What is the best treatment approach for a patient presenting with chorea, possibly due to Huntington's disease or Sydenham's chorea?

Treatment of Chorea

For Huntington's disease chorea, tetrabenazine is the first-line pharmacological treatment when chorea interferes with daily functioning, causes social isolation, gait instability, falls, or physical injury, with a proven 3.5-point reduction in Total Chorea Score compared to placebo. 1

When to Initiate Pharmacological Treatment

Treatment should be started when chorea causes:

• Patient stigma or social isolation 2
• Physical injury or gait instability with falls 3, 2
• Work interference or inability to perform activities of daily living 2
• Disturbed sleep 2
• Speech and swallowing difficulties 3, 4

Do not treat chorea simply because it is present—only treat when it functionally impairs the patient. 2

Huntington's Disease Chorea: Pharmacological Algorithm

First-Line Monotherapy Options

Tetrabenazine (VMAT2 inhibitor):

• Start at 12.5 mg daily, titrate weekly in 12.5 mg increments until satisfactory control, intolerable side effects, or maximum 100 mg/day reached 1
• Produces statistically significant 3.5-unit reduction in Total Chorea Score over 12 weeks 1
• 50% of patients achieve ≥6-point improvement versus 7% with placebo 1
• Major caveat: Can worsen depression and should be avoided in actively depressed patients 2
• Most common first-line choice (49.9% of treated patients in real-world data) 5

Antipsychotic drugs (olanzapine, risperidone, tiapride):

• Preferred in Europe as first-line 6, 2
• Mandatory choice when comorbid psychotic symptoms, aggressive behaviors, or active depression are present 2
• Similar efficacy to tetrabenazine but without depression risk 2
• 27.7% of patients receive antipsychotics as first-line in real-world practice 5

Second-Line and Combination Therapy

When monotherapy fails to adequately control severe chorea:

• Combine tetrabenazine with an antipsychotic 2
• This combination is the most common second-line approach 5
• 92% of patients started on VMAT2 inhibitors remain on them alone or in combination 5

Benzodiazepines as adjunctive therapy:

• Ineffective as monotherapy but useful when anxiety exacerbates chorea 2
• Should only be added to primary agents, never used alone 2

Agents to Avoid

Amantadine:

• Broad expert disagreement on efficacy 2
• Described benefit is small and transient when used 2
• Not recommended as a reliable option 2

Sydenham's Chorea: Distinct Treatment Approach

For acute-onset chorea in children, consider Sydenham's chorea first (96% of pediatric acute chorea cases), confirmed by elevated antistreptolysin O, anti-deoxyribonuclease B, or positive streptozyme 7

Treatment Options for Sydenham's Chorea:

Levetiracetam (emerging alternative):

• Demonstrated complete symptom resolution in case reports 8
• Reduced Universidade Federal de Minas Gerais Sydenham's Chorea Rating Scale from 47 to 5 points 8
• Advantage: Fewer adverse effects compared to traditional agents like haloperidol 8
• Symptoms may recur if discontinued prematurely 8

Traditional agents:

• Haloperidol has been used but may leave residual symptoms 8

Secondary Chorea: Treat the Underlying Cause First

The primary treatment for secondary chorea is addressing the causative disorder, not symptomatic chorea suppression. 3, 9

Autoimmune Causes:

• Antiphospholipid syndrome: Antiplatelet and/or anticoagulation therapy 3
• Systemic lupus erythematosus: Glucocorticoids alone or combined with immunosuppressive therapy (azathioprine, cyclophosphamide) 3
• Refractory autoimmune cases: Pulse IV methylprednisolone with IV cyclophosphamide 3

Metabolic Causes:

• Correct thyroid dysfunction, calcium-phosphate abnormalities, glucose disturbances 7
• Wilson's disease requires chelation therapy after confirming low serum ceruloplasmin 7, 9

Drug-Induced Chorea:

• Discontinue the offending agent immediately 7
• Monitor patients on long-term neuroleptics for tardive dyskinesia development 7
• Tardive dyskinesia has the strongest evidence for treatment with pre-synaptic dopamine-depleting agents 9

Essential Diagnostic Workup Before Treatment

Brain MRI without contrast is the optimal imaging modality to identify structural causes and neurodegenerative patterns 3, 7

Genetic testing:

• For suspected HD: CAG repeat expansion ≥40 confirms diagnosis with 100% specificity 4
• Mandatory genetic counseling before testing due to autosomal dominant inheritance 4

Essential blood tests to exclude secondary causes:

• Thyroid function, serum calcium, phosphorus, parathyroid hormone 7
• Blood glucose, serum ceruloplasmin (Wilson's disease) 7
• Alpha-fetoprotein (ataxia-telangiectasia) 7

Non-Pharmacological Management

Speech therapy is beneficial for orofacial chorea affecting speech and swallowing (moderate evidence strength) 3, 4

Occupational therapy assists with activities of daily living impacted by choreiform movements (moderate evidence strength) 3, 4

Interdisciplinary team approach is essential, including dementia subspecialist, movement disorder specialist, neuropsychologist, psychiatrist, speech and occupational therapists 4

Critical Practice Gaps

Only 36.1% of patients with chorea receive treatment despite indications, and approximately half of treated patients receive off-label alternatives instead of evidence-based VMAT2 inhibitors 5. This represents a significant undertreatment problem in clinical practice that should be addressed by following the algorithm above.

Psychiatric symptoms are major drivers of morbidity and institutionalization—often more than motor symptoms—and require aggressive treatment with SSRIs or low-dose amitriptyline, with psychiatric consultation when needed 4.