CHAPTER

Editor: CHRISTINE B. HUNTER, RN, CCRN

20 Movement Disorders
MS, APN-CNS, CNRN,

Authors: PAM WILLSON, PhD, RN, FNP-C, LISETTE K. BUNTING-PERRY, MSCN, RN, CCRN, JEAN ARZBAECHER, GWYN VERNON, MSN, CRNP, and CAROL BROWN MOSKOWITZ, MS, APRN-C, CNRN

OBJECTIVES 1. Differentiate between hypokinetic and hyperkinetic movement disorders. 2. Identify the clinical presentation, diagnostic workup, and treatment of Wilsons disease. 3. Describe the pathophysiology, appropriate assessment, diagnostic workup, and management of Parkinsons disease. 4. Identify the causes, pathophysiology, clinical presentation, and treatment of dystonia. 5. List the etiology, clinical presentation, and treatment interventions for patients with Gilles de la Tourettes syndrome. 6. Describe the pathophysiology, clinical presentation, diagnostic workup, and treatment of Huntingtons disease. 7. Characterize the pathophysiology, clinical presentation, diagnostic workup, and treatment of essential tremor. 8. Describe the pathophysiology, clinical presentation, diagnostic workup, and treatment of restless legs syndrome.

INTRODUCTION TO MOVEMENT DISORDERS

A. According to Clinical Overview and Phenomenology of Movement Disorders (Fahn et al, 1998), movement disorders are neurological syndromes in which there is either an excess of movement or a paucity of voluntary and automatic movements, unrelated to weakness or spasticity (Box 20-1). BOX 20-1 MOVEMENT DISORDERS
Hypokinesias (decreased amplitude, slowness, loss of movement; parkinsonism is most common category) Akinesia, bradykinesia (parkinsonism) Apraxia Blocking (holding) tics Cataplexy and drop attacks Catatonia, psychomotor depression, and obsessional slowness Freezing phenomenon Hesitant gait Hypothyroid slowness Rigidity Stiff muscles Hyperkinesias (excessive, abnormal, involuntary movements; asterisked items are most common) Abdominal dyskinesias Akathisic movements Asynergia, ataxia Athetosis Ballism Chorea* Dysmetria Dystonia* Hemifacial spasm Hyperekplexia Hypnogenic dyskinesias Jumpy stumps Moving toes and/or fingers Myoclonus* Myokymia

Myorhythmia Paroxysmal dyskinesias Restless legs Stereotypy Tics* Tremor*

B. Origins of abnormal movements: Most movement disorders are associated with pathological alterations in the basal ganglia or their connections. The basal ganglia are that group of gray matter nuclei lying deep within the cerebral hemispheres (caudate nucleus, putamen, and globus pallidus), the diencephalon (subthalamic nucleus), and the mesencephalon (substantia nigra). There are some exceptions to this general rule. Pathology of the cerebellum or its pathways typically results in impairment of coordination (asynergy, ataxia), misjudgment of distance (dysmetria), and intention tremor. Myoclonus and many forms of tremor do not appear to be related primarily to basal ganglia pathology and often arise elsewhere in the central nervous system, including the cerebral cortex (cortical reflex myoclonus), brainstem (reticular reflex myoclonus, hyperekplexia, and rhythmical brainstem myoclonus disorders such as palatal myoclonus and ocular myoclonus), and spinal cord (rhythmical segmental myoclonus and nonrhythmic propriospinal myoclonus). A growing body of evidence supports the notion that some movement disorders are peripherally induced. C. Epidemiology: Movement disorders are common neurological problems, but epidemiological studies are lacking for many of them. Several such studies of Parkinsons disease have been carried out in various countries. Table 20-1 lists the prevalence rates of some movement disorders based on studies in the United States. TABLE 20-1 Prevalence of Movement Disorders
Disorder Restless legs syndrome Essential tremor Parkinsons disease Gilles de la Tourettes syndrome Primary torsion dystonia Hemifacial spasm Hereditary ataxia Huntingtons disease Wilsons disease Progressive supranuclear palsy Multiple system atrophy Prevalence* 9800 415 187 29-1052 2990 33 7.4-14.5 6 12-Feb 3 2 6.4 4.4 Reference Rothdach et al, 2000 Haerer et al, 1982 Kurland, 1958 Caine et al, 1988; Comings et al, 1990 Mason et al, 1998 Nutt et al, 1988 Auger et al, 1992 Schoenberg et al, 1985 Harper and Newcombe, 1992; Kokmen et al, 1994 Reilly et al, 1993 Golbe, 1993; Golbe et al, 1988 Schrag et al, 1999 Schrag et al, 1999

*Rates are given per 100,000 population. For restless legs syndrome, the rate cited is in a population <65 years of age. For Parkinsons disease, the rate is 347 per 100,000 among persons >40 years of age.

D. Genetics: A large number of movement disorders have genetic causes. Some of the diseases have now been mapped to specific regions of the genome, and some have even been localized to a specific gene. For example, several gene locations have been identified for Parkinsons disease with and without Lewy bodies. Seven genetic loci have so far been linked with Parkinsons disease or variants of classical Parkinsons disease. Several of them have been correlated with a specific gene and protein. A comprehensive list of movement disorders for which the associated genes have been mapped is beyond the scope of this document. However, neurogenetics is one of the most rapidly developing research areas in neurology, so the list is constantly changing.

WILSONS DISEASE
A. Description: Wilsons disease (WD) is a disorder of copper metabolism inherited as an autosomal recessive trait that causes excessive accumulation of copper in the liver and other organs such as the brain and cornea. Clinical presentation may therefore include hepatic symptoms (e.g., hepatitis, cirrhosis, and hepatic failure), neurological symptoms (e.g., dysarthria, tremor, dystonia, and incoordination), as well as psychiatric and behavioral disturbances (e.g., loss of ability to focus on mental tasks, uncontrolled emotions, and depression). WD is a progressive disease that can prove fatal, but it can be completely reversed if identified and treated early after onset. B. Epidemiology 1. Incidence: Rare, approximately 1 in 30,000 to 1 in 40,000 2. Prevalence: In general population, 1 per 50,000 to 1 per 100,000 3. Age of symptom onset: From 6 to 50 years; typically presents in late teens or early twenties; average age of onset is 19 years 4. Ethnicity: Affects all races; increased incidence among European Jews, Italians, Sicilians, and Japanese C. Etiology and contributing factors 1. Copper metabolism is abnormal with defective biliary excretion of copper. 2. Defect occurs in the energy-mediated secretory mechanism for copper in hepatocytes. 3. Responsible mutation is in the ATP7B gene, which encodes a copper-transporting P-type adenosine triphosphatase. 4. Gene locus for the defect is chromosome band 13q14.3, coding a liver-specific copper transporter. 5. Rate of copper transfer from albumin into the globulin fraction is reduced and ceruloplasmin level is decreased. a. Serum levels of free copper are increased. b. Biliary excretion of copper is reduced. c. Iron-binding globulin levels are low to low normal. 6. Persistent aminoaciduria is present. 7. Excess copper is deposited in several tissues: Liver, brain, kidneys, corneas D. Affected systems 1. Liver a. Because of copper deposition, copper is sequestered in the lysosomes, which causes necrosis, coarse nodularity, and postnecrotic cirrhosis. b. Deposition of copper results in hepatosplenomegaly. 2. Central nervous system a. Hyperplasia of protoplasmic astrocytes in cerebral cortex, basal ganglia, brainstem nuclei, and cerebellum b. Nerve cell loss and degeneration of myelinated fibers in ventricular nuclei, substantia nigra, and dentate nuclei c. Cavitation of putamen, globus pallidus, and caudate nucleus d. Deposition of copper in corneas, which produces Kayser-Fleischer (KF) rings, rusty brown corneal deposits 3. Other systems a. Kidney: Renal disease secondary to renal tubular necrosis from excessive excretion of copper b. Skeletal (1) Osteoporosis: Caused by associated calcium and phosphate abnormalities (2) Arthropathy: Bone or joint pain caused by tissue destruction from copper and iron deposition in joints c. Hematological: Hemolytic anemia (negative results on Coombs test), secondary hematological abnormalities E. Phenotypic classification 1. Hepatic presentation: No neurological or psychiatric symptoms at diagnosis a. H1: Acute hepatic WD (1) Acute jaundice in a previously healthy person, either caused by a hepatitis-like illness, a Coombs testnegative hemolytic disease, or both

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May progress to liver failure and emergency liver transplantation H2: Chronic hepatic WD Any type of chronic liver disease, symptomatic or not May progress to decompensated cirrhosis (a) Standard biochemical and/or radiological evidence or biopsy findings are used to make the diagnosis. 2. Neurological presentation: Neurological and/or psychiatric symptoms of WD at diagnosis a. N1: Associated with symptomatic liver disease (1) Patients often have cirrhosis at the time of diagnosis. (2) Chronic liver disease may precede neurological symptoms. b. N2: Not associated with symptomatic liver disease Clinical presentation 1. Clinical manifestations a. Hepatic disease b. Extrapyramidal dysfunction c. KF corneal rings 2. Variability in initial presentation a. Forty percent present initially with liver disease. b. Thirty percent present initially with neurological symptoms. c. Thirty percent have psychiatric or behavioral symptoms. 3. Liver disease a. Asymptomatic hepatosplenomegaly b. Acute hepatitis, chronic active hepatitis c. Cirrhosis and/or hepatic failure 4. Neurological symptoms a. Dysarthria: Damage to the extrapyramidal pathways causes mixed hypotonic changes (e.g., hypophonia) and dystonic changes (e.g., changes in voice quality, rate, or volume); dysarthria can progress to anarthria (inability to speak); stuttering or palilalia (compulsive repetition of a word or phrase) may be exhibited. b. Tremor: Variable types (1) Postural: Most common; involves any body part; exaggerated with postural change; worsens with anxiety or stress; worsens with arms elevated and flexed (wing-beating tremor) or arms extended with wrists dorsiflexed and fingers spread (asterixis or hand-flapping tremor) (2) Resting: Regular and rhythmic tremor present while at rest; usually not present when asleep (3) Intention: Occurs with purposeful movement (e.g., eating) (4) Mixed: Shows components of both resting and postural tremor c. Other involuntary movements (1) Athetosis: Recurrent change of position of a body part (e.g., writhing movements of neck, foot, or leg) (2) Chorea: Rapid, jerky movements of the face or extremities d. Dystonia: Increased muscle contractility (e.g., cramps, facial grimacing, stiff posture); progressive dystonia accounts for rigidity and sialorrhea (drooling) e. Incoordination: Often begins with fine motor movements of fingers and hands (e.g., micrographia or macrographia); loss of dexterity; dysdiadochokinesia (rapid alternating movements), posture and gait abnormalities f. Seizure: Rare 5. Psychiatric and behavioral symptoms: Often precede appearance of neurological symptoms a. Cognitive changes (e.g., trouble concentrating, difficulty with previously acquired skills) causing difficulties in school and at work in tasks that require mental focus and persistence b. Personality changes (e.g., irritability and emotional lability) c. Depression: Can be severe and lead to suicide d. Loss of inhibitions, exhibitionism e. Insomnia f. Anxiety g. Psychosis: Hallucinations, delusions, catatonia; rare

(2) b. (1) (2)

6. Corneal symptoms a. KF rings: Rusty brown color; corneal copper deposits (1) Present in about 50% of patients presenting with hepatic symptoms (2) Almost always present in patients presenting with neurological or psychiatric symptoms (3) Require slit-lamp examination by an experienced ophthalmologist (a) KF rings are easier to visualize in blue or hazel eyes. (b) Deposition of the copper begins in the superior aspect of the cornea, then the inferior aspect, and finally the lateral aspects until a ring is formed around the cornea. (4) Do not usually interfere with vision b. Sunflower cataract: Copper deposition in the lens (1) Occurs in <20% of patients (2) Does not usually interfere with vision G. Prevention 1. Primary prevention: Prevention of occurrence a. Genetic counseling of affected persons and their families (1) Estimates are that 1% of the general population are carriers for WD. (2) Children of parents with WD have a 1 in 200 chance of having WD; risk for nieces and nephews is 1 in 600, and for cousins, 1 in 800. 2. Secondary prevention: Early detection of the disease a. Health care providers should have a high index of suspicion for the disease. b. The chronicity of the disease and the need for life-long medication and therapy should be reinforced. c. Case finding from the index case should be performed. d. All persons under age 30 who have clinical symptoms of WD should be screened. 3. Tertiary prevention: Rehabilitation a. Psychiatric and/or psychological counseling b. Educational tutoring c. Occupational therapy d. Physical therapy H. Data assessment 1. Subjective data a. Health history (1) Family history of WD: If sibling has WD the person has a 1 in 4 chance of having the disease (2) New onset of symptoms (within last 3 to 5 years): Behavioral, psychiatric, neurological, and/or hepatic b. Psychologic and neurologic symptoms (1) Abnormal behavior: Argumentative, excessively emotional (2) Impairment of intellectual faculties (3) Fatigue, decreased energy level, feeling of sleep deprivation (4) Gait abnormalities: Incoordination, slowness of movements and walking, history of falls (5) Mask facies, gaping mouth, drooling of saliva c. Hepatic symptoms (1) Weight loss, thinness, cachexia, jaundice, ascites, fluid retention (2) Easy bruising and bleeding after injury; bleeding of gums with brushing; nosebleeds; blood in stool, urine, or sputum; hepatic coma 2. Objective data a. Psychiatric and neurological findings (1) Cognitive deterioration: Memory deficits, inability to concentrate, inability to complete tasks (2) Dementia (3) Schizophrenia: Hallucinations or delusions (4) Depression: Unipolar or bipolar (5) Neurosis: Nervousness around strangers, anxiety, suspiciousness; bizarre behavior (6) Brainstem and cerebellar signs: Dysarthria, dysphagia, excessive drooling, fixed facial muscles, ataxia, bradykinesia, seizures

I.

