eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases

Chorea Gravidarum: Differential Diagnoses & Workup

Author: Tarakad S Ramachandran, MBBS, FRCP(C), FACP, Professor of Neurology, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Chair, Department of Neurology, Crouse Irving Memorial Hospital
Contributor Information and Disclosures

Updated: Feb 10, 2009

Differential Diagnoses

Other Problems to Be Considered

Briefly, genetic syndromes with chorea include Huntington disease; HDL1-3; inherited prion disease; spinocerebellar ataxias 1, 3, and 17; neuroacanthocytosis; dentatorubro-pallidoluysian atrophy (DRPLA); brain iron accumulation disorders; Wilson's disease; benign hereditary chorea; Friedreich ataxia; and mitochondrial disease. Acquired causes of chorea include vascular disease, postinfective autoimmune central nervous system disorders (PANDAS), drugs, systemic lupus erythematosus, antiphospholipid syndrome, thyrotoxicosis, AIDS, chorea gravidarum, and polycythaemia rubra vera.²¹

Primary differential diagnosis is as follows:

• Familial paroxysmal choreoathetosis
• Benign hereditary chorea

• Drugs/toxicity
  • Anticonvulsants (eg, phenytoin, carbamazepine, phenobarbital)
  • Antiparkinson agents
  • Neuroleptics (eg, chlorpromazine, haloperidol, pimozide)
  • Noradrenergic stimulants
  • Steroids
  • Estrogens
  • Lead toxicity
• Infectious
  • AIDS
  • Meningovascular syphilis
  • Infectious mononucleosis
  • Lyme disease
  • Sydenham chorea
  • Viral encephalitis
  • Subacute sclerosing panencephalitis
  • Ramsay-Hunt syndrome (ie, progressive myoclonic ataxia)
• Genetic
  • Heredodegenerative/degenerative disorders
  • Ataxia telangiectasia
  • Hallervorden-Spatz disease
  • Huntington disease (including Westphal variant)
  • Neuronal ceroid lipofuscinoses
  • Pelizaeus-Merzbacher disease
  • Wilson disease
  • Dentatorubral pallidoluysian atrophy
  • Cerebellar system degenerations
  • Pallidonigral degeneration
  • Multiple system atrophy
  • Olivopontocerebellar atrophy
  • Striatonigral degeneration
  • Progressive pallidal atrophy
  • Fahr disease
  • Paroxysmal dystonic choreoathetosis
  • Familial intention tremor and lipofuscinosis
  • Ataxia telangiectasia
  • Dystonia musculorum deformans
  • Dihydroxyphenylalanine-responsive dystonia
  • Spasmodic torticollis
  • Meige syndrome
  • Task-specific tremor (writer's or voice tremor)
  • Senile chorea
• Inherited disorders of metabolism
  • Abetalipoproteinemia
  • Fahr disease
  • Glutaric aciduria
  • Lesch-Nyhan syndrome
  • Pyruvate decarboxylase deficiency
  • Sulfite oxidase deficiency
• Metabolic/endocrine disorders
  • Encephalopathies (eg, hepatic, renal)
  • Hyperparathyroidism
  • Hyperthyroidism
  • Hypoglycemia
  • Hyponatremia
  • Hypernatremia
• Miscellaneous
  • Systemic lupus erythematosus
  • Henoch-Schönlein purpura
  • Peripheral neuropathies (eg, Charcot-Marie-Tooth disease, Guillain-Barré syndrome)
  • Space-occupying lesions of the brain
  • Tic disorders
  • Transient tic disorder
  • Chronic motor or vocal tic disorder
  • Tourette syndrome
• Vascular/trauma
  • Cardiac surgery
  • Cerebral hemorrhage
  • Transient cerebral ischemia
  • Vasculitis
  • Antiphospholipid antibody syndrome
• Other systemic disorders
  • Lupus erythematosus
  • Polycythemia vera
  • Neuroacanthocytosis
  • Acquired hepatocerebral degeneration

Sydenham chorea first was described by Thomas Sydenham in his Schedula Monitoria in 1686. He named this new disease "St. Vitus' dance" to differentiate it from "dancing mania," a practice seen in the religious ceremonies of the day by those who danced to exorcise prevalent epidemic illnesses.²² Along with carditis and arthritis, Sydenham chorea is a diagnostic indicator of rheumatic fever.

