Huntington's Disease

Question 1

What is huntington’s disease?

Answer 1

• Autosomal dominant inherited disease.
• Expansion of an unstable CAG trinucleotide repeat producing a polyglutamine tract in the huntingtin (htt) protein
• Progressive chorea and cognitive impairments beginning in adulthood
• No cure, only to alleviate some symptoms

Question 2

HUNTINGTON’S DISEASE SYMPTOMS

Answer 2

Motor Symptoms
• Involuntary jerking or writhing movements (chorea)
• Involuntary, sustained contracture of muscles (dystonia)

Cognitive Symptoms
• Difficulty planning & organizing
• Slow processing thoughts, finding words
• Slow learning, etc - eventually declines into dementia

Psychiatric Symptoms
• Depression
• Social withdrawal
• Loss of interest, & others

Question 3

Huntington Disease’s Pathophysiology (Basal Ganglia)

Answer 3

D2 receptor neurons function loss → loss of inhibition of GPe → increased activity at thalamus

Thalamus increases output to certain regions of the cerebral cortex: may lead to the disorganized, excessive movement patterns or chorea

As disease progresses, damage to other pathways and dopamine receptors cause decreased stimulation to cortex and thus rigid bradykinetic features

Question 4

Haloperidol

Answer 4

MOA: Dopamine receptor blockers

USE: suppress movements

Question 5

Tetrabenazine; Deutetrabenazine

Answer 5

MOA: Dopamine depletion; VMAT2 inhibitors

Tetrabenazine (Xenazine®, reserpine-like) – suppresses involuntary movements

Deutetrabenazine (Austedo®, longer acting)

Question 6

Clonazepam

Answer 6

MOA: Anti-seizure agent; Benzodiazepines

USE: suppress chorea, dystonia & muscle rigidity

Question 7

Diazepam

Answer 7

MOA: Benzodiazepines

USE: Muscle-relaxant