(7) Motor findings: Resting and intention tremors of head and limb, chorea, dystonia, rigidity, spasticity, flexed posture; flexion deformities (a) Other signs: Presence of Babinskis reflex, absence of abdominal reflex, abnormal saccadic eye movements b. Hepatic findings: Splenomegaly, hepatomegaly, ascites, varices, hepatic encephalopathy, jaundice, acute transient hepatitis, acute fulminant hepatitis, chronic active hepatitis, hepatic failure c. Corneal findings: KF rings and/or sunflower cataracts 3. Diagnostics: No single diagnostic test is available that excludes or confirms WD 100% of the time a. Urinary copper excretion (1) High urinary copper excretion: >100 g in 24-hour period (a) Use copper-free containers for collection. (b) Accurate pediatric 24-hour urinary collection may require admission to an inpatient facility. (c) Pediatric values may be false-positive, and an oral challenge test with d-penicillamine (500 mg given at the beginning and 500 mg given after 12 hours of a 24-hour urine collection period) may be warranted. b. Serum copper determination (1) Low serum copper: 3 to 10 M (normal range is 11 to 24 M) (a) Level of nonceruloplasmin-bound plasma copper (free copper) is obtained by subtracting the ceruloplasmin-bound copper value from the total plasma copper value; 1 mg of ceruloplasmin = 3 g of copper. (2) Low serum ceruloplasmin: <20 mg/dl (a) Measurement of ceruloplasmin level using a nephelometric assay (oxidative assay is more accurate) may yield false-negative results if the patient has active liver disease, is pregnant, or is using hormonal contraception. (b) In the radioactive copper ceruloplasmin incorporation test (oral copper-64), radiolabeled copper is taken orally and serum levels are measured 1 to 2 hours and 48 hours later. In patients with WD, there is a rise in the plasma radioactivity early at 1 to 2 hours but only a meager secondary rise in plasma radioactivity at 48 hours (the defect prevents the hepatic incorporation of radioactive copper into ceruloplasmin). c. Pathology (1) Liver biopsy reveals elevated copper levels (>200 g/g). (2) Mass spectroscopy is the most reliable test for measuring hepatic copper content. (3) Patients with chronic liver disease (e.g., cholestasis) have elevated liver copper levels in the absence of WD. d. Computed tomography (CT) of brain (1) May be abnormal in hepatic stage H1 without neurological signs (2) Lateral ventricles enlarged (3) Cerebral and cerebellar sulci widened (4) Brainstem shrunken (5) Lenticular nuclei hypodense e. Hepatic disease indices (1) Bilirubin >2 mg/dl (2) Albumin <3.5 g/dl (3) Prothrombin time >4 seconds (4) Increased serum alkaline phosphatase levels f. Slit-lamp examination of corneas: Shows KF rings Patient problems: Vary by the patients mode of presentation, stage of treatment, and severity of disease and/or sequelae 1. Problem 1: Knowledge deficit related to WD and the consequences of not adhering to prescribed regimen a. Defining characteristics: Initial diagnostic evaluation and lack of knowledge about WD cause and treatment b. Interventions (1) Medical

(a) Copper-chelating agents (prevent absorption of copper) or cupruretic agents (promote excretion of copper) 1) Zinc acetate (Galzin) a) Mechanism of action: Intestinal metallothionein induction from saliva and blood (binds copper within the intestinal mucosal cell, which is excreted in the stool); prevents intestinal absorption of copper b) Advantages: Effective, nontoxic, easily to monitor c) Disadvantages: Can cause gastric distress, slow acting d) Uses: Treatment of choice for presymptomatic or pregnant patients; used for maintenance therapy e) Dosage i. Adult: 50 mg three times per day (tid), can be increased to up to 250 mg/day; taken on an empty stomach, 1 hour from food ii. Pediatric: 25 mg tid for children 10 years of age or older iii. Pregnancy: 25 mg tid 2) d-Penicillamine (Cuprimine, Depen) a) Mechanism of action: Chelates copper and promotes cupruresis b) Advantages: Effective, fast acting c) Disadvantages: Elicits hypersensitivity reaction during first 14 days i. Symptoms include rash, fever, leukopenia, thrombocytopenia, lymphadenopathy, proteinuria. ii. Symptoms resolve with prednisone therapy. d) Dosage: Administered with pyridoxine hydrochloride 50 mg/day i. Adult: 1 to 2 g/day by mouth in divided doses; one half hour before or 2 hours after meals ii. Pediatric: 250 to 1250 mg/day by mouth in divided doses; dosage low initially and increased at weekly intervals 3) Ammonium tetrathiomolybdate a) Mechanism of action: Binds copper with drug and protein to prevent absorption b) Advantages: Effective, very fast acting, little toxicity c) Disadvantages: Not commercially available d) Dosage: 120 mg/day (20 mg with each meal and an additional 20 mg between meals) (b) Other therapeutic agents 1) Sulfurated potash, 20 mg tid with meals 2) Potassium sulfide dimercaprol (British anti-Lewisite; 2,3-dimercaptopropanol) 3) Trimethylene tetramine dihydrochloride (Trien, trientine, TETA; Food and Drug Administration [FDA] orphan drug) (2) Surgical: Liver transplantation (a) Advantages: May correct underlying defect (b) Disadvantages: 30% mortality risk, limited organ donor availability (3) Nursing team (a) Assess patient, family, and/or caregiver knowledge of WD. (b) Educate patient and caregiver about WD: Pathophysiology; genetic inheritance; purpose of medications, side effects and symptoms to report to the health care provider; need for follow-up care; community resources (c) Educate about copper and need to decrease copper intake. 1) Average American diet contains about 1 mg of copper per day. 2) Encourage consumption of a high-protein, low-copper diet. 3) Instruct patient to avoid foods high in copper: Liver, shellfish, and other foods with a copper content of 0.2 mg. Some physicians allow these foods to be eaten periodically after anticopper therapy is instituted: Pork, duck, lamb, squid, tofu, all types of shellfish; avocados, dried beans, mushrooms, dried fruits, raisins, dates, prunes; bran breads, wheat germ, cereals; chocolate; nuts.

4) Educate about water: The Environmental Protection Agency allows 1.2 parts per million (PPM) of copper in drinking water (equivalent to 1.2 g/L). If drinking or cooking water contains >0.1 PPM of copper, an alternate water source should be used. c. Expected outcomes (1) Patient demonstrates an understanding of WD by defining WD and describing the impact of WD on the activities of daily living (ADLs). (2) Patient describes anticopper medication regimen, possible side effects, and symptoms warranting attention. (3) Patient identifies community resources. d. Potential complications (1) Ineffective therapeutic outcomes (2) Noncompliance with treatment regimen (3) Fear and/or guilt of inherited disease (4) Missed opportunity for WD case finding (5) Liver failure 2. Problem 2: Alteration in thought process related to cognitive and personality changes a. Defining characteristics (1) Difficulty functioning at school or work, lapses in memory, trouble concentrating, and difficulty with mathematics and vocabulary (2) Irritability, emotional lability, anxiety, and/or depression b. Interventions (1) Medical (a) Systemic copper reduction medications (b) Consultation with educational tutors (2) Nursing team (a) Identify and eliminate or decrease precipitating factors. (b) Alleviate environmental distractions. (c) Encourage calming and stress-reducing interventions (e.g., listening to music). (d) Teach caregiver about managing inappropriate behavior. c. Expected outcomes (1) Patient exhibits appropriate behavior and has normalized thought processes. (2) Patient overcomes educational delays and achieves grade promotion on schedule. d. Potential complications (1) Permanent cognitive changes due to late diagnosis and therapy (2) Limited educational achievement (e.g., patient drops out of high school or college) 3. Problem 3: Activity intolerance related to fatigue a. Defining characteristics: Tremors, athetosis, chorea, dystonia, rigidity, spasticity, and/or incoordination b. Interventions (1) Medical (a) Dystonia medication: Botulinum toxin (2) Nursing team (a) Teach patient to space activities throughout the day to avoid fatigue. (b) Explain the need to avoid extremes of environmental temperature. (c) Rearrange environment to help prevent unnecessary energy expenditure. (d) Describe techniques to avoid infection. c. Expected outcome (1) Patient reaches maximum achievable mobility. (2) Patient schedules activities realistically. (3) Patient achieves optimal strength and endurance. d. Potential complications (1) Patient physical deconditioning (fatigability, loss of muscle strength and functional capacity) (2) Social isolation 4. Problem 4: Impaired physical mobility related to weakness and increased muscle tone

a. Defining characteristics: Tremors, athetosis, chorea, dystonia, rigidity, spasticity, and/or incoordination b. Interventions (1) Medical: Antitremor medications (2) Nursing team (a) Maintain head in midline position. (b) Use spasticity to promote leg strength. (c) Encourage proper use of adaptive strategies and devices. c. Expected outcomes (1) Patient reaches optimal achievable strength. (2) Patient falls less frequently. d. Potential complications: Contractures, falls 5. Problem 5: Bathing and dressing self-care deficit related to physical immobility and incoordination a. Defining characteristics: Tremors, athetosis, chorea, dystonia, rigidity, spasticity, and/or incoordination b. Interventions (1) Provide privacy and warmth for performance of ADLs. (2) Consult occupational therapist for adaptive equipment as needed. (3) Teach caregivers how to assist patient and use adaptive equipment. c. Expected outcome (1) Patient provides self-care in bathing and dressing to the extent possible while experiencing rigidity, incoordination, tremor, and/or balance deficits. d. Potential complications: Patient self-care dependency, low self-esteem 6. Problem 6: Risk for injury related to falls due to shuffling steps and bradykinesia a. Defining characteristics: Chorea, dystonia, rigidity, spasticity, incoordination, balance, and/or gait difficulties b. Interventions (1) Encourage patient to wear good, sturdy shoes. (2) Teach patient proper use of cane or walker. (3) Teach patient to concentrate on standing upright and picking up the feet to take steps. (4) Remove environmental hazards: Throw rugs, electrical cords, and other clutter. (5) Ensure adequate lighting and availability of safety equipment: Bath chair, grab bars, and raised toilet seat. c. Expected outcome (1) Patient avoids injury. d. Potential complications: Falls, fractures 7. Problem 7: Impaired swallowing related to progressive muscle weakness a. Defining characteristics: Drooling, dysphagia, and/or choking b. Interventions (1) Medical (a) Use of anticholinergic medications (e.g., glycopyrrolate [Robinul] 1 to 2 mg tid) to decrease the amount of saliva produced (b) Consult with speech pathologist or otolaryngologist for videofluoroscopic swallowing study (2) Nursing team (a) Promote frequent, small, high-nutrition feedings. (b) Encourage patient to allow adequate time to eat. (c) Teach use of suction device if needed. (d) Teach caregiver to perform Heimlich maneuver if suction device fails to alleviate choking. (e) Encourage use of straws or cup with spout for drinking liquids. (f) Encourage the use of commercial thickening agents to achieve a better consistency of food. (g) Encourage weekly weighing of the patient. c. Expected outcomes (1) Patient maintains adequate nutritional status and weight. (2) Aspiration and its complications are avoided.

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d. Potential complications: Aspiration pneumonia, asphyxia 8. Problem 8: Impaired communication (written and gestures) related to weakness of face and throat muscles a. Defining characteristics: Fixed facial muscles, bradykinesia, and/or dysarthria b. Interventions (1) Help patient and caregivers to develop methods to communicate if voice volume is too low. (2) Encourage patient to take a deep breath and project voice from diaphragm. (3) Encourage exaggerated pronunciation of words. (4) Encourage patient to speak slowly and in short phrases. (5) Consult speech therapist to assist patient and caregiver. c. Expected outcome (1) Patient is able to communicate effectively. d. Potential complications: Social isolation, low self-esteem 9. Problem 9: Impaired self-concept (body image, role performance, personal identity); grief, altered coping mechanisms, altered body image, anxiety a. Defining characteristics (1) Tremors, incoordination, balance, and/or gait difficulties (2) Mood lability, crying, and anxious behaviors b. Interventions (1) Medical (a) Antidepressant medications (b) Psychotherapy (2) Nursing team (a) Assess patients perception of loss for self and/or family. (b) Involve consultants for crisis counseling. (c) Encourage verbalization of feelings. (d) Facilitate the grieving process. (e) Promote social interaction. (f) Teach the use of pharmacological interventions if needed (e.g., anxiolytics, antidepressants). (g) Involve family or caregivers. (h) Encourage participation in support groups. c. Expected outcomes (1) Resolution of grief, depression, or anxiety is achieved. (2) Patient demonstrates positive coping behaviors. d. Potential complications: Suicide, strained family relationships 10. Problem 10: Noncompliance with anticopper medication regimen related to lack of understanding of WD and its treatment a. Defining characteristics: Refusal or failure to remember to take medications b. Interventions (1) Nursing team: Educate patient and caregiver. (a) Initiation of medication therapy resolves symptoms but does not correct pathology. (b) Discontinuation of therapy results in return of symptomatology. (c) Improvement noted with early treatment. (d) Disease is fatal without treatment. (e) Therapy must be continued throughout life. (f) Some neurological dysfunction may be permanent if treatment is not begun prior to neuronal loss. (g) Interventions are tailored to functional abilities. c. Expected outcome (1) Patient complies with treatment regimen. Outcomes 1. The goal of treatment is to achieve a negative copper balance by using strategies such as reduction of copper intake or copper absorption and increase in copper elimination. 2. Liver transplantation may be necessary.

