74. Huntington's chorea.

Huntington’s disease

• Autosomal dominant disorder characterized clinically by hyperkinesias and intellectual degradation, usually beginning in middle age.
• Results from a gene mutation (on chromosome 4) causing abnormal repetition of the DNA sequence CAG that codes for the protein huntingtin.

Pathomorphology

• Atrophy of frontal lobes and striatum, especially severe at the head of the caudate nucleus.
• Major damage of striatal medium spiny neurons, which are inhibitory neurons projecting to external pallidum
• Significantly decreased levels of GABA and N-methyl D-aspartate receptors in the striatum and cerebral cortex

Clinical Symptoms

• Onset typically between 35-40 years; juvenile form (5-10% of all cases) begins <20 years
• Typically begins with nonspecific complaints such as agitation, lack of concentration and clumsiness, difficulties in performing routine daily duties. These symptoms evolve gradually into the cardinal symptoms of the disease- hyperkinesias and cognitive deficit
• Choreic hyperkinesias are the most characteristic clinical symptom; initially presents with grimaces, periodic stretching of the lips and frequent blinking. Gradually encompass all muscles. Patient shrugs shoulders, jerks the head and moves the limbs. Gait becomes disorderly taking the form of dance. Speech disorders. Mastication, deglutition and respiratory muscles are affected. Choreic hyperkinesias intensify in emotional stress and disappear during sleep.
• Cognitive disorders have nature of subcortical dementia with retard reasoning, inability to plan and execute complex tasks, but without aphasia, agnosia and apraxia. Disease slowly evolves to grave dementia after 10-20 years.
• Emotional and affectation disorders are another symptom specific to the disease; rarely psychosis is seen.
• Juvenile form of the disease also characterise by muscular rigidity, epileptic disorders and mental disorders
• Onset typically between 35-40 years

Diagnosis

• Clinical evaluation, confirmed by genetic testing
• CT reveals internal hydrocephaly due to atrophy of the caudate nucleus
• Diagnosis is based on typical symptoms and signs plus a positive family history and is confirmed by genetic testing. Neuroimaging is done to exclude other disorders

Treatment

• Neuroleptics are included in cases of pronounced hyperkinesias, most efficient one being Haloperidol
• Agonists of N-methyl D-aspartate receptors such as Lamotrigine have been applied recently but with unconfirmed effect