What is the recommended evaluation and management for a patient presenting with chorea or dyskinesia?

Evaluation and Management of Chorea and Dyskinesia

Initial Diagnostic Approach

When a patient presents with chorea or dyskinesia, immediately obtain a detailed medication history to identify drug-induced causes, as this is the most common and reversible etiology in clinical practice. 1, 2

Critical History Elements

• Medication exposure: Document all current and recent dopamine receptor-blocking agents (antipsychotics, antiemetics like metoclopramide), as well as atypical agents like trazodone that can cause tardive dyskinesia 1, 2
• Temporal relationship: Determine if movements began after medication initiation or dose changes 1
• Movement triggers: Kinesigenic triggers (sudden movements) suggest paroxysmal kinesigenic dyskinesia (PKD), while non-kinesigenic triggers (stress, caffeine, alcohol) suggest PNKD 3
• Duration of episodes: PKD attacks last <1 minute, while PNKD lasts 10 minutes to hours 3
• Autoimmune history: Screen for systemic lupus erythematosus, antiphospholipid syndrome, and recent streptococcal infections (Sydenham chorea) 3, 4

Physical Examination Findings

• Movement characteristics: Chorea presents as irregular, involuntary, jerky movements in random sequence involving any body part 3
• Associated features: Look for rigidity, altered mental status, or autonomic instability that may indicate neuroleptic malignant syndrome 3
• Neurologic signs: Focal deficits suggest structural lesions requiring urgent imaging 3

Diagnostic Testing Algorithm

First-Tier Laboratory Studies

• Thyroid function (TSH, free T4): Hyperthyroidism is a reversible cause 3, 4
• Calcium, phosphorus, parathyroid hormone: Screen for hypoparathyroidism and basal ganglia calcification 3
• Blood glucose: Rule out hyperglycemia-induced chorea 3
• Complete blood count: Evaluate for polycythemia rubra vera 4
• Antiphospholipid antibodies: If autoimmune etiology suspected 3

Neuroimaging

MRI brain without contrast is the optimal initial imaging modality for all patients with new-onset chorea or dyskinesia. 3

• MRI identifies structural lesions (stroke, demyelination, tumors), basal ganglia calcification, and caudate atrophy in Huntington's disease 3
• CT head is acceptable only when MRI is contraindicated or unavailable, though it has limited soft-tissue characterization 3
• Contrast is unnecessary unless infection or inflammatory conditions are suspected 3

Genetic Testing

• Huntington's disease: Order HTT gene CAG repeat analysis in patients with progressive chorea, family history, and caudate atrophy on imaging—this requires genetic counseling 3, 4
• PRRT2 gene: Test for paroxysmal kinesigenic dyskinesia if clinical features match 3

Specialized Testing

• EEG: Obtain only if frontal lobe epilepsy is in the differential (attacks during sleep, altered consciousness) 3
• High-knee exercise test: Perform in suspected PKD to provoke attacks and confirm diagnosis 3

Management by Etiology

Drug-Induced Tardive Dyskinesia (Most Common)

Immediately discontinue the offending medication if clinically feasible—this is the primary treatment and offers the best chance for symptom resolution. 1, 2

Acute Management

• Discontinue dopamine-blocking agents (antipsychotics, metoclopramide, trazodone) 1, 2
• Document baseline severity using the Abnormal Involuntary Movement Scale (AIMS) 1, 2
• Monitor every 1-2 weeks initially for improvement 1

Pharmacologic Treatment for Persistent or Severe TD

For moderate to severe tardive dyskinesia that persists after medication discontinuation, initiate a VMAT2 inhibitor (deutetrabenazine or valbenazine) as first-line therapy. 1, 2, 5

• Deutetrabenazine dosing: Start 6 mg twice daily (12 mg/day total), titrate weekly by 6 mg/day increments based on response and tolerability, up to maximum 48 mg/day 5
• These are the only FDA-approved medications specifically for tardive dyskinesia with proven efficacy in randomized trials 1, 6
• Continue monitoring with AIMS every 3-6 months 2

Critical Pitfalls to Avoid

• Never increase antipsychotic doses to mask TD symptoms—this worsens the condition long-term 1
• Never prescribe anticholinergics for TD—they are ineffective and may worsen symptoms 1

Paroxysmal Kinesigenic Dyskinesia

Initiate low-dose carbamazepine (50-200 mg/day) or oxcarbazepine (75-300 mg/day) as first-line treatment—over 85% of PKD patients achieve complete remission. 3, 7

• Start carbamazepine 50 mg or oxcarbazepine 75 mg at bedtime to minimize dizziness 7
• Screen for HLA-B*15:02 allele before starting carbamazepine to prevent severe cutaneous reactions 7
• Titrate gradually based on attack frequency 3, 7

Huntington's Disease-Associated Chorea

For chorea causing functional impairment in Huntington's disease, initiate deutetrabenazine starting at 6 mg twice daily. 5, 6

• Titrate weekly by 6 mg/day up to maximum 48 mg/day based on chorea control and tolerability 5
• Critical warning: Deutetrabenazine is contraindicated in patients who are suicidal or have untreated/inadequately treated depression 5
• Monitor closely for emergence of depression, suicidality, or behavioral changes 5
• Alternative: Tetrabenazine is effective but has more side effects than deutetrabenazine 8, 9

Autoimmune Chorea (SLE, Antiphospholipid Syndrome)

Treat with dopamine antagonists for symptomatic control plus immunosuppression (glucocorticoids with azathioprine or cyclophosphamide) to address underlying disease activity. 3

• Most patients (55-65%) experience a single self-limited episode 3
• Add antiplatelet or anticoagulation therapy in antiphospholipid antibody-positive patients 3

Sydenham Chorea

• Most cases are self-limited and resolve within weeks to months 4, 10
• Symptomatic treatment with dopamine antagonists if movements are severe 4
• Consider penicillin prophylaxis to prevent rheumatic fever recurrence 10

Special Populations

Elderly Patients

• Start VMAT2 inhibitors at lower doses due to increased sensitivity 2
• If using benzodiazepines (clonazepam), start with very low doses due to fall risk 2

Pregnant Patients

• Deutetrabenazine may cause fetal harm based on animal data—avoid if possible 5

Monitoring and Follow-Up

• Drug-induced TD: Reassess with AIMS at 1-2 weeks initially, then every 3-6 months 1, 2
• PKD on treatment: Monitor attack frequency and medication side effects 3
• HD chorea: Regular assessment for depression, suicidality, and motor function 5