conceptual approach and assessment of handicap. Int J of Rehab Res 1998;21:127-141. Gray DB, Hendershot GE. The ICIDH-2: developments for a new era of outcomes research. Arch Phys Med Rehabil 2000;81:S10-S14. Gray D, Hollingworth H, Stark S, Morgan K. Participation Survey/Mobility: Psychometric Properties of a Measure of participation for People with Mobility Impairments and Limitations. Arch Phys Med Rehabil 2006;87:189-197. Hall K, Dijkers M, Whiteneck G, Brooks C, Krause J. The Craig Handicap Assessment and reporting technique (CHART): Metric properties and scoring. Topics in Spinal Cord Injury Rehabilitation 1998;4:16-30. Hansen NS, Forchheimer M, Tate DG, Luera G. Relationships among community re-integration, coping strategies, and life satisfaction in a sample of persons with spinal cord injury. Top Spinal Cord Inj Rehabil 1998;4:56-72. Jette AM, Haley SM, Kooyoomjian JT. Are the ICF Activity and Participation dimensions distinct? J Rehabil Med 2003;35:145-149. Latimer A, Martin Ginis K, Craven B, Hicks A. The Physical Activity Recall Assessment for People with Spinal Cord Injury: Validity. Med Sci Sports Exerc 2006;38:208-216. Lund M, Nordlund A, Nygard L, Lexell J, Bernspang B. Perceptions of participants and predictors of perceived problems with participation in persons with spinal cord injury. J Rehabil Med 2005; 37:3-8. Martin Ginis K, Latimer A, Hicks A, Craven B. development and Assessment of an Activity Measure for People with Spinal Cord Injury. Med Sci Sports Exerc 2005;37:1099-1111.

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May LA, Warren S. Measuring quality of life of persons with spinal cord injury: external and structural validity. Spinal Cord 2002;40:341-350. Noreau L, Fougeyrollas P. Long-term consequences of Spinal Cord Injury on social participation: The Occurrence of Handicap Situations. Disabil Rehabil 2000;22:170-180. Noreau L, Fougeyrollas P, Labb A, Larame MT. Comparison of 2 measurement tools addressing the concept of handicap:CHART and LIFE-H. J Spinal Cord Med 1998;21:151. Noreau L, Fougeyrollas P, Post M, Asano N. Participation after spinal cord injury: the evolution of conceptualization and measurement. J Neurol Phys Ther 2005;29:147-156. Noreau L, Fougeyrollas P, Vincent C. The LIFE-H: Assessment of the quality of social participation. Technology and Disability 2002;14:113-118. Pollock N. Client-centred assessment. Am J Occup Ther 1995;47:298-301. Whiteneck G. Conceptual models of disability: past, present, and future. In: Institute of Medicine, ed. Workshop on Disability in America: A New Look..: National Academies Press, Washington DC, 2006, p 50-66. Whiteneck GG. Measuring what matters: key rehabilitation outcomes. Arch Phys Med Rehabil 1994;75:1073-1076. Whiteneck G, Charlifue S, Gerhart K, Overholser J, Richardson G. Quantifying handicap: a new measure of long-term rehabilitation outcomes. Arch Phys Med Rehabil 1992;73:519-526. World Health Organization. International Classification of Functioning, Disability and Health. Geneva, Switzerland: World Health Organization, 1980. World Health Organization. International Classification of Functioning, Disability and Health. Geneva, Switzerland: World Health Organization, 2001.

