AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Causes of Chorea
• Pathophysiology and General Principles in Treatment of Chorea
• Rheumatic (Sydenham) Chorea
• Juvenile Huntington Disease
• Other Choreiform Disorders
• Paroxysmal Choreas
• Drug Treatment of Chorea
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Causes of Chorea
• Pathophysiology and General Principles in Treatment of Chorea
• Rheumatic (Sydenham) Chorea
• Juvenile Huntington Disease
• Other Choreiform Disorders
• Paroxysmal Choreas
• Drug Treatment of Chorea
• References

Chorea is defined as brief, irregular, unpredictable, purposeless movements that flow from one body part to another without a rhythmic pattern.

The term chorea is derived from the Greek word for dancing and was applied initially to epidemics of dancing mania in the Middle Ages, in which large numbers of people danced together for days.

• Many such dances were described, but the most renowned was chorea Sancti Viti.
• Sydenham used this term in his Schedula Monitoria to describe rheumatic chorea in 1686.
• Two hundred years later, Huntington described hereditary chorea and suggested that this movement disorder was similar to that described by Sydenham.

CAUSES OF CHOREA

Section 3 of 10  

• Authors and Editors
• Introduction
• Causes of Chorea
• Pathophysiology and General Principles in Treatment of Chorea
• Rheumatic (Sydenham) Chorea
• Juvenile Huntington Disease
• Other Choreiform Disorders
• Paroxysmal Choreas
• Drug Treatment of Chorea
• References

Inherited

• Ataxia-telangiectasia
• Benign hereditary chorea
• Hallervorden-Spatz disease
• Hereditary spinocerebellar ataxias
• Huntington disease
• Inborn errors of metabolism
  • Glutaric acidemia
  • Propionic acidemia
  • Homocystinuria
  • Phenylketonuria
  • Sulfite oxidase deficiency
• Mitochondrial encephalomyopathies
• Neuroacanthocytosis
• Paroxysmal disorders
  • Paroxysmal kinesiogenic choreoathetosis
  • Paroxysmal nonkinesiogenic choreoathetosis
• Pyruvate carboxylase deficiency
• Wilson disease

Drugs

• Anticholinergics
• Anticonvulsants (eg, phenytoin, carbamazepine, phenobarbital)
• Antidopaminergic agents (eg, phenothiazines, haloperidol, metoclopramide)
• Antihistamines
• CNS stimulants (eg, amphetamines, methylphenidate, pemoline)
• Dopamine agonists (eg, levodopa)
• Lithium
• Oral contraceptives

Endocrine

• Hyperthyroidism
• Chorea gravidarum
• Hypoparathyroidism, pseudohypoparathyroidism

Immune/infectious

• Behçet disease
• Other infections - Pertussis, diphtheria, varicella
• Primary antiphospholipid antibody syndrome
• Sydenham chorea
• Systemic lupus erythematosus
• Bacterial endocarditis
• Herpes simplex encephalitis
• HIV related
• Infectious mononucleosis
• Lyme disease
• Mycoplasmal pneumonia
• Viral meningoencephalitis (eg, mumps, measles, varicella)

Vascular

• Arteriovenous malformation
• Basal ganglia infarction or hemorrhage
• Moyamoya

Metabolic

• Hypocalcemia
• Hypoglycemia and hyperglycemia
• Hypomagnesemia
• Hyponatremia, hypernatremia, and central pontine myelinolysis
• Renal failure

Miscellaneous

• Cerebral palsy
• Head trauma
• Bronchopulmonary dysplasia (infantile chorea)
• Cardiopulmonary bypass - "Postpump chorea"

Neoplastic

• Primary and metastatic brain tumors
• Primary CNS lymphoma

Nutritional

• Vitamin B-12 deficiency in infants
• Wernicke encephalopathy

Toxins

• Carbon monoxide
• Manganese
• Organophosphate poisoning

PATHOPHYSIOLOGY AND GENERAL PRINCIPLES IN TREATMENT OF CHOREA

Section 4 of 10  

• Authors and Editors
• Introduction
• Causes of Chorea
• Pathophysiology and General Principles in Treatment of Chorea
• Rheumatic (Sydenham) Chorea
• Juvenile Huntington Disease
• Other Choreiform Disorders
• Paroxysmal Choreas
• Drug Treatment of Chorea
• References

Connections of the basal ganglia can be categorized as the following:

• Input from the cerebral cortex and the thalamus
• Interconnections among the basal ganglia
• Output from the basal ganglia to other nuclear masses

The main neurotransmitters associated with the basal ganglia include gamma aminobutyric acid (GABA), dopamine, acetylcholine, and glutamate. Other neurotransmitters include enkephalin, substance P, dynorphin, cholecystokinin, and somatostatin.

