What is the management and treatment of chorea?

Management and Treatment of Chorea

The management of chorea requires first identifying and treating the underlying cause when possible, followed by symptomatic pharmacological treatment with deutetrabenazine (or tetrabenazine) as first-line therapy for Huntington's disease-associated chorea, with supportive therapies including speech and occupational therapy for functional impairment. 1, 2, 3

Initial Diagnostic Evaluation

The diagnostic workup must identify the specific etiology before initiating treatment:

• Brain MRI without contrast is the optimal imaging modality to identify structural causes, assess neurodegenerative patterns, and detect basal ganglia lesions, though it may be normal early in disease course 1, 4
• Genetic testing for CAG repeat expansions in the huntingtin gene is definitive for Huntington's disease (the most common cause of adult-onset chorea), with ≥40 repeats confirming diagnosis with 100% specificity 2, 4
• Essential blood tests must exclude secondary metabolic causes: thyroid function, serum calcium, phosphorus, parathyroid hormone, blood glucose, and serum ceruloplasmin 4
• Evaluate for cerebrovascular disease, infectious etiologies, autoimmune conditions, and drug-induced syndromes 1, 2

Treatment Algorithm by Etiology

Autoimmune Chorea

For antiphospholipid antibody-associated chorea:

• Initiate antiplatelet and/or anticoagulation therapy in addition to symptomatic treatment 1

For systemic lupus erythematosus or other autoimmune conditions:

• Use glucocorticoids alone or combined with immunosuppressive therapy (azathioprine, cyclophosphamide) 1
• For refractory cases with generalized autoimmune activity, administer pulse intravenous methylprednisolone with intravenous cyclophosphamide 1

Metabolic Causes

Correct the underlying metabolic disturbance:

• Treat thyroid dysfunction, calcium-phosphate abnormalities, or glucose disturbances 4

Drug-Induced Chorea

Discontinue the offending agent and monitor patients on long-term neuroleptics periodically to detect tardive dyskinesia development 4

Huntington's Disease and Heredodegenerative Choreas

Pharmacological Management:

Deutetrabenazine (AUSTEDO/AUSTEDO XR) is FDA-approved for chorea associated with Huntington's disease 3:

• Starting dose: 6 mg twice daily (12 mg/day) for AUSTEDO, or 12 mg once daily for AUSTEDO XR 3
• Titration: Increase by 6 mg per day at weekly intervals based on chorea reduction and tolerability 3
• Maximum dose: 48 mg per day (36 mg per day for poor CYP2D6 metabolizers or patients on strong CYP2D6 inhibitors) 3
• Administration: AUSTEDO must be taken with food; AUSTEDO XR can be taken with or without food; swallow tablets whole 3
• Evidence strength: High-quality evidence demonstrates statistically significant reduction in Total Chorea Score compared to placebo 2

Critical Safety Considerations for Deutetrabenazine:

⚠️ BOXED WARNING: Increases risk of depression and suicidality in Huntington's disease patients 3:

• Contraindicated in patients who are suicidal or have untreated/inadequately treated depression 3
• Monitor patients for emergence or worsening of depression, suicidality, or unusual behavioral changes 3
• Exercise extreme caution in patients with history of depression or prior suicide attempts 3

Additional warnings:

• Avoid in patients with congenital long QT syndrome or arrhythmias with prolonged QT interval 3
• Discontinue if neuroleptic malignant syndrome develops 3
• May cause akathisia, agitation, restlessness, and parkinsonism—reduce dose or discontinue if these occur 3
• Causes sedation/somnolence that may impair driving or operating machinery 3
• Contraindicated in hepatic impairment and with concurrent use of reserpine, MAOIs, tetrabenazine, or valbenazine 3

Alternative pharmacological options (when deutetrabenazine is contraindicated or ineffective):

• Amantadine may be used for heredodegenerative choreas 5
• Benzodiazepines, neuroleptics, and antiepileptic medications for nonspecific symptom control 5

Comprehensive Neuropsychiatric Management for Huntington's Disease

The American Academy of Neurology recommends aggressive treatment of psychiatric manifestations, as they significantly impact quality of life and are major drivers of emergency department visits, hospital admissions, and institutionalization—often more than motor symptoms 2:

• SSRIs or low-dose amitriptyline should be considered for mood symptoms 2
• Cognitive Behavioral Therapy strategies may address maladaptive beliefs and avoidance behaviors 2
• Psychiatric consultation is warranted given that neuropsychiatric dysfunction increases morbidity and care burden 2

Supportive Therapies

Speech therapy is beneficial for patients with orofacial chorea affecting speech and swallowing (moderate strength of evidence) 1, 2, 4

Occupational therapy assists with activities of daily living impacted by choreiform movements (moderate strength of evidence) 1, 2, 4

Interdisciplinary Team Approach

A comprehensive interdisciplinary team is essential for managing the triad of motor dysfunction, cognitive decline, and psychiatric disturbances 2:

• Include dementia subspecialist, movement disorder specialist, neuropsychologist, psychiatrist, speech therapist, and occupational therapist 2
• Psychiatric symptoms must not be neglected as they drive institutionalization more than motor symptoms 2

Cognitive Monitoring

Comprehensive neuropsychological testing should focus on specific vulnerable cognitive domains 2:

• Perform at baseline, then repeat at 1-year, 2-year, and 4-5 year intervals 2
• Adjust compensatory strategies and support services to address progressive deterioration in attention, executive function, and visuospatial abilities 2

Critical Pitfalls to Avoid

• Never initiate deutetrabenazine without screening for depression and suicidality in Huntington's disease patients—this is a boxed warning with serious consequences 3
• Do not miss treatable causes: vitamin B12 deficiency, autoimmune disorders (Sydenham chorea), and metabolic disturbances require specific interventions beyond symptomatic treatment 5
• Distinguish drug-induced tardive dyskinesia from neurodegenerative disease in patients on long-term neuroleptics—this requires careful medication history 6
• Genetic counseling is mandatory before testing for Huntington's disease given autosomal dominant inheritance with complete penetrance 2