Alexander D. Rae-Grant, MD
ALERT 
Choreoathetosis may result from a variety of medications and this should be considered early in the differential diagnosis.
Geriatric Considerations
Dopaminergic agents particularly levodopa/carbidopa are prescribed commonly in this population and may cause variable choreoathetosis. Senile chorea occurs in this population as well.
Pediatric Considerations
There are specific syndromes of choreoathetosis in childhood.
Pregnancy Considerations
Choreoathetosis may occur in pregnancy de novo (see below).
DESCRIPTION
Choreoathetosis is a combination of the term chorea and the term athetosis. These are two abnormal types of movement that are often combined in the same disorder. Chorea refers to rapid, involuntary, brief, irregular, and unpredictable jerks of muscles and can occur in the limbs, face, or trunk muscles. Athetosis is characterized by slow, writhing, uncoordinated involuntary movements usually involving the limbs, though similar movements may affect the face and trunk muscles as well.
- Definitions
- Chorea: Rapid, involuntary, brief, irregular movements
- Athetosis: Writhing, involuntary, slow, uncoordinated movements
- Parakinesia: A choreic movement camouflaged by a superimposed purposeful act
- Clinical characteristics
- Choreoathetosis may occur acutely or on a chronic basis, be transient, or be a persistent, lifelong phenomenon. It may interfere with the ability to speak, use the limbs, walk, or stand still. The movements may be unilateral (hemichorea), and at times are flinging (merging into hemiballismus, a separate but related disorder). Tone is usually reduced, but strength is unaffected. Patients may be unable to sustain a tight hand grip (milkmaid's hand). The tongue may dart in and out irregularly while attempting to protrude it
EPIDEMIOLOGY
Incidence/Prevalence
There is limited data on the prevalence of choreoathetosis. Huntington's disease (HD) is estimated to affect 1 in 10,000 persons of European descent.
RISK FACTORS
Genetics
- HD: Autosomal dominant, onset in 20s and 30s, with a combination of progressive chorea, a personality disorder and dementia. HD gene (IT15) on short arm of chromosome 4 (4p16.3).
- Other rarer genetic syndromes which can cause choreoathetosis.
GENERAL PREVENTION
- Avoiding use of medications that cause chorea, or limiting duration of use.
- Prevention of rheumatic fever from Streptococcus.
PATHOPHYSIOLOGY
Choreoathetosis is caused by a degeneration or fixed injuries to the striatum (putamen, globus pallidus, caudate), or is due to a biochemical imbalance affecting these parts of the brain. The basal ganglia are critical in modulating motor activity from the corticospinal tract, and help maintain the posture, tone, and amplitude of motor activity both at rest and in action. In HD selective loss of “spiny” neuron gabaergic cells may disinhibit thalamic neurons leading to hyperkinesis.
ETIOLOGY
- There are a large number of possible causes of choreoathetosis (1) including inherited genetic disorders such as HD, choreoacanthocytosis, Wilson's disease, and rarer syndromes; focal striatal pathology (stroke, tumor, etc.); drug induced, chorea gravidarum; thyrotoxicosis; SLE/antiphospholipid antibody syndrome; Postinfectious (Sydenham's chorea, PANDAS, Herpes encephalitis); Polycythemia rubra vera: AIDS affecting the brain; variant Creutzfeldt–Jakob disease.
- Medications that are associated with drug-induced choreoathetosis include Amantadine, Amphetamines, Anticonvulsants including phenytoin, carbamazepine and valproic acid, carbon monoxide poisoning, Cocaine-induced chorea (“Crack dancing”), Anticholinergics, Antihistamines, Azithrimycin, Benzodiazepines, Bronchodilators, Levo-dopa and dopa agonists, Lithium, Oral contraceptives, Phenothiazines, Sildenifil in PD males, Tricyclic antidepressants.
COMMONLY ASSOCIATED CONDITIONS
The commonly associated conditions include HD.
[Outline]
HISTORY
In a patient presenting with choreoathetosis, symptoms suggesting cognitive dysfunction (memory loss, altered judgment, impulsivity, altered sexuality) may suggest HD. The clinical setting suggests Sydenham chorea, chorea gravidarum, and chorea related to systemic disease or medications. Choreoathetosis related to prenatal and perinatal insults is usually self-evident. Signs to seek include presence of associated neurologic findings (hyporeflexia, sensory loss suggesting neuropathy; cognitive dysfunction; presence of focal signs suggesting stroke).
PHYSICAL EXAM
Watch patient for choreoathetosis at rest, while walking, or while doing tasks (may be incorporated into tasks). Other signs include associated neurologic findings (hyporeflexia, sensory loss suggesting neuropathy; cognitive dysfunction; focal signs suggesting stroke).
DIAGNOSTIC TESTS AND INTERPRETATION
Lab
Initial Lab Tests
Directed by clinical circumstances. In suspected cases of systemic causes of choreoathetosis, with blood smear (polycythemia vera, neuroacanthocytosis), glucose (hyperosmolar nonketotic hyperglycemia), thyroid indices (thyrotoxicosis), liver function studies (Wilson's disease, kernicterus), antiphospholipid antibodies (antiphospholipid antibody syndrome). Genetic testing is available in HD but should be linked with counseling.
Follow-Up & Special Considerations
See individual disorders.
Imaging
Initial Approach
CT scanning and MRI may both show focal basal ganglia lesions causing choreoathetosis. In situations such as acute chorea, imaging to assess for infarction, hemorrhage, tumor, or vascular malformation may be useful. Carbon monoxide poisoning may show hypodensities in the globus pallidus bilaterally. In HD, MRI later in disease may show atrophy of both caudate nuclei. PET scanning may show caudate hypermetabolism in choreoathetotic disorders.
