Neurosurgery notes/Other specialities/Neurology/Post column dysfunction/Friedreich’s ataxia

Friedreich’s ataxia

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Post column dysfunction

Numbers

  • Incidence 2 per 100,000 per year;
  • Prevalence 1 in 30,000;
  • Rare in Black/Asian populations.
  • No recognised gender predilection.
  • Typically present in childhood to adolescence
  • Shows genetic “anticipation”
    • Higher number of trinucleotide repeats (>500) are thought to present at an earlier age and with more severe symptoms
  • The commonest hereditary ataxia (50% cases)

Genetics

  • Autosomal recessive inheritance
  • The condition results from an expansion of an unstable GAA trinucleotide repeat in the FXN gene located on chromosome 9q.
  • FXN gene → encodes frataxin, a protein that has multiple important roles in relation to iron in various tissues of the body, but most prominently the brain, heart and pancreas → spinocerebellar degeneration

Location

  • Optic atrophy
  • Cerebellar
    • Vermis
    • Dentate nucleus
  • Whole spinal cord
    • Corticospinal tracts
    • Spinocerebellar tracts
    • Posterior column

Pathology

  • Macroscopic
    • Brain usually appears normal, but possibly atrophy of cerebellar vermis and dentate nucleus;
    • Diffuse atrophy of spinal cord, particularly dorsal and lateral columns.
  • Microscopic
      • Degeneration (pallor