A Clinical Review of Huntington's Disease


Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unsteady gait often follow. It is also a basal ganglia disease causing a hyperkinetic movement disorder known as chorea. As the disease advances, uncoordinated, involuntary body movements of chorea become more apparent. Physical abilities gradually worsen until coordinated movement becomes difficult and the person is unable to talk. Mental abilities generally decline into dementia.  The specific symptoms vary somewhat between people. Symptoms usually begin between 30 and 50 years of age but can start at any age. The disease may develop earlier in each successive generation.  About eight percent of cases start before the age of 20 years, and are known as juvenile HD, which typically present with the slow movement symptoms of Parkinson's disease rather than those of chorea. Neurodegeneration is the progressive loss of structure or function of neurons, which may ultimately involve cell death.

Many neurodegenerative diseases—such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, and prion diseases—occur as a result of neurodegenerative processes. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable. Biomedical research has revealed many similarities between these diseases at the sub-cellular level, including atypical protein assemblies (like proteopathy) and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.

The nuclear symptoms and signs of Huntington's disease (HD) consist of motor, cognitive and psychiatric disturbances. Other less well-known, but prevalent and often debilitating features of HD include unintended weight loss, sleep- and circadian rhythm disturbances and autonomic nervous system dysfunction. The characteristic motor changes are involuntary, unwanted movements. Initially, the movements often occur in the distal extremities such as fingers and toes, but also in small facial muscles. For bystanders these muscle twitches are often invisible or can be explained as nervousness. In daily life, walking becomes unstable and the person can look as if he/she is slightly drunk.

Gradually the unwanted movements spread to all other muscles from distal to more proximal and axial. Choreatic movements are present all the time the patient is awake. Psychiatric symptoms are very frequently present in the early stage of the disease, often prior to the onset of motor symptoms. Cognitive decline is the other main sign of HD and can be present long before the first motor symptoms appear, but can also be very mild in far advanced stages of the disease. The diagnosis is based on the clinical symptoms and signs in a person with a parent with proven HD. Despite the fact that the pathogenesis of HD has still not been resolved and a cure is not available, many therapeutic options are available for treating symptoms and signs with a view to improving quality of life.