Sydenham chorea is characterized by involuntary movements that tend to be generalized or unilateral, involving predominantly the extremities and the face. The movements occur at rest, may start gradually or abruptly, and are exacerbated by stress. Like other tremors of extrapyramidal origin, they disappear during sleep. Neurologic examination often reveals hypotonia, motor restlessness, and choreic movements in combination, resulting in incoordination, gait disturbances, and dysarthria. When weakness caused by hypotonia is severe, these patients have a special form of Sydenham chorea termed chorea paralytic or chorea mollis.²³ In addition, Sydenham chorea can present with psychiatric manifestations including depression, anxiety, personality changes, emotional lability, obsessive-compulsive disorder, tics, and attention deficit disorder. Behavior disturbances may include crying, irritability, and inattentiveness.

In the 1980s, an outbreak of group A streptococcal tonsillitis in Rhode Island was associated with a 10-fold increase in the incidence of motor tics (without chorea); the concept of poststreptococcal tics was born.²⁴ Subsequent identification of further patients led to the development of a new acronym: PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections).²⁵ In addition to tics, patients with PANDAS had a high incidence of psychiatric disorders, particularly obsessive-compulsive disorder. However, Dale et al have demonstrated that cohorts of Sydenham chorea are predominantly female, whereas poststreptococcal tic cohorts are predominantly male.²⁶

Huntington disease

Huntington disease is an autosomal dominant inherited progressive neurodegenerative disorder characterized by chorea, complete motor disability, and mental status changes culminating in dementia and mental status changes. The average age at onset is 35-45 years, but it can occur in individuals from childhood to those older than 80 years. 

Huntington disease is relentlessly progressive and characterized by generalized chorea, which is a hallmark of the disorder. The chorea is mild initially, and affected persons appear fidgety or restless. The movements may be merged into intentional gestures and may seem to be semipurposeful or unusual mannerisms. The patient eventually develops a wide-based gait associated with lurching, dipping, and falling, often resembling a marionette. Myoclonus and seizures might occur. Ocular motility abnormalities might include difficulty in generating saccadic movements. Other movement disorders, including parkinsonism, dystonia, and tic, also may be present in patients with Huntington disease.

Other clinical features include personality and behavioral changes, progressive memory loss, lack of attention span and, most commonly, depression. Neuro-psychiatric abnormalities are present in almost all patients. Suicide accounts for about 7.5% of deaths. The average duration of the natural course of the disease before death is about 17 years. The autosomal dominant inheritance is fully penetrant and confers a 50% risk of passage to offspring of affected individuals. The gene for Huntington disease codes for a protein that has been designated huntingtin. The function of the gene product and its mechanism of pathogenesis are not yet known.

A genetic test result of greater than 39 CAG repeats in the Huntington disease gene is diagnostic. However, genetic counseling is recommended strongly before testing, particularly in at-risk patients who are asymptomatic.

Currently, no treatment is available to prevent progression of Huntington disease. Patients are given symptomatic treatment for the chorea. Although progressive intellectual impairment generally occurs, mental status problems in individuals with Huntington disease are difficult to treat; therapy with antidepressant, antipsychotic, and antianxiety agents may be tried. Nonpharmacologic interventions, including speech therapy, swallowing evaluation, physical therapy, adaptation strategies, and counseling, are also important. Social service intervention is often necessary.

Relationship to antiphospholipid antibody syndrome

Antiphospholipid syndrome (APS) is a disorder characterized by recurrent venous or arterial thrombosis, recurrent fetal loss, and thrombocytopenia associated with the presence of lupus anticoagulant, anticardiolipin antibody, or both. Anticardiolipin and antiphospholipid are essentially interchangeable terms. Depending on the assay used to detect them, they cross-react. Several subtypes that do not cross-react have been identified but are currently of little clinical significance.

Antiphospholipid antibodies (aPLs) include anticardiolipin antibodies (aCL), the lupus anticoagulant (LAC), antibodies to other phospholipids such as phosphatidylserine²⁹ and phosphatidylethanolamine, and antibodies to phospholipid-binding proteins.³⁰

The presence of LAC is characterized by prolonged activated partial thromboplastin time (aPTT) that is not corrected by addition of normal plasma but is corrected by freeze-thawed platelets or phospholipids. aCL is measured by enzyme-linked immunosorbent assay (ELISA).

In select high-risk pregnant populations without SLE, aPLs have been linked with adverse pregnancy outcomes such as preeclampsia, intrauterine growth retardation (IUGR), fetal distress, chorea gravidarum³¹ , and postpartum morbidity. However, the relationship between aPL and pregnancy complications in the general obstetric population is less clear. Some evidence indicates that the HELLP syndrome (ie, hemolysis, elevated liver enzymes, and low platelets) may be a manifestation of APS.^32,33

A case of chorea gravidarum and progressive cerebral infarction due to factor V Leiden homozygosity has been reported.³⁴ This was the first such case in the literature, and treatment with unfractionated intravenous heparin had produced a good clinical response.