PARKINSONS DISEASE
A. Description: Parkinsons disease (PD) is a neurodegenerative disease caused by a depletion of dopamineproducing cells in the substantia nigra. The cardinal features of PD are a resting tremor, rigidity, bradykinesia, and diminished postural stability. B. History 1. Parkinsons disease was first described in 1817 by an English physician, James Parkinson, in a composition entitled An Essay on the Shaking Palsy. 2. From 1919 to 1926 a worldwide epidemic of encephalitis resulted in the development of PD secondary to exposure to the infectious agent. 3. L-Dopa was discovered and first used successfully in oral form to treat PD in 1969. 4. In 1979, a drug-induced form of parkinsonism was discovered when individuals attempting to manufacture heroin instead produced and injected MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), which resulted in a parkinsonian state. The discovery of MPTP has allowed the development of important animal models for PD research. C. Epidemiology 1. Incidence: The incidence of PD worldwide is difficult to determine. Estimates range from 4.9 to 25.6 per 100,000 population. 2. Prevalence: Estimates are that 1.5 million Americans have PD, with approximately 50,000 new cases diagnosed each year. a. Age: The average age of onset is about 60 years. b. Gender: The prevalence is slightly higher in males. c. Race: The prevalence is slightly higher in whites. D. Etiology: No single causative agent has been identified in PD. However, several genetic, environmental, cardiovascular, and secondary causes of PD have been proposed. 1. Genetics: Any hypothetical genetic factors contributing to PD would account for only a small number of cases. However, the study of families with genetic mutations that result in PD is a promising avenue for research. a. Mutations in the -synuclein gene (PARK1) showing an autosomal dominant mode of transmission have been identified in an Italian-Greek family and account for <70 cases. b. Mutations in the parkin gene (PARK2) are more common than mutations in PARK1. 2. Environmental factors a. Occupation: Occupational exposure to heavy metals, such as prolonged exposure to copper and manganese, has been associated with an increased risk of PD. b. Rural living: Rural living has been reported in several studies to be a risk factor for the development of PD. Exposure to pesticides and consumption of well water have been associated with PD in epidemiological studies. c. Oxidative stress: The production of free radicals that damage DNA, proteins, and lipids causes oxidative stress. Evidence of oxidative stress is evident in postmortem preparations of brains from individuals with PD. 3. Parkinsonism: Accurate diagnosis of idiopathic PD is essential for appropriate treatment. There are common Parkinson-like syndromes, referred to as parkinsonism, that initially present as PD but are differentiated from idiopathic PD on the basis of history and progression of the disease. a. Drug effects: Neuroleptic blockade of the dopamine (D2 receptor subtype) system is the most common cause of drug-induced parkinsonism. Thus, obtaining a detailed history of medication use is essential in the care of patients presenting with a movement disorder. Common D2-blocking medications are the phenothiazines, prochlorperazine (Compazine), thioridazine (Mellaril), chlorpromazine (Thorazine), fluphenazine (Prolixin), the butyrophenones, haloperidol (Haldol), the benzamides, and metoclopramide (Reglan). b. Cerebrovascular disease: Vascular disease or strokes to the basal ganglia can produce symptoms similar to those of idiopathic PD. Vascular PD does not respond to L-dopa therapy and shows a stepwise progression.

c. Normal-pressure hydrocephalus (NPH): NPH is characterized by a classic triad of gait abnormality, urinary incontinence, and dementia. The gait disorder of NPH is wide based and irregular. Patients may demonstrate difficulty lifting their feet off the floor. d. Parkinson-plus syndromes: Parkinson-plus syndromes often present as PD in the early stages of the disease. Patients with Parkinson-plus syndromes develop postural instability with gait disturbances more rapidly than patients with idiopathic PD. (1) Progressive supranuclear palsy (PSP): PSP is differentiated from PD by an ataxic gait and uncompensated loss of postural reflexes. Patients with PSP fall frequently in the early stages of the disease. In addition, supranuclear ophthalmoparesis, demonstrated by paralysis of downward gaze, is a significant mark of PSP. (2) Corticobasal ganglionic degeneration (CBD): Patients with CBD present with asymmetric symptoms of limb rigidity, bradykinesia, ideomotor apraxia, postural imbalance, and dystonia. Cortical dementia is also seen early in the course of CBD. (3) Multisystem atrophy (MSA): MSA refers to a collection of syndromes that are progressive and present with autonomic dysfunction. Shy-Drager syndrome, striatonigral degeneration, and olivopontocerebellar atrophy fall under the classification of MSA. E. Neuropathology: Pathophysiological changes in the brains of patients with PD include changes in the substantia nigra and the presence of Lewy bodies. 1. Degeneration of the nigrostriatal system: Depigmentation and loss of neurons in the substantia nigra result in a reduction in the number of dopaminergic neurons, which leads to a depletion of striatal dopamine. 2. Pathological intracellular inclusions: Lewy bodies are intracytoplasmic inclusions found in the cytoplasm of the nigral neurons on postmortem examination. Lewy bodies are considered to be the pathological hallmark of PD. F. Anatomy: See Chapter 2 G. Neurochemistry 1. Dopamine metabolism: In PD, the normal equilibrium between dopamine and acetylcholine is disrupted because of the loss of dopamine in the dopaminergic nigrostriatal system. This produces an increase in aminobutyric acid transmitting or secreting (GABAergic) output from the striatum. Thus, the patient with PD has abnormal motor fluctuations. 2. Dopamine receptors: The central effects of dopamine are mediated by five different molecular receptor subtypes: D1, D2, D3, D4, and D5. Depletion of dopamine-containing neurons in the substantia nigra contributes to the development of PD. Dopamine (D2) agonists are used in the treatment of PD. 3. Other neurochemical systems: Norepinephrine is also depleted in PD, as the result of a loss of neurons in the brain. H. Clinical presentation: The clinical presentation of PD can be complex. There are often discussions as to whether there is a true diagnosis of PD, or whether there is a collection of symptoms. 1. Classic triad a. Resting tremor: Described as a pill-rolling tremor present when the arm and hand are at rest. Tremor is not present with action. Tremor may initially present as a unilateral feature of PD. b. Rigidity: When passive movement is assessed, the arms, legs, and neck are stiff, and full range of motion may be difficult to obtain. This is often described as resistance to passive movement. c. Bradykinesia: The patient moves slowly and in a deliberate manner. 2. Other motor features a. Postural instability: Seen in late stages of PD. The patient has a stooped posture and may become wheelchair or bed bound. (1) Loss of postural reflexes: As PD progresses, the patient develops diminished postural reflexes. (2) Retropulsion: In testing for postural stability, the patient with PD is often unable to maintain an upright posture when given the pull test. In the pull test, the examiner gives the patient a backward tug to the shoulders. The PD patient often is unable to maintain position and experiences retropulsion, so that the examiner must stop the patients fall. (3) Falls: Develop late in PD as postural instability, gait problems, and diminished reflexes become more prominent with the progression of disease. b. Gait: The patient with PD may present with classic features of a parkinsonian gait. (1) Diminished arm swing: The patient may show diminished arm swing as a unilateral feature.

(2) Shuffling: The patient may shuffle his or her feet on the floor and not pick up the feet, which results in short, restricted steps. (3) Festination: The patient may lean forward and walk with fast, shortened steps, which can result in an involuntary forward acceleration. (4) Freezing: The patient may experience freezing of gait. Typically this occurs in narrow spaces, in doorways, or on turning. Often the patient will describe feeling stuck or frozen to the floor. c. Dystonia: The patient may experience a sustained muscle contracture that causes twisting, repetitive movements or abnormal posturing. d. Loss of dexterity: The patient with PD often presents with diminished fine motor movements. (1) Micrographia: Handwriting samples from a patient with PD are often small and illegible. 3. Secondary manifestations of Parkinsons disease a. Neuropsychiatric: Psychiatric comorbidities are common and lead to considerable disability and emotional distress in patients and their families and/or caregivers. Frequently, psychiatric problems can be more disabling than the motor dysfunction. The neuropsychiatric problems may be caused by antiparkinsonian medications, the pathophysiology of the progressing disease, or a combination of both factors. (1) Depression: The reported prevalence of depression is 40%. (2) Dementia: The reported prevalence of dementia is 21%. (3) Anxiety: Anxiety disorders have been found to be more frequent in PD patients than in patients with other neurological diseases. The actual prevalence of anxiety is unknown. However, estimates suggest that 40% of patients with PD experience some form of anxiety disorder. (4) Psychosis: Psychosis related to dopaminergic treatment occurs in approximately 20% of patients. (5) Apathy: Apathy or amotivation in PD patients is well documented. However, the prevalence is unknown. It is often difficult to distinguish apathy in PD from a depressive symptom. (6) Sleep disturbance: Approximately 75% of PD patients experience sleep disturbances such as difficulty falling asleep, fragmented sleep, reversal of the sleep cycle, and excessive daytime sleepiness. In addition, medications used to treat PD, primarily the dopamine-agonist class of antiparkinsonian medications, can result in sudden daytime somnolence. b. Autonomic dysfunction: Autonomic dysfunction is common in PD and other Parkinson-plus syndromes and can lead to considerable disability. Autonomic dysfunction is related to degenerative changes in the autonomic nervous system. In addition, medications used to treat PD have autonomic side effects. (1) Urinary incontinence: Urinary urgency, urinary frequency, and nocturia are common problems for the elderly. Patients experience additional problems with rigidity and akinesia, which limits their mobility in getting to the bathroom. (2) Sexual dysfunction: Male impotence or erectile dysfunction is not a frequently addressed issue in patient care and can be a significant burden to patients partners. Studies of sildenafil (Viagra) have demonstrated its effectiveness in the treatment of erectile dysfunction in patients. (3) Constipation: Constipation, also referred to as gastrointestinal dysautonomia, is an annoying problem for patients and is often difficult to manage. Decreased activity, low-fiber diet, and antiparkinsonian medications can all contribute to constipation in the patient. (4) Orthostatic hypotension (OH): The patient with PD may complain of feeling dizzy or light-headed when experiencing OH. In addition, falls may be related to OH. To assess for OH, blood pressure (BP) and pulse are measured in both the sitting and standing positions. The patient is instructed to sit, and vital signs are measured. Then the patient stands for 3 minutes before vital signs are measured again. Observations should focus on the change in BP and pulse from the sitting to the standing position. (5) Impaired thermoregulation: Thermoregulatory dysfunction in PD is well documented and can present as hyperhydrosis (excessive sweating), intolerance to heat and cold, and accidental hypothermia. Thermoregulation problems can be related to motor fluctuations from narrowing of the therapeutic window of PD medications. (6) Sensory abnormalities: Patients may complain of sensory changes, which may be mild to severe and may be related to the peaks and troughs of medication action. However, the patient should be evaluated for other causes of sensory changes, such as nerve compression.

I.

(a) Pain: Patients often report painful dystonia of the feet or legs in the early morning. Shoulder pain can be a presenting feature. (b) Paresthesias: Complaints of numbness, burning, or tingling are common. (7) Craniofacial abnormalities (a) Dysphagia: Swallowing problems in the patient are caused by motor dysfunction in the muscles of the tongue and pharynx. Dysphagia can severely impair the patients nutritional status. In advanced PD, patients may benefit from placement of gastrostomy tubes. (b) Blepharitis: Involuntary closure of the eyes is a variant of dystonia experienced by patients. (c) Masked facies: The patient may present with a fixed, immobile, and expressionless face with staring eyes and a slightly open mouth. (d) Anosmia: Many patients report a loss or impairment in the sense of smell. (e) Dysarthria or hypophonia: Speech changes in the patient are caused by dysfunction of the muscles responsible for speech. A referral to a speech therapist can assist the patient in learning techniques to project and annunciate words. (f) Excessive drooling: Excessive drooling, or sialorrhea, is caused by the inability of the patient to swallow involuntarily. The patient has normal saliva production. Inability to involuntarily swallow causes the pooling of saliva in the mouth, which results in drooling. Treatment for sialorrhea includes injection of the salivary glands with botulinum toxin to decrease saliva production. (8) Other manifestations (a) Seborrhea: Seborrheic dermatitis is common in PD. It is caused by the hyperactivity of the parasympathetic component of the autonomic nervous system, which results in the overexcretion of sebum by the sebaceous glands of the skin. (b) Weight loss: Weight loss can be attributed to several factors. Patients with tremor or dyskinesias burn more calories. In addition, the patient may have difficulty with choking and aspiration, which leads to diminished oral intake. (c) Peripheral edema: Edema of the lower extremities can be a symptom of immobility in the patient. Medications such as dopamine agonists or amantadine used to manage PD symptoms can also cause peripheral edema. 4. Secondary complications: The classic symptoms of PD are treated with a wide variety of pharmacotherapeutic agents that are tailored to each patients symptoms and tolerance. As the disease progresses, pharmacotherapy is less effective, which results in the appearance of secondary complications. a. Wearing-off phenomenon: Many PD patients describe times when their medications become less effective. They may feel slowed down or fatigued. This experience is called wearing off. b. On-off phenomena: Patients describe the period when their medications are working as on time and the period when their effectiveness has worn off as off time. c. Peak-dose dyskinesias: As PD patients experience more off time, medication levels are titrated upward to treat the symptoms and lengthen on time. Unfortunately, increased doses of L-dopa can produce high peak serum levels. Thus, the patient is on but experiences dyskinesias or athetoid movements of the arms, legs, and trunk, which can be disabling. Diagnostics: The diagnosis is clinical and involves careful history taking and physical examination. Traditional laboratory studies do not contribute significantly to the diagnosis. 1. History: A careful history of initial symptoms and progression of the disease will demonstrate a picture of unilateral onset, diminished gait, diminished fine motor movements, and possible tremor. Often a family member will notice that the patient is not picking up a foot or is dragging a leg. 2. Physical examination: The neurological examination for the diagnosis of PD focuses on the motor system the presence of tremor, rigidity, impaired balance, gait abnormalities, and diminished arm swing. Diminished eye downward gaze may suggest a Parkinson-plus syndrome. 3. Neuroimaging studies: Neuroimaging is of little benefit to the clinician. CT and magnetic resonance imaging (MRI) are essentially normal. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are expensive and are used primarily in PD research protocols. a. CT: Normal scans with varying degrees of atrophy b. MRI: Normal scans with varying degrees of atrophy c. PET: Can demonstrate presynaptic nigral cell loss d. SPECT: Can demonstrate presynaptic dopaminergic deficits in patients

4. Rating scales: A variety of rating scales are used to measure PD. a. The Unified Parkinsons Disease Rating Scale (UPDRS) was developed to bring a standard of evaluation to the bedside for measurement of the progression of disease. It is composed of six subscales. (1) Mentation, behavior, and mood (2) Activities of daily living (3) Motor examination (4) Complications of therapy (5) Modified Hoehn and Yahr staging: Rates PD from stage 0 to 4 (6) Schwab and England Activities of Daily Living scale: Rates independence in performing ADLs from 100% to 0% J. Treatment: The plan of care is multipronged and highly individualized. Pharmacological and multidisciplinary treatment assist in the early stages of the disease. During mid- to late-stage disease, motor complications are treated through surgical techniques and additional pharmacotherapy. Late-stage PD can be managed through supportive measures that lead to hospice services and end-of-life care. K. Patient problems 1. Problem 1: Difficulty in carrying out work-related or home activities or ADLs because of the PD process a. Defining characteristics (1) Tremor, rigidity, impaired balance, gait abnormalities, excessive drooling, diminished arm swing, diminished fine motor movements (2) Postural instability and falling (3) Dystonia and lack of dexterity (4) Difficulty in performing or inability to perform work or home activities b. Interventions (1) Medical (a) Pharmacological therapy: L-Dopa therapy continues to be the gold standard of treatment, and new medications have been formulated to assist in L-dopa metabolism and absorption. Continued research in the pharmacotherapy for PD brings new treatment options and new hope to the patient with PD. 1) Treatment of symptoms: Symptomatic treatment is the basis of therapy for PD. If the patient presents with symptoms of PD that are not interfering with ADLs, treatment may not be indicated. The decision to treat PD depends on the patients lifestyle, activity, and age. a) L-Dopa: Carbidopa plus L-dopa (Sinemet) is the standard of treatment for PD symptoms. CarbidopaL-dopa comes in regular and sustained-release preparations. However, long-term treatment may result in diminished efficacy and motor fluctuations. Patients with early PD should not be started on L-dopa therapy until symptoms of the disease interfere with ADLs. b) Dopamine agonists: Dopamine agonists are typically the first-line treatment for early PD and have been shown to slow the progression of the disease and reduce symptoms. Examples of dopamine agonists are ropinirole (Requip), pramipexole (Mirapex), pergolide (Permax), and bromocriptine (Parlodel). c) Anticholinergics: Anticholinergic medications can be helpful in treating tremor. However, they may cause confusion in patients with cognitive decline. Examples of anticholinergics used in the treatment of PD are trihexyphenidyl (Artane) and benztropine (Cogentin). d) Amantadine (Symmetrel): Amantadine is an antiviral agent and has been used in the treatment of PD since 1968. Amantadine is effective in early disease and also is beneficial in treating dyskinesias in middle to late disease. The mechanism of action of amantadine in the treatment of PD is not clear. 2) Management of motor complications a) Dyskinesias: Dyskinesias are typically related to peak doses of L-dopa in the on state. The L-dopa dosages are reduced, a dopamine agonist is added, or amantadine is started. b) Motor fluctuations: Motor fluctuations can be sudden and unpredictable. They can be managed with the addition of catechol-O-methyl transferase (COMT) inhibitors and dopamine agonists. If on-off fluctuations are severe, the patient with PD may benefit from deep brain stimulation (DBS) surgery.