Follow-Up & Special Considerations
See individual disorders.
Diagnostic Procedures/Other
These will depend on the specific etiologies under consideration. For example, slit lamp examination for Kayser–Fleischer rings in Wilson's disease.
Pathological Findings
Pathological findings vary depending on etiology.
DIFFERENTIAL DIAGNOSIS
- HD: Autosomal dominant, onset in 20s and 30s, with a combination of progressive chorea, a personality disorder and dementia. HD gene (IT15) on short arm of chromosome 4 (4p16.3).
- Sydenham chorea: Rheumatic chorea in childhood and adolescence, often hemichorea, occurring after rheumatic fever, now rare. Self-limited disease.
- Senile chorea: Late onset, generalized chorea, no family history, no dementia. Mild, slowly progressive. Various causes.
- Chorea gravidarum: Chorea occurring with pregnancy. May also be seen with use of oral contraceptives.
- Choreoathetosis with medications: May occur with dopaminergic medications (L-dopa, bromocriptine, newer dopaminergic medications). Occasionally with famciclovir (in dialysis patients), digoxin, oral contraceptives, and gabapentin. Case reports with cocaine use.
- Choreoathetosis with surgery: Choreoathetosis has been described after cardiac transplantation or after open heart surgery, usually in children.
- Choreoathetosis with systemic diseases: May occur with lupus erythematosus, thyrotoxicosis, polycythemia vera, and hyperosmolar, nonketotic hyperglycemia, antiphospholipid antibody syndrome, Creutzfeldt–Jakob disease.
- Neuroacanthocytosis: Familial multisystem progressive disorder with chorea, cognitive impairment, neuropathy, reduced reflexes, abnormal red cells (acanthocytes).
- Developmental disorders: A variety of prenatal and perinatal insults including kernicterus may cause choreoathetosis, which is nonprogressive and present from infancy or early childhood.
- Rarer associations with choreoathetosis: Neuro-Behçet's disease, stroke, tumors, vascular malformations, moyamoya, tuberculous meningitis, multiple sclerosis, Wilson's disease.
- Hereditary nonprogressive chorea: Rare autosomal-dominant disorder, with chorea, no dementia or progression, no other neurologic signs.
- Paroxysmal kinesigenic choreoathetosis: Choreoathetotic movements brought on by volitional movements. May be familial.
- Dentatorubral-pallidoluysian atrophy: Rare autosomal-dominant disorder sometimes confused with HD. Patients show chorea, myoclonus, ataxia, seizures, and dementia.
[Outline]
MEDICATION
First Line
Treatment is primarily symptomatic unless there are specific medications for the etiology. There is no standard practice for suppression of choreoathetosis. Removal or reduction of offending medications first line.
Second Line
- Atypical and typical antipsychotics are moderately effective for suppressing choreoathetosis due to their dopamine depleting action. Potential side effects include akathisia, sedation, and tardive dyskinesia.
- Other dopamine depleting agents such as reserpine and tetrabenazine.
- Gabaergics such as clonazepam, gapentin, valproic acid.
- Intravenous immunoglobulin or plasmapheresis may shorten course of Sydenham's chorea.
- Chorea after heart transplant may respond to steroids.
ADDITIONAL TREATMENT
General Measures
Treatment is directed at symptomatic management of the movements of chorea and athetosis, if necessary. If choreoathetosis is the result of a specific disease, that disease management should be used. For severe chorea attention to avoiding injury is paramount.
Issues for Referral
Patients with choreoathetosis not due to readily identifiable medications or causes should be referred to either adult or pediatric neurology for evaluation. Families considering genetic testing for HD especially in presymptomatic candidates should have formal genetic counseling prior to testing to review the issues related to such testing.
Additional Therapies
Minocycline and coenzyme Q10 have been tried in animal models of HD but there is limited data on human trials.
COMPLEMENTARY AND ALTERNATIVE THERAPIES
Coenzyme Q10 as noted. Otherwise there are no specific CAM recommendations.
SURGERY/OTHER PROCEDURES
No reports available.
IN-PATIENT CONSIDERATIONS
Initial Stabilization
See IV fluids. Avoid self-harm due to flinging movements if needed. Assess suicidality in HD cases.
Admission Criteria
Patients with acute onset of chorea may require hospitalization for diagnosis and stabilization. Patients with HD may require admission if at risk of harming themselves or others based on their psychiatric state.
IV Fluids
Some patients with severe choreoathetosis (e.g., Hemiballismus) may suffer from dehydration due to exertion and may need IV fluid replacement.
[Outline]
FOLLOW-UP RECOMMENDATIONS
Follow-up recommendations depend on causation and disease course.
Patient Monitoring
Patient monitoring depends on causation.
DIET
No special diet in most cases.
PATIENT EDUCATION
The movement should be named and described for the patient. The etiology and prognosis if known or the possibilities if not known should be reviewed. If medication is used to suppress the movements the dosing, side effects, and expected effect should be reviewed.
PROGNOSIS
Prognosis depends on etiology.
COMPLICATIONS
The complications vary depending on etiology and severity.
[Outline]
- Walker FO. Huntington's disease. Lancet 2007;369:218–228.
SEE-ALSO
http://www.movementdisorders.org/UserFiles/file/flow%20chart.pdf (Flow chart evaluation chorea)
