Classification and Complications of

Traumatic Brain Injury

Author: Percival H Pangilinan, Jr, MD; Chief Editor: Stephen Kishner, MD, MHA
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Contributor Information and Disclosures

Author
Percival H Pangilinan, Jr, MD Associate Professor, Department of Physical
Medicine and Rehabilitation, University of Michigan Health System

Percival H Pangilinan, Jr, MD is a member of the following medical societies:

American Academy of Physical Medicine and Rehabilitation, Association of
Academic Physiatrists

Disclosure: Nothing to disclose.

Coauthor(s)
Brian M Kelly, DO Associate Professor, Associate Medical Director, Division of
Orthotics and Prosthetics, Department of Physical Medicine and Rehabilitation,
University of Michigan Medical School; Assistant Program Director, Residency
Training Program, University of Michigan Health System

Brian M Kelly, DO is a member of the following medical societies: American

Academy of Physical Medicine and Rehabilitation, American Osteopathic
Association, American Osteopathic College of Physical Medicine and Rehabilitation,
Association of Academic Physiatrists

Disclosure: Nothing to disclose.

Joseph E Hornyak, IV, MD, PhD Associate Professor, Department of Physical
Medicine and Rehabilitation, University of Michigan Medical School; Consulting
Staff, Medical Director of Human Performance Laboratory, Department of Physical
Medicine and Rehabilitation, University of Michigan Medical Center

Joseph E Hornyak, IV, MD, PhD is a member of the following medical societies:
American Academy of Physical Medicine and Rehabilitation, American College of
Sports Medicine, Association of Academic Physiatrists, American Academy of
Cerebral Palsy and Developmental Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of
Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug
Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

 Michael T Andary, MD, MS Professor, Residency Program Director, Department of
Physical Medicine and Rehabilitation, Michigan State University College of
Osteopathic Medicine

Michael T Andary, MD, MS is a member of the following medical societies:

American Academy of Physical Medicine and Rehabilitation, American Association
of Neuromuscular and Electrodiagnostic Medicine, American Medical Association,
Association of Academic Physiatrists

Disclosure: Received honoraria from Allergan for speaking and teaching.

Chief Editor
Stephen Kishner, MD, MHA Professor of Clinical Medicine, Physical Medicine and
Rehabilitation Residency Program Director, Louisiana State University School of
Medicine in New Orleans

Stephen Kishner, MD, MHA is a member of the following medical societies:

American Academy of Physical Medicine and Rehabilitation, American Association
of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Additional Contributors
Everett C Hills, MD, MS Assistant Professor of Physical Medicine and
Rehabilitation, Assistant Professor of Orthopaedics and Rehabilitation, Penn State
Milton S Hershey Medical Center and Pennsylvania State University College of
Medicine

Everett C Hills, MD, MS is a member of the following medical societies: American

Academy of Disability Evaluating Physicians, Association of Academic Physiatrists,
American Academy of Physical Medicine and Rehabilitation, American Association
for Physician Leadership, American Congress of Rehabilitation Medicine, American
Medical Association, American Society of Neurorehabilitation, Pennsylvania Medical
Society

Disclosure: Nothing to disclose.

Practice Essentials
Traumatic brain injury (TBI), also known as acquired brain injury, head injury, or brain
injury, causes substantial disability and mortality. It occurs when a sudden trauma damages
the brain and disrupts normal brain function. TBI may have profound physical,
psychological, cognitive, emotional, and social effects.

According to the Centers for Disease Control and Prevention (CDC), approximately 2.5
million TBI-related emergency department visits, hospitalizations, or deaths occurred in the
United States in 2010.[1]

See Pediatric Concussion and Other Traumatic Brain Injuries, a Critical Images slideshow, to
help identify the signs and symptoms of TBI, determine the type and severity of injury, and
initiate appropriate treatment.
Classification

Primary and secondary injuries

Primary injury: Induced by mechanical force and occurs at the moment of injury; the
2 main mechanisms that cause primary injury are contact (eg, an object striking the
head or the brain striking the inside of the skull) and acceleration-deceleration [2]

Secondary injury: Not mechanically induced; it may be delayed from the moment of
impact, and it may superimpose injury on a brain already affected by a mechanical
injury [2]

Focal and diffuse injuries

These injuries are commonly found together; they are defined as follows:

Focal injury: Includes scalp injury, skull fracture, and surface contusions; generally
caused by contact

Diffuse injury: Includes diffuse axonal injury (DAI), hypoxic-ischemic damage,

meningitis, and vascular injury; usually caused by acceleration-deceleration forces

Measures of severity

See the list below:

Glasgow Coma Scale (GCS): A 3- to 15-point scale used to assess a patient's level of
consciousness and neurologic functioning [3, 4] ; scoring is based on best motor
response, best verbal response, and eye opening (eg, eyes open to pain, open to
command)