i. COMT inhibitors are used in conjunction with L-dopa therapy to reduce the peripheral metabolism of L-dopa and thus increase the efficiency of L-dopa delivery across the blood-brain barrier. This results in the smoothing out of L-dopa plasma levels and reduction in motor fluctuations. COMT inhibitors should be given with carbidopaL-dopa (Waters, 2002). Examples of COMT inhibitors are tolcapone (Tasmar) and entacapone (Comtan). 3) Neuroprotection: Neuroprotective agents safeguard degenerating neurons from oxidative injury. Clinical trials of the use of neuroprotective agents in the treatment of PD have generated controversial findings. a) Monoamine oxidase type B (MAO-B) inhibitors: The use of MAO-B inhibitors in the treatment of PD has been intensely studied. Selegiline, a MAO-B inhibitor, is currently prescribed for patients with early PD in hope of slowing the progression of the disease. The exact mechanism of action and the actual benefits of selegiline are controversial. b) Dopamine agonists: Clinical studies of the use of dopamine agonists as monotherapy for treatment of early PD have demonstrated a decrease in the development of motor complications later, as the disease progresses. c) Coenzyme Q10: Coenzyme Q10 is a natural nutrient and is essential in the production of adenosine triphosphate (ATP). A small study of 80 PD patients who took 1200 mg/day of coenzyme Q10 found evidence of improvement in symptoms. Additional research must be conducted on the efficacy of coenzyme Q10 in the treatment of PD. (2) Surgical: Neurosurgical treatments for PD started in the mid-1950s and consisted of ablative procedures. With the advent of L-dopa therapy in the 1960s, neurosurgical treatment of PD declined. In 1987, a French neurosurgeon began clinical trials of DBS surgery to control tremor. (a) Ablation: Prior to the advent of L-dopa therapy for management of PD, neurosurgeons were using surgical techniques to treat the disorder. In recent years, pallidotomy and thalamotomy have been revived in the surgical treatment of PD. Both techniques result in the permanent destruction of brain tissue to control tremor. However, thalamotomy controls only tremor and does not help other symptoms, and therefore is no longer a recommended treatment for patients with PD. Pallidotomy relieves tremor as well as other common PD symptoms such as dyskinesias, rigidity, motor fluctuations, and gait disorders. Pallidotomy is not recommended as a bilateral procedure because it is associated with a high incidence of cognitive, speech, and swallowing side effects. (b) DBS: DBS surgery was first introduced in France in the late 1980s. The FDA approved DBS for treatment of PD in January 2002. The exact mechanism behind the effects of DBS is not known; however, it is postulated that DBS either electrically inhibits or excites the hyperactive pathways in the basal ganglia of PD patients and permits normal or near-normal motor function. Two targets for implantation of DBS electrodes are the subthalamic nucleus and the globus pallidus interna. Stimulation of both the subthalamic nucleus and globus pallidus interna targets has been found to suppress PD symptoms. Current research is investigating the difference in effectiveness of electrode placement in the subthalamic nucleus and globus pallidus interna in a large clinical trial. Bilateral DBS can be safely implemented, and the stimulation device can be adjusted or turned off for patient evaluations. (c) Cell transplantation: Clinical trials of cell transplantation for treatment of PD started in the late 1980s and continue today in small numbers of patients in research protocols. Findings in animal models are the basis of cell transplantation in PD. The long-term effects of cell transplantation in humans with PD are still unknown. 1) Human fetal cells: Clinical trials of embryonic nigral grafts to treat PD have produced variable results. The benefits are contingent on several factors, such as the age of the patient and the age of the embryonic nigral grafts at the time of implantation. 2) Xenografts: The use of porcine neural xenografts for transplantation is being researched in clinical trials. Several problems arise in the use of tissue from another species (xenografts) for transplantation, including the possibility of cross-species infection, rejection, and functional capacity. 3) Stem cells: Neural stem cell transplantation for treatment of PD has received attention in the popular press and is a promising area of research. Embryonic neural stem cells can be isolated and cultured to grow and differentiate into neurons, astrocytes, and oligodendrocytes. Researchers can thus produce a line of dopamine-producing cells for transplantation into the brains of patients with PD. (3) Nursing and multidisciplinary team

(a) Nonpharmacological management: The management of PD is complex. The patient is best served through use of a multidisciplinary team to support pharmacological, psychiatric, rehabilitative, and neurosurgical treatment. 1) Education: Provision of education to the patient and his or her family and/or caretakers is the most important intervention. A well-informed patient is better able to understand the treatment plan, comply with the regimen, and maintain optimal functioning within the limitations of a progressive neurological disorder. 2) Nutrition: Overall good nutrition is essential for optimal functioning. Swallowing problems may inhibit oral intake in the patient with PD and lead to weight loss. In addition, the development of tremor and dyskinesias can require increased caloric intake to maintain body weight. Medications such as a carbidopa and L-dopa combination are more effective when taken on an empty stomach. Patients with PD will achieve optimum effect from L-dopa therapy if they consume a low-protein diet. 3) Exercise: Exercise helps keep the patient with PD from losing muscle mass and can improve mobility and diminish injury from falls. 4) Physical therapy: Physical therapy can assist the patient with PD in learning techniques to improve ambulation, increase flexibility, and reduce falls. 5) Psychiatry: Psychiatric comorbidities are common in PD and lead to considerable disability. Medications to treat psychosis, anxiety, and depression can greatly reduce disability in patients with PD. 6) Psychotherapy: The effects of PD have an impact on the mental lives of patients with PD and their families and/or caregivers. Married couples can also benefit from couples therapy to assist in coping with changing roles within the relationship. 7) Occupational therapy: Adaptive equipment can aid the patient in eating, bathing, and dressing, and thus help in maintaining independence. 8) Speech and swallowing therapy: Evaluation and treatment by a speech and swallowing specialist and/or otolaryngologist can be useful. Formal studies to assess swallowing problems can help the clinician make recommendations on food selection and preparation. Techniques to aid in swallowing can further reduce the risk of aspiration and improve oral intake. Speech therapy can teach the patient with PD how to use muscles to improve vocalization and projection. (b) Nursing interventions across the continuum of care 1) Early PD: The role of the nurse in the early stages of PD is to educate and support the patient and family or caregiver. The treatment plan should focus on medication compliance, evaluation of disease progression, assessment of the ability to performs ADLs, and provision of speech, occupational, and physical therapy. For patients in the early stage of PD, referral to a PD support group may not be appropriate, because many members of community support groups are at an advanced stage of disease. Some patients with early PD find it distressing to see those with advanced cases. This option should be explored with the patient prior to referral to a community support group. All patients should be encouraged to prepare an advance medical directive in the initial stage of PD. 2) Mild to moderate PD: As the disease progresses, the assessment is focused on the symptoms of the disease and the way these symptoms affect ADLs. Continued education on medication management is essential. Motor fluctuations may present in mild to moderate PD, and the patient may experience wearing off or on-off phenomena, and possibly develop dyskinesias. Communicating these complications of therapy to the physician will assist in tailoring the treatment plan. In those with moderate PD, speech and swallowing problems may present. Aspiration is a risk. Balance impairment limits mobility, and the patient may begin to experience falls. Evaluation and treatment by a physical therapist can help the patient in learning techniques or using assistive devices to maintain mobility and reduce falls. Patients with moderate PD may be candidates for DBS surgery if motor fluctuations or dyskinesias are disabling.

3) Advanced PD: The nurses role at this stage is to educate and support the patient and family and/or caregiver. The incidence of neuropsychiatric problems increases with complex pharmacotherapy and progressing disease. Patients with advanced PD can wander and be difficult to manage at home. Dementia affects 21% of patients and is the leading cause of placement of the elderly into nursing homes. The nurse assists the family in coordinating social services for placement issues. However, the majority of patients with advanced PD are cared for at home. Patients can become confined to the wheelchair or bed. Home care services and durable equipment delivery are coordinated, and the need for gastrostomy tube placement is assessed. The use of wheelchairs with companion controls can assist the caregiver in transporting the patient with advanced disease. The family is educated in the maintenance of hydration, nutrition, and skin integrity; bowel maintenance and management of incontinence; aspiration precautions; and observation for signs and symptoms of urinary tract infections. Weighing the patient weekly helps the treatment team in managing nutritional intake. When the PD patient has progressed to the end-of-life stage, introduce the concept of palliative care and discuss this treatment option with the treating physician. Coordination of services with a hospice program is an appropriate mechanism for the patient to end life with dignity. (c) Care settings: Nurses interact with the patient with PD in a variety of settings. The majority of care for the patient with PD is managed on an outpatient basis. Hospitalizations are intermittent and often related to acute illness or surgery. 1) Outpatient clinics: PD patients receive the majority of care in private physicians offices or specialty movement disorder centers. Nurses interact with patients in these clinic settings and develop long-term relationships with patients and their families and/or caregivers. It is often the clinic nurse who takes on the role of case manager for the patient with PD. 2) Acute care hospital: Patients with PD are hospitalized for a variety of medical reasons. The need for DBS surgery, hip replacement, peg-tube placement, and psychiatric care are a few of the medical problems that may bring the PD patient to an acute care facility. 3) Rehabilitation facility: Inpatient and outpatient rehabilitation services are a widely used resource for patients with PD after DBS surgery to assist patients in ambulating with regained motor control. 4) Home care: Skilled nursing care greatly benefits the PD patient at home. After medication adjustments or initiation of new medications the patient needs to be monitored for compliance with the regimen and adverse reactions. Family and patient teaching is a hallmark of home care nursing. 5) Day care: In maintaining a patient in the community the family often uses adult day care services to assist in patient care. 6) Traditional nursing home: Nursing home placement of a patient with PD is usually the last resort for the family. Patients placed in nursing homes typically are in an advanced stage of PD and in need of skilled nursing services. Maintenance of skin integrity, hydration, and mobility, nutritional management, and aspiration precautions are a focus of care in the nursing home. The patient should have an advance directive on medical care, and the family should be in agreement with the specification of lifesustaining treatment options. 7) Life-care community: More people are entering life-care communities and living in a variety of settings within one complex. The role of the nurse in these facilities spans the continuum of care from independent living to assisted living to long-term care. c. Expected outcome (1) Patients disease process is managed optimally to support patients ability to work and/or carry out ADLs. 2. Problem 2: Altered thought processes a. Defining characteristics: Dementia, delirium, psychosis, depression b. Interventions (1) Medical (a) Evaluate for treatable causes of altered thought processes. Blood tests include levels of vitamin B12 and thyroid-stimulating hormone (TSH), rapid plasma reagin test, complete blood count with differential, and chemistry panel. (b) Evaluate for a urinary tract infection. (c) Perform CT or MRI of the brain.

(d) Reduce or adjust medication levels. (e) Refer the patient to a geriatric psychiatrist and/or neuropsychologist for evaluation of dementia, delirium, depression, or psychosis. (2) Nursing team (a) Provide patient and family education on depression, delirium, dementia, and psychosis. (b) Administer antipsychotic and antidepressant medication as ordered. (c) Assess mental status. c. Expected outcome (1) Altered thought process resolves. 3. Problem 3: Altered physical mobility a. Defining characteristics: Motor fluctuations, freezing of gait, dyskinesias b. Interventions (1) Medical (a) Order appropriate medication. (b) Refer to physical therapy. (2) Nursing team (a) Administer antiparkinsonian medications on time in accordance with the patients individualized medication schedule. (b) Have the patient record motor fluctuations in daily diaries. (c) Encourage exercise. (d) Administer carbidopaL-dopa on an empty stomach. If this is not tolerated, give with a nonprotein snack. (e) Encourage the patient to maintain a low-protein diet during the waking day to improve L-dopa absorption. Daily protein portion can be eaten in the evening when the patient needs less mobility. (f) If motor fluctuations are severe and medication has been optimized, refer the patient to a neurosurgeon for evaluation for DBS surgery. c. Expected outcome (1) Motor fluctuations are reduced. 4. Problem 4: Inadequate nutritional status a. Defining characteristics (1) Increased caloric utilization from tremors and dyskinesias (2) Swallowing problems that result in weight loss b. Interventions (1) Medical (a) Swallowing evaluation (b) Placement of gastrojejunal tube for feeding (2) Nursing team (a) Monitor weight. (b) Evaluate diet with a dietitian. (c) Provide tube care if a feeding tube is in place for nutrition. (d) Provide supplemental feedings to increase caloric intake. c. Expected outcome (1) The patient maintains or gains weight.

