What is the initial approach to managing a patient presenting with Chorea?

Initial Management of Chorea

MRI brain without IV contrast is the optimal initial imaging study for patients presenting with chorea, combined with genetic testing for Huntington's disease when clinically suspected, while simultaneously evaluating for treatable causes including stroke, metabolic derangements, drug exposure, and autoimmune conditions. 1, 2

Immediate Diagnostic Workup

Imaging Approach

• Obtain MRI brain without IV contrast as the first-line imaging modality to identify structural causes, assess for neurodegenerative patterns (particularly caudate atrophy), and exclude cerebrovascular disease, though imaging may be normal early in disease course 1, 2
• CT head has limited utility but may be useful for rapidly excluding acute stroke, hemorrhage, or infectious/inflammatory processes when MRI is unavailable 1
• IV contrast is generally unnecessary unless infectious or inflammatory conditions are being considered 1

Laboratory and Genetic Testing

• Obtain genetic testing for Huntington's disease (HD) with CAG repeat analysis in patients with suspected HD, as this is the diagnostic test of choice and should be pursued with genetic counseling 1
• Check glucose levels immediately, as nonketotic hyperglycemia is a major treatable cause of acute chorea 3
• Evaluate for antiphospholipid antibodies and systemic lupus erythematosus markers when autoimmune etiology is suspected 2
• Consider antistreptolysin O (ASO) titer, anti-DNase B, or streptozyme testing for Sydenham chorea, particularly in children and adolescents 1, 4

Clinical Assessment Priorities

History and Examination

• Determine time course: acute onset (hours to days) suggests vascular, toxic-metabolic, or inflammatory causes; gradual onset suggests neurodegenerative disease 3, 5
• Assess for drug exposure: neuroleptics, anticonvulsants, stimulants, and dopamine agonists are common culprits 1, 3
• Document whether chorea is unilateral (suggests structural lesion) or bilateral 3, 4
• Evaluate for associated features: behavioral changes, dysarthria, gait abnormalities, and deteriorating handwriting suggest Sydenham chorea or HD 1, 4
• Obtain family history, as 30% of Sydenham chorea patients have family history of acute rheumatic fever 4

Differential Diagnosis Framework

The DANCE acronym provides a systematic approach 3:

• Diagnosis of chorea (confirm phenomenology)
• Acute stroke protocol (if acute onset)
• Normal glucose levels (check immediately)
• Check neuroimaging (MRI preferred)
• Exposure to drugs (detailed medication history)

Management Based on Etiology

Acute/Treatable Causes (Priority)

• Stroke: In acute ischemic stroke with chorea, consider thrombolysis if within appropriate time window; note that only a minority show classical subthalamic nucleus lesions 3
• Hyperglycemia: Correct metabolic derangement promptly 3
• Drug-induced: Discontinue offending agent 3, 6
• Autoimmune/inflammatory:
  • For antiphospholipid syndrome-related chorea, initiate antiplatelet or anticoagulation therapy 2
  • For systemic lupus erythematosus, use glucocorticoids alone or combined with immunosuppressive therapy (azathioprine or cyclophosphamide) 2
  • Pulse IV methylprednisolone with IV cyclophosphamide for refractory cases with generalized autoimmune activity 2

Symptomatic Treatment

• VMAT2 inhibitors are first-line for symptomatic chorea management: deutetrabenazine (FDA-approved for HD chorea and tardive dyskinesia) starting at 6 mg twice daily or 12 mg once daily for extended-release formulation, titrating weekly by 6 mg/day up to maximum 48 mg/day 7, 6
• Maximum dose is 36 mg/day in poor CYP2D6 metabolizers or when combined with strong CYP2D6 inhibitors 7
• Alternative VMAT2 inhibitors include tetrabenazine and valbenazine 6
• Dopamine receptor blockers (antipsychotics) are second-line options 6

Supportive Care

• Speech therapy for patients with orofacial chorea affecting speech and swallowing 2, 8
• Occupational therapy for activities of daily living impacted by choreiform movements 2, 8

Critical Warnings for Huntington's Disease

When prescribing deutetrabenazine for HD-associated chorea, the drug carries a black box warning for depression and suicidality 7:

• Contraindicated in suicidal patients or those with untreated/inadequately treated depression 7
• Monitor closely for emergence or worsening of depression, suicidality, or unusual behavioral changes 7
• Balance risks against clinical need for chorea treatment 7
• Exercise extreme caution in patients with history of depression or prior suicide attempts 7

Common Pitfalls

• Do not assume neuroimaging will confirm Sydenham chorea: 96% of pediatric chorea cases in endemic areas are Sydenham chorea, which can be diagnosed clinically with laboratory confirmation of streptococcal infection; neuroimaging is unnecessary unless presentation is atypical (e.g., hemichorea, acute neurologic deficits) 4
• Do not overlook reversible causes: prioritize evaluation for stroke, hyperglycemia, drug exposure, and autoimmune conditions before attributing chorea to neurodegenerative disease 3, 5
• Do not delay genetic counseling: HD genetic testing should always be accompanied by appropriate counseling given implications for patient and family 1
• Recognize that early HD may have normal imaging, so negative MRI does not exclude diagnosis 1