A variety of microangiopathic antiphospholipid-associated syndromes like HELLP syndrome, thrombotic thrombocytopenic purpura, and thrombotic microangiopathic syndromes should be differentiated from the microvascular occlusions that are seen in the antiphospholipid syndrome. In these conditions, the antibodies might not be pathogenic, but, alternatively, generated by small vessel endothelial damage.³⁵

Treatment consists of long-term anticoagulation with warfarin and antiplatelet drugs. During pregnancy, heparin may need to be substituted for warfarin. For acute exacerbations, steroids and immunosuppressive therapy have been used. No evidence supports prophylactic therapy as helpful in patients who have been and are asymptomatic.

Moyamoya disease

In 2000, Unno et al reported a case of chorea gravidarum associated with moyamoya disease. A 16-year-old girl developed acute left choreic movements during her fourth week of pregnancy. She has had transient ischemic attacks since she was 10 years old. During the eighth week of pregnancy, a brain MRI showed old ischemic lesions deep in the right frontal white matter. Her angiograph revealed a complete obstruction of the terminal portion of the right internal carotid artery with a developed moyamoya network. After her abortion, all involuntary movements completely subsided. The choreic movements might have been caused not only by ischemia but also by enhanced dopaminergic sensitivity mediated by elevations in female sex hormones due to pregnancy.⁶

In a 2007 report, Kim et al reported the association of chorea gravidarum with moyamoya disease.³⁶

Workup

Laboratory Studies

• Maintain a high index of suspicion and vigilance when making the diagnosis of chorea gravidarum and considering the differential diagnosis.
• Acute rheumatic fever- Erythrocyte sedimentation rate (ESR), throat culture, C-reactive protein, and ASO titer
• Wilson disease - Serum ceruloplasmin and urinary copper (24 h)
• Systemic lupus erythematosus - ESR, antinuclear antibody, anticardiolipin antibodies, and lupus anticoagulant assays
• Phenothiazine reaction history - Therapeutic trial of intravenous (IV) benztropine
• Polycythemia - CBC, hemoglobin, and hematocrit
• Hyperthyroidism - Thyroxine (T4), thyroid-stimulating hormone (TSH)
• Hypoparathyroidism - Serum calcium and phosphate
• Vascular disease
  • Hypercoagulability of pregnancy; investigations for hyperlipidemia, diabetes, valvular heart disease, hyperviscosity states, hemoglobinopathies, or congenital cerebrovascular disease (moyamoya)
  • In a young patient with cerebral infarction, in the absence of hypertension and atrial fibrillation, vasculitides and thrombophilic tendencies must be considered. Testing for thrombophilia with estimation of anticardiolipin antibody, antithrombin III levels, prothrombin gene, protein S, protein C resistance, and factor V Leiden should be considered.
• Meningovascular syphilis - Venereal Disease Research Laboratory test (VDRL), fluorescent treponemal antibody absorption test (FTA-ABS)
• Drugs - Serum levels of anticonvulsants, theophylline, lithium, and tricyclic antidepressants
• Drug toxicity due to amphetamine and cocaine - Serum levels and urine screening
• Lead toxicity - Serum lead level
• Neuroacanthocytosis peripheral smear for acanthocytes
• Adult-onset Tay-Sachs disease - Assay of serum lysosomal enzymes
• Husby has described antineuronal antibodies using an immunofluorescent technique in 46% of patients with Sydenham chorea (n = 30) compared with 14% of patients with rheumatic fever (without chorea) (n = 50) and only 1.8-4% of control subjects (n = 203). He further demonstrated a potential correlation between antibody reactivity and the clinical status, with antibody disappearance on chorea remission.³⁷

Imaging Studies

• Hypoparathyroidism: CT scan may reveal bilateral basal ganglia calcificans.
• MRI
  • Huntington disease (MRI of the brain to exclude caudate atrophy) and neuroacanthocytosis
  • Wilson disease - Striatal damage
  • Systemic lupus erythematosus, locular infarcts - Small arterial damage
  • Rare basal ganglia tumor

Other Tests

• Obtain ECG whenever a suspicion of rheumatic fever exists to exclude carditis. EEG may show evidence of rheumatic encephalopathy.
• Perform a slit-lamp examination to rule out Kayser-Fleischer rings that would indicate Wilson disease.

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