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22.5 Quality of Life Conceptualization and definition of QOL Although the term goodness of life (Baker & Intagliata 1982) seems appropriate to express the overall concept of quality of life (QOL), its apparent simplicity hides a multidimensional concept that is among the most difficult one to define and to translate into a functioning and operating reality. Nonetheless, 2 main conceptualizations of QOL are well-accepted: (1) the subjective approach whose focal point is the persons emotional or cognitive assessment of the congruence between his/her life expectations and achievement, usually associated with life satisfaction or well-being and (2) the objective approach, based on ones characteristics that can be objectively measured by an external appraiser or outsider (Dijkers 2003). The latter includes the concept of Health-related Quality of Life (HRQOL) that focuses mostly on physical and mental health, social and role achievements, and thus it is more oriented toward functional performance than is subjective QOL (Wood-Dauphinee et al. 2002). As the HRQOL tends to address dimensions that influence subjective QOL (health status, functioning), Post et al. proposed a superordinate construct of QOL that includes both HRQOL and well-being which was operationalized from the International Classification Functioning, Disability and Health (ICF) (Post et al. 1999; WHO 2001; Post & Noreau 2005). This approach is quite useful for the rehabilitation community as it permits to integrate most of the dimensions that might be measured to cover the construct of QOL in the field of disability and rehabilitation. Thus QoL tools are either investigator-determined enabling statistical comparisons between an experimental and control group or they are more individualized allowing the participating subject to weight the value (importance) of any individual field in the self-assessment of their own QoL. Measurement issues On an operational basis, Dijkers (2003) nicely summarized that QOL measures focus on three dimensions: 1) the persons achievements (performance) or 2) expectations, or 3) the reaction to the congruence between his/her life expectations and achievements. The HRQOL measures mainly (but not exclusively) focus on achievement as the subjective QOL measures address the reaction (or satisfaction) regarding the achievements. The current review focuses on a number of HRQOL and subjective measures that were previously reported in the field of SCI for which psychometric testing has been published and assessed as adequate or excellent. Most of the measures are not disability-specific, meaning that they have not been specifically developed for the context of people with disability in general or specifically for individuals with SCI. As such, psychometric properties are usually stronger with general population or groups having conditions other than SCI. Recommendations (HRQOL) Three generic instruments addressing the concept of HRQOL are recommended despite some limitations: The short version of the World Health Organization Quality of Life Assessment (WHOQOL-BREF), the Sickness Impact Profile (SIP-68), and the MOS 36-Item Short-Form Health Survey (SF-36) or its shorter form (SF-12). The WHOQOL (BREF) is a promising instrument with a strong conceptualization but its psychometric testing in SCI is limited. Despite their wide use, SIP-68 and SF-36 should be used with caution as limitations were previously reported (Andresen & Meyers 2000; Post & Noreau 2005). For example, the SF-36 physical functioning scale has been found inappropriate in individuals with mobility impairments because several items refer to climbing or walking. Post et al. (1996) found the SIP68 valid for use in persons with SCI but had to develop a recoding procedure to deal with several questions about

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walking difficulties that are not applicable to persons who cannot walk. Moreover, to answer the questions in the context of health can be problematic as some persons with SCI will distinguish health from disability. People perceive themselves as healthy, defining SCI and its consequences as a disability, and not as a disease. A utility measure (Quality of Well-being) has been reviewed but little work has been done to establish its psychometric properties in individuals with SCI. Moreover, the usefulness of the concept (utility) in the field of rehabilitation might be limited in regards of clinical purposes. Finally, the Qualiveen a SCI specific measure of urinary related QOL has been reviewed. Despite excellent psychometric properties its scope is limited. Recommendations (subjective QOL) Four different instruments focusing on life satisfaction have been included in the current review: The Satisfaction with Life Scale (SWLS), the Life Satisfaction Questionnaire (LISAT-11), The Quality of Life Index (QLI) and the Quality of Life for Adults with Physical Disabilities (QOLP-PD) With some pros and cons, they addresses the life satisfaction as a whole, or with a few questions focusing on general life dimensions or with a more-in depth assessment of importance and satisfaction regarding life