What is the best course of treatment for chorea?

Best Treatment Approach for Chorea

For patients with chorea, tetrabenazine is the first-line pharmacological treatment due to its proven efficacy in reducing choreiform movements with a significant treatment effect compared to placebo. 1

Etiology-Based Treatment Algorithm

Step 1: Determine the Underlying Cause

• Huntington's Disease (HD): Most common cause of chorea in adults 2
• Secondary Causes:
  • Cerebrovascular disease
  • Infectious/inflammatory processes
  • Autoimmune disorders (including antiphospholipid syndrome)
  • Metabolic disorders
  • Drug-induced syndromes

Step 2: Diagnostic Workup

• Brain MRI without contrast: Optimal imaging modality for patients with chorea 2, 3
• Genetic testing: Essential for suspected HD (testing for CAG repeats in huntingtin gene) 2
• Additional tests based on suspected etiology:
  • Antiphospholipid antibodies
  • Metabolic panel
  • Medication review

Treatment Approach by Etiology

For Huntington's Disease Chorea:

1. First-line: VMAT2 Inhibitors

   • Tetrabenazine: Start at 12.5 mg/day, titrate weekly by 12.5 mg increments 1
     • Maximum recommended daily dose: 100 mg
     • Maximum single dose: 37.5 mg
     • Typical effective dose range: 25-75 mg/day
   • Clinical trial evidence shows tetrabenazine reduced Total Chorea Scores by 5.0 units compared to 1.5 units with placebo 1
   • Dosing caution: Requires CYP2D6 genotyping for doses >50 mg/day 1

2. Alternative options:

   • Deutetrabenazine: Similar to tetrabenazine but with potentially fewer peak-dose side effects 4
   • Antipsychotics: Particularly tiapride (in Europe), olanzapine, or risperidone 4

3. Important monitoring:

   • Depression and suicidality: Tetrabenazine carries a boxed warning for increased risk 1
   • Parkinsonism and akathisia: Common side effects requiring dose adjustment 1

For Secondary Chorea:

1. Treat the underlying cause first 5:

   • Autoimmune/inflammatory: Glucocorticoids with immunosuppressive agents 2
   • Antiphospholipid antibody-related: Antiplatelet and/or anticoagulation therapy 2
   • Drug-induced: Discontinuation of offending agent

2. Symptomatic treatment (if needed):

   • VMAT2 inhibitors: Tetrabenazine is effective for various chorea etiologies 6
   • Antipsychotics: Consider for refractory cases 4

Special Considerations

Paroxysmal Kinesigenic Dyskinesia (PKD)

• First-line: Low-dose carbamazepine (50-200 mg/day) or oxcarbazepine (75-300 mg/day) 2
• Efficacy: >85% of patients achieve complete remission with these agents 2
• Dosing: Start with 50 mg carbamazepine or 75 mg oxcarbazepine, adjust based on response 2

Side Effect Management

• Depression/suicidality: Close monitoring required, especially with tetrabenazine 1
• Movement disorders: Dose reduction if akathisia or parkinsonism develop 1
• Sedation: Consider nighttime dosing to minimize impact 1

Treatment Pitfalls to Avoid

1. Failure to identify and treat underlying cause: Secondary chorea often resolves when primary condition is addressed 5

2. Inadequate titration: Start with low doses and titrate slowly to minimize adverse effects 1

3. Overlooking depression risk: Particularly important in HD patients receiving tetrabenazine 1

4. Neglecting genetic testing: Essential for HD diagnosis and for determining CYP2D6 status when using tetrabenazine at higher doses 2, 1

5. Inappropriate imaging: MRI is preferred over CT for evaluating chorea due to superior soft-tissue characterization 2

By following this treatment algorithm and addressing both the underlying cause and symptomatic management of chorea, clinicians can effectively reduce the burden of this movement disorder and improve patients' quality of life.