• Dopamine is highly concentrated in the substantia nigra.
  • It is released in the postsynaptic area in the striatum from axons originating in the substantia nigra.
  • It is inactivated by reuptake in the presynaptic terminal and degraded by monoamine oxidase and catechol-O-methyltransferase.
• GABA is concentrated mainly in the globus pallidus, the substantia nigra, and to a lesser extent in the caudate and the putamen.
  • It functions mainly in the interneurons of the striatum and the striatonigral pathways.
  • It is synthesized from glutamic acid by glutamic acid decarboxylase and is inactivated by GABA transaminase through the formation of a succinic semialdehyde.
• Glutamic acid is an excitatory neurotransmitter that is involved primarily in the pathways leading from the cerebral cortex to the striatum.
• Acetylcholine is active in both the central and peripheral nervous systems.
  • It exerts its greatest activity as a neurotransmitter in the striatum, hippocampus, and ascending reticular activating system.
  • It is synthesized from choline through choline acetyltransferase, which exerts its greatest activity in the caudate nucleus.
  • It is degraded by cholinesterase with the formation of choline, which may be used once again for synthesis by the presynaptic neuron.
• Dopaminergic neurons within the substantia nigra project rostrally to the neostriatum (caudate and putamen).
  • The feedback loop from the neostriatum appears to be segregated into 2 parallel pathways.
    • The so-called indirect pathway consists of GABAergic/encephalinergic neurons that project to the external segment of the globus pallidus. Inhibitory neurons from the external globus pallidus synapse on neurons of the subthalamic nucleus, which then provide excitatory input (presumably glutamatergic) to the final output structures of the basal ganglia (the internal globus pallidus and the substantia nigra pars reticulata), which then inhibit the ventral thalamus.
    • The so-called direct pathway consists of GABAergic neurons that project directly to the internal globus pallidus and substantia nigra pars reticulata, inhibiting these nuclei.
  • The 2 output pathways are modulated differentially by dopamine. The GABA-containing neostriatal neurons that form the indirect pathway preferentially express dopamine type 2 receptors and are inhibited by dopamine, while the GABAergic neostriatal neurons that form the direct pathway tend to express dopamine type 1 receptors and are excited by dopamine.
  • Chorea may be viewed as resulting from increased dopaminergic activity in the projections from the substantia nigra to the striatum, resulting in decreased GABAergic projection from the striatum to the globus pallidus.
    • Most of the drugs used in symptomatic treatment of chorea act through attenuation of dopaminergic transmission or enhancement of GABA transmission.
    • Anticonvulsant drugs may suppress chorea but also may induce chorea, especially in patients with basal ganglia dysfunction.

RHEUMATIC (SYDENHAM) CHOREA

Section 5 of 10  

• Authors and Editors
• Introduction
• Causes of Chorea
• Pathophysiology and General Principles in Treatment of Chorea
• Rheumatic (Sydenham) Chorea
• Juvenile Huntington Disease
• Other Choreiform Disorders
• Paroxysmal Choreas
• Drug Treatment of Chorea
• References

Introduction

In 1686, Thomas Sydenham described the clinical syndrome that now bears his name. Originally termed St. Vitus' dance, it now is referred to more commonly as rheumatic chorea. The relationship between arthritis and chorea was established by Roger (1866 and 1868).

In 1889, Cheadle described the full rheumatic syndrome of carditis, polyarthritis, chorea, subcutaneous nodules, and erythema marginatum. Several decades later, epidemiologic and microbiologic studies confirmed the etiological role of streptococcal infection in rheumatic fever.

More recently, Sydenham chorea (SC) has been linked to the obsessive-compulsive disorder (OCD) spectrum. Studies demonstrate a high prevalence of obsessive-compulsive symptoms as well as OCD in children with SC.

Epidemiology

Few studies have examined the prevalence of SC in the apparently healthy population.

• In the United States, the incidence of rheumatic fever is approximately 0.5 to 2 per 100,000 population per year.
• The incidence of rheumatic fever is clearly higher in developing countries, where the absence of consistent and early antibiotic treatment makes rheumatic fever a more endemic problem.

