Bradykinesia

Inability to initiate changes in activity or perform ordinary volitional movements rapidly and easily. There is a slowness of movement and a paucity of automatic motions such as eye blinking and arm swinging while walking. Usually due to Parkinson's disease or other causes of parkinsonism (Chap. 186 Parkinson's Disease).

Tremor

Rhythmic oscillation of a part of the body due to intermittent muscle contractions, usually involving the distal limbs and less commonly the head, tongue, or jaw. A coarse tremor at rest, 4-5 beats/s, is usually due to Parkinson's disease. A fine postural tremor of 8-10 beats/s may be an exaggeration of normal physiologic tremor or indicate familial essential tremor (ET). An intention tremor, most pronounced during voluntary movement toward a target, is found with cerebellar pathway disease.

Essential Tremor

This is the most common movement disorder, affecting approximately 5% of the population. It can present in childhood but dramatically increases in prevalence over the age of 70 years. The tremor is most often manifest as a postural or action tremor and, in severe cases, can interfere with functions such as eating and drinking. It is typically bilateral and symmetric but may begin on one side and remain asymmetric. Tremor involves the head in ∼30% of cases, voice in ∼20%, tongue in ∼20%, face/jaw in ∼10%, and lower limbs in ∼10%. Multiple body parts are involved in at least 50%. The tremor is characteristically improved by alcohol and worsened by stress. The tremor of ET must be distinguished from dystonic tremor and early Parkinson's disease (Table 56-1 Advanced Examination Pearls: Differentiating Essential Tremor from Parkinsonian Tremor). The pathophysiology of ET is unknown. Approximately 50% of cases have a positive family history with autosomal dominant inheritance.

• Many pts with ET have mild symptoms and require no treatment.
• When activities of daily living such as eating and writing are impaired, therapy with propranolol (20-120 mg/d) or primidone (12.5-250 mg tid) benefits ∼50% of pts; hand tremor tends to be most improved, while head tremor is often refractory.
• Botulinum toxin injections may be helpful for limb or voice tremor.
• Surgical therapies targeting the ventro-intermediate (VIM) nucleus of the thalamus may be effective in refractory cases.
• Focal ultrasound, a procedure that does not require surgery, has also been shown to be effective.

Dystonia

Consists of sustained or repetitive involuntary muscle contractions, frequently causing twisting movements and abnormal posture. May be generalized or focal; frequency estimated at 16 per 100,000 (approximately 50,000 cases in the United States), but is likely to be much higher because many cases are not recognized.

Focal dystonia is by far the most frequent form. It typically presents in the fourth to sixth decade; women affected about twice as often as men. Major forms: (1) Cervical dystonia-contractions of neck muscles causing the head to deviate to one side (laterocollis), twist (torticollis), or move in a forward (anterocollis), or backward (retrocollis) direction. (2) blepharospasm-contractions of the eyelids with increased blinking that can interfere with reading, watching television, working on a computer, and driving. (3) Oromandibular dystonia (OMD)-contractions of the lower face, lips, tongue, and jaw (opening or closing). Meige's syndrome, a combination of OMD and blepharospasm, predominantly affects women aged >60. (4) Spasmodic dysphonia-contractions of the vocal cords during phonation, causing impaired speech. Speech can sound choking and strained, or breathy and whispering. (5) Limb dystonias-can be present in arms or legs and often brought out by specific activities such as handwriting (writer's cramp), playing a musical instrument (musician's cramp), or putting in golf (the yips). Most pts have dystonia of the neck (cervical dystonia; ∼50%) or eyelid (blepharospasm; ∼20%). Focal dystonias can extend to involve other body regions (about 30% of cases) and are frequently misdiagnosed as psychiatric or orthopedic in origin. The cause is usually not known, but genetic factors, autoimmunity, and trauma have been suggested.

Generalized dystonia is often hereditary and, unlike focal dystonia, generally has an onset in childhood or adolescence. At least four well-established genes for isolated dystonia; TOR1A, THAP1, ANO3, and GNAL. Dopa-responsive dystonia (DRD; also known as Segawa syndrome) is caused by mutations in the GCH1 gene (GTP cyclohydrolase-1) encoding the rate-limiting enzyme in the biosynthesis of dopamine. It is a childhood-onset dystonia with diurnal fluctuations and is important to recognize as the condition dramatically responds to low doses of levodopa. Parkinsonism can be a major, or even the only finding. Other generalized dystonias occur as a consequence of drugs such as antiemetics, neuroleptics, and treatments for Parkinson's disease.