domains. SWLS is quite brief, mostly useful in research setting but does not bring about information that can be assessed as useful for clinical interventions. At the opposite, QLI and QOLP-PD can inform a lot on some areas of life dissatisfaction hut they might be seen as lengthy in some setting. QOLP-PD is a promising instrument with a good conceptualization but it is at an early stage of development with a few psychometric characteristics already tested. The LISAT-11 might be seen a good compromise for research and clinical purposes as it contains items (life dimensions) that are relevant to SCI. Some data has already been published in the field (Post et al. 1998; Schnherr et al. 2005; Kennedy et al. 2006) and it has previously been recommended by an expert committee on QOL (Wood-Dauphinee et al. 2002). Its main limitation remains the lack of psychometric information relative to the field of SCI. Conclusion In the process of selecting tools to assess QOL, one should consider the purposefulness, usefulness and psychometric properties of measures. For example, generic and global outcomes measures might be useful for comparison across populations but might not bring about information for needs related to community interventions. At the opposite, more specific or detailed measures might be seen as too lengthy for some research or survey settings or as having complex scoring procedures. In many situations, the choice might be driven by a tradeoff between a measure that fully meets ones needs and another one that will limit the respondents burden. But in all cases, a careful evaluation of the psychometric characteristics is mandatory before making the final choice. The outcome measures reviewed under this category include. 22.5.1 22.5.2 22.5.3 22.5.4 22.5.5 22.5.6 22.5.7 22.5.8 22.5.9 Life Satisfaction Questionnaire (LISAT -9 -11) .........................................................22-79 Quality of Life Index (QLI, Ferrans & Powers) ..........................................................22-80 Quality of Life Profile for Adults with Physical Disabilities (QOLP-PD) .....................22-81 Quality of Well Being.................................................................................................22-82 Qualiveen..................................................................................................................22-83 Satisfaction with Life Scale (SWLS, Deiner Scale) ...................................................22-84 The Short Form 12 (SF-12) and Short Form 36 (SF-36) ..........................................22-85 The Sickness Impact Profile 68 (SIP 68) ..................................................................22-86 WHOQOL (BREF).....................................................................................................22-87 22-78

22.5 Quality of Life 22.5.1 Life Satisfaction Questionnaire (LISAT -9 -11) The Life Satisfaction Questionnaire (LISAT) was originally developed as a checklist rather than a measure of life satisfaction (Fugl-Meyer et al. 1991). The LISAT-9 is comprised of 1 general question about satisfaction with life as a whole and 8 other questions targeting important life domains: vocational, financial and leisure situations, contacts with friends, sexual life, self-care management, family life, and partner relationships. More recently, physical and psychological health were added (LISAT-11) (Melin et al. 2003). Procedure: Each item (domain) is scored on a 6-point scale from 1, very dissatisfied, to 6, very satisfied. Item scores can be summed and an average score is produced. It seems more appropriate to use mean item scores rather than a total score in order to keep the information on each domain available for clinical interventions. Advantages: The LISAT is available in many languages, which makes it suitable for international collaborations. Although it is a relatively short questionnaire, it assesses life satisfaction in several domains, which can provide the information necessary for clinical interventions. Its conciseness and simple coding system are also advantages for research and surveys. It is generic and can be applied for comparisons between groups, as it holds no bias due to specific disability (Post et al. 1998). It has already been used in the field of SCI (Post et al. 1998, 1999; Kennedy et al. 2006). Limitations: Depending on when the test is administered with respect to discharge, the questions targeting vocational situation may or may not have missing data. Potential ceiling effects can be expected, as mean scores of ~5 were reported for some life dimensions (e.g. Post et al. 1998). Although the LISAT is beyond the first stages of development, its psychometric testing in the field of SCI remains limited. Interpretability: Scores can be seen as meaningful as they represent satisfaction in different domains of life. Norms have not been developed per se, but a certain level of comparability exists among the studies using the LISAT and amongst the various populations reported (including SCI). Acceptability: The LISAT can be completed in approximately 5 minutes; however, a few extra minutes may be required to clarify the meaning of terms such as vocational and leisure situation. It has been validated in 8 languages (Conway et al. 2000). Feasibility: No equipment or training is necessary to use the LISAT. A copy of the tool can be obtain in the Fugl-Meyer et al. (1991) article. Clinical Summary: The LISAT provides meaningful information for clinical and research purposes in the field of SCI. To date, it has been used in several studies involving a SCI population. Its psychometric properties have been partially tested in different groups; however, there is limited information for SCI populations (e.g. no data on test-retest reliability), which remains its most important limitation. Psychometric Summary