DYSTONIA
A. Description: Dystonia is a neurological syndrome characterized by involuntary sustained, patterned, and often repetitive contractions of opposing muscles that causes twisting movements or abnormal postures. B. Epidemiology 1. Third most common movement disorder after PD and essential tremor 2. Affects an estimated 300,000 persons in North America 3. Prevalence estimated to be 3.4 per 100,000 for generalized dystonia and 30 per 100,000 for focal dystonia 4. Incidence estimated at 2 per million for generalized dystonia and 24 per million for focal dystonia 5. More common in Jews of Eastern European or Ashkenazi ancestry

C. Clinical manifestations 1. Repetitive movements 2. Patterned movements a. The same groups of muscles are repeatedly involved. b. Additional muscles may be involved later, but the pattern usually remains the same. 3. Usually, exacerbation by voluntary motor activity 4. Change in intensity of dystonic movements under influence of various conditions a. Stress and fatigue: Often increase dystonic movements b. Geste antagonistique: Sensory tricks can temporarily relieve dystonic postures 5. Associated tremor a. Pathogenic relationship between dystonia and essential-type tremor b. In patients with cervical dystonia, 25% prevalence of postural hand tremor D. Classification 1. By distribution: Most useful classification a. Focal: Affecting a single body part (1) Cranial dystonia (a) Blepharospasm: Involuntary bilateral eye closure produced by spasmodic contractions of the entire orbicularis oculi muscle (b) Oromandibular dystonia: Involuntary jaw closure, jaw opening, or jaw deviation (c) Laryngeal dystonia 1) Adductor (most common): Excessive and uncontrolled closing of the vocal folds producing effortful, strained voice 2) Abductor: Prolonged vocal cord fold openings producing breathy and whispering voice (2) Cervical dystonia or spasmodic torticollis: Most common form of focal dystonia (a) Laterocollis: Rotation of the head (b) Anterocollis: Abnormal flexion of the head forward (c) Retrocollis: Abnormal extension of the head backward (3) Limb dystonia (a) Task-specific idiopathic arm dystonia: Writers cramp, musicians dystonia (b) Leg dystonia: Legs involved very frequently in children, rarely in adults (4) Trunk dystonia: Truncal movements that can result in abnormal postures b. Segmental: Affecting one or more contiguous body parts (1) Crural: One leg plus trunk or both legs c. Multifocal: Affecting two or more noncontiguous body parts (i.e., cervical dystonia and leg dystonia) d. Generalized: Segmental crural dystonia and dystonia in at least one additional body part e. Hemidystonia: Unilateral dystonia (1) CT or MRI evidence of contralateral basal ganglia lesion (e.g., infarction, infection, hemorrhage), a history of hemiparesis, or both in 75% of cases 2. By age: Generally, the earlier the onset of symptoms, the more likely the chance of progression with advancing age a. Early-onset or childhood dystonia (1) Begins in childhood or adolescence (2) Symptoms start in one part of the body and then become generalized (3) Most common hereditary form of dystonia 3. By etiology a. Primary (idiopathic) dystonia: Occurs as an isolated neurological disorder without any evidence of other causes b. Secondary dystonia (1) Results from environmental or disease-related damage to the basal ganglia (a) Specific neurological event such as head trauma, encephalitis, stroke (b) Exposure to certain drugs or toxins, such as neuroleptics, antipsychotics, dopamine receptor blocking agents (c) Other neurodegenerative disorder (2) Usually begins with dystonia at rest

4. By response to L-dopa a. Dopa-responsive dystonia (1) Shows dramatic and sustained response to low-dosage L-dopa therapy (2) Typically presents in mid-childhood b. Nondopa-responsive dystonia E. Genetics 1. Mutation with autosomal dominant transmission 2. Abnormal DYT-1 gene a. Identified in 1992 by Ozelius (Ozelius et al, 1989 and 1997) b. Guanine-alanine-guanine deletion in coding sequence c. No development of symptoms in 70% of people with the mutated gene F. Pathophysiology 1. Excessive co-contraction of antagonistic muscles 2. Overflow of contractions to adjacent or remote muscles 3. Paradoxic contraction of passively shortened muscles 4. Trace metals in basal ganglia and thalamus identified in some studies: Questionable increase of copper and/or manganese in the globus pallidus, putamen, or thalamus G. Patient problems 1. Problem 1: Impaired physical mobility a. Defining characteristics (1) Involuntary movements (2) Gait disturbance (3) Abnormal postures (4) Range-of-motion limitations b. Interventions (1) Medical (a) Pharmacological therapy 1) Anticholinergic agents (e.g., trihexyphenidyl) a) The drugs block the action of acetylcholine and thereby deactivate muscle contractions. b) Central and peripheral adverse effects limit the dosage. 2) Benzodiazepines (e.g., diazepam [Valium], lorazepam [Ativan]) lorazepam 3) Skeletal muscle relaxants (e.g., baclofen [Lioresal]) 4) Dopaminergics: Stimulation, blocking, and depletion (e.g., carbidopaL-dopa, clozapine [Clozaril], tetrabenazine [Xenaxine]) 5) Intrathecal agents (e.g., baclofen) a) Degree of benefit remains to be shown b) May be beneficial for patients with secondary dystonia and associated spasticity (b) Chemical denervation with botulinum toxin 1) Botulinum toxin is a neurotoxin produced by the antagonistic bacterium Clostridium botulinum that inhibits the release of acetylcholine. 2) The goal is to weaken the muscle enough to reduce spasms but not so much as to cause paralysis. 3) Ideal candidates are those with dystonia limited to a body region that is accessible by a needle. 4) The toxin is injected directly into several sites in the overactive dystonic muscle. 5) The onset of effect occurs within 72 hours; effect peaks at 1 week. Meaningful relief of symptoms persists for 3 to 4 months. 6) Maximum dosage a) Botulinum toxin A (Botox): 50 U per injection site with 400 U maximum dose per visit b) Botulinum toxin B (Myobloc): 2500 U per injection site with 15,000 maximum dose per visit c) Minimum of 3 months between injections 7) Chemical denervation is used in conjunction with other therapies. 8) Treatment is dramatically effective for many focal dystonias.

9) Antibodies develop in 5% to 10% of patients, which results in resistance to therapy. (2) Surgical: For patients with severe dystonia who have not responded or have ceased to respond to medical therapy (a) Selective peripheral denervation: Aim is to abolish the abnormal movement in all muscles involved while preserving the innervation of normal muscle 1) Removes nerves at the point where they enter the contracting muscles 2) Indicated for patients with cervical dystonia with resistance to botulinum toxin therapy 3) Carries risk of permanent excessive weakness and dysphagia (b) Lesioning surgery: Some reported benefit in the past 1) Thalamotomy 2) Pallidotomy 3) DBS: Used in place of conventional lesioning surgery a) Permanent radiofrequency stimulating electrode is placed in the brain and is connected to a pulse generator implanted in the chest wall. b) The target is the bilateral globus pallidus interna. c) The stimulation mimics the positive effects of surgical ablation but does not cause permanent destruction of the area. d) Microelectrode recording is important because of the delayed clinical response intraoperatively. e) The clinical effect is delayed; it may take hours to days to see clinical movement. f) Candidates include those with significant disability despite optimal medical therapy, individuals in whom the expected benefit is greater than the inherent risks, and those with minimal medical comorbidities. g) Advantages over lesioning i Reversibility ii Decreased risk iii Ability to change parameters to enhance efficacy or reduce side effects h) Disadvantages i No-long term studies ii Hardware-related problems iii Reimbursement issues: FDA approved for compassionate use (3) Nursing team (a) Provide physical and occupational therapy. (b) Strengthen weakened muscles that may be underused. (c) Promote awareness of optimal body posture and maintenance of individual optimal body posture. (d) Avoid sudden manipulations or extremes in movement (fighting the contractions and postures may aggravate the dystonia). (e) Initiate the use of assistive devices as appropriate for the patient. c. Expected outcomes (1) Patient reaches optimal achievable strength. (2) Patient reaches optimal achievable posture. (3) Patient uses appropriate assistive devices to promote safety and mobility. 2. Problem 2: Impaired body image a. Defining characteristics (1) Abnormal movements and postures (2) Negative feelings about the body including helplessness, hopelessness, powerlessness, and vulnerability (3) A change in social involvement b. Interventions: Nursing team (1) Provide supportive social treatment. (2) Encourage patient to express feelings and ask questions. (3) Refer patient to support groups. (4) Refer patient to international foundations providing education and research.

(5) Instruct patient in stress management and relaxation. c. Expected outcomes (1) Negative feelings are resolved. (2) Patient demonstrates coping patterns. 3. Problem 3: Impaired comfort a. Defining characteristics (1) Subjective complaints of pain (2) Objective signs of pain (guarding behavior, distraction, indicative facial expression) (3) Altered muscle tone b. Interventions (1) Medical: Pharmacological therapysee medical interventions under Problem 1 on impaired physical mobility (2) Nursing team (a) Promote optimal body postures. (b) Teach relaxation techniques. c. Expected outcomes (1) Patient reports a tolerable level of pain. (2) Patient shows decreased objective signs of pain. 4. Problem 4: Self-care deficit a. Defining characteristics: Inability to feed self, bathe, or dress due to abnormal movements and postures b. Interventions: Nursing team (1) Evaluate patients ability to participate in each self-care activity. (2) Promote patients optimal participation in self-care. (3) Promote patients self-esteem and self-determination. (4) Initiate use of assistive devices as appropriate. c. Expected outcomes (1) Patient identifies preferences in self-care activities. (2) Patient participates in self-care activities when able. (3) Patient demonstrates appropriate use of assistive devices. 5. Problem 5: Knowledge deficit a. Defining characteristics (1) Verbalization of a deficiency in knowledge or request for information. (2) Expression of an inaccurate perception of health status b. Interventions: Nursing team (1) Assess patient and family knowledge about dystonia. (2) Educate patient and family about dystonia. (3) Refer patient to international foundations providing education and research. c. Expected outcomes (1) Patient demonstrates subjective increase in knowledge regarding disease process and treatments. (2) Patient complies with interventions.

GILLES DE LA TOURETTES SYNDROME

A. Clinical definition, classification, and spectrum of tic disorders 1. Definition of tic: Sudden, rapid, recurrent, nonrhythmic, stereotyped motor movement or vocalization (American Psychiatry Association, 2000) 2. Classification of tics a. Motor: Brief jerklike movement(s) such as blinking, nose twitching, head jerk b. Vocal: Meaningless sounds such as sniffing, grunting, blowing, coughing c. Simple tic: Movement involving one group of muscles or a single meaningless sound d. Complex tic: Coordinated, sequenced, repetitive groups of tics (1) Complex motor: A head tic sequentially followed by a shoulder shrug and throat clearing

(2) Complex vocal: Repetition of words or phrases (echolalia) or use of socially unacceptable words (coprolalia) 3. Spectrum of tic disorders a. Chronic motor or vocal tic disorder: Character unchanging over time b. Transient tic disorder: Lasting weeks to months, often occurring when child is stressed c. Gilles de la Tourettes syndrome: Nine patients with involuntary motor and phonic tics were first described by Georges Gilles de la Tourette in 1885 B. Diagnostics 1. Diagnostic criteria of the American Psychiatry Association (2000) a. Both multiple motor and one or more vocal tics have been present, not necessarily concurrently b. Tics occur many times a day, nearly every day, or have occurred intermittently for >1 year, and during this time a tic-free period of >3 consecutive months has never occurred. c. Onset is before age 18. d. Disturbance is not due to the direct physiological effects of a substance (e.g., stimulants) or a general medical condition. 2. Additional criteria for diagnosis established by the Tourette Syndrome Classification Study Group in 1993 a. Tics witnessed directly by a reliable examiner at some point in the illness or recorded on examination b. Associated clinical features (1) Premonitory sensations or urge to tic occur in 80% of cases. (2) Tics often can be voluntarily suppressed, at least temporarily. (3) Feeling of relief follows the expression of the tic. (4) Intrusive thoughts, obsessions, and compulsions are often present. (5) Tics may persist during sleep. (6) Tics increase in both severity and frequency with stress. c. Associated behavioral disturbances sometimes seen (1) Obsessions (intensive, intrusive thoughts and concerns) (2) Compulsions (urge to repeat actions and rituals) (3) Attention deficit hyperactivity disorder (4) Loss of impulse control (5) Sexual aggressiveness (6) Self-injurious behaviors (7) Antisocial or violent behavior (8) Phobias d. Clinical course (1) Variable over short and long term (2) Can be mild, moderate, or severe; can wax and wane (3) May peak at age 8 to 12 and then diminish in adolescence (4) Gets more severe in adulthood in <10% of cases e. Differential diagnosis (1) Stereotyped behavior or habit disorder: Rhythmic, intentional, repetitive movements such as hand banging (2) Compulsions (3) Excessive startle response (4) Other movement disorders (chorea, dystonia, athetosis, myoclonus, spasms, tremors, dyskinesias) (5) Restless legs syndrome (6) Wilsons disease (7) Perinatal injury (8) Drug-induced tics (amphetamines, L-dopa, cocaine, anticonvulsants, antipsychotics) (9) Infections (Creutzfeldt-Jacob disease, Sydenhams chorea, encephalitis) (10) Seizure disorders C. Epidemiology 1. The disorder is three to four times more common in males than in than females. 2. Studies of prevalence report rates varying from 0.7% to nearly 3%. 3. Ascertainment bias is a large issue in determining prevalence: Occurs worldwide.

D. Pathogenesis 1. Many areas have been investigated including genetics (see later) and environmental, neuroimmune, and infectious influences. No concrete event or factor has been proven to trigger development of the disorder; the cause may be multifactorial. 2. Transcranial magnetic stimulation studies suggest decreased inhibition of the motor cortex. a. MRI volumetric studies have reported volume abnormalities and asymmetry in caudate and lenticular nuclei. b. Functional MRI suggests increased cerebral activation in sensorimotor cortex. 3. Neurotransmitter investigations have studies presynaptic and postsynaptic dopamine receptors, dopamine release and reuptake regulation, and serotonin transmission, but no consistent abnormality has been found. E. Genetics 1. Gene mapping is inconsistent and nonreproducible; however, genetic transmission is highly probable. Some studies suggest an autosomal dominant pattern of transmission. 2. The concordance rate is approximately 86% in monozygotic twins and 20% in dizygotic twins. 3. Possible sex-linked transmission, variable gene expression, bilineal versus unilineal inheritance, and environmental contributors are being studied. F. Patient problem 1. Problem 1: Mannerisms and behaviors of Gilles de la Tourettes syndrome interfering with home, work, and social activities a. Defining characteristics (1) Uncontrolled brief jerklike motor movement(s) such as blinking, nose twitching, and head jerk (2) Meaningless vocal sounds such as sniffing, grunting, blowing, and coughing b. Interventions: Comprehensive approach including strong emphasis on education of patient, family, teachers, school personnel, and peers (1) Medical (a) Pharmacological therapy: Drug therapy is often burdened with dose-limiting side effects. 1) Neuroleptics including D2 receptor blockers such as haloperidol (Haldol) and pimozide (Orap) 2) Atypical neuroleptic agents such as risperidone (Risperdal), olanzapine (Zyprexa), ziprasidone (Geodon), and clozapine 3) The dopamine receptor agonist pergolide 4) The central muscle relaxant baclofen 5) The central -agonist clonidine (Catapres) 6) Patients with associated obsessive-compulsive disorders may benefit from selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), paroxetine (Paxil), or sertraline (Zoloft), or the tricyclic antidepressant clomipramine (Anafranil) 7) Patients with associated attention deficit hyperactivity disorder may benefit from stimulants such as methylphenidate (Ritalin), pemoline (Cylert), or dextroamphetamine (Dexedrine). 8) Medications being studied experimentally include but are not limited to botulinum toxin, mecamylamine, SSRIs, and ondansetron (2) Surgical: Stereotactic DBS has been proposed; controlled clinical trials are pending. (3) Nursing team (a) Psychologists, counselors, support groups, and psychiatrists may be valuable in assisting the patient and family in coping with the embarrassment of the disorder. (b) Nonpharmacological measures have included relaxation training, biofeedback, hypnosis, and acupuncture; none has been studied scientifically. (c) Patient and family should be provided with education and resources: Tourette Syndrome Association, Inc., 718-224-2999, http://www.tsa-usa.org. WE MOVE (Worldwide Education and Awareness for Movement Disorders), 800-437-MOV2, http://www.wemove.org.