Duration of loss of consciousness: Classified as mild (mental status change or loss of

consciousness [LOC] < 30 min), moderate (mental status change or LOC 30 min to 6
hr), or severe (mental status change or LOC >6 hr)

Posttraumatic amnesia (PTA): The time elapsed from injury to the moment when
patients can demonstrate continuous memory of what is happening around them [5]

Complications

Complications include the following:

Posttraumatic seizures: Frequently occur after moderate or severe TBI

Hydrocephalus

Deep vein thrombosis: Incidence as high as 54% [6]

 Heterotopic ossification: Incidence of 11-76%, with a 10-20% incidence of clinically
significant heterotopic ossification [7]

Spasticity

Gastrointestinal and genitourinary complications: Among the most common sequelae

in patients with TBI

Gait abnormalities

Agitation: Common after TBI

Chronic traumatic encephalopathy (CTE)

Long-term physical, cognitive, and behavioral impairments are the factors that most
commonly limit a patient's reintegration into the community and his/her return to
employment. They include the following:

Insomnia

Cognitive decline

Posttraumatic headache: Tension-type headaches are the most common form, but
exacerbations of migraine-like headaches are also frequent

Posttraumatic depression: Depression after TBI is further associated with cognitive

decline, [8, 9] anxiety disorders, substance abuse, dysregulation of emotional
expression, and aggressive outbursts

Outcome measures

The following tools are commonly used to measure outcome after TBI[10, 11] :

Functional Independence Measure (FIM): An 18-item scale used to assess the patient's
level of independence in mobility, self-care, and cognition

Glasgow Outcome Scale (GOS)

Disability Rating Scale (DRS): Measures general functional changes over the course
of recovery after TBI (see the image below)
 Disability Rating Scale (DRS).

Epidemiology
Traumatic brain injury (TBI), also known as acquired brain injury, head injury, or brain
injury, causes substantial disability and mortality. It occurs when a sudden trauma damages
the brain and disrupts normal brain function. TBI may have profound physical,
psychological, cognitive, emotional, and social effects. The diagnosis of mild TBI appears to
be vastly underdiagnosed in the setting of systemic trauma, even in trauma centers.[12]

According to the CDC, approximately 2.5 million TBI-related emergency department visits,
hospitalizations, or deaths occurred in the United States in 2010. The following annual
statistics from the CDC also apply in the United States[1, 13] :

TBI contributes to approximately 50,000 deaths.

Approximately 475,000 TBIs occur among infants, children, and adolescents aged 0-
14 years.

About 80,000-90,000 people experience the onset of a long-term disability due to a

TBI.

The following groups are at particular risk for TBI[13] :

Males are about twice as likely as females to sustain a TBI.

Infants and children aged 0-4 and adolescents aged 15-19 years are the 2 age groups
at highest risk for a TBI.
 Adults aged 75 years or older have the highest rates of TBI-related hospitalization and
death.

A TBI is caused by an excessive force, blow, or penetrating injury to the head. The leading
causes of TBI are as follows[13] :

Falls (28%)

Motor vehicle crashes (20%)

Being struck by or against objects (19%)

Assaults (11%)

Mortality rates after brain injury are highest in people with a severe TBI. In the first year after
a TBI, people who survive are more likely to die from seizures, septicemia, pneumonia,
digestive conditions, and all external causes of injury than are other people of similar age,
sex, and race.[14] However, the mortality rate after severe TBI has decreased since the late 20th
century.[15]

According to the CDC, the economic cost of TBI in the United States in 2010, including
direct and indirect medical costs, was estimated at $76.5 billion.[16]

See also the following related Medscape Drugs & Diseases topics:

Initial Evaluation and Management of CNS Injury

Traumatic Brain Injury in Children

Traumatic Brain Injury: Definition, Epidemiology, Pathophysiology

See also the following related Medscape resource:

Resource CenterTrauma

Pathophysiology
Classification as Primary or Secondary injury

TBI may be divided into primary injury and secondary injury. Primary injury is induced by
mechanical force and occurs at the moment of injury. Secondary injury is not mechanically
induced. It may be delayed from the moment of impact, and it may superimpose injury on a
brain already affected by a mechanical injury.[2]

Primary injury

The 2 main mechanisms that cause primary injury are contact (eg, an object striking the head
or the brain striking the inside of the skull) and acceleration-deceleration. Primary injury due
to contact may result in injury to the scalp, fracture to the skull, and surface contusions.
Primary injury due to acceleration-deceleration results from unrestricted movement of the
head and leads to shear, tensile, and compressive strains. These forces can cause intracranial
hematoma, diffuse vascular injury, and injury to cranial nerves and the pituitary stalk.[2]

Contusions are distinct areas of swollen brain tissue.[17] They are typically found on the poles
of the frontal lobes, the inferior aspects of the frontal lobes, the cortex above and below the
operculum of the sylvian fissures, and the lateral and inferior aspects of the temporal lobes.