Validity Responsiveness Results Rigor Results Floor/ceiling Criterion* = ++ N/A N/A Ceiling effect* = + Criterion**= ++ Potential ceiling Discriminant*= + effect in SCI + TR*= ++ Discriminant**= + Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; IC=internal consistency * (Other populations than SCI) ** (SCI population) Rigor ++ Rigor +++ Reliability Results IC* = ++ IC**= ++

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22.5 Quality of Life 22.5.2 Quality of Life Index (QLI, Ferrans & Powers) The QLI was designed to measure subjective quality of life in terms of satisfaction within different life domains. It originates from Flanagans perception of life satisfaction, which holds that two aspects, importance and satisfaction, must be addressed when measuring QOL (Ferrans & Powers 1998). Importance ratings are used to weight the satisfaction responses, such that scores reflect the respondents satisfaction with the aspects of life they value. Items that are rated as more important have a greater impact on scores than those of lesser importance. The original QLI (Ferrans & Powers 1985) is comprised of 32 items within 4 domains: health and functioning, psychological/spiritual, social and economic, and family. A SCI version has been developed with 37 items (May & Warren 2001). Procedure: The scales (satisfaction and importance) are on a 6-point Likert scale, ranging from 1, very dissatisfied (very unimportant), to 6, very satisfied (very important). Five scores are generated (i.e. total and 4 domains) on a 0 - 30 scale and scoring instructions are available on the instrument website (Ferrans & Powers 1998). Advantages: The QLI is a suitable tool when one aims at having information on various aspects of life satisfaction. It has adequate psychometric properties for different populations and scores can be compared across populations (Ferrans & Powers 1985; 1992). Limitations: The same total score can reflect two very different QOL profiles. The scoring information seems to be relatively complex and is greatly facilitated by computer assistance. The domains of QOL that are addressed were pre-selected and a uniquely important life dimension for a person may not be included. Psychometric properties for SCI populations remain to be established, particularly with respect to test-retest reliability. Interpretability: Scores represent the satisfaction with different aspects of life. Norms are available for the general population, as well as different groups with disabilities (Ferrans & Powers 1992). Acceptability/ Feasibility: The QLI can be administered in an interview or by client self-report. It takes about 10 minutes to complete and no special training is required. The QLI is a copyright instrument that can be used (no charge) in non-profit research or clinical practice and copies can be downloaded from the QLI website http://www.uic.edu/orgs/qli/. Clinical Summary: The QLI can provide good information to guide interventions on an individual basis. For that purpose, it may be advisable to use the two scales independently in order to establish the precise importance and satisfaction of the specific life domains. Psychometric Summary:
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling IC* = +++ ++ Construct*= +++ N/A N/A N/A TR* = +++ Construct**=+++ TR**= N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test ; IC=internal consistency * (Other populations than SCI) ** (SCI population) Rigor +

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22.5 Quality of Life 22.5.3 Quality of Life Profile for Adults with Physical Disabilities (QOLP-PD) The QOLP-PD has been designed to offer a new approach to measuring QOL that is grounded in and congruent with the perspective and experience of people with disabilities. It has been based on the Center for Health Promotion (CHP) Quality of Life model that views QOL as arising out of the ongoing relationship between the person and his/her environment (Renwick & Brown 1996). In this sense, CHP addresses concepts similar to various disability models (e.g. ICF, DCP). The QOLP-PD is comprised of 102 items classified into the 3 CHP domains: being, belonging, and becoming. Procedure: The items in the 3 domains are grouped into 9 sub-scores. All items are rated on a 5-point scale for satisfaction and importance, ranging from 1 (not at all satisfied/important) to 5 (extremely satisfied/important). Overall scores are made more comprehensible by subtracting 3, leading to a range of scores from negative 10 (not at all satisfied/extremely important issues) to positive 