Chorea typically occurs in about 10-20% of patients with acute rheumatic fever.

• In some outbreaks, chorea has been present in over 30% of the patients.
• The female-to-male ratio is approximately 2:1, and most patients present between 5-15 years of age.

Family studies demonstrated a high frequency of a positive family history in patients with both SC and rheumatic fever. Aron et al found that 3.5% of parents and 2.1% of siblings of children with SC also were affected with SC.

Clinical features and course

SC is a major manifestation of acute rheumatic fever.

• With the 1992 modifications of the Jones criteria, SC alone is sufficient to make the diagnosis of a first attack of acute rheumatic fever.
• SC often presents with other rheumatic fever manifestations during the acute episode, although an isolated form characterized by chorea alone has been described.

The main features of SC are involuntary movements, hypotonia, and muscular weakness. Chorea can be generalized or unilateral, predominantly involving the extremities and face. Movements occur at rest and are exacerbated by stress; they disappear during sleep.

• Children may attempt to hide the movements in quasi-purposeful actions (such as flinging hair back), or they may sit on their hands is an attempt to prevent these movements.
• In about 20% of patients, one side of the body may be affected more severely than the other to a degree that leads to the description of hemichorea; careful examination usually reveals that the other side also is affected.
• The choreic movements interfere with volitional movements and result in a clumsy gait, dropping and spilling, and explosive bursts of dysarthric speech.
  • Muscular weakness leads to inability to sustain a contraction (milkmaid's grip).
  • The pronator sign consists of hyperpronation of the hands, causing the palms to face outward when the arms are held over the head.
• Some children may have such profound weakness that they appear paralyzed. Not uncommonly, children are restricted to bed or are unable to attend school for the duration of the illness.

Patients with SC also present with a number of psychological and psychiatric manifestations such as depression, anxiety, personality changes, emotional lability, OCD, and attention deficit disorder (ADD).

• Whether the psychological symptoms are secondary to the movement disorder or an integral part of the disease is not clear.
• Occasionally, these symptoms precede the onset of the movement disturbance.

On average, the disease usually resolves spontaneously in 3-6 months and rarely lasts longer than 1 year.

• Mild chorea without functional disability may be found in a small proportion of patients up to 10 years after the initial attack of SC.
• About 20% of patients experience a recurrence, usually within 2 years after the initial attack.

Pathophysiology

Immunology: Husby was the first to describe antineuronal antibodies in patients with SC. The antineuronal antibodies, which are postulated to arise in response to the group A beta-hemolytic streptococcal infection, cross-react with an unknown epitope on basal ganglia neurons. Antineuronal antibodies also have been reported from the cerebrospinal fluid (CSF) of patients with acute rheumatic chorea. These antibodies were found to specifically stain cells within the caudate and subthalamic nuclei.

• Serum antineuronal antibody titers were found to decrease as the chorea improved.
• In children who suffered a relapse, the increase in symptom severity correlated with a rise in the antibody titer.

Neurochemistry: The main symptoms of SC are believed to arise from an imbalance among the dopaminergic system, intrastriatal cholinergic system, and inhibitory gamma-aminobutyric acid (GABA) system. Evidence of this imbalance has been suggested by the successful control of chorea by dopaminergic blockers and valproic acid, a drug that is known to enhance GABA levels at the striatum and substantia nigra.

Neuroimaging

Giedd et al demonstrated an increased size of the caudate, putamen, and globus pallidus in patients with SC as compared to controls.

Konagaya and Konagaya reported MRI changes in the basal ganglia that resolved 2 weeks later.

Functional neuroimaging using fluorine F 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) showed reversible striatal hypermetabolism.

Diagnosis

Diagnosis of SC may be difficult, because no single, established diagnostic test is available.

• The patient may have no recent history of rheumatic fever, and a preceding streptococcal infection cannot always be documented.
• When SC is the first and isolated manifestation of rheumatic fever, excluding other possible causes of chorea is necessary.

Treatment

SC is usually self-limited, and treatment should be limited to patients with chorea severe enough to interfere with function.

• Valproic acid at a dose of 15-20 mg/kg/day has been reported to control choreic movements within 1 week.
• Another anticonvulsant, carbamazepine, may have a similar effect. Diazepam in nonsedative doses also may be used.
• Steroids have been used widely, but no controlled studies have been done to confirm steroid efficacy in chorea.
• Dopaminergic blockers (pimozide and haloperidol) and depletors have been used widely, but they have significant side effect profiles. Pimozide has fewer side effects than haloperidol, and in low doses pimozide has a lower risk of tardive dyskinesia.

