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Huntington's Disease

Summary

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  • Autosomal dominant neurodegenerative disorder characterised by progressive motor, cognitive, and psychiatric symptoms
  • Caused by CAG trinucleotide repeat expansion in the huntingtin (HTT) gene
  • Imaging shows characteristic striatal atrophy and white matter changes1

Pathophysiology

  • Mutation in HTT gene on chromosome 4p16.3
  • CAG repeat expansion leads to production of mutant huntingtin protein
  • Accumulation of mutant protein causes neuronal dysfunction and death
  • Preferential degeneration of medium spiny neurons in the striatum
  • Widespread cortical and subcortical atrophy as disease progresses

Demographics

  • Prevalence: 5-10 per 100,000 in Western populations
  • Age of onset: typically 30-50 years, but can occur at any age
  • Juvenile-onset HD (< 20 years) accounts for 5-10% of cases
  • No gender predilection
  • Higher prevalence in populations of European descent

Diagnosis

  • Clinical features:
    • Motor symptoms: chorea, dystonia, bradykinesia
    • Cognitive decline: executive dysfunction, memory impairment
    • Psychiatric symptoms: depression, anxiety, irritability
  • Genetic testing: CAG repeat expansion ≥ 36 repeats is diagnostic
  • Family history: often positive due to autosomal dominant inheritance
  • Neurological examination and cognitive assessment

Imaging

  • MRI findings:
    • Striatal atrophy (caudate and putamen)
    • Cortical atrophy, particularly in frontal and temporal lobes
    • White matter changes, including reduced fractional anisotropy on DTI
  • PET/SPECT:
    • Reduced striatal glucose metabolism (FDG-PET)
    • Decreased dopamine D2 receptor binding (raclopride PET)
  • Functional MRI:
    • Altered activation patterns in task-based and resting-state studies
  • Quantitative imaging:
    • Volumetric analysis to track disease progression
    • MR spectroscopy shows reduced N-acetylaspartate in the striatum

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  • A 50-year-old male presented with increasing clumsiness, jerky arm movements and mood swings.
  • MRI showed relatively mild caudate head atrophy and putaminal T2-hyperintensity.

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  • 50-year-old male with increasing clumsiness and jerky arm movements.
  • MRI showed atrophy and hyperintensity of the corpora striata on both sides.
  • A 55-year-old patient with a history of depression presented after worsening incoordination.
  • Imaging showed marked atrophy of the caudate head. There was less pronounced atrophy of the T2-hyperintense putamina.

Treatment

  • No cure; symptomatic (tetrabenazine for chorea). The imaging hallmark is caudate head atrophy, widening the frontal horns ("boxcar" ventricles)

Differential diagnosis

Differential Diagnosis Distinguishing Feature
Wilson's disease Presence of Kayser-Fleischer rings; abnormal copper metabolism
Spinocerebellar ataxia Prominent cerebellar signs; different genetic mutation
Neuroacanthocytosis Presence of acanthocytes on blood smear; orofacial dyskinesia
Frontotemporal lobar degeneration More frontal or temporal lobar atrophy

  1. F Walker. Huntington's disease. 2007. Lancet (London, England) - Open in new tab. ↩