10 (extremely satisfied/extremely important issues). Advantages: The QOLP-PD comes from a strong conceptual model (CHP-QOL; see Renwick & Brown 1996). It is applicable across a wide range of disabilities and it can provide information for clinical interventions (Renwick et al. 2003). Limitations: The major limitation is the fact that this instrument is in the early stages of development with few documented psychometric characteristics. Other limitations may be similar to those of the Quality of Life Index (QLI), as the measurement approaches are similar. Interpretability: Being in the early stages of development, the meaningfulness of scores, the definitions and classifications of the results and norm-based scores are undetermined. Acceptability/ Feasibility: Owing to the 102 items that must be assessed on 2 scales, the QOLP-PD is a lengthy instrument compared to some others already available. For a copy of the tool, contact the author, Rebecca Renwick, at r.renwick@utoronto.ca. It is currently available in English. Clinical Summary: The QOLP-PD is a promising instrument that can provide good information to support interventions on an individual basis. Further testing is necessary prior to appraising its usefulness. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling + IC +++ + Construct= + , ++ N/A N/A N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency

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22.5 Quality of Life 22.5.4 Quality of Well Being Quality of Well Being (QWB) is a preference measure that was designed to measure health related quality of life (Andresen et al. 1999). It was developed based on theory from the General Health Policy Model which incorporates the concepts of mortality, morbidity, the preference of an individual for a certain health state and the duration in that particular health state. The QWB self-administered (QWB-SA) version combines three scales (mobility; physical activity and social activity) with a measure of symptoms/problems. It contains 71 questions. The self-administered version contains slightly different content and the recall period was decreased from six days to three days to reduce recall bias. Procedure: The original version of the QWB was designed to be interviewer administered and there is now a self-administered version. The QWB-SA score is calculated by subtracting from 1.0 the combination of the maximum weighted symptom/problem item and the weights associated with mobility, social activity and physical function. An overall utility score is calculated between 0.0 and 1.0, where 0.0 represents death and 1.0 represent perfect health. Advantages: The QWB-SA can produce utility values which can be used in economic analyses. The utility is a generic measure and so it is easy to compare utilities of different health conditions. The score combines multiple types of information into one summary score which can be useful in statistical analyses. The QWB-SA correlates well with other health related tools. Limitations: Since the QWB-SA combines all of the information into one score, the amount of specific information is lost (i.e. it is not possible to obtain just information on mobility). It does not also capture the unique needs of individuals with SCI since it was designed as a generic measure. Research has also indicated that not all preference-based measures produce equivalent utility values. There has been a considerable amount of research assessing the psychometric properties of the QWB-SA in the general population and in many health states, but very little work has been done to establish reliability, validity, and responsiveness in individuals with SCI (Andresen et al. 1999). Interpretability: The QWB-SA provides an overall utility value which represents the preference an individual places on their specific health state, scored between 0.0 and 1.0. Data exists on numerous health conditions for example community dwelling older adults have a utility value between 0.70-0.75 and individuals with SCI were reported to be 0.55 (Andresen et al. 1999). Acceptability: The QWB-SA is reported to be easier to complete compared to the original QWB measure (Andresen et al. 1999). The QWB-SA is available in various languages. It is not recommended to complete the QWB-SA by proxy. Feasibility: Information on the QWB and the QWB-SA can be obtained from the UCSD Health Outcomes Assessment Program, http://www.medicine.ucsd.edu/fpm/hoap/ . The QWB-SA is reported to take approximately 10 minutes to complete. A copy of the User Manual can be obtained on-line and a copyright agreement must be signed before a copy of the tool can be obtained. Depending on the purpose for using the QWB-SA, a fee may be charged. A webbased version of the QWB-SA was scheduled to be ready in 2004. Clinical Summary: The QWB-SA is a preference-based measure that has been used in individuals with SCI. It can provide information on health related quality of life and produces a utility value which can be used to calculate quality adjusted life years required for economic analyses. To date, very little research has been conducted on the use of preference based measures in individuals with SCI and their validity still needs to be determined. Psychometric Summary:
Reliability Validity Rigor Results Rigor Results Rigor N/A N/A ++ Construct + N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information Responsiveness Results Floor/ceiling N/A N/A

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22.5 Quality of Life 22.5.5 Qualiveen Qualiveen was developed as a disease specific quality of life measure for individuals with SCI who have urinary disorders that could be used in international multi-centre trials (Costa et al. 2001). The tools were developed by a multi-disciplinary group of experts and the questions were derived based on the literature and individuals with SCI. There are 30 items which are part of four scales: limitations (9 items); constraints (8 items); fears (8 items); and feelings (5 items). The Qualiveen was originally developed in French and translated in English. Procedure: The Qualiveen can be administered by interviewer or be self-administered. The questionnaire is based on a 5 point Likert scale. Each of the four scales are scored from 0 to 100, where lower scores indicated a better quality of life (i.e. no limitations, fears, constraints, or negative feelings) and higher scores indicate poorer quality of life. Advantages: The Qualiveen provides detailed information regarding the impact on urinary disorders which was developed specifically for individuals with SCI (Costa et al. 2001). There were no ceiling or floor effects in the initial study. Limitations: The Qualiveen provides a disease specific perspective on measuring quality of life which has traditionally measured more globally (Costa et al. 2001). A limitation of disease specific measures is that it is not possible to compare results to other patient populations. Quality of life is a very broad and complex concept and it may be difficult to attribute the urinary disorders to an individuals overall quality of life. No information was provided on how the English version was translated from the French version. More research is needed to compare it to other quality of life measures and to assess if it is responsive before being used in clinical trials. Interpretability: The four scales provide information on quality of life for individuals with urinary disorders. Only data is provided from one study, so no normative data exists. Acceptability: The Qualiveen was developed with input from individuals with SCI. Individuals reported that it was easy to understand and was comprehensive (Costa et al. 2001). Feasibility: The Qualiveen is easy to administer but no details are provided on the scoring. Qualiveen is in the process of getting a pending registration trade mark of Coloplast and to obtain a copy of the questionnaire the primary author Dr. Pierre Costa should be contacted at Pierre.costa@chu-nimes.fr. Since it is still in the pilot phase it would be important to check to see if there have been any modifications to the questions or the scoring. Clinical Summary: The Qualiveen is a quality of life tool designed to assess issues pertaining to urinary disorders specifically for individuals with SCI. It would be relevant to administer it to individuals living in the community to understand the impact of urinary issues but it is likely not measuring the same concept as in other quality of life measures which assess life satisfaction and well-being. Psychometric Summary:
Reliability Validity Responsiveness Rigor Results Rigor Results Rigor Results Floor/ceiling ++ TR +++ ++ Construct ++ N/A N/A ++ ++ IC +++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; IC=internal consistency

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22.5 Quality of Life 22.5.6 Satisfaction with Life Scale (SWLS, Deiner Scale) The SWLS was designed to address the concept of life satisfaction as a whole and thus, to reflect a global perspective of the individuals values rather than to assess satisfaction with subdimensions of life (Diener et al. 1985). Conceptually, SWLS measures subjective QOL and in particular, the reaction to the discrepancy or balance between ones life achievements and expectations. SWLS was developed using a classical test construction approach, in which an initial item pool was subsequently reduced to a smaller collection of items. The current version consists of 5 statements, scored on a 7-point Likert scale, ranging from strongly disagree (1) to strongly agree (7). Procedure: A global score (5 35) is computed by summing the scores of each question. No reports have been presented wherein the scores of a single question were used. Advantages: SWLS is a suitable tool when one aims to evaluate subjective QOL specifically. It is generic, in that it holds no bias due to particular disability (e.g. SCI). It has adequate psychometric properties across various populations and scores can be compared between these populations (see Pavot & Diener 1993 for review). Limitations: SWLS lacks specificity regarding life domains and it does not provide any information on the source of potential dissatisfaction. Furthermore, it may not be useful for guiding clinical intervention and reliability with SCI groups is relatively weak compared to other populations (Dijkers 1999). Interpretability: Scores