What is the initial management and treatment for a patient presenting with Chorea (involuntary, abrupt movements)?

Initial Management and Treatment of Chorea

The initial management of chorea requires first identifying and treating the underlying cause—particularly ruling out reversible etiologies like autoimmune, metabolic, drug-induced, and vascular causes—before initiating symptomatic treatment with VMAT2 inhibitors such as tetrabenazine for disabling choreiform movements. 1, 2

Immediate Diagnostic Evaluation

Essential Workup to Identify Reversible Causes

The priority is excluding treatable secondary causes before assuming a neurodegenerative etiology. 2

• Brain MRI without contrast is the optimal initial imaging modality to identify structural causes, assess for neurodegenerative patterns, and detect basal ganglia lesions, though it may be normal early in disease course 1, 2, 3

• Essential blood tests must include thyroid function, serum calcium, phosphorus, parathyroid hormone, blood glucose, and serum ceruloplasmin to exclude metabolic causes such as hyperthyroidism, hypoparathyroidism, hypoglycemia, and Wilson disease 2

• Medication review is critical—discontinue any offending agents if drug-induced chorea is suspected, and monitor patients on long-term neuroleptics for tardive dyskinesia 2

Differential Diagnosis Considerations

In children and young adults, consider acute rheumatic fever (Sydenham chorea), which presents with purposeless, involuntary movements often associated with muscle weakness and emotional lability. 4 The key challenge is that evidence of recent group A streptococcal infection may be difficult to document due to the long latent period between infection and chorea onset 4

Critical conditions to exclude include: 4, 2

• Huntington disease (most common cause of adult-onset chorea)
• Systemic lupus erythematosus
• Wilson disease
• Antiphospholipid syndrome
• Drug reactions
• Cerebrovascular disease
• Infectious etiologies

Treatment Algorithm Based on Etiology

For Autoimmune Causes

Autoimmune chorea requires immunomodulatory therapy as first-line treatment, not just symptomatic management. 1, 2

• For antiphospholipid antibody-associated chorea: Initiate antiplatelet and/or anticoagulation therapy in addition to symptomatic treatment 1, 2

• For systemic lupus erythematosus-related chorea: Use glucocorticoids alone or combined with immunosuppressive therapy (azathioprine or cyclophosphamide) 1, 2

• For refractory cases with generalized autoimmune activity: Pulse intravenous methylprednisolone with intravenous cyclophosphamide has demonstrated effectiveness 1

For Metabolic Causes

Correcting the underlying metabolic disturbance is essential and may completely resolve the chorea. 2

• Address thyroid dysfunction, calcium-phosphate abnormalities, or glucose disturbances 2

For Drug-Induced Chorea

Discontinue the offending agent immediately and monitor for resolution. 2 This is particularly important for patients on long-term neuroleptics who may develop tardive dyskinesia 2

Symptomatic Pharmacological Treatment

First-Line Symptomatic Therapy

For disabling chorea requiring symptomatic control, VMAT2 inhibitors are the treatment of choice. 5

Tetrabenazine is FDA-approved specifically for chorea associated with Huntington's disease and has high-strength evidence showing statistically significant reduction in Total Chorea Score compared to placebo 3, 6, 5

Tetrabenazine Dosing Protocol

Critical safety warning: Tetrabenazine carries a black box warning for increased risk of depression and suicidality in patients with Huntington's disease 6

The drug is contraindicated in patients who are actively suicidal or have untreated/inadequately treated depression. 6

Dosing up to 50 mg/day (no genetic testing required): 6

• Start at 12.5 mg once daily in the morning
• After one week, increase to 25 mg/day (12.5 mg twice daily)
• Titrate slowly at weekly intervals by 12.5 mg daily
• Doses of 37.5-50 mg/day should be divided three times daily
• Maximum single dose is 25 mg

Dosing above 50 mg/day (requires CYP2D6 genotyping): 6

• Patients must be genotyped for CYP2D6 metabolizer status before exceeding 50 mg/day
• For extensive/intermediate metabolizers: titrate weekly by 12.5 mg daily
• Maximum daily dose is 100 mg; maximum single dose is 37.5 mg
• Doses above 50 mg/day should be divided three times daily

If adverse reactions occur (akathisia, restlessness, parkinsonism, depression, insomnia, anxiety, sedation), stop titration and reduce the dose 6

Alternative VMAT2 inhibitors include deutetrabenazine and valbenazine, which are also considered first-line options 5

Alternative Symptomatic Agents

Dopamine receptor blockers (antipsychotics) are used by some clinicians, though they carry risk of tardive dyskinesia with long-term use 5

Anti-epileptics and anti-glutamatergics are sometimes employed, though evidence is less robust than for VMAT2 inhibitors 5

Non-Pharmacological Management

Supportive therapies are essential for functional improvement and should be initiated early. 1, 2, 3

• Speech therapy is beneficial for patients with orofacial chorea affecting speech and swallowing (moderate strength of evidence) 1, 3

• Occupational therapy assists with activities of daily living impacted by choreiform movements (moderate strength of evidence) 1, 3

Special Considerations and Pitfalls

Genetic Testing Considerations

For suspected Huntington's disease (most common cause of adult-onset chorea), genetic testing for CAG repeat expansions in the huntingtin gene provides 100% specificity when ≥40 repeats are detected 2, 3

Genetic counseling is mandatory before testing, particularly given the autosomal dominant inheritance with complete penetrance 3

Monitoring Requirements

Close observation for emergence or worsening of depression, suicidality, or unusual behavioral changes must accompany tetrabenazine therapy. 6 Patients, caregivers, and families should be informed of these risks and instructed to report concerning behaviors promptly 6

Particular caution is required in patients with history of depression or prior suicide attempts, which occur with increased frequency in Huntington's disease 6

Deep Brain Stimulation

Deep brain stimulation is reserved for patients with disabling chorea despite optimal medical therapy. 5