From the Guidelines
Sporadic Huntington's disease does not actually exist, as Huntington's disease is always genetic and inherited in an autosomal dominant pattern. Huntington's disease is a neurodegenerative disease of mid-life onset that produces choreic movements and cognitive decline, often accompanied by psychiatric changes, affecting ~3–5 out of 100,000 individuals 1. The symptoms result from the selective loss of neurons, most notably in the caudate nucleus and putamen, and there is currently no effective treatment. What might appear as "sporadic" cases are typically situations where the family history was unknown, the parent died before showing symptoms, or there was a new mutation (extremely rare).
The disease causes progressive neurodegeneration, leading to movement disorders, cognitive decline, and psychiatric symptoms. Symptoms typically begin between ages 30-50, though juvenile onset can occur, presenting with rigidity, spasticity, and intellectual decline before the age of 20 years 1. There is no cure for Huntington's disease, but medications can help manage symptoms. Treatment includes tetrabenazine or deutetrabenazine for chorea (involuntary movements), antipsychotics for behavioral issues, antidepressants for mood symptoms, and physical therapy to maintain function.
- Key points to consider in managing Huntington's disease include:
- Genetic testing is available for those at risk, but should be accompanied by proper counseling due to the significant psychological implications of a positive result.
- The prevalence of HD exceeds 15 per 100,000 in some populations, mostly of western European origin 1.
- Juvenile-onset HD occurs in approximately 5% of affected patients, and is a rapidly progressive variant 1.
From the Research
Definition and Characteristics of Huntington's Disease
- Huntington's disease (HD) is a neurodegenerative disorder characterized by motor impairments, including chorea, along with behavioral, psychiatric, and cognitive symptoms 2, 3.
- HD is typically diagnosed based on clinical findings in the setting of a family history and may be confirmed with genetic testing 3.
Treatment Options for Chorea in Huntington's Disease
- Tetrabenazine is a dopamine-depleting agent that may be one of the more effective agents for reducing chorea, although it has a risk of potentially serious adverse effects 3, 4.
- Tetrabenazine was the first US Food and Drug Administration (FDA)-approved treatment for chorea related to HD 2, 3, 4.
- Other substances, such as haloperidol, fluphenazine, and olanzapine, have been considered "possibly useful" for the treatment of chorea in HD 5.
- Newer antipsychotic agents, such as olanzapine and aripiprazole, may have adequate efficacy with a more favorable adverse-effect profile than older antipsychotic agents for treating chorea and psychosis 3.
Efficacy and Safety of Tetrabenazine
- Tetrabenazine has been shown to be significantly more efficacious than placebo at improving adjusted mean Unified HD Rating Scale (UHDRS) total maximum chorea scores 4.
- The antichorea efficacy of tetrabenazine was maintained in an 80-week extension study, with the adjusted mean UHDRS total maximum chorea score significantly reduced from baseline 4.
- Treatment-emergent adverse events in the tetrabenazine group mainly occurred during the dosage-titration phase, and most were mild to moderate and manageable with dosage adjustments or discontinuation of study drug 4.
Current State of Research and Management
- There is a need for more high-quality clinical trials to develop robust evidence-based guidelines for the symptomatic management of HD 6.
- A comprehensive and systematic approach to the management of HD is necessary, taking into account the complexity of the disease and the variety of symptoms that can occur 6.