Intracranial hematoma is the most common cause of death and clinical deterioration after
TBI. Hematomas are categorized as follows[2] :

Epidural hematomas - These are usually caused by fracture of the temporal bone and
rupture of the middle meningeal artery. With epidural hematomas, clotted blood
collects between the bone and the dura. Because the source of bleeding is arterial, this
type of hematoma can grow quickly and create pressure against the brain tissue.

Subdural hematomas - Such hematomas are usually caused by rupture of the bridging
veins in the subdural space. They can grow large enough to act as mass lesions, and
they are associated with high morbidity and mortality rates.

Subarachnoid hematomas - These result from damage to blood vessels in the posterior
fossa stalk.

Diffuse axonal injury (DAI) is one of the most common and important pathologic features of
TBI. It constitutes mostly microscopic damage, and it is often not visible on imaging studies.
The main mechanical force that causes DAI is rotational acceleration of the brain, resulting in
unrestricted head movement. Rotational acceleration produces shearing and tensile forces,
and axons can be pulled apart at the microscopic level. Microscopic evaluation of the brain
tissue often shows numerous swollen and disconnected axons. Rapid stretching of axons is
thought to damage the axonal cytoskeleton and, therefore, disrupt normal neuron function.[18]

Secondary injury

Secondary injury may occur hours or even days after the inciting traumatic event. Injury may
result from impairment or local declines in cerebral blood flow (CBF) after a TBI. Decreases
in CBF are the result of local edema, hemorrhage, or increased intracranial pressure (ICP). As
a result of inadequate perfusion, cellular ion pumps may fail, causing a cascade involving
intracellular calcium and sodium. Resultant calcium and sodium overload may contribute to
cellular destruction. Excessive release of excitatory amino acids, such as glutamate and
aspartate, exacerbates failure of the ion pumps. As the cascade continues, cells die, causing
free radical formation, proteolysis, and lipid peroxidation. These factors can ultimately cause
neuronal death.[19]

The exact role of the inflammatory response in secondary injury is not known. However, it is
believed to contribute to cell damage.[19]

Clinical conditions associated with the risk of a decreased CBF are arterial hypotension,
hypoxemia, intracranial hemorrhage and malignant brain edema, and hyperthermia.[19]
Classification as Focal or Diffuse Injury

Another injury classification based on clinical and neuroradiologic evaluation has been
proposed. In this classification, TBI would be described as focal or diffuse. Focal injuries
include scalp injury, skull fracture, and surface contusions and are generally be caused by
contact. Diffuse injuries include DAI, hypoxic-ischemic damage, meningitis, and vascular
injury and are usually caused by acceleration-deceleration forces. These 2 forms of injury are
commonly found together.

See also the following related Medscape Drugs & Diseases topic:

Brain Contusion Imaging

Measures of Severity
The classification of TBIs plays an important role in determining the patient's treatment,
rehabilitation potential, and prognosis.

Glasgow Coma Scale

The most common classification system for TBI severity is based on the Glasgow Coma
Scale (GCS) score determined at the time of injury. The GCS is a 3- to 15-point scale used to
assess a patient's level of consciousness and level of neurologic functioning.[3, 4] It consists of
3 sections, each of which is scored: best motor response, best verbal response, and eye
opening (Table 1). A total score of 3-8 for the 3 sections indicates severe TBI, a score of 9-12
indicates moderate TBI, and a score of 13-15 indicates mild TBI.

Table 1. Glasgow Coma Scale (Open Table in a new window)

Score Best Motor Response Best Verbal Response Eye Opening

1 None None None
2 Decorticate posturing Mutters unintelligibly Opens to pain
3 Decerebrate posturing Inappropriate speech Opens to command
4 Withdraws to pain Confused Opens spontaneously
5 Localizing response to pain Alert and oriented NA
6 Obeys commands NA NA
*
Total 1-6 1-5 1-4
SourceTeasdale and Jennett, 1974.[4]

NoteNA = not applicable.

