Huntington's Disease: Clinical Presentation and Treatment

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Abstract

Huntington's disease (HD) is a devastating inherited neurodegenerative disease characterized primarily by progressive motor, cognitive, and psychiatric symptoms. It is caused by autosomal dominant inheritance of an expanded CAG repeat within the Huntington's gene on chromosome 4. In this chapter, we characterize the typical and variant motor phenotypes of the disease and then proceed to describe the cognitive and psychiatric profile. We then give an overview of a suggested multidisciplinary approach to the management of HD, emphasizing the fact that it is a disease which impacts on entire families rather than affecting individuals in isolation. We then describe the pharmacological and nonpharmacological options available for management of specific symptoms.

Section snippets

The Motor Disorder

The motor symptoms of HD can be divided into two categories: added involuntary movements such as chorea, and impaired voluntary movements, which cause limb incoordination and impaired hand function. These symptoms are worsened by loss of postural reflexes. The pattern of symptoms tends to change over time in typical adult-onset HD: typically chorea dominates in early disease, but then tends to decline as the disease progresses, with dystonia, rigidity, and bradykinesia then becoming more marked

The Atypical Phenotype, including Juvenile Huntington's Disease

Although the majority of people with HD have the typical hyperkinetic phenotype with symptom onset in adulthood, variant phenotypes exist. Juvenile Huntington's Disease (JHD) is HD which manifests in people before they are 20 years old, and is typically associated with a CAG repeat length of greater than 50. Andrew et al. (1993), for example, found that CAG repeat length ranged from 46 to 121 with a median repeat length of 56.5 in a sample of 20 juvenile HD patients. Juvenile HD causes many of

Advanced Disease and End of Life Issues

Patients with advanced HD require significant support in all activities of daily living, usually because of a combination of motor, cognitive, and behavioral symptoms. Communication may be severely limited and muteness is common, often resulting in agitation and frustration due to inability to speak. HD does not cause a global dementia, however, and the ability to recognize and interact with people is frequently relatively well preserved.

As HD progresses, it often becomes increasingly difficult

Looking to the Future: Research into New Treatments for Huntington's Disease

At the time of writing, there is a major drive to find disease-modifying and new symptomatic treatments for HD; many new developments have been made in recent years, and phase 3 trials are ongoing (Novak and Tabrizi, 2010). Much progress has also been made in developing and evaluating sensitive biomarkers which will help to measure the effects of disease modifying therapies in future clinical trials, particularly in the premanifest and early stages of the disease (Paulsen et al., 2008, Tabrizi

Conclusions

HD is a multisystem disease that is characterized primarily by progressive motor, cognitive, and psychiatric symptoms. Management of the disease is challenging, but there are many options which can ameliorate symptoms and improve quality of life; these are best provided in a collaborative multidisciplinary setting. Extensive research is currently being carried out with the aim of developing treatments that will delay or halt the disease process in the premanifest phase.

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