What is the appropriate work‑up and treatment for a patient presenting with choreiform movements?

Work-up and Treatment of Choreiform Movements

Begin with brain MRI without contrast as the optimal imaging modality to identify structural causes, assess neurodegenerative patterns, and detect basal ganglia lesions, while simultaneously obtaining essential blood tests and considering the patient's age and clinical context to guide further evaluation. 1, 2

Initial Diagnostic Approach

Imaging

• Brain MRI without contrast is the preferred initial imaging study to evaluate for structural lesions, vascular abnormalities, basal ganglia changes, and neurodegenerative patterns 3, 1, 2
• MRI may be normal early in disease course but can reveal caudate atrophy, striatal signal changes, or other pathology in established disease 4
• Neuroimaging is not necessary for typical Sydenham's chorea and should be reserved for atypical presentations including hemichorea, acute neurological deficits, or when the clinical picture is unclear 5

Essential Laboratory Testing

• Thyroid function tests (hyperthyroidism can cause chorea) 2
• Serum calcium, phosphorus, and parathyroid hormone (hypoparathyroidism is a metabolic cause) 2
• Blood glucose (hypoglycemia can precipitate chorea) 2
• Serum ceruloplasmin (to exclude Wilson disease, particularly in younger patients) 3, 2
• Antistreptolysin O, anti-deoxyribonuclease B, or streptozyme (to document recent streptococcal infection in suspected Sydenham's chorea) 2, 5
• Alpha-fetoprotein (elevated in ataxia-telangiectasia) 2

Age-Specific Diagnostic Considerations

Children and Adolescents

• Sydenham's chorea is the most common cause of acute-onset chorea in childhood, accounting for 96% of cases in endemic areas 2, 5
• Characterized by involuntary, purposeless, non-stereotyped movements of trunk or limbs, frequently with muscle weakness and emotional lability 3, 2
• Can be unilateral in 30% of patients, requiring careful neurological examination 3, 5
• Associated features include behavior change (46%), dysarthria (67%), gait disturbance (51%), and deteriorating handwriting (29%) 5
• Evidence of recent group A streptococcal infection can be documented in 99% of cases when appropriate testing is performed 5
• Carditis is the most common concurrent major Jones criterion (44%), while arthritis (11%), erythema marginatum (3%), and subcutaneous nodules are uncommon 5

Adults

• Huntington's disease is the most common cause of adult-onset chorea 1, 2, 4
• Drug-induced chorea (particularly tardive dyskinesia from neuroleptics) accounts for a substantial proportion of adult cases 6
• Average age of onset for Huntington's disease is 35-45 years 4

Genetic Testing

When to Order

• Genetic testing for CAG repeat expansion in the huntingtin gene is recommended for suspected Huntington's disease, providing 100% specificity when ≥40 repeats are detected 4
• Mandatory genetic counseling before testing given autosomal dominant inheritance with complete penetrance for alleles ≥40 repeats 4
• Consider NKX2-1/TITF1 gene testing for suspected benign hereditary chorea 2
• ATM gene testing for suspected ataxia-telangiectasia when clinical features include cerebellar ataxia, choreoathetosis, oculomotor apraxia, and immunodeficiency 2

Differential Diagnosis to Exclude

Critical Exclusions

• Huntington disease, systemic lupus erythematosus, Wilson disease, and drug reactions must be systematically excluded 3
• Differentiate choreiform movements from tics, athetosis, conversion reaction, and hyperkinesis 3
• Consider cerebrovascular disease, infectious etiologies, autoimmune conditions, metabolic disorders, and drug-induced syndromes 4

Drug-Induced Chorea

• Review medication history carefully, particularly neuroleptics, dopaminergic agents, anticonvulsants, and stimulants 2
• Discontinue the offending agent and monitor patients on long-term neuroleptics periodically to detect tardive dyskinesia development 2

Treatment Strategies

Treat Underlying Cause First

• For autoimmune chorea associated with antiphospholipid antibodies/syndrome: antiplatelet and/or anticoagulation therapy plus symptomatic treatment 1, 2
• For systemic lupus erythematosus-related chorea: glucocorticoids alone or combined with immunosuppressive therapy (azathioprine, cyclophosphamide) 1, 2
• Pulse intravenous methylprednisolone with intravenous cyclophosphamide for refractory cases with generalized autoimmune activity 1
• Correct metabolic abnormalities: thyroid dysfunction, calcium-phosphate disturbances, or glucose abnormalities 2

Symptomatic Pharmacological Management for Huntington's Disease

• Tetrabenazine has high-strength evidence for statistically significant reduction in chorea severity compared to placebo 4
• Alternative agents include deutetrabenazine (Austedo) and valbenazine (Ingrezza) for alleviating chorea 3
• Antidepressants (SSRIs or low-dose amitriptyline) for mood symptoms 4
• Antipsychotics such as haloperidol, sulpiride, and quetiapine for chorea and psychiatric abnormalities 3

Non-Pharmacological Interventions

• Speech therapy is beneficial for orofacial chorea affecting speech and swallowing (moderate strength of evidence) 1, 4
• Occupational therapy assists with activities of daily living impacted by choreiform movements (moderate strength of evidence) 1, 4
• Cognitive Behavioral Therapy strategies for maladaptive beliefs and avoidance behaviors accompanying mood disturbances 4

Special Considerations

Sydenham's Chorea Pitfalls

• Evidence of recent streptococcal infection may be difficult to document due to the long latent period between infection and chorea onset 3
• Worsening of choreiform movements in a child with previous low-grade residual chorea may be difficult to distinguish from a new attack 3
• Neuroimaging obtained in 58% of Sydenham's chorea patients did not aid in diagnosis and should be reserved for atypical presentations 5

Ataxia-Telangiectasia Warning

• Patients should avoid ionizing radiation and x-rays due to increased radiosensitivity, requiring adjustment of cancer treatment regimens accordingly 2

Huntington's Disease Management

• Psychiatric manifestations require aggressive treatment as they significantly impact quality of life and are major drivers of emergency department visits, hospital admissions, and institutionalization 4
• Comprehensive interdisciplinary team including dementia subspecialist, movement disorder specialist, neuropsychologist, psychiatrist, speech and occupational therapists 4
• Disease progression leads to death within 15-20 years of onset 4
• Juvenile HD (onset <20 years, ~5% of cases) presents with rigidity, spasticity, and intellectual decline rather than chorea, often with CAG repeats exceeding 55 4