• Therapy for focal dystonias usually involves botulinum toxin injections into the affected musculature.
• All forms of dystonia may respond to anticholinergics (e.g., trihexyphenidyl 20-120 mg/d), baclofen (20-120 mg/d), or tetrabenazine (initial dose 12.5 mg/d, usual maintenance 25-75 mg/d).
• Surgical therapies, including deep brain stimulation (DBS), may be effective in refractory cases.

Choreoathetosis

A combination of chorea (rapid, graceful, dance-like movements) and athetosis (slow, distal, writhing movements). The two usually exist together, though one may be more prominent. Choreic movements predominate in rheumatic (Sydenham's) chorea and Huntington's disease (HD). Systemic lupus erythematosus is the most common systemic disorder that causes chorea, but it can also be seen with hyperthyroidism, various autoimmune disorders including Sjogren's, infections including HIV, NMDA antibody positive encephalitis, metabolic alterations, and with a variety of medications (especially anticonvulsants, cocaine, CNS stimulants, estrogens, and lithium). Chorea-acanthocytosis (neuroacanthocytosis) is a progressive autosomal recessive disorder characterized by chorea coupled with red cell abnormalities on peripheral blood smear (acanthocytes). The chorea can be severe and associated with self-mutilating behavior, dystonia, tics, seizures, and a polyneuropathy. Hemiballismus is a violent form of chorea that comprises wild, flinging movements on one side of the body; the most common cause is a lesion (often infarct or hemorrhage) of the subthalamic nucleus. Athetosis (slow, distal, writhing movements) is prominent in some forms of cerebral palsy. Chronic neuroleptic use may lead to tardive dyskinesia, in which choreoathetotic movements are usually restricted to the buccal, lingual, and mandibular areas.

Huntington's Disease (Hd)

A progressive, fatal, autosomal dominant disorder characterized by motor, behavioral, and cognitive dysfunction. Onset is typically between 25 and 45 years. Rapid, nonpatterned, semipurposeful, involuntary choreiform movements are the hallmark feature; dysarthria, gait disturbance, oculomotor abnormalities, and behavioral and cognitive disturbances also occur, and the latter can be a major source of disability. In late stages, chorea becomes less prominent, and the picture is dominated by dystonia, rigidity, bradykinesia, myoclonus, and spasticity. HD is caused by an expansion in the number of polyglutamine (cytosine-adenine-guanine [CAG]) repeats in coding sequence of the HTT gene encoding the protein huntingtin.

• Treatment involves a multidisciplinary approach with medical, neuropsychiatric, social, and genetic counseling for pts and families.
• Dopamine-blocking agents may control the chorea; tetrabenazine may also treat chorea but can cause secondary parkinsonism.
• Depression and anxiety should be treated with appropriate antidepressant and antianxiety drugs such as clozapine (50-600 mg/d), quetiapine (50-600 mg/d), and risperidone (2-8 mg/d).
• Psychosis can be treated with atypical neuroleptic agents.
• No disease-modifying agents currently exist.

Tics

Brief, rapid, recurrent, and seemingly purposeless stereotyped muscle contractions. Tourette syndrome (TS) is a neurobehavioral, multiple tic disorder that may involve motor tics (especially twitches of the face, neck, and shoulders) and phonic tics (grunts, words, coprolalia, echolalia). Pts may experience an irresistible urge to express tics but characteristically can voluntarily suppress them for short periods of time. Onset is usually between 2 and 15 years of age, and tics often lessen or even disappear in adulthood.

• Drug treatment is only indicated when tics are disabling and interfere with quality of life.
• Therapy is generally initiated with clonidine, starting at low dose, or guanfacine (0.5-2 mg/d). If these agents are not effective, atypical neuroleptics (risperidone, olanzapine, ziprasidone) may be used.

Myoclonus

Brief, rapid (<100 ms), shock-like, jerky, movements, usually multifocal. Like asterixis, often occurs in a diffuse encephalopathy. Following cardiac arrest, diffuse cerebral hypoxia may produce multifocal myoclonus. Metabolic disturbances or spinal cord injury can also cause myoclonus. Myoclonus occurs in normal individuals when waking up or falling asleep.

• Treatment, indicated only when function is impaired, consists of treating the underlying condition or removing an offending agent.
• Drug therapies include valproic acid (800-3000 mg/d), piracetam (8-20 g/d), clonazepam (2-15 mg/d), levetiracetam (1000-3000 mg/d), or primidone (500-1000 mg/d).

Asterixis

Brief, arrhythmic interruptions of sustained voluntary muscle contraction, usually observed as a brief lapse of posture of wrists in dorsiflexion with arms outstretched, “negative myoclonus.” This “liver flap” may be seen in any encephalopathy related to drug intoxication, organ system failure, or CNS infection. Therapy is correction of the underlying disorder.