represent a global perspective of life satisfaction. Norms/profiles are available for a SCI population, other disability populations and non-disabled populations. It is available in multiple foreign languages. Acceptability: The SWLS can be completed in less than 5 minutes. The items on the questionnaire present no potential discomforts. Feasibility: No equipment or specific training is required to administer the SWLS. An online pdf version of the SWLS can be obtained from http://www.ppc.sas.upenn.edu/lifesatisfactionscale.pdf. Clinical Summary: Overall, the SWLS provides global information on life satisfaction. It is useful for drawing general profiles in various populations and thus, it is an appropriate tool for research purposes or epidemiological databases (e.g. the US National SCI Database). Its use in clinical settings may be less useful, in that it does not establish appropriate interventions; however, it does document the overall appreciation of ones life. Psychometric Summary:
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling IC = +++ +++ Criterion*= +++ N/A N/A N/A TR*= +++ Construct**= ++ TR**= ++ Concurrent** = +++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; IC=internal consistency * (Other populations than SCI) ** (SCI population) Rigor ++

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22.5 Quality of Life 22.5.7 The Short Form 12 (SF-12) and Short Form 36 (SF-36) The SF-36 (Ware & Sherbourne 1992) is a generic health status measure that has been translated into various languages and is used world-wide. It was designed to be applied to all health conditions and to assess general health concepts, such as functional status and wellbeing. The SF-36 contains 36 items covering eight domains: physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems and mental health. The SF-12 was introduced as a shorter alternative to the SF-36 for use in population studies (i.e. large sample sizes) and includes one or two items from each of the eight domains. Procedure: The SF-36 and SF-12 can be administered by the interviewer or the client. The scoring is norm-based, with a general population mean score of 50 and a standard deviation of 10. Higher scores indicate higher levels of health. The SF-12 is scored using two summary scores, a physical and a mental component score, which are norm based (the SF-36 can also be scored in this manner). Advantages: The SF-36 and SF-12 are the most widely used measures of health status and allows the evaluation of various patient populations (McHorney et al. 1994). Economic methods have been applied to the SF-36 and the data can be used to complete a new preference based measure, the SF-6D, which has the advantage of being able to obtain utility values needed to report quality adjusted life years (Brazier et al. 2002). Limitations: Since the SF-36 and SF-12 were designed to be generic, some of the walking/stair climbing questions are not applicable to individuals with SCI and thus, it has been suggested that the wording of these questions be changed from walking/climbing to going. Another limitation is the differing interpretations of health as distinct or equivalent to disability. Interpretability: There is published data and norms available for most health conditions as well as for the general population (in Canada and the United States). Further research is needed for the establishment of psychometric properties of the SF-36 and SF-12 for SCI populations. Acceptability: The SF-36 requires 5-10 mins to complete and the SF-12 requires 2-4 mins. Feasibility: The SF-36 and SF-12 is easy to administer and the manuals are very informative. Permission to use the tools must be obtained from Quality Metric at www.qualitymetric.com and this incurs a cost. The SF-36 and SF-12 have been translated into various languages. Alternate versions are available (e.g. 1- and 4-week recalls). Clinical Summary: The SF-36 and SF-12 are the most widely used health surveys. These tools have been used extensively to discriminate, evaluate and predict outcomes in various health conditions; however, more work is required to study the validity of the questions and the proposed modifications to the questions for a SCI patient population. Psychometric Summary:
Rigor ++ Reliability Results IC +++ (SF-36) Rigor +++ ++ Validity Results Construct ++** (SF-36) Rigor N/A Responsiveness Results Floor/ceiling N/A +* (SF-36)

Construct (SF-12) ++ Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency * Note: ceiling / floor effects were noted in some scales in SF-36 V1 when reporting the scores using 0-100, however, the scales on the role physical and role emotional items were changed from dichotomous to a Likert scale in V2 which should reduce the floor and ceiling effects. No floor and ceiling effects are evident using the MCS and PCS. ** Note: since there is no gold standard to compare the SF-36 and the authors tested convergent / divergent validity using hypotheses, this was classified as construct validity as per the Stroke recommendations. The hypotheses were also tested using ANOVA (F-test). Also results from Andresen 1999, comparing SF-36 to QWB, BFSS and IADL. I used my judgment to derive an overall rating.

