Advancements in surgical treatments for Huntington disease: From pallidotomy to experimental therapies.

Abstract

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized by choreic movements, behavioral changes, and cognitive impairment. The pathogenesis of this process is a consequence of mutant protein toxicity in striatal and cortical neurons. Thus far, neurosurgical management of HD has largely been limited to symptomatic relief of motor symptoms using ablative and stimulation techniques. These interventions, however, do not modify the progressive course of the disease. More recently, disease-modifying experimental therapeutic strategies have emerged targeting intrastriatal infusion of neurotrophic factors, cell transplantation, HTT gene silencing, and delivery of intrabodies. Herein we review therapies requiring neurosurgical intervention, including those targeting symptom management and more recent disease-modifying agents, with a focus on safety, efficacy, and surgical considerations.