*
The total of the motor, verbal, and eye-opening scores (range, 3-15) indicates the severity of
a TBI, as follows: 3-8 is severe TBI, 9-12 is moderate TBI, and 13-15 is mild TBI.
Loss of consciousness

The duration of loss of consciousness (LOC) is another measure of the severity of a TBI
(Table 2).[20]

Table 2. Severity of TBI Based on the Duration of LOC (Open Table in a new window)

Severity of TBI Finding

Mild Mental status change or LOC < 30 min
Moderate Mental status change or LOC 30 min to 6 h
Severe Mental status change or LOC > 6 h
SourceGreenwald et al, 2003.[20]

Other classifications of severity

As early as 1932, Russell introduced the concept of posttraumatic amnesia (PTA) and later
defined it as the time elapsed from injury to the moment when patients can demonstrate
continuous memory of what is happening around them.[5] Lack of accurate records may make
this system difficult to use retrospectively. Zafonte found that the duration of PTA (as
measured by using the Galveston Orientation and Amnesia Test) appeared to be a significant
predictor of functional outcome after a TBI and may best reflect the overall severity of injury.
[21, 22]

Relatively uncommon measures of severity include the number of days that are required to
achieve a total GCS score of 15, the number of days that are needed to achieve a GCS motor
score of 6, and the Abbreviated Injury Scale Head score.

Another system for assessing TBI severity is the Simplified Motor Score (SMS). The SMS is
a 3-point scale developed to address the perceived limitations of the GCS, such as its
complexity and poor interrater reliability.

Table 3. Simplified Motor Score (Open Table in a new window)

Score Best Motor Response

0 Withdraws to pain or worse
1 Localizes pain
2 Obeys commands

A study by Thompson et al determined that in an out-of-hospital setting, the SMS was similar
to the GCS score for predicting TBI outcomes.[23]

Medical Complications
Posttraumatic seizures

Posttraumatic seizures (PTS) frequently occur after moderate or severe TBI. Seizures are
usually general or partial, and absence seizures are uncommon. Seizures are classified
according to the time elapsed after the initial injury: Immediate seizures occur in the first 24
hours. Early seizures occur in the first 2-7 days, and late seizures occur after 7 days.

The incidence of late PTS is in the range of 5-18.9%. Risk factors include chronic
alcoholism, older age at the time of injury, and a history of seizure disorder. Approximately
one half to two thirds of patients with these risk factors develop late PTS within the first year
after injury.[24] If a patient with TBI has 1 PTS, his or her likelihood of having another is
approximately 50%.[25]

Temkin showed that prophylactic use of phenytoin is effective during the first week after a
TBI.[26] However, the author recommended discontinuation after 1 week if no seizures
develop because of its lack of effect in preventing late PTS and because of possible cognitive
adverse effects.

Although phenytoin maybe effective in preventing seizures in the first week after a TBI, at
least 50% of patients with TBI have late seizure activity for which phenytoin may not be
effective.

Hydrocephalus

Hydrocephalus is characterized as communicating or noncommunicating on the basis of the

causative obstruction. Noncommunicating hydrocephalus occurs secondary to an obstruction
in the ventricular system before the point at which cerebrospinal fluid (CSF) exits the fourth
ventricle. Communicating hydrocephalus is the most common form after TBI and occurs
when the obstruction is in the subarachnoid space.[27]

Patients with hydrocephalus can clinically present with nausea, vomiting, headache,
papilledema, obtundation, dementia, ataxia, and/or urinary incontinence. The diagnosis is
based on clinical suspicion, diagnostic imaging, and radio-isotope cisternography. Treatment
usually consists of lumbar puncture or shunt placement.

Deep vein thrombosis

Deep vein thrombosis (DVT) is common in persons with TBI, with an incidence as high as
54%.[6] In patients with TBI, risk factors for DVT include immobility, lower extremity
fracture, paralysis, and disruption in coagulation and fibrinolysis.

Complications of DVT include pulmonary embolism (PE), postthrombotic syndrome, and

recurrence. Because DVT can result in PE, it can be critical. Given the rapid decline in
pulmonary function when a PE has completely occluded the pulmonary capillary system,
sudden death may be the first clinical sign.[28] Other clinical signs of PE include shortness of
breath, chest pain, and pulmonary crackles; these are usually present with small emboli.
However, clinical signs and symptoms are often absent in the patient with DVT. Therefore, a
high index of suspicion and timely medical intervention are of utmost importance.
The most common modalities for detecting DVT are venous Doppler ultrasonography and
contrast-enhanced venography. Venography remains the criterion standard for diagnosing
DVT. Noninvasive Doppler ultrasonography is most commonly used because of its low risk
of adverse effects compared with venography.[29]

Prophylaxis for DVT should be started as soon as possible. These measures include use of
elastic compression stockings, intermittent pneumatic compression, vena cava filters,
warfarin, unfractionated heparin (UH), and/or lowmolecular weight heparin (LMWH).
Mechanical methods of prophylaxis are generally used in patients with a high risk of bleeding
or in combination with anticoagulation.[29] The choice of prophylaxis should be patient
specific and based on his/her existing comorbidities.

