Early Warnings: Neuropsychiatrie Manifestations of Huntington Disease.

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Date: Mar. 2021
From: Psychiatric Times(Vol. 38, Issue 3)
Publisher: Intellisphere, LLC
Document Type: Article
Length: 2,394 words
Lexile Measure: 1640L

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First recognized in 1872 by George Huntington, MD, Huntington disease (HD) is a neurodegenerative disorder that is characterized by progressive decline in motor functioning, cognition, and behaviors. (1) In North America, approximately 30,000 individuals have this illness, and an additional 150,000 individuals are at risk for developing it. (2) HD tends to occur more commonly among individuals of European descent, with a prevalence rate of 10 to 15 per 100,000. The incidence of HD is approximately 4.7 to 6.9 new cases per million per year in the Western population. (3) The median age of diagnosis for HD is approximately 40 years. (2) It is rare for HD to be diagnosed among individuals 20 years or younger, or among individuals 65 years or older. HD affects men and women equally.

Neuropathology of HD

The neuropathological hallmark among individuals with HD is the progressive atrophy of caudate nucleus and putamen due to neuronal loss. (4) The clinical features of HD occur due to the loss of medium-sized projection spiny neurons in the dorsal striatum, which express the dopaminergic type 1 or 2 receptors. As the illness progresses, global neuronal loss and generalized cerebral atrophy occur, and the overall brain weight can decrease by up to 40%. These medium-sized projection spiny neurons use the inhibitory transmitter [gamma]-aminobutyric acid and either dynorphin, enkephalin, or substance P as cotransmitters. It is thought that the loss of inhibitory input from the medium-sized spiny neurons, which usually exert an inhibitory effect, is the reason for the uncontrolled movements characteristic of individuals with HD. Individuals with HD also have intranuclear inclusions and protein aggregates in the dystrophic neurons of both the striatum and cortex. (5) Additionally, the number of cortical inclusions correlates directly with the length of the CAG repeat expansion and the age of onset of the illness. Furthermore, these intranuclear inclusions tend to appear before the loss in brain weight. The loss of brain weight precedes the loss of body weight and the onset of neurological symptoms.

Clinical Features of HD

There is significant variability in the type, timing, and progression of clinical symptoms. (4) The clinical course can be divided into premanifest and manifest periods. (6) The premanifest period can be further divided into presymptomatic and prodromal periods. During the presymptomatic period, which is approximately 10 to 15 years before the onset of symptoms, individuals are not clinically distinguishable from those individuals without HD. During the prodromal period, individuals present with subtle motor, cognitive, and behavioral symptoms. Once individuals enter the manifest period with prominent motor, cognitive, and behavioral symptoms, the symptoms continue to progress and worsen, and the illness is ultimately fatal. The median survival time from the onset of motor symptoms is approximately 18 years. (3)

The symptoms of HD can be divided into 2 broad categories: progressive motor symptoms and neuropsychiatric symptoms. (2) A diagnosis of HD is made only when the characteristic motor features manifest, even among individuals who are gene positive.

The motor symptoms of HD can be divided into...

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Gale Document Number: GALE|A676445538