HUNTINGTONS DISEASE
A. Description: Huntingtons disease (HD) is a neurodegenerative disorder characterized by a triad of symptoms and signs that progresses slowly over a mean of 15 to 20 years after insidious onset at mid-life.

1. Cognitive changes, which usually precede motor signs a. Memory loss: Explicit, implicit, impaired retention of new information b. Loss of executive function: Inability to initiate or plan, inability to switch plans, loss of verbal fluency, perseveration c. Visual-motor deficits: Slow motor skill learning, slow performance of learned motor task, inability to sequence task d. Slow mental processing (bradyphrenia): Slow retrieval, poor recall; recognition preserved, language preserved e. Impulsivity 2. Emotional changes, which may precede motor signs a. Depression and/or vegetative signs and/or apathy and/or episodic mania b. Irritability and aggression; insight may or may not be preserved: Usually has subtle concrete environmental triggers; often accompanies depression c. Anxiety and/or guilt and/or low self-esteem: May cause insomnia d. Fear of abandonment e. Obsessive-compulsive symptoms: Concrete concerns, such as dirt; overeating or limitation of foods; alcoholism, binge drinking f. Psychosis: Suspiciousness, delusions in 4%; rarely hallucinations g. Increased risk of suicide 3. Movement changes, which may signal to family the onset of disease: Reported as fidgeting, restlessness, clumsiness, or drunken gait a. Volitional (1) Motor impersistence: Jerky ocular motor signs; milkmaid grip, dropping of objects, and handwriting changes; unstable stance and variable stride length; postural instability; alternating muscle tone; fidgeting, restlessness, and postural adjustments (2) Bradykinesia: Loss of speed, which may reflect cognitive changes; slow gait, which may relate to postural instability; start hesitation may or may not be present (3) Impaired oral phase of swallowing: Incomplete chewing; impaired tongue control; food stuffing may reflect extreme hunger or impulsivity (4) Speech: Rapid rate may reflect anxiety or obsessions; low volume may reflect impaired respiratory control; irregular rhythm may reflect impaired respiratory control; dysarthria may reflect impaired tongue control b. Involuntary (1) Chorea: Involuntary, irregular, purposeless, nonrhythmic, abrupt, rapid, unsustained movements flowing from one body part to another with a dancelike, graceful quality (a) These signs are the most commonly recognized, but least disabling. (b) Treatment to reduce chorea does not improve gait. (c) Treatment may prevent social embarrassment or job loss. (d) Common signs include eyebrow elevation, lip pursing, shoulder shrugging, piano-playing finger motions, ankle rotations, dancing motions with toes. (2) Dystonia: Twisting sustained postures caused by the co-contraction of opposing muscle groups; may be present at rest and often worsens on action (a) Blepharospasm: Sustained bilateral eyelid closure (b) Jaw closing: Contributes to dysarthria, prevents adequate chewing, may be present at rest and during sleep (bruxism) (c) Torticollis: Twisting, turning neck postures (d) Axial deviation, unilateral sustained shoulder elevation, hip displacement (e) Ankle inversion or eversion, or equinovarus foot postures (3) Rigidity (a) On activation (b) With or without action tremor (4) Action tremor (5) Tics (a) Simple motor progressing to complex motor

(b) With or without respiratory involvement (primarily on inspiration) (c) Phonic: Brief sounds, clicks, hums, grunts (d) Prolonged sounds (snoring, moaning): May indicate life-threatening airway occlusion or stridor B. Epidemiology 1. Prevalence has been calculated in only a few populations. a. In a U.S. white population, 4.1 to 7.5 per 100,000 b. In a U.S. African American population, 0.97 to 6.37 per 100,000 c. Higher among populations of northern European origin than among populations of Asian and African descent 2. Duration of disease a. For individuals with a mid-life onset of HD in a Maryland sample, the mean duration of illness was 14.85 years and the maximum was 40 years. b. For individuals and families who voluntarily registered in a national database, the mean duration of illness was 21.4 years. c. When onset occurs before age 20, duration of illness is shorter, presumably because progression is faster. 3. Long-term residential care a. Approximately 30% of HD patients will enter residential care. b. Predictors of residential care admission include loss of social supports and motor decline. (1) Disability or death of caregiver (2) Inability of individual to live alone (3) Escalating needs not met at home (4) Bradykinesia, gait impairment, and impaired tandem gait, all contributing to an increased risk of falls c. Median length of residential care stay in two U.S. populations was 2.5 to 3 years with a range of 2 months to 11 years; worldwide studies suggest average lengths of stay ranging from 2 to 8 years. C. Etiology and genetics 1. HD is a disease transmitted by an autosomal dominant trait. The pattern of inheritance is through successive generations, with both males and females equally affected. a. The gene was mapped to the distal end of chromosome arm 4p in 1983 and was identified in 1993 as a trinucleotide repeat of CAG (cytosine, adenine, and guanine). (1) HD is one of eight trinucleotide-repeat diseases. The mutant HD gene has 40 or more CAG repeats. (2) The HD allele with reduced penetrance has 36 to 39 CAG repeats. (3) The mutable normal allele shows 27 to 35 CAG repeats. (4) The normal allele has 26 CAG repeats. b. Consequences are different depending on the number of repeats. (1) With 40 CAG repeats: HD signs and symptoms, unpredictable age of onset (2) With 36 to 39 CAG repeats: Carrier may or may not develop HD signs and symptoms; greater risk in the next generation of expanded CAG repeats (a phenomenon known as anticipation) (3) With 27 to 35 CAG repeats: No HD signs and symptoms in carrier; unstable repeat length may expand in next generation into the HD range and cause HD (4) With 26 CAG repeats: No HD signs and symptoms in carrier; stable repeat length; will not expand into the HD range in the next generation c. In juvenile-onset HD beginning at or before age 20, the tendency is seen for a much higher number of CAG repeats. 2. Age-of-onset variations do not appear to be directly related solely to CAG repeats in the gene; other genetic or environmental factors are being studied. a. Maternal inheritance (1) Age of onset in HD gene carrier offspring of women with HD varies little from maternal age of onset. (2) Clinical characteristics and disease course are not predictable. b. Paternal inheritance (1) Age of onset in HD gene carrier offspring of men with HD tends to be earlier than paternal age of onset. (2) Clinical characteristics and disease course are not predictable. (3) CAG repeats in the sperm of men with HD tend to be longer than somatic CAG repeats.

c. New mutations (1) The mechanism that expands CAG repeats into the HD range is not known, but increases can range from one to five repeats. (2) Ten percent of HD patients report no family history of other affected relatives. (3) In an estimated 10% of the U.S. population, paternity is uncertain. This may contribute to the high rate of so-called new mutations. D. Classification 1. By history a. Family history: If an hour can be spent with a patient and family, spend 55 minutes obtaining an accurate family history; draw a pedigree of first- and second-degree relatives, that is, include aunts, uncles, cousins, and all known members in the previous generations as far back as possible to document the pattern of inheritance; record the age at disease onset and progression in other relatives, level of care received, signs and symptoms recalled, date and place of death, and postmortem tissue donation and location; report history and method of suicide in other relatives, relationship and closeness to patient, circumstances preceding suicide, and story told by the family. b. Age of onset (1) Juvenile-onset HD (age 20 or earlier) may occur as early as age 2. (2) Late-onset HD (age 55 or after) may occur as late as age 82. (3) Mid-lifeonset HD (between ages 30 and 54) is most common. 2. By functional level a. ADL and independence scale score: Has 5% increments and is a sensitive scale in early HD. (1) One hundred percent: No special care needed. (2) Eighty percent: Predisease level of employment changes or ends; individual cannot perform household chores to predisease level; may need help with finances. (3) Sixty percent: Minor assistance needed in dressing, toileting, and bathing; food must be cut for safe eating. (4) Forty percent: Chronic care facility needed; limited self-feeding is possible; modified diet is required. (5) Twenty percent: Patient has no speech; must be fed. (6) Ten percent: Tube feeding required; total bed care. b. Functional assessment: Unified Huntington Disease Rating Scale (UHDRS)25 items that delineate in detail and support the Total Functional Capacity Scale c. Total functional capacity (Shoulson and Fahn, 1979) (1) Capacity to perform usual job (2) Capacity to manage finances (3) Capacity to perform domestic chores (4) Capacity to perform ADLs (5) Need for assistance or skilled nursing care 3. By examination findings a. Cognitive assessment is performed with the patient alone in a quiet, well-lit room. (1) Mini-Mental State Examination, 57-item version (2) Verbal fluency test: Task is for patient to recall and name all words possible that begin with a certain letter in 1 minute. (3) Symbol-digit test (4) Stroop test: Three-part task (color naming, word reading, and interference), with each task lasting 45 seconds b. Assessment of behavior as an expression of mood should be performed with the patient and caregiver. (1) UHDRS scale measures frequency and severity of depression: Individual shows distress, low selfesteem, anxiety, disruption of everyday life, suicidal thoughts, disruptive or aggressive behavior, irritable behavior, perseverative or obsessional thinking, compulsive behavior, delusions, hallucinations, and apathy. (2) Neuro-Psychiatric Inventory: Provides helpful framing questions to elicit patient responses (3) Beck Depression Scale c. Motor assessment should be performed with the patient barefoot and with limbs exposed.

(1) UHDRS: 15 items (2) Videotape recording: Not commonly used due to confidentiality and privacy issues 4. By results of genetic testing (see section on etiology and genetics) E. Prevention 1. Family planning decisions are best made by the couple who have been informed of all the options currently available in a genetic counseling program and who are able to weigh the financial and emotional costs versus the benefits of each decision for the couple and for other family members. a. Person at risk decides not to learn individual genetic status. (1) Decides not to have children (2) Decides to have amniocentesis and nondisclosing genetic screening of any fetus and to carry to term only children who have less risk than the parent (3) Decides to have preimplantation genetic screening and to be implanted only with fertilized eggs that do not carry the HD gene (4) Decides to use donor gametes in place of those of the at-risk parent (5) Decides to carry to term any child conceived and not to test fetus b. Person at risk decides to learn individual genetic status and carries the HD gene. (1) Decides not to have children (2) Decides to have amniocentesis and carry to term only children who are HD gene free (3) Decides to have preimplantation genetic screening and to be implanted only with fertilized eggs that do not carry the HD gene (4) Decides to use donor gametes in place of those of the at-risk parent (5) Decides to carry to term any child conceived and not to test fetus c. Family planning decisions are never the prerogative of the health care professional. 2. No nutriceuticals, pharmaceuticals, or life-style changes are available to delay the onset of HD, slow the progression of HD, or rescue dysfunctional medium spiny neurons and reverse HD signs. 3. This is a rapidly changing field of research. Up-to-date information is available from the following reliable sources: Huntingtons Disease Society of America (http://www.HDSA.org), Huntington Society of Canada (http://www.hsc-ca.org), Hereditary Disease Foundation (http://www.hdfoundation.org), and Huntington Study Group, an international consortium of academic research clinicians and basic scientists (http://www.Huntington-Study-Group.org). F. Pathophysiology 1. Postmortem studies a. Atrophy (1) The mean brain weight in HD is 1067 g. Normal brain weight is 1350 g. (2) Ninety-five percent of HD brains have bilateral symmetric striatal atrophy. (3) Eighty percent of HD brains have frontal lobe atrophy. b. Projection neurons (1) Projection neurons in the neostriatum and in the cortex are more sensitive than large nonspiny interneurons to huntingtin, the abnormal product of the HD gene. (2) Huntingtin is widely expressed throughout the brain but causes pathology initially only in the tail of the caudate nucleus. (3) Degeneration progresses from the tail of the caudate nucleus to the body of the caudate nucleus to the head of the caudate nucleus to the cerebral cortex and cerebellum. (4) A 5-point grading system (grades 0 to 4) of postmortem brain tissue specifies the distinct topographic and cellular alterations seen in HD. c. Medium spiny neurons (1) Medium spiny neurons, located in the tail of the caudate nucleus, appear to be the first population of nerve cells to undergo changes that lead to premature cell death. (2) Normally functioning medium spiny neurons send radiations to the frontal lobe, the cortex, and the cerebellum, as well as to other deep brain structures; are GABAergic; and contain multiple glutamine receptors. (3) The mutant HD gene product, the abnormal protein huntingtin, contains multiple glutamine residues.

(4) In response to mutant huntingtin, the dendrites of the medium spiny neuron recurve (resembling fishhooks), and the spines change their density, size, and shape. (5) Several theories have been put forward to explain the cause of premature medium spiny nerve cell death. (a) Changes occur in the mitochondrial synthesis of ATP, which no longer support normal cell functions (the energy theory). (b) Changes occur in the glutamine receptor that either prevent egress of toxic metabolites or allow toxins to enter the cytoplasm (the glutamine theory). (c) Proteins accumulate and aggregate in the cytoplasm, disrupt normal cell function, and hold hostage one or more proteins essential for cell survival. (d) The glutamine receptors are overstimulated, which increases the calcium ion concentration, causing cell death (the excitotoxin theory). (e) The dopamine receptors, D1 and D2, are lost early in asymptomatic HD gene carriers, which suggests an early role for dopamine. G. Data assessment 1. Subjective data a. Behavioral symptoms (1) Sleeping: Problems may be independent of or the result of depression and anxiety; >30 minutes to fall asleep, anxiety at bedtime; fragmented sleep, difficulty in falling back to sleep; early morning awakening; excessive daytime sleepiness (2) Eating: Loss of appetite; early satiety; forgetting to eat; eating only when presented with food; inability to maintain or gain weight; overeating, binging, food obsessions; limiting of meals or types of food, nausea, anorexia b. Health history (1) Exercise history: Past exercise levels, interest in physical activities; current routine and frequency, duration, and type of activities; reasons for choices, leisure preferences, and current barriers (2) Social history: Family of origin, early childhood, teen and early adult socialization, education, work history, smoking, drugs, alcohol patterns, current family constellation, current social patterns, levels of satisfaction, degree of isolation, feelings of inclusion, intimacy, thoughts about the future, concerns about abandonment (3) Medical and surgical history: Current and prior exposure to dopamine receptor blockers; history of head trauma, loss of consciousness, or general anesthesia; past use of traditional and nontraditional therapies 2. Objective data: Cognitive, behavioral and motor assessment 3. Diagnostics a. Positive family history with autopsy-proven disease in a relative b. Laboratory tests (1) Thyroid profile including TSH levels to document normal thyroid function (a) Hypothyroidism may enhance cognitive deficits or depression. (b) Hyperthyroidism may contribute to restlessness, anxiety, and insomnia. (2) Ceruloplasmin levels to document normal copper metabolism (a) Normal copper-binding protein is 20 to 50 mg/dl. (b) Low copper-binding protein levels may indicate a common cause of chorea, which is hepatolenticular degeneration (Wilsons disease). c. MRI and CT (1) To detect subdural hematomas, basal ganglia lesions (2) To document caudate atrophy in symptomatic individual with mid-stage disease (3) Do not correlate with early signs and symptoms because thin layer of tissue that comprises the tail of the caudate nucleus is not evident in scans d. Confirmatory blood DNA testing (1) Pretest genetic counseling with the symptomatic individual and a person who is not at risk is the standard of care. The counseling partner attends pretest counseling sessions to support the individual throughout the genetic counseling.