Parents and school officials should be informed that emotional lability is characteristic of this organic condition.

Immunologic treatment includes the following:

• The presence of antineuronal antibodies suggests that intravenous immunoglobulin (IVIg) and plasma exchange may be effective.
• Garvey and Swedo showed sustained improvement in 3 children who were treated with plasma exchange.
• Three other children treated with IVIg showed initial improvement but had recurrences after subsequent streptococcal infection.

JUVENILE HUNTINGTON DISEASE

Section 6 of 10  

• Authors and Editors
• Introduction
• Causes of Chorea
• Pathophysiology and General Principles in Treatment of Chorea
• Rheumatic (Sydenham) Chorea
• Juvenile Huntington Disease
• Other Choreiform Disorders
• Paroxysmal Choreas
• Drug Treatment of Chorea
• References

Introduction

Huntington chorea is an autosomal-dominant, neurodegenerative disorder in which chorea is a primary clinical manifestation. Other prominent clinical features include progressive cognitive decline and an array of psychiatric disturbances.

The average age of onset is at 35-40 years; however, the disease has been reported in children as young as 4 years.

• The age of onset varies among families, with some showing consistently older age of onset than others.
• Age of onset among individuals of the same family also can vary widely; children of an affected father may have a younger age of onset than children of an affected mother.

The term "juvenile Huntington disease" designates patients whose clinical manifestations begin before the age of 20 years. This group also may be divided further into those with onset before the age of 10 years and those with onset in adolescence.

Genetics

Huntington disease (HD) is an autosomal-dominantly inherited disease with complete penetrance. The responsible gene, IT-15, is located on the p16.3 subband of chromosome 4. The genetic mutation is an unstable, expanded DNA trinucleotide (cytosine-adenosine-guanosine or CAG) repeat within the coding region for a 348-kD protein named huntingtin.

• All individuals possess this repeat sequence; it is the number of triplet repeats that is significant. Patients with HD have 38 or more repeats. The earlier the age of onset, the greater the number of repeats for a given individual.
• The correlation between repeat length and rate of disease progression is unclear. Approximately 10% of HD gene carriers develop signs of illness before age 20 years.
• Between 70% and 80% of patients with childhood-onset HD have inherited the gene from an affected father.
• Note that as many as 1% of individuals with HD may have a negative test result.

Clinical features

HD in childhood presents with a slightly different constellation of symptoms than the adult form. The former presents with rigidity, a conspicuous slowing of eye movements from loss of rapid saccadic eye movements, and occasionally seizures as early features. It can also present as difficulty in school, even before clinical signs relating to the movement disorder become apparent.

• The patient may appear to be primarily clumsy, rather than either rigid or choreiform.
• Reflexes are usually brisk, and pyramidal signs with extensor plantar responses are common.
• Seizures occur in about 30-50% of patients; they usually appear late in the disease and are difficult to control.

Diagnosis

The availability of a DNA-based testing (to reliably identify the HD mutation) greatly facilitates diagnosis of the disease. Prior to direct DNA testing, clinical findings and family history were the cornerstones of diagnosis.

Brain MRI in juvenile HD usually demonstrates striatal hyperintensity on T2-weighted images (a feature that is not present in most hyperkinetic patients with HD), indicating greater striatal damage.

Presymptomatic testing should be executed only under rigid guidelines.

• It should be performed only at the request of the patient.
• Test results should be released only to the patient; if the result is to be released to another party, written consent is required from the patient.
• Testing minors is considered inappropriate at this time, because results may have significant negative repercussions in raising the child.

Treatment

Presently, no specific therapy is available for HD. Management consists of symptomatic therapy and counseling.

• Some patients benefit from antidepressants; carbamazepine may be useful for mood swings.
• Agents used to treat symptoms of bradykinesia and rigidity, such as L-dopa or directly acting dopamine agonists, can be helpful but often exacerbate chorea and provoke hallucinations and psychosis.

Experimental therapies (eg, agents that improve mitochondrial energy metabolism, agents that attenuate glutamate neurotransmission and free radical scavengers) have been ineffective.