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22.5 Quality of Life 22.5.8 The Sickness Impact Profile 68 (SIP 68) The Sickness Impact Profile is a generic health status measure. The original version contains 136 items (Bergner et al. 1981). The length of the measure is considered a barrier to using it and thus, a modified version containing 68 items (SIP 68) was developed (de Bruin et al. 1994). This measures physical, mental and social aspects of health-related functioning in 6 subscales: somatic autonomy, mobility control, mobility range, social behavior, emotional stability, and psychological autonomy/communication. The SIP 68 contains statements regarding behavior sickness impact and the individual is asked to respond by checking items that describe their health status. Procedure: The SIP 68 can be administered by the interviewer or the client (i.e. self-report). All items are scored dichotomously (no=0, yes=1). The items reported as yes are used to calculate the scores and higher scores indicate more health-related behavioral problems (i.e. worse health state). The SIP-68 can be reported as an overall total score, three dimension scores (physical, psychological and social) or six sub-scale scores. The questions regarding walking are not relevant to wheelchair-dependent individuals and a scoring modification is proposed in such cases for a yes response to the item I cannot walk at all, all 7 items related to walking are scored positively (Post et al. 1996). Advantages: The SIP 68 is a commonly used health status measure and it is possible to compare results with various patient populations, including those with SCI (Post et al. 2001). Limitations: Floor effects (i.e. reflecting poor health) have been reported for the mobility control scale and ceiling effects (i.e. no reported problems) for the emotional stability and psychological autonomy/communication scales. The evidence on the psychometric properties of the SIP 68 for a SCI population is limited and more research is needed to assess reliability and responsiveness. Interpretability: The scores provide an assessment of health behavior problems. There is published data and norms available for a SCI population, as well as for individuals with other disabilities (Post et al. 2001). Acceptability: The SIP 68 requires approximately 15-20 minutes to complete. Feasibility: The SIP 68 is easy to administer. It is available in English and Dutch, but the administration guidelines are published in Dutch. The SIP 136 version can be obtained from the Medical Outcomes Trust at: http://www.outcomes-trust.org/instruments.htm and the SIP 68 is available in the literature (de Bruin 1994). Clinical Summary: The SIP 68 has been used to assess health-related quality of life of individuals living in the community. Modifications made to the scoring of the walking/mobilityrelated items in the SIP 68 make it a suitable tool for this patient population. Psychometric Summary
Validity Responsiveness Rigor Results Rigor Results Floor/ceiling +++ Construct ++ N/A N/A ++ ++ Predictive +* Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; IC=internal consistency * Note: Predictive validity was assessed by determining that social functioning and psychological functioning from the SIP 68 were significant predictors of life satisfaction. Rigor +++ Reliability Results IC +++

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22.5 Quality of Life 22.5.9 WHOQOL (BREF) The short version of the World Health Organization Quality of Life Assessment (WHOQOLBREF) has been developed using data from the field trial version of the WHOQOL-100 (WHOQOL Group 1998). It can be used in situations in which time is restricted or the burden placed upon the respondent must be minimized (WHOQOL Group 1998). This is an instrument that conceptually fits with the WHO definition of QOL and substantial effort has been put forth to properly operationalize the sub-concepts (various aspects of life) included in the instrument (WHOQOL Group 1998). WHOQOL-BREF is a self-report questionnaire that is comprised of 24 items grouped into 4 domains of QOL (physical health, psychological health, social relationships, and environment) and 2 items which measure overall QOL and general health. Procedure: The instrument uses a 5-point Likert scale (e.g. 1, Not at all 5, Completely). The respondents express how much they have experienced the items in the preceding 2 weeks. All domain scores are reported between 4 and 20 (mean scores for each multiplied by 4). Advantages: WHOQOL-BREF is a suitable tool when the goal is to acquire information on various aspects of life satisfaction; however, it also includes 2 questions targeting overall QOL and general health. Its conceptualization is strong and some psychometric properties were tested with different populations (Skevington et al. 2004). Furthermore, it can be used to compare results across populations (cross-cultural validity) (Skevington et al. 2004). Limitations: Lack of information on concurrent validity, test-retest reliability, and responsiveness. Interpretability: Scores represent ones personal experience and satisfaction regarding various aspects of life. Norms are available for different groups of people. Acceptability: The WHOQOL-BREF can be completed within a few minutes. Feasibility: No equipment or specific training is required to administer it. Copies can be downloaded from the WHO website. Clinical Summary: WHOQOL-BREF is among the rare instruments that can provide data for research and clinical purposes. Although it is a relatively brief instrument, its structure allows one to acquire specific information covering many aspects of life. The adequate cross-cultural validity makes it suitable for use in multinational collaborative research (Skevington et al. 2004). Psychometric Summary:
Reliability Validity Responsiveness Results Rigor Results Rigor Results Floor/ceiling IC*= +++ +++ Discriminant*= ++ N/A N/A Only 2 items IC**= +++ Discriminant**= ++ reported a slight N/A except for SR= Construct* **= +++ floor effect with ++ ++ Concurrent **= +++ SCI TR*= N/A TR**= N/A Note: +++ = Excellent; ++ = Adequate; + = Poor; N/A=Insufficient information; TR=Test re-test; IC=internal consistency, SR= Social Relationships. * (Other populations than SCI) ** (SCI population) Rigor ++

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