Treatment for DVT and/or PE in patients with TBI is similar to treatment for these conditions
in the general population. Treatment generally consists of the administration of an immediate-
acting anticoagulant (UH or LMWH), followed by chronic anticoagulation with warfarin
(target international normalized ratio [INR], 2-3). Heparin or LMWH should be continued
until the desired INR is achieved and stable. The duration of anticoagulation is specific to the
indication and the patient.[30] Use of anticoagulation in the patient with TBI could increase the
risk for intracerebral hemorrhage. Each patient should be evaluated for his/her risk of
intracerebral hemorrhage and of falling.

Heterotopic ossification

Heterotopic ossification is described as ectopic bone formation in the soft tissue surrounding
the joints. In TBI, the incidence of heterotopic ossification is 11-76%, with a 10-20%
incidence of clinically significant heterotopic ossification.[7] Heterotopic ossification generally
causes joint pain and decreases range of motion (ROM). It is often associated low-grade
fever, peri-articular swelling, peri-articular warmth, and peri-articular erythema.

In decreasing order of frequency, heterotopic ossification occurs in the hips, knees, elbows,
shoulders, hands, and spine. Risk factors associated with the development of heterotopic
ossification after TBI are a posttraumatic coma lasting longer than 2 weeks, limb spasticity,
and decreased mobility. The risk of heterotopic ossification is greatest during the first 3-4
months after injury.[28]

The pathophysiology of heterotopic ossification remains unclear. However, inappropriate

differentiation of mesenchymal cells into osteoblasts is believed to be the basic defect.
Autonomic dysregulation (due to increased vascularity and venous hemostasis), humoral
factors, and local inflammatory mediators contribute to the development of heterotopic
ossification.

Laboratory and radiologic data are critical in the diagnosis of heterotopic ossification.
Although serum alkaline phosphatase levels and erythrocyte sedimentation rates are
nonspecific markers, they are often elevated in the early phases of heterotopic ossification.
Therefore, elevated levels might suggest additional evaluation.

Three radiologic modes are useful for diagnosing heterotopic ossification: plain radiography,
ultrasonography, and triple-phase bone scanning. Triple-phase bone scanning reveals
heterotopic ossification the earliest. Plain radiographic and ultrasonographic findings may lag
behind results of bone scans because of lack of early calcification in heterotopic ossification.
Plain radiographic findings lag behind triple-phase bone scan results by 2-3 weeks. However,
plain radiography can be used early to rule out an underlying fracture.

The mainstay of preventing heterotopic ossification in patients with TBI is ROM exercise.
The use of forceful ROM is somewhat controversial because it is thought to be a cause of
heterotopic ossification, but data from human studies have not demonstrated this mechanism.

The prophylactic role of nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose radiation,

or bisphosphonates remains unclear. NSAIDs and etidronate can help with pain management.
The risks and benefits of these drugs in managing established heterotopic ossification should
be assessed.

Heterotopic ossification may result in functional impairment, and patients may require
surgical excision. To minimize risk of recurrence, surgical excision has traditionally been
delayed 12-18 months to allow the heterotopic bone to mature. However, authors have
questioned this delay.[7]

Spasticity

Tone is defined as resistance to stretch or movement across a joint during relaxation.

Spasticity is defined as velocity-dependent increase in tone. Rigidity is also a function of
tone, but it is defined as the nonvelocity-dependent increase in tone. These 3 terms are not
interchangeable.

In one inpatient rehabilitation unit, spasticity was found in an estimated 25% of patients with
TBI.[31]

Spasticity is most often encountered in lesions of the upper motor neurons, whereas rigidity is
most common in disorders of the basal ganglia. The morbidity associated with spasticity is
variable, because in some people, spasticity may assist in leg extension for walking or finger
flexion for grasping. Prolonged low tone after TBI is generally predictive of poor motor
recovery.

Guidelines for the treatment of spasticity are generally based on (1) any resulting limitation in
function, (2) pain, (3) prevention of contracture, and (4) assistance with positioning.[31] First-
line treatments for spasticity are correct positioning of the involved body segment and ROM
exercises. Second-line treatments include splinting, casting, and other modalities.

Treatment varies according to whether the spasticity is generalized or local. Generalized

spasticity is usually treated systemically. Dantrolene sodium is preferred in patients with TBI
because of its lack of cognitive and sedative adverse effects.

Other drugs used to manage spasticity include baclofen, tizanidine, clonidine, and
benzodiazepines. Their use may be limited because of their sedative and cognitive adverse
effects. Local treatments for spasticity include chemical neurolysis with phenol or alcohol
injections and with botulinum toxin type A and type B injections.

GI and GU complications
GI and GU complications remain among the most common sequelae in patients with TBI.
Some of the most frequent GI complications are stress ulcers, dysphagia, bowel incontinence,
and elevated levels on liver function tests. Underlying constipation and/or impaired
communication and mobility are often the causes of bowel incontinence. The use of oral stool
softeners, laxatives, and rectal suppositories may facilitate full bowel evacuation and improve
incontinence.

