What is the diagnosis and treatment for chorea (involuntary movements)?

From the Guidelines

Chorea should be initially evaluated with genetic testing to determine the CAG repeat number for each allele, particularly to confirm or exclude Huntington's disease, as it is the most common cause of chorea in adults. Chorea is characterized by involuntary, flowing, non-stereotyped movements that often possess a writhing quality, and its differential diagnosis includes a number of genetic and neurodegenerative disorders, as well as acquired conditions such as cerebrovascular, infectious, autoimmune, metabolic, neurodegenerative, and drug-induced syndromes 1. The diagnostic workup must consider these other potential etiologies, but given the high incidence of Huntington's disease (HD) among chorea cases, with an incidence of approximately 10/100,000 and an average age of onset between 35 to 45 years, genetic testing is crucial 1.

Key points to consider in the evaluation and management of chorea include:

• Genetic testing for HD, which involves determining the CAG repeat number for each allele, is commercially available and the diagnostic test of choice 1.
• Patients with suspected HD should undergo genetic counseling and testing to exclude or confirm HD in concert with initial imaging, as imaging may be normal early on in the disease course 1.
• Treatment depends on the underlying cause but may include dopamine blockers or antipsychotics to reduce abnormal movements.
• For cases where the cause is not immediately clear, a comprehensive approach including blood tests, brain imaging, and sometimes genetic testing is necessary to identify reversible causes and provide appropriate management.

Given the complexity and variability of chorea's presentation, a thorough diagnostic workup, including genetic testing for HD, is essential for guiding treatment and improving patient outcomes, as the prognosis and management can significantly differ based on the underlying cause, with HD being a fatal neurodegenerative disorder characterized by progressive behavioral symptoms, choreoathetosis and/or rigidity, and cognitive dysfunction 1.

From the FDA Drug Label

The efficacy of tetrabenazine tablets as a treatment for the chorea of Huntington’s disease was established primarily in a randomized, double-blind, placebo-controlled multi-center trial (Study 1) conducted in ambulatory patients with a diagnosis of HD. The primary efficacy endpoint was the Total Chorea Score, an item of the Unified Huntington’s Disease Rating Scale (UHDRS). As shown in Figure 1, Total Chorea Scores for patients in the drug group declined by an estimated 5.0 units during maintenance therapy (average of Week 9 and Week 12 scores versus baseline), compared to an estimated 1.5 units in the placebo group. The treatment effect of 3.5 units was statistically significant.

Tetrabenazine is effective in treating chorea associated with Huntington’s disease, as demonstrated by a statistically significant reduction in Total Chorea Score compared to placebo 2.

• The treatment effect was 3.5 units, which is statistically significant.
• Approximately 50% of patients treated with tetrabenazine achieved a 6-point or greater improvement in Total Chorea Score, compared to about 7% of placebo patients.

From the Research

Definition and Diagnosis of Chorea

• Chorea is a hyperkinetic disorder characterized by abnormal, involuntary, continuous, random movements 3, 4, 5, 6
• The diagnosis of chorea can be challenging, especially if it occurs during the treatment of neuropsychiatric conditions, and it is difficult to distinguish between medication side effects and the development of a neurodegenerative disease 4
• The first step in the approach to a patient with chorea is accurately defining the phenomenology, and once it has been determined that the patient has chorea, the investigation into determining an etiology can begin 3

Etiology of Chorea

• Chorea can be acquired or hereditary, and key historical and clinical features can aid in determining the etiology 3
• Chorea can be caused by a large variety of diseases, including neurodegenerative diseases, metabolic diseases, and autoimmune diseases, or can be secondary to structural changes 4
• In children, chorea may present at all stages of life, and the main causes include Sydenham chorea, dyskinetic cerebral palsy, anti-NMDAR receptor encephalitis, and mutations in several genes 6

Treatment of Chorea

• Treatments for most causes of chorea are purely symptomatic, although it is essential to recognize causes that are reversible or have disease-modifying interventions 3
• Oral tetrabenazine is currently the only drug approved by the US FDA for the treatment of chorea associated with Huntington's disease (HD) 7
• New-generation presynaptic dopamine-depleting agents provide more options for symptomatic treatment of chorea with fewer adverse effects 5
• Deep brain stimulation has been performed in several choreic disorders, but features other than chorea and the neurodegenerative nature should be taken into consideration 5