(2) Blood DNA testing remains an option chosen by the individual and/or family during the counseling process and is not mandated by the health care professional. (3) Blood DNA testing is often helpful when there is no clear family history, signs and symptoms are atypical, or the individual is adopted. (4) If the genetic test does not confirm HD, then further analysis may reveal the presence of another disorder. (a) The gene may be identified for one of the rare choreic disorders: Dentatorubral-pallito-luysian atrophy or the spinal-cerebellar ataxias. (b) A wet blood or Wright-stained blood smear may reveal over 15% red blood cells with morphological changes that classify them as acanthocytes, which is diagnostic for neuroacanthocytosis. (5) Banking blood DNA at Indiana University is an option if the individual and/or family chooses to not obtain direct HD gene test results. H. Patient problems 1. Problem 1: Loss of executive function a. Defining characteristics (1) Inability to plan and initiate an activity, inability to switch from one plan to another (2) Diminished verbal fluency (3) Perseverative behaviors b. Interventions: Nursing team (1) Patients with HD should be presented with two choices instead of open-ended questions. They should be presented with an activity and encouraged to begin with verbal prompting. (2) Nonverbal modeling can be a helpful trigger to overcome apathy. Interest in the activity can be sustained if the caregiver also participates in the activity. (3) Perseveration should be addressed by distracting the individual, coaxing onto another topic, changing location, and giving a positive response. (4) Repeated demands by the patient should be addressed as quickly as possible to avoid escalation to angry outbursts, as calmly as possible to get the persons attention, and with a positive response. A refusal will not stop perseveration. c. Expected outcome (1) Patient maintains composure and participates in activities. 2. Problem 2: Adverse social effects of abnormal movements a. Defining characteristics: Abnormal involuntary movements (AIMs) and loss of volitional control. AIMs include dancelike movements (chorea), twisting or sustained postures (dystonia), rigidity, motor restlessness, tremor, and jerky movements (myoclonus). Loss of volitional control, including motor impersistence, tends to be more disabling. Interrupted saccadic and smooth pursuit eye movements and uncoordinated speech, swallowing, grasp, and gait with AIMs make the person appear awkward, drunk, boisterous, and cognitively and behaviorally more impaired than he or she actually is. When strangers react with curiosity and families with embarrassment, this intensifies anxiety and amplifies movements. Staying home, only attending events with close friends and family, and abandoning favorite group activities in favor of solitary ones may reduce the patients anxiety but the net result is social isolation, guilt, boredom, loneliness, grief, and loss for the person with HD and increased burden expressed by the caregiving family. b. Interventions (1) Medical (a) Anxiolytics and antidepressants have helped people resume favorite activities and accept the risk but not assume the inevitability of social embarrassment. (2) Nursing team (a) Structured group activitiesdancing, martial arts, exercise, swimming, hiking, and camping allow reentry into a social life outside the family and provide respite for caregivers. c. Expected outcome (1) Patient participates in social activities.

ESSENTIAL TREMOR

A. Description: Tremor versus benign essential tremor 1. Tremor: A rhythmic oscillatory movement produced by alternating or synchronous contractions of opposing muscle groups a. Classified based on posture or activity (1) Rest tremor: Present when hands are at rest, such as in lap or at sides (a) Idiopathic PD, parkinsonian syndromes (b) Secondary parkinsonism, often described as pill-rolling tremor (c) Drug-induced rest tremor (d) Hereditary chin tremor (2) Postural tremor: Present when maintaining a posture, such as having hands outstretched or holding a glass (a) Benign essential tremor (see later) (b) Exaggerated physiological tremor as seen in anxiety, fear, caffeine overconsumption, thyrotoxicosis, and drug or alcohol toxicity or withdrawal (c) Cerebellar disorders (3) Intention, action, or kinetic tremor: Seen when performing intentional activity, such as when the person is asked to touch his or her nose (a) Cerebellar tremor as seen in multiple sclerosis or infarctions (b) Primary writing tremor (c) Brainstem disease (4) Mixed tremors: Seen in a variety of postures or activities, such as the tremors in Wilsons disease (often described as wing beating) (5) Tremors caused by toxicities (heavy metal poisoning, drugs, alcohol) (6) Tremors caused by psychiatric problems 2. Benign essential tremor a. Diagnostic inclusion criteria (proposed by the Movement Disorder Society, 2003) (1) Bilateral, largely symmetrical postural or kinetic tremor involving hands and forearms that is visible (2) Possible additional or isolated tremor of the head but absence of abnormal posturing b. Diagnostic exclusion criteria (proposed by the Movement Disorder Society, 2003) (1) Other neurological signs, especially dystonia (2) Presence of known causes of enhanced physiological tremor, including current or recent exposure to drugs that are known to cause tremor or a drug-withdrawal state (3) Historical or clinical evidence of psychogenic tremor (4) Convincing evidence of sudden onset or evidence of a stepwise deterioration (5) Primary orthostatic tremor (6) Isolated voice, tongue, chin, or leg tremor (7) Isolated position- or task-specific tremor B. Differential diagnosis 1. Most often confused with PD (but note that PD is a rest tremor); these disorders can be concurrent 2. Exaggerated physiological tremor a. Orthostatic tremor of trunk and legs (seen only with standing) b. Task-specific tremors such as primary writers tremor c. Dystonic tremors such as torticollis with tremor d. Head titubation as seen with midline or bilateral cerebellar lesions e. Drug-induced tremors f. Tremors with metabolic causes (vitamin B12 deficiency, hyperthyroidism, hyperparathyroidism, hypocalcemia, hyponatremia, low magnesium levels, kidney or liver disease) C. Epidemiology 1. Benign essential tremor is the most common movement disorder. 2. It is estimated to be 10 to 20 times more common than PD. 3. Age of onset has a bimodal distribution with peaks in the second and sixth decades. 4. Prevalence is estimated at 0.4% to 3.9% in the general population; the prevalence may be as high as 20% in the elderly. 5. The incidence may be underestimated because many do not seek medical attention.

D. Genetics 1. Inheritance follows an autosomal dominant pattern with linkage to a specific locus 2. The trait shows high but incomplete penetrance. a. Fifty percent of first-degree relatives of those with tremor develop the disease during their lifetimes. b. First-degree relatives are 5 times more likely to develop tremor than control subjects and 10 times more likely to develop the disorder if the probands tremor began at any early age 3. Sporadic cases do occur. E. Pathophysiology: No distinct pathology 1. Several models propose the existence of interconnected oscillatory loops in the nervous system with oscillations in the olivo-cerebello-rubral loops that release normal dampening influences and thus allow spinal reflex loop oscillations; unstable circuits in the CNS that drive muscle contractions; or cerebellar synaptic overactivity. 2. PET scans have demonstrated increases in blood flow in the red nucleus and cerebellum, and possible increased glucose metabolism in the inferior olivary nucleus of the medulla. F. Data assessment 1. Subjective data a. History should be taken with attention to mode of onset, progression, and medication usage. b. Family history may be supportive of the diagnosis, as is a positive response to alcohol. c. Tremor is most common in the hands (95%), followed by the head (34%) and voice (12%). The tongue, trunk, and lower extremities are affected less commonly. 2. Objective data: Complete neurological examination to rule out other focal findings a. Obtain a handwriting sample with Archimedes spirals (tremor may be worse in the dominant hand; the test brings out the kinetic component). b. Check for a postural component by having the patient hold a cup or hold the tips of the two index fingers close without touching. c. Check for a kinetic component by using finger-to-nose testing and having the patient pour water between two cups. 3. Diagnostics a. No imaging is needed unless focal signs are present or the disorder shows sudden onset or stepwise progression. b. Laboratory investigations include electrolyte panel; levels of TSH, blood urea nitrogen, and creatinine; and liver function tests. Drug levels should be measured if the patient is taking any potentially tremor-causing agent such as an anticonvulsant, lithium, or theophylline. c. Consider measuring serum ceruloplasmin levels to screen for Wilsons disease in younger patients. d. Electromyography or tremographic accelerometer testing is rarely performed (outside of research studies) but can assist in documenting movement amplitude and intensity, and extensor and flexor muscle activity. G. Clinical course 1. The disorder can be relatively static or slowly progressive over decades. 2. Quality-of-life issues range from social embarrassment to problems with employment and ADLs. a. Is seriously disabling in 15% of patients b. Can be worsened by stress, fatigue, temperature changes, pain, sleep deprivation, and comorbidities c. Can be improved by alcohol; disappears with sleep H. Patient problem 1. Problem 1: Tremor interfering with work life and/or ADLs a. Defining characteristic: Tremors b. Interventions (1) Medical: Pharmacological therapy (a) Oral agents can offer modest benefit (up to 50% to 60%), but often with dose-limiting side effects. Rarely medications relieve tremor fully. Agents to consider as monotherapy or in combination include the following: 1) 2-receptor antagonists (propranolol [Inderal]) 2) Primidone (Mysoline) 3) Benzodiazepines, particularly alprazolam (Xanax) and clonazepam (Klonopin)

4) 5) 6) 7)

GABAmimetic agents such as gabapentin (Neurontin) Mirtazapine (Remeron) Atypical antipsychotics such as clozapine (Clozaril) in refractory cases Botulinum toxin (Botox or Myobloc): May help head tremor, benefit in hands limited by

weakness (2) Surgical (a) Stereotaxic thalamotomy (surgical destruction) of the ventral intermediate nucleus relieves tremor on the contralateral side; surgical complications (intercerebral hemorrhage, motor or speech impairment, mental status changes, ataxia) increase if bilateral thalamotomies are necessary. (b) DBS procedure provides high-frequency chronic stimulation to the ventral intermediate nucleus that is reversible and adjustable, and carries less risk if bilateral procedures are needed. 1) DBS results in complete resolution of tremor in 30% of cases. 2) Ninety percent of patients report moderate to marked improvement. (3) Nursing team (a) Advise the patient to restrict or eliminate the use of caffeine and other stimulants. (b) Suggest lifestyle modifications. (c) Consult with occupational therapist regarding adaptive devices for eating, writing, and performing ADLs. (d) Instruct patient to get adequate rest and manage stress. (e) Provide patient with education and resources. 1) International Essential Tremor Foundation, 913-341-3880, http://www.essentialtremor.org 2) Western Essential Tremor Network, 510-559-4669 c. Expected outcome (1) Patient functions in work activities and ADLs with decrease in tremor.

RESTLESS LEGS SYNDROME

A. Restless legs syndrome (RLS) is an underdiagnosed movement disorder in which patients have an irresistible urge to move their legs and, less frequently, their arms. Patients experience uncomfortable leg sensations paresthesias or dysesthesias (e.g., aching, motor restlessness, throbbing, or crawling sensation)that begin or worsen during times of inactivity. Symptoms usually subside with activity or movement. Primary RLS (idiopathic RLS) often follows a slow progressive pattern with daily symptoms not occurring for many years. RLS can be effectively managed with an individualized medication regimen. Secondary RLS is often cured when the underlying cause is treated. RLS is associated with sleep complaints, chronic sleep deprivation, and wakeful discomfort of the legs, which has a substantial negative impact on the patients quality of life. B. Epidemiology 1. Incidence: RLS is a relatively common disorder. Incidence is higher if RLS is present in a first-degree relative; incidence is slightly higher in women than in men. The mode of inheritance is unknown; an autosomal dominant inheritance pattern is suggested. 2. Prevalence: Estimates range from 2% to 15% of the general population. 3. Often patients are symptomatic for years before seeking treatment. First symptoms may have occurred before age 20 for patients diagnosed later in life. Missed diagnosis and misdiagnosis are both common. 4. Occurrence can be at any age, from childhood throughout the life span. 5. Average age of diagnosis is 53 years of age. Early-onset RLS is more likely to be familial. The severity of the disease increases with age. 6. The disorder affects all races. 7. Periodic limb movement disorder (PLMD) is the most frequent coexisting disorder80% of RLS patients have PLMD, characterized by jerking or flexion of the toe, knee, hip, or leg that occurs while the patient sleeps and compounds sleep disturbances. C. Etiology and contributing factors 1. Central nervous system disorder with unknown etiology 2. Characteristics and possible related factors a. Anatomic location of dysfunction

(1) Centrally acting L-dopa and dopamine agonists reduce RLS symptoms. (2) Spinal cord excitability is increased during sleep. (3) Anatomic area of dysfunction is subcortical, with decreased inhibition of sensorimotor cortical and spinal systems. b. Neurotransmitter systems (1) Main neurotransmitter involved appears to be dopamine, with added influences of opioid and other neurotransmitters. (2) Low levels of dopaminergic medications produce excellent treatment results. (3) Benefits from opiate treatment suggest endogenous opiate system involvement. c. Iron metabolism (1) Abnormal ratio of ferritin to transferritin in the cerebrospinal fluid indicates lower availability of iron in the brain. This abnormality is believed to reflect a problem in the transport of iron across the blood-brain barrier. (2) Both RLS and iron levels show a circadian rhythm; iron concentration decreases by 30% to 50% during the night. 3. Secondary causes of RLS a. Iron deficiency: Decreased iron stores (ferritin levels below 50 g/L) exacerbate RLS symptoms. b. Neurological lesions: Spinal cord and peripheral nerve lesions, or vertebral disk disease can lead to RLS; mechanism is unknown. c. Pregnancy: RLS affects about 20% of women during pregnancy and subsides soon after delivery. d. Uremia: RLS occurs in up to 50% of patients with end-stage renal failure; improvement in RLS frequently occurs after renal transplantation. e. Drug effects: Some evidence exists that the use of tricyclic antidepressants, SSRIs, lithium, and dopamine antagonists may worsen RLS symptoms; additional aggravating medications are calciumchannel blockers, antinausea medications, and some cold and allergy medications; dietary caffeine may aggravate RLS symptoms. D. Diagnostics: The International Restless Legs Syndrome Study Group (Walters, 1995) established minimum criteria for diagnosis of RLS in 1995. 1. A compelling urge to move the limbs, usually associated with paresthesias or dysesthesias 2. Motor restlessness such as pacing, tossing and turning in bed, rubbing the legs 3. Symptoms worse or exclusively present at rest (i.e., lying, sitting), with variable and temporary relief with activity 4. Symptoms worse in the evening and at night 5. Other associated features (not necessary for diagnosis) a. Sleep disturbance and daytime fatigue b. Normal neurological examination in idiopathic RLS c. Involuntary, repetitive, periodic, jerking limb movements, either in sleep or while awake and at rest d. Polysomnographic readings that demonstrate limb movement (PLMD) e. No comorbid medical or psychiatric disorder E. Clinical presentation 1. Clinical manifestations a. Abnormal sensations usually occur deep within the calves; other less common sites are the arms (up to 30%), trunk, and genital area. b. Sensations may be unilateral or bilateral, and the site of predominant discomfort may shift. c. Motor restlessness is voluntary movement that is repetitive and includes pacing, shaking, leg stretching, or deep bending; movement appears nervous. d. Sensorimotor symptoms occur at rest (sitting, lying down) and are partially or totally ameliorated by activity only to return again with inactivity. e. Symptoms are worse during the evening and night; peak discomfort occurs at about midnight; best times are 4 AM to 10 AM. 2. Neurological symptoms a. In idiopathic RLS the neurological examination is normal. b. Dysesthesias and paresthesias may be present. Paresthesias are most often proclaimed as being uncomfortable and not particularly painful; few patients are bothered with painful paresthesias.