GU complications include urethral strictures, urinary tract infections, and urinary

incontinence. An appropriate workup to evaluate GU symptoms and rule out infection is
indicated. When the causes of urinary incontinence are impaired communication and
mobility, a trial of a timed voiding is indicated to manage overflow incontinence. Patients are
taken to the bathroom and given the opportunity to void without instrumentation every 2
hours during the day and every 4 hours overnight.

If the patient is unable to void or cannot evacuate the urinary bladder to completion,
intermittent straight catheterization may be necessary in the acute recovery period. Although
not preferred, diapers and condom catheters may be needed if urinary incontinence does not
improve.

Voiding dysfunction and upper urinary tract status were studied in 57 survivors of coma
resulting from TBI. Direct statistical links were found between urge incontinence, detrusor
overactivity, and poor neurologic functional outcome, as well as between detrusor
overactivity and right hemisphere injuries, and between impaired detrusor contractility and
left hemisphere damages.[32]

Gait abnormalities

Martini et al performed gait analysis on subjects with and without a remote concussion
history, measuring velocity, step length, stride width, and time in single-leg versus double-leg
stance. They found that subjects with a remote concussion history showed slowed walking
velocity, greater time in double-leg stance, and less time in single-leg stance, speculating that
the patients with concussion histories are trying to limit injury risk from falls. They suggest
that patients with even remote concussion histories may have prolonged risk for fall injuries.
[33]

Chronic traumatic encephalopathy

Persons with a history of repetitive brain trauma, including boxers and football players, are at
risk for developing chronic traumatic encephalopathy (CTE), a progressive degenerative
disease. Degenerative changes, which can begin months to decades after the patients last
brain trauma, include atrophy of the cerebral hemispheres, medial temporal lobe, thalamus,
mammillary bodies, and brainstem. The condition is also characterized by ventricular
dilatation and by fenestration of the cavum septum pellucidum, as well as the accumulation
of phosphorylated tau in the brain, with deposits of the protein being found in the sulci and in
perivascular areas of the cerebral cortex.

According to a consensus panel of the National Institute of Neurological Disorders and

Stroke/National Institute of Biomedical Imaging and Bioengineering, the pathognomonic
lesion of CTE is an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons
and astroglia distributed around small blood vessels at the depths of cortical sulci and in an
irregular pattern.[34]

A study by Armstrong et al of 11 cases of CTE found dotlike lesions to be consistently

present in the brain, suggesting a similarity between CTE and both argyrophilic grain disease
and Parkinson disease dementia.[35]

Symptoms of CTE include memory loss, confusion, impaired judgment, reduced impulse
control, aggression, explosive anger, depression, and progressive dementia.[36, 37, 38, 39]

According to a report from the US Department of Veterans Affairs and Boston University, 87
of 91 deceased former players for the National Football League (NFL) (96%) who donated
their brains for study were found to have CTE (although the donors had, prior to death,
expressed concern that they might have CTE and so may have had a higher proportion of the
disease than does the overall population of former NFL players).[40, 41]

See also the following related Medscape Drugs & Diseases topic:

Post Head Injury Autonomic Complications

Post Head Injury Endocrine Complications

Agitation
Posttraumatic agitation is common after TBI. Baguley and colleagues found that 25% of
patients with TBI were classified as being aggressive during the follow-up periods in their 5-
year study.[42] Furthermore, aggression was consistently associated with depression or young
age at the time of injury.

Corrigan developed a 14-item instrument, the Agitated Behavior Scale (ABS), to quantify
levels of agitation after TBI (see image below).[43] Bogner and colleagues found the ABS a
reliable instrument for measuring agitation in patients following TBI.[44]
 Agitated Behavior Scale, developed by John D
Corrigan, PhD, ABPP, Professor, Department of Physical Medicine and Rehabilitation, The
Ohio State University. Permission for publication granted by Dr. Corrigan.

Before posttraumatic agitation is treated, other medical conditions should be considered.

After TBI, the patient may be uncomfortable, and impaired recognition and an inability to
communicate are often agitating factors. Pain is a common (but often overlooked) cause of
posttraumatic agitation. Combined with a diminished ability to communicate and/or an
inability to cope with pain, agitation is not surprising. Furthermore, clinicians should consider
the possibility of infection, electrolyte imbalance, adverse effects of drugs, psychosis, and
insomnia.