OTHER CHOREIFORM DISORDERS

Section 7 of 10  

• Authors and Editors
• Introduction
• Causes of Chorea
• Pathophysiology and General Principles in Treatment of Chorea
• Rheumatic (Sydenham) Chorea
• Juvenile Huntington Disease
• Other Choreiform Disorders
• Paroxysmal Choreas
• Drug Treatment of Chorea
• References

Benign hereditary chorea

Introduction

Benign hereditary chorea (BHC) is an inherited neurologic disorder that consists of childhood-onset, nonprogressive chorea. Inheritance appears to be autosomal dominant, although rare cases of autosomal-recessive and X-linked inheritance have been reported.

The suggestion has been made that BHC could be allelic to HD. One family was reported to have expanded CAG repeats, suggesting that some families with the so-called "benign" chorea may in fact have a phenotypic variant of HD. More recently, de Vries demonstrated linkage between BHC and markers on chromosome arm 14q in a large Dutch family.

Clinical features

The age of onset ranges through most of childhood and the disease progresses little, if at all, beyond adolescence. Affected children usually are described as clumsy with frequent falls, and they may present with delayed motor development. Later on in childhood, their inability to write legibly hampers schooling.

Choreic jerks vary greatly in severity and frequency among affected persons and potentially can involve any part of the body. Few other neurological abnormalities are present with the exceptions of ataxia, dysarthria, and action tremor. Intellectual function is typically normal in patients with BHC.

• Intellectual impairment has been reported in one family in which affected individuals had intelligence quotient scores averaging 10 points lower than unaffected relatives.
• Functional neuroimaging showed decreased striatal FDG metabolism in one study.

Treatment

Various drugs have been used with mixed results. Commonly used drugs include anticonvulsants (phenytoin and carbamazepine), haloperidol, and prednisone. The chorea frequently does not require treatment.

Neuroacanthocytosis

Neuroacanthocytosis is a progressive multisystem disease with a wide range of symptoms. Characteristic features include acanthocytosis, normal beta-lipoprotein levels, and multiple movement disorders.

Genetics

Neuroacanthocytosis is most likely an autosomal-recessive disorder, although autosomal-dominant and X-linked inheritances have been proposed. In a recent genetic study, neuroacanthocytosis was linked to a 6-cM region of chromosome band 9q21.

Clinical features

Onset usually occurs in adults aged 20-40 years. In a large British survey of neuroacanthocytosis, the mean age for disease onset was 32 years. Death occurs approximately 10 years after onset.

Chorea is the most prominent finding, but dystonia, motor and vocal tics, and parkinsonism all can occur (possibly simultaneously).

• Oromandibular dystonia and orolingual dyskinesia commonly lead to dysarthria, and most of the patients have major problems with eating and swallowing early in the disease's course. Lingual-labial dyskinesia may be so severe as to cause self-mutilating behavior.
• Axonal sensorimotor polyneuropathy with amyotrophy, elevated creatine phosphokinase (CPK), and decreased or absent deep tendon reflexes also occurs.
• Epileptic seizures occur in about one third of patients.
• MRI may demonstrate atrophy of the caudate nucleus or T2-weighted hyperintensities in the striatum.

Diagnosis

Identify characteristic clinical features, a positive family history, the presence of acanthocytes on peripheral blood smear, and a normal plasma lipid profile.

Treatment

Treatment is symptomatic.

• Antidopaminergic agents may suppress the chorea, but they may worsen concomitant parkinsonism.
• Seizures should be treated with appropriate anticonvulsants.

Wilson disease

Wilson disease is an inborn error of copper metabolism, which manifests as hepatic cirrhosis and basal ganglia damage. It is inherited in an autosomal-recessive fashion.

In 1993, Bull et al suggested that Wilson disease is the result of a defect in the Wc1 gene (chromosome 13), which encodes a copper transporting P-type adenosine triphosphatase that is expressed in the liver and kidney. Excess copper accumulates in the liver, brain, cornea, kidneys, and other tissues of untreated patients. The serum ceruloplasmin is low and excessive copper exists in the plasma and urine.

Clinical features

Hepatic dysfunction is the most frequent mode of presentation, representing the initial feature in more than 50% of cases. The liver disease is mostly in the form of acute hepatitis that either resolves spontaneously or progresses to fulminant hepatic failure. Less common are asymptomatic hepatomegaly, chronic active hepatitis, or cirrhosis.

• The disease rarely presents before age 6 years, and the average age of onset of hepatic symptoms is 11.4 years.
• If untreated, most individuals eventually develop manifestations of neurologic dysfunction.

