Huntington Disease

Snapshot

• A 20-year-old man presents with a two-year history of motor restlessness that has progressed to uncontrollable choreiform movements. He has moderate dementia with a severe gait disturbance as well as agitation and problems with his mood. CT scan of the brain shows atrophy of the cerebral cortex and caudate nucleus.

Introduction

• An autosomal dominant disorder characterized by
  • choreiform movements
  • progressive intellectual deterioration
  • exhibits genetic anticipation
• Epidemiology
  • demographics
    • symptoms usually begin to appear in the 3rd-5th decade of life
    • both sexes are affected equally
  • incidence
    • 0.38 cases per 100,000 per year
• Genetic 
  • inheritance
    • autosomal dominant
  • mutation
    • CAG triplet repeat expansion in huntingtin gene (chromosome 4)    
      • HUNT 4 an animal, put it in a CAGe
    • demonstrates anticipation
    • mutation leads to atrophy of striatum (especially caudate nucleus) with neuronal loss and gliosis 
    • decrease in the levels of GABA and ACh 
• Pathophysiology
  • changes in neurotransmitters with Huntington’s disease
    • ↑ dopamine (in ventral tegmentum and substantia nigra) and ↓ GABA (in nucleus accumbens) and ACh (in basal nucleus of Meynert)
      • high dopamine can act on the nigro-striatal pathway to result in hyperkinesis
• high dopamine can act on the meso-limbic pathway to result in psychotic symptoms

Presentation

• Symptoms
  • progressive choreiform movements of all limbs
  • ataxic gait
  • dementia
  • depression
• grimacing

Evaluation

• MRI
• shows atrophy of caudate

Treatment

• Pharmacologic
  • no known cure
  • medications used to treat Huntington’s disease include 
    • amine-depleting agents (inhibit VMAT, involved in monoamine transport)
      • reserpine
        • ↓ release of amines (dopamine)
      • tetrabenazine 
        • ↑ degradation of amines (dopamine)
    • antipsychotics
      • haloperidol
        • dopamine receptor antagonist
        • ↓ effect of excess dopamine resulting in psychotic symptoms
        • antipsychotics 
    • muscle relaxants
• benzodiazepines 

Prognosis, Prevention, and Complications

• Death inevitable
• Suicide common cause of death