c. Abnormal sensations are described as creeping, burning, tingling, cramping, aching, tugging, pulling, or crawling, or indescribable or like water flowing deep within the leg. F. Prevention 1. Primary prevention: Prevention of occurrence a. Maintenance of normal serum iron levels b. Prevention of renal failure c. Genetic counseling: Not presently available 2. Secondary prevention: Early detection of disease a. High degree of suspicion for disease by health care providers b. Screening of all persons about their sleep patterns and sleep-onset or sleep-maintenance problems c. Suspicion of RLS in children who exhibit symptoms concurrent with attention deficit hyperactivity disorder, oppositional-defiance disorder, or other activity-related behaviors 3. Tertiary prevention: Rehabilitation a. Psychiatric and/or psychological counseling on living with chronic disease b. Nutritional counseling (regarding protein intake when taking carbidopaL-dopa and as well as nutrition for general health) c. Lifestyle counseling: Proper nutrition, sleep hygiene, smoking cessation, moderate exercise, relaxation techniques d. Physical therapy: Transcutaneous electrical nerve stimulation or electroencephalographic biofeedback may be helpful G. Data assessment 1. Subjective data a. Health history (1) Family history of RLS (2) New onset of symptoms or exacerbation of symptoms (frequency and/or intensity) (a) Restlessness of leg(s), arm(s), trunk (b) Dysesthesia of leg(s), arm(s), trunk, or genital area (c) Paresthesias (discomfort or pain) of leg(s), arm(s), trunk, or genital area (d) Abnormal sensations: As previously described; abnormal sensations are usually temporarily relieved by movement (3) Case finding: Assessment questions (a) When resting (sitting or lying down) do you have a strong urge to move your legs or arms because of unpleasant or crawling sensations? (b) Does your urge to move your legs (arms) begin when you are at rest and is it relieved with movement? (c) Do unusual sensations occur most frequently in the evening and at night? (d) Do you have difficulty falling asleep or staying asleep? (e) Does anyone else in your family experience similar urges to move or have uncomfortable sensations in the legs (arms)? b. Neuropsychosocial symptoms (1) Impaired daily functioning (a) Fatigue; decreased energy level; sleep deprivation (2) Diminished sleep quality (3) Disruption of emotional well-being (e.g., moodiness or irritability) (4) Disruption of social functioning (e.g., employment, school, social activities) 2. Objective data a. Psychiatric and neurological signs (1) Sleep deprivation may lead to temporary cognitive changes. (a) Inability to complete tasks (b) Inability to concentrate (c) Memory deficits b. Motor restlessness (1) Repetitive behaviors that appear nervous or fidgety: Walking, pacing, shaking of feet or arms (2) Inability to remain seated for extended time periods: Rubbing of legs or arms

3. Diagnostics a. Idiopathic RLS (1) Diagnosis is usually based on history and clinical findings. (2) Polysomnography (sleep study) is not routinely indicated but may be helpful. b. Secondary RLS (1) Serum ferritin level (abnormal if <50 g/L) (2) Serum chemistry panel to rule out uremia H. Differential diagnosis 1. Nocturnal leg cramps: Unilateral painful, palpable, involuntary muscle contractions that have a sudden onset 2. Akathisia or excessive movement without sensory complaints: No correlation with time of day; often caused by neuroleptic medications 3. Peripheral neuropathy: Typically presents with symptoms of numbness, tingling, or pain; unassociated with motor restlessness, nighttime worsening, and unrelieved by activity 4. Vascular disease, such as deep vein thrombosis I. Patient problems: Vary in severity of symptoms, progression of the disease, and effects on quality of life 1. Problem 1: Decreased quality of life due to persistent movement, interference with sleep, and pain a. Defining characteristics (1) Dysesthesia (2) Paresthesias: Most often proclaimed as being uncomfortable and not particularly painful; few patients are bothered with painful paresthesias (3) Abnormal sensations: As previously described (4) Jerking or flexion of the toe, knee, hip, or leg: Occurs while the patient sleeps, compounding sleep disturbances (5) Progressive disease b. Interventions (1) Medical (a) Pharmacological therapy: Relieves or mitigates symptoms 1) Regimen must be individualized for each patient. Initiation of dopaminergic agents (carbidopa plus L-dopa) may cause augmentation of symptoms in up to 80% of patients. Does not correct pathology. Discontinuation of therapy results in return of symptoms. 2) Medications should be begun at a low dosage with the amount increased slowly until the desired effective dose is achieved. If a medication is helpful and without adverse side effects, dosage can be increased to improve symptom control. Administration in divided doses is often helpful to achieve consistent symptom relief. Side effects and effectiveness of medications vary among individuals; drug diaries kept by patients can aid in establishing the best dosing. Medications become less effective over time and adjustments are required. Laboratory testing should be used to confirm cause in deficiency-induced RLS (i.e., deficiency of iron, magnesium, folic acid, or vitamin B 12). 3) Interventions are tailored to balance symptom relief with the fewest side effects of medication (e.g., insomnia, sleepiness, cognitive impairment, nausea, and hypotension). a) No RLS medications are safe for use during pregnancy. b) Children with RLS are first treated nonpharmacologically; weight-adjusted dosages of clonidine and carbidopaL-dopa are used cautiously. 4) Primary medications a) Dopamine precursors: L-Dopa, combination of carbidopa and L-dopa i. Mechanism of action: Converted to dopamine in the substantia nigra of the brain. Advantages: Faster onset of action than that of dopamine agonists, which makes them ideal for patients with intermittent symptoms. Disadvantages: Short duration of action, which can lead to rebound symptoms. May augment symptoms in some patients (e.g., symptoms occur earlier in the day, symptoms have increased severity, or symptoms affect other areas of the body). ii. Dosage: Adult carbidopa plus L-dopa, 12.5/50.0 to 75/300 mg/day regular tablet and 25/100 to 100/400 mg/day sustained-release tablet is usual dosage range. Should be taken on an empty stomach 1 hour from food.

b) Dopamine-receptor agonists: Pergolide mesylate, pramipexole dihydrochloride, ropinirole i. Mechanism of action: Activate dopamine receptors. Advantages: Treatment of choicewell tolerated and have less chance for symptom augmentation. Disadvantages: Can cause severe sleepiness and nausea. ii. Dosage: Average adult effective dosagespergolide mesylate, 0.1 to 1.0 mg/day; pramipexole dihydrochloride, 0.3 mg/day; ropinirole, slow titration up to 3 mg/day. c) Opioids: Propoxyphene (Darvon), hydrocodone (Vicodin), oxycodone (Roxicodone), codeine i. Mechanism of action: May have effect through action in the opioid and dopamine neurotransmitter systems. Advantages: Analgesic and sedative qualities. Disadvantages: Potential for addiction. d) Benzodiazepines: Clonazepam, triazolam (Halcion) i. Useful for mild symptoms of RLS, for sleep deprivation, or if other medications are ineffective. e) Anticonvulsants: Carbamazepine (Tegretol), gabapentin i. Used if other medication options prove ineffective or intolerable; helpful if coexisting peripheral neuropathy or painful leg sensations are present. 5) Secondary medications a) Clonidine i. Mechanism of action: Antiseizure medication; potentiates action of neurotransmitters. ii. Dosage: Adult0.1 to 0.9 mg/day. b) Baclofen i. Mechanism of action: Skeletal muscle relaxant; inhibits impulse transmission. ii. Dosage: Adult20 to 40 mg/day. c) Bromocriptine d) Tramadol (Ultram) (2) Nursing team (see also other patient problems for nursing team interventions) (a) Educate patient regarding medication dosing, timing, and side effects. c. Expected outcomes (1) Sensations, pain, and movements are controlled. (2) Patient gets sleep at night. 2. Problem 2: Knowledge deficit related to RLS and the consequences of failure to adhere to the prescribed regimen a. Defining characteristics (1) Initial diagnostic evaluation and lack of knowledge about RLS cause and treatment (2) RLS progression b. Interventions (1) Assess patient, family, and/or caregiver knowledge of RLS. (2) Educate patient and caregiver about RLS and/or progressive symptomatology. (a) Pathophysiology (b) Genetic inheritance (c) Purpose of medications, side effects and symptoms to report to the health care provider (d) Need for follow-up care (e) Community resources c. Expected outcomes (1) Patient demonstrates an understanding of RLS. (a) Patient defines RLS and/or progression of symptoms. (b) Patient describes impact that RLS has on ADLs. (2) Patient describes medication regimen, possible side effects, and symptoms warranting attention. (3) Patient identifies community resources. d. Potential complications (1) Ineffective therapeutic outcomes

(2) Intentional noncompliance with medication regimen (3) Fear of and/or guilt about inherited disease (4) Missed opportunity for RLS case finding 3. Problem 3: Sleep pattern disturbance related to RLS a. Defining characteristics (1) Interrupted sleep (2) Less than normal amount of sleep (i.e., <7 to 8 hours/day) (3) Difficulty initiating sleep, restlessness during sleep, or daytime somnolence (4) Altered behavior or mood in the presence of any of the aforementioned symptoms b. Interventions (1) Teach patient sleep hygiene practices: Make sure that bedroom is cool and quiet and that bed mattress is comfortable; establish a pattern or ritual for preparing for sleep (e.g., going to bed and getting up at the same time every day); maintain a daily cycle of light and darkness. (2) Encourage regular moderate exercise, preferably 1 hour a day 5 to 7 days a week; moderate exercise should take place at least 6 hours before bedtime. (3) Discuss a trial of leg exercise just prior to bedtime (e.g., stationary bicycle or treadmill for 10 to 20 minutes) as a possible aid to sleep. (4) Describe reports that the best sleep hours for RLS patients may be between 2:00 AM and 10:00 AM. (5) Suggest that patient consume a glass of warm or cold milk and a light snack prior to bedtime to facilitate sleep. (6) Instruct patient that caffeine-containing products may worsen RLS symptoms and advise avoidance of caffeinated food and beverages such as coffee, tea, chocolate, and carbonated soft drinks. (7) Discuss other sleep-aggravating agents such as alcoholic beverages and cigarette smoking. (8) Instruct patient to provide for toileting needs before sleeping. (9) Discuss the need to limit the frequency and length of daytime naps. c. Expected outcome (1) Establishment of a bedtime routine aids patient in achieving quality sleep and restoration of energy and comfort. (2) Patient demonstrates knowledge of effective sleep-enhancing modalities. (a) Plays low music with gentle rhythm patterns (e.g., classical or chamber music). (b) Ensures low levels of light, sound, and voices during the night. (3) Patient participates in regular moderate exercise. (4) Patient eliminates sleep-aggravating elements from diet or lifestyle. d. Potential complications (1) Ineffectual sleep patterns, fatigue, mood changes, cognitive changes (2) Loss of employment or school achievement (3) Social isolation (4) Disturbance of bed partners sleep patterns 4. Problem 4: Alteration in thought process related to sleep deprivation a. Defining characteristics (1) Difficulty functioning at school or work, lapses in memory, trouble concentrating (2) Irritability, emotional lability, anxiety, and/or depression b. Interventions (1) Administer systemic medications. (2) Teach symptoms that denote medication failure and need for provider reevaluation. (3) Help patient identify and eliminate or decrease precipitating factors. (4) Help patient alleviate environmental distractions. (5) Encourage calming and stress-reducing practices (e.g., listening to music). (6) Teach caregiver about managing inappropriate behavior. c. Expected outcome (1) Patient exhibits appropriate sleep pattern and has normalized thought processes. d. Potential complications (1) Inappropriate sleep pattern

(2) Inability to tolerate long durations of inactivity required for job, school, etc. (e.g., 8 hours of sitting at a computer) to achieve goals (3) Social isolation 5. Problem 5: Activity intolerance related to fatigue a. Defining characteristics: Less than 7 hours of sleep per night and fatigue b. Interventions (1) Teach patient to space activities throughout the day to avoid fatigue. (2) Teach patient sleep hygiene techniques and exercise regimens, and identify aggravating factors to eliminate from diet and/or lifestyle. (3) Explain the need to avoid extremes of environmental temperature. (4) Teach patient how to rearrange the environment to help prevent unnecessary energy expenditure. (5) Describe techniques to avoid infection. c. Expected outcome (1) Patient attains maximum achievable mobility. (a) Patient schedules activities realistically. (b) Patient achieves optimal strength and endurance. d. Potential complications (1) Patient physical deconditioning (fatigability, loss of muscle strength and functioning capacity) (2) Social isolation

RESOURCES
Am erican Sleep Association: http://www. americansleepassociation.org. N ational Center on Sleep Disord ers Research: http://rover2.nhlbi.nih.gov. N ational Sleep Found ation: http://www. sleepfoundation.org. Restless Legs Synd rom e Found ation, Inc., 819 Second Street SW, Rochester, MN 55902-2985, 507-287-6465, http://www.rls.org. Restless Legs Synd rom eQuality of Life Instrum ent (research or clinical tool to assess the patients social function, d aily function, sleep quality, and em otional w ell-being): http://www.rls.org/pdf/ RLS%20QLI%207-2-02.pdf. WE MOVE (World w id e Ed ucation and Aw areness for Movem ent Disord ers): http://www.wemove.org/.

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Parkinsons Disease
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Huntingtons Disease
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Essential Trem or
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Restless Legs Syndrome

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