In 40% of individuals, neurological symptoms are the presenting feature.

• Neurologic manifestations vary widely and may include chorea as well as dystonia, tremor, dysarthria, dysphagia, bradykinesia, and gait disorder. Most patients have gradual decline in school performance and intellectual abilities. Seizures are uncommon.
• The average age of onset in those who present with neurologic symptoms is 18.9 years.

Almost all patients with neurologic involvement also have Kaiser-Fleischer rings, which result from deposition of copper in the Descemet membrane of the peripheral cornea.

Psychiatric manifestations include depression, personality changes, and emotional lability. Hemolytic anemia and renal tubular acidosis also may occur.

Diagnosis

Determining hepatic copper content via liver biopsy is the single most sensitive and accurate test for Wilson disease. Assay of serum ceruloplasmin is a simple and practical test, but it may fall within or slightly below normal range in 5-15% of affected patients. Other tests include the following:

• Slit-lamp examination to check for the presence of corneal Kaiser-Fleischer rings is a vital part in the diagnostic evaluation.
• Twenty-four-hour urinary copper excretion rises dramatically in symptomatic patients. It is a useful test to monitor therapy.

Because of its protean manifestations, Wilson disease should be excluded in any patient who presents with unexplained neurological dysfunction, especially if the basal ganglia or cerebellum is involved.

Treatment

The 4 primary strategies for managing Wilson disease are as follows:

• Limiting copper intake
• Therapy to reduce copper absorption
• Copper chelation therapy
• Liver transplantation

PAROXYSMAL CHOREAS

Section 8 of 10  

• Authors and Editors
• Introduction
• Causes of Chorea
• Pathophysiology and General Principles in Treatment of Chorea
• Rheumatic (Sydenham) Chorea
• Juvenile Huntington Disease
• Other Choreiform Disorders
• Paroxysmal Choreas
• Drug Treatment of Chorea
• References

Demirkiran and Jankovic divided paroxysmal dyskinesias into 4 groups according to the precipitating circumstances.

• Paroxysmal kinesiogenic dyskinesia
• Paroxysmal nonkinesiogenic dyskinesia
• Paroxysmal exertion-induced dyskinesia
• Paroxysmal hypnogenic dyskinesia

Paroxysmal kinesiogenic dyskinesia

These choreas consist of any combination of these paroxysmal attacks: dystonia, chorea, athetosis, and ballismus. Goodenough et al noted choreoathetosis in 64% of patients. The age of onset ranges from 6-15 years. The attacks typically last less than 1 minute but occur frequently (over 100 times per day).

• The extremities are affected primarily, but facial, neck, and trunk muscles also can be affected.
• The attacks may be disabling and interfere with walking, working, and daily activities.
• Neurologic examination findings between the attacks are normal.

About half of the reported cases are familial, with both autosomal-dominant and -recessive patterns of inheritance. Multiple sclerosis, head trauma, thalamic infarcts, hypoparathyroidism, hypernatremia, and hyperglycemia represent common causes of secondary paroxysmal kinesiogenic dyskinesia.

The response to anticonvulsant medications is often striking.

• Phenytoin has been considered the drug of choice and generally is used in dosages similar to those used in epilepsy; however, it also has been shown to be effective in smaller doses.
• Satisfactory response has been obtained with other anticonvulsants, particularly carbamazepine; acetazolamide also may be used.
• In one case, haloperidol worsened paroxysmal kinesiogenic dyskinesia.

Paroxysmal nonkinesiogenic dyskinesia

The attacks occur spontaneously without any specific precipitant. The duration ranges from 2-3 minutes to 4 hours, a major feature that differentiates it from paroxysmal kinesiogenic dyskinesia.

In one series, 81% of cases were familial. Multiple sclerosis is the leading cause of secondary paroxysmal nonkinesiogenic dyskinesia. Other causes include encephalitis, hypoparathyroidism, thyrotoxicosis, head injury, basal ganglia calcification, AIDS, and Leigh syndrome.

Attacks of paroxysmal nonkinesiogenic dyskinesia may diminish with age in frequency and severity.

It is more difficult to treat than paroxysmal kinesiogenic dyskinesia, since the nonkinesiogenic form does not respond to anticonvulsant drugs. Clonazepam (1-2 mg/d) appears to be the drug of choice; phenobarbital and valproic acid also may be effective.