Environmental modifications are usually the first treatment. Minimizing unnecessary stimuli
and assisting with tools for orientation may help to reduce the onset of agitation. External
stimuli, such as noisy rooms, bright lights, and frequent visitors, should be minimized. Use of
centrally acting drugs that may exacerbate agitation should be minimized. Physical restraints
often exacerbate posttraumatic agitation and should not be used routinely. Restraints should
be used only as a last resort to secure patient, staff, and visitor safety. However, the use of
less restrictive restraints, such as net-covered beds (eg, Vail beds), has become acceptable and
popular in the treatment of the agitated patient with a brain injury.

In addition to environmental and behavioral modifications, various drugs, such as high-dose

beta blockers, anticonvulsants, and antidepressants (particularly selective serotonin re-uptake
inhibitors [SSRIs]), have had some success in the management of posttraumatic agitation.[45]
Brooke and colleagues found that the intensity of agitation was significantly lower in patients
with TBI who were treated with propranolol than in subjects who were treated with placebo.
[46]
In addition, amantadine has shown some usefulness in reducing posttraumatic agitation.[47,
48]
Case studies support the use of lamotrigine[49] or divalproex[50] to manage posttraumatic
agitation.
The use of antipsychotics to treat posttraumatic agitation is controversial. Their effects on
cognition and recovery are poorly studied. Antipsychotics may cause excessive drowsiness,
exacerbate cognitive deficits, and inhibit neuronal recovery. Stanislav suggested that select
areas of cognition may improve after thioridazine and haloperidol are discontinued.[51]

Symptoms Of TBI
Long-term physical, cognitive, and behavioral impairments are the factors that most
commonly limit a patient's re-integration into the community and his/her return to
employment.

In a study by Kraus and colleagues of 235 patients, the symptoms most commonly reported 6
months after mild TBI were fatigue (43%), weakness (43%), memory deficits (40%),
headache (36%), and dizziness (34%).[52] Other investigators found similar complaints after
mild TBI.[53, 54] The symptoms have collectively been referred to as postconcussion syndrome.
Kraus and co-authors found that approximately 83% of patients with mild TBI reported 1 or
more physical complaints at the end of their 6-month follow-up period.[52, 55]

Insomnia

In one study, patients with TBI reported higher rates of sleep changes than did sex-matched
control subjects (80% vs 23%).[27] The TBI group reported more nighttime awakenings and
longer sleep-onset latency than did the other group. Increased levels of anxiety and
depression were risk factors that may have partly accounted for increased complaints of
excessive daytime sleepiness.

Light therapy may mitigate TBI-related sleep disturbances. In a small study that included 18
adults with a history of at least 1 mild TBI and sleep disturbance that developed after, or was
exacerbated by, the most recent injury, morning bright-light therapy led to improvements in
sleep, cognition, emotion, and brain function.[56, 57]

Cognitive decline

Khateb and colleagues found that patients with chronic TBI who were treated with donepezil
had slight improvements in neuropsychological test results, including in speed of processing,
learning attention, and divided attention.[58] Light therapy may also be helpful.[57]

Posttraumatic headache

Walker and co-authors found that nearly 38% of patients with moderate or severe TBI had
acute posttraumatic headache, usually daily and most commonly in the frontal region.[59]
Almost all of the patients who reported posttraumatic headache at 6 months also reported
symptoms at 12 months.

Chronic posttraumatic headache is common, and the pathophysiology is not well understood.
Tension-type headaches are the most common form, but exacerbations of migrainelike
headaches are also frequent. Treatment of posttraumatic headache is similar to that of primary
headache if structural lesions or abnormalities are absent.[60]
Posttraumatic depression

Mood disorders, particularly depression, are common sequelae of TBI. Major depression is
found in about 40% of patients hospitalized for TBI.[61] Depression after TBI is further
associated with cognitive decline,[8, 9] anxiety disorders, substance abuse, dysregulation of
emotional expression, and aggressive outbursts.[62] Whitnall and colleagues reported that
persistent disability (5-7 years after TBI) was strongly associated with depression and
anxiety, and that it was more poorly associated with initial severity or persistent cognitive
impairments.[63]

Dikmen et al found that the following factors are predictive of posttraumatic depression:
educational level less than high school, unstable work history prior to injury, and alcohol
abuse.[62]

Treatment options for posttraumatic depression include counseling, participation in support

groups, and antidepressant medication. Early after TBI, a grief reaction is common, and this
is better treated with supportive therapies than with other approaches. If drugs are used, their
profiles, including their adverse effects and interactions, must be carefully considered to
prevent worsening sedation or cognitive impairment. Methylphenidate and sertraline are
beneficial in treating posttraumatic depression.[64]

Methylphenidate is commonly used to treat patients with hypo-arousal, initiation, and

attention problems associated with TBI. Methylphenidate may hasten recovery after TBI. The
positive effects of methylphenidate are improved speed in processing and sustained attention.
[65]
By potentiating dopamine, amantadine may improve arousal, attention, and executive
functions.[66]

Outcome Measures
Tools to effectively measure outcome are needed to quantify results.[67] Outcome measures
can be used to assess the effectiveness of different treatments.

Three tools commonly used to measure outcome after TBI are the Functional Independence
Measure (FIM),[10] the Glasgow Outcome Scale (GOS),[11] and the Disability Rating Scale
(DRS).

The FIM is one of the most widely used measures of function in rehabilitation (Table 3). It is
an 18-item scale used to assess the patient's level of independence in mobility, self-care, and
cognition. However, it may lack sensitivity in patients with very low or very high levels of
function. Therefore, the FIM may be an inadequate outcome measure for patients at either
extreme of TBI recovery.

Table 4. Functional Independence Measure (Open Table in a new window)

Clinical Area
Self-care A. Eating
B. Grooming
C. Bathing
D. Dressing - upper body
 E. Dressing - lower body
F. Toileting
G. Bladder management
Sphincter control
H. Bowel management
I. Bed, chair, wheelchair
Transfers J. Toilet
K. Tub, shower
L. Walking, wheelchair
Locomotion
M. Stairs
Motor subtotal score:
N. Comprehension
Communication
O. Expression
P. Expression
Social interaction Q. Problem solving
R. Memory
Cognitive subtotal score:
TOTAL FIM SCORE:
SourceKeith et al, 1987.[10]

The GOS is a scoring system commonly used to rate outcomes after TBI (Table 4).[11]

Table 5. Glasgow Outcome Scale (Open Table in a new window)

Score Rating Definition

1 Dead Nonsurvival
2 Persistent vegetative Minimal responsiveness
3 Severe disability Conscious but disabled; dependent on others for daily support
4 Moderate disability Disabled but independent; can work in sheltered setting
5 Good recovery Resumption of normal life despite minor deficits
SourceJennett and Bond, 1975.[11]

The DRS (see the image below) is intended to accurately measure general functional changes
over the course of recovery after TBI, where a score of 0 indicates no disability and 29
indicates an extreme vegetative state.[68] The DRS includes 8 items, including the GCS score
and disability and return-to-work measures.
 Disability Rating Scale (DRS).

Prognosis
Determining the patient's prognosis after TBI remains difficult and complex. The
heterogeneity of patients' premorbid health status, the natures and severities of injury, the
intervals from injury to initial treatment, the acute interventions, and the differences in
follow-up create difficulty in developing a simple and accurate scoring system.

Brown and co-authors found the following variables to be predictive of outcome[69] :

Initial GCS score

Duration of PTA

Amnesia [70]

Sex

Age

Years of education

Cuthbert et al investigated injury severity and sociobiological and socioeconomic factors to

predict discharge location (home vs not to home) in adults with moderate to severe TBI. They
found GCS and acute hospital length of stay to be the most predictive in discharges to home
versus not to home (ie, higher GSC and shorter LOS were more likely to be discharged to
home). They also found that old age was associated with a decreased likelihood of discharge
to rehabilitation and more likely to be discharged to subacute rehabilitation.[71]
Bogner and colleagues found that substance abuse contributed to the prediction of life
satisfaction and productivity, while violent etiology was not a significant contributor to
prediction.[72] Corrigan and co-authors found that a lack of pre-injury history of substance
abuse and the possession, at the time of follow-up, of gainful employment were associated
with higher life satisfaction 1-2 years after TBI.[73] An evaluation of the employment outcome
in patients with moderate to severe TBI found that patients with comorbid psychiatric
symptoms and impaired cognitive functioning are at the highest risk of long-term
unemployment.[74]

Three-month GOS scores are powerful independent predictors of long-term outcome after
severe TBI.[75, 76] Davis and colleagues found that GCS scores in the field and on the patient's
arrival in the emergency department are highly predictive of mortality and of a need for
neurosurgical care.[77] Davis's study also found that an increase in the GCS score from the
field to the emergency department is highly predictive of survival. Studies have shown that
the level of abnormality on brain computed tomography (CT) scans and the early loss of
autoregulation of ICP are predictive of the outcome.[78, 79, 80]

In a secondary analysis of data on 365 patients with moderate or severe TBI from a
randomized trial, Badri et al found that average ICP in the first 48 hours of monitoring
independently predicted mortality as well as a composite endpoint of functional and
neuropsychological outcome at 6 months. Average ICP, however, was not independently
associated with neuropsychological functioning.[81] In patients with severe TBI due to acute
subdural hematoma, TBI severity, age and neurological status are the primary factors
influencing outcomes, and nonoperative management is associated with a significantly
increased mortality risk.[82]

Further research is needed to develop simple prognostic tools. Improved prognostic tools, if
available, would assist clinicians in planning for patients' long-term care and needs.
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