What is the best course of treatment to manage chorea, mood disturbances, and cognitive symptoms in a patient with Huntington's disease?

Management of Chorea, Mood Disturbances, and Cognitive Symptoms in Huntington's Disease

For this elderly patient with confirmed Huntington's disease, tetrabenazine is the evidence-based first-line treatment for chorea, while mood disturbances require psychiatric management with SSRIs or antipsychotics, and cognitive symptoms should be monitored through serial neuropsychological testing rather than treated pharmacologically, as no disease-modifying therapies exist. 1

Chorea Management

Tetrabenazine represents the highest-quality evidence for chorea reduction in HD, demonstrating statistically significant improvement in Total Chorea Score compared to placebo. 1 This should be the primary pharmacological intervention for this patient's moderate generalized chorea.

Non-Pharmacological Interventions for Chorea

• Speech therapy is beneficial for orofacial chorea affecting speech and swallowing (moderate strength of evidence), which is particularly relevant given the patient's movement abnormalities. 1
• Occupational therapy assists with activities of daily living impacted by choreiform movements (moderate strength of evidence), helping maintain functional independence. 1
• Continue the current exercise regimen, as the provider notes significant improvement with this intervention—exercise represents a safe, evidence-based adjunctive therapy. 1

Mood Disturbance Management

The psychiatric manifestations in HD require aggressive treatment as they significantly impact quality of life and are major drivers of emergency department visits, hospital admissions, and transfer to residential care. 2

Treatment Approach

• SSRIs or low-dose amitriptyline should be considered for mood symptoms, as these have demonstrated benefit in functional neuropsychiatric disorders. 2
• Cognitive Behavioral Therapy (CBT) strategies may be useful for addressing maladaptive beliefs, self-reported sensations, and avoidance behaviors that commonly accompany mood disturbances in HD. 2
• Psychiatric consultation is warranted given that neuropsychiatric dysfunction increases morbidity, care burden, and resource utilization in dementia syndromes. 2

Cognitive Symptom Management

Critical Caveat About Treatment Expectations

There is currently no effective disease-modifying treatment for HD, and all available therapies are purely symptomatic. 3 This fundamentally shapes the approach to cognitive decline.

Neuropsychological Testing Strategy

The MOCA score of 27/30 suggests mild cognitive impairment, but comprehensive neuropsychological testing should focus on specific cognitive domains vulnerable in HD: 4, 5

• Attention and processing speed (Symbol Digit Modalities Test)
• Working memory (Digit Span Backwards, Block Span)
• Executive functions (Trail Making Test-B, Stroop Test, Conditional Associative Learning)
• Verbal learning and delayed recall (Hopkins Verbal Learning Test)
• Language (Boston Naming Test)
• Visuospatial perception (Object and Space Perception tests)

Testing Frequency and Interpretation

• Serial assessments over 2.5-year intervals effectively track disease progression in manifest HD, particularly for attention, executive function, and visuospatial tasks. 4
• The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) can detect cognitive deficits in manifest HD but shows limited utility in premanifest disease. 6 Given this patient has manifest disease with moderate chorea, RBANS may be appropriate for serial monitoring.
• Performance-rating methods (having patients rate their own performance on a bell curve) can identify anosognosia, which is common in HD and affects treatment adherence. 7

Monitoring Recommendations

Testing should occur at baseline and repeated at 1-year, 2-year, and 4-5 year intervals to track emerging cognitive deficits, adapting the assessment battery as higher-order cognitive skills evolve. 2 This timing allows for:

• Detection of progressive deterioration in attention, executive function, and visuospatial abilities
• Adjustment of compensatory strategies and support services
• Realistic counseling about disease trajectory (15-20 year course from onset to death) 1

Integrated Care Approach

A comprehensive interdisciplinary team approach is essential for managing the devastating triad of motor dysfunction, cognitive decline, and psychiatric disturbances. 2, 3 This should include:

• Dementia subspecialist (behavioral neurology or neuropsychiatry) for ongoing management 2
• Movement disorder specialist for chorea optimization 2
• Neuropsychologist for serial cognitive assessment and compensatory strategy development 5
• Psychiatrist for mood disturbance management 2
• Speech and occupational therapists for functional interventions 1

Common Pitfalls to Avoid

• Do not rely solely on brief cognitive screens (like MOCA) to characterize the cognitive profile—comprehensive domain-specific testing is required to guide interventions. 4, 5
• Do not assume lack of subjective cognitive complaints means absence of impairment—anosognosia is common in HD, and patients often overestimate their performance. 7
• Do not pursue disease-modifying therapies—none exist, and treatment expectations must be realistic and focused on symptomatic management. 3
• Do not neglect psychiatric symptoms—these are major drivers of morbidity and institutionalization, often more so than motor symptoms. 2