Paroxysmal hypnogenic dyskinesia

This condition consists of brief, occasionally painful dystonic or choreoathetoid movements occurring during non–rapid eye movement sleep. In some cases, daytime kinesigenic or nonkinesigenic attacks also have been described along with hypnogenic attacks. Short-lasting paroxysmal hypnogenic dyskinesia generally is regarded as a form of mesiofrontal epilepsy.

Paroxysmal exertion-induced dyskinesia

This disorder consists of attacks of dystonia, sometimes combined with chorea and athetosis, that are triggered by exertion such as walking or running. The attacks usually involve the lower limbs and are often bilateral. They may last from a few minutes to 30 minutes. Most of the described cases suggest an autosomal-dominant mode of inheritance. Treatment with anticonvulsants and levodopa has proven unsatisfactory.

DRUG TREATMENT OF CHOREA

Section 9 of 10  

• Authors and Editors
• Introduction
• Causes of Chorea
• Pathophysiology and General Principles in Treatment of Chorea
• Rheumatic (Sydenham) Chorea
• Juvenile Huntington Disease
• Other Choreiform Disorders
• Paroxysmal Choreas
• Drug Treatment of Chorea
• References

Dopaminergic blockers

• Haloperidol
• Pimozide

Dopaminergic depletors

• Tetrabenazine
• Reserpine

Benzodiazepines

• Clonazepam
• Diazepam

Anticonvulsants

• Phenytoin
• Carbamazepine
• Valproic acid

Antidopaminergic agents

• The hyperdopaminergic theory supports the use of dopamine antagonists.
  • In children, particularly those who will need treatment for long periods of time, neuroleptics present a potentially serious problem (ie, the risk of tardive dyskinesia).
  • Using neuroleptics only as a last resort is preferred.
• The incidence of tardive dyskinesia in children is not known.
  • In a study of 41 children and adolescents who were treated with various neuroleptic medications, 3 patients had tardive dyskinesia.
  • Haloperidol should be started at a low dose (0.5-2 mg/d). Dose may be titrated gradually for a satisfactory response.
• Aside from tardive dyskinesia, side effects include sedation, cognitive impairment, akathisia, acute dystonic reactions, and parkinsonism.
  • Pimozide (usually 0.2 mg/kg/d) may be associated with fewer side effects.
  • Baseline and follow-up ECGs are recommended to monitor for Q-T prolongation.
• Tetrabenazine, a presynaptic dopamine depletor, also may be effective. It does not produce tardive dyskinesia, but side effects include depression, orthostatic hypotension, weight gain, and drowsiness.

Drugs acting through GABA

• Benzodiazepines such as clonazepam and diazepam may be used to treat chorea, particularly in the early stages. Sedation is a major concern. They may be useful in the first few days until a satisfactory response to other drugs is achieved.
• In one study, 15 children with SC were treated with sodium valproate (15-20 mg/kg/d) for a mean duration of 19.2 months. In 13 of the children, the choreiform movements disappeared within 1 week of beginning therapy.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Causes of Chorea
• Pathophysiology and General Principles in Treatment of Chorea
• Rheumatic (Sydenham) Chorea
• Juvenile Huntington Disease
• Other Choreiform Disorders
• Paroxysmal Choreas
• Drug Treatment of Chorea
• References

• ARON AM, FREEMAN JM, CARTER S. THE NATURAL HISTORY OF SYDENHAM''S CHOREA. REVIEW OF THE LITERATURE AND LONG-TERM EVALUATION WITH EMPHASIS ON CARDIAC SEQUELAE. Am J Med. Jan 1965;38:83-95. [Medline].
• Aasly J, Skandsen T, Ro M. Neuroacanthocytosis--the variability of presenting symptoms in two siblings. Acta Neurol Scand. Nov 1999;100(5):322-5. [Medline].
• Abbas S, Khanna S, Taly AB. Obsessive-compulsive disorder and rheumatic chorea: is there a connection?. Psychopathology. 1996;29(3):193-7. [Medline].
• Beskind DL, Keim SM. Choreoathetotic movement disorder in a boy with Mycoplasma pneumoniae encephalitis. Ann Emerg Med. Jun 1994;23(6):1375-8. [Medline].
• Bird MT, Palkes H, Prensky AL. A follow-up study of Sydenham''s chorea. Neurology. Jul 1976;26(7):601-6. [Medline].
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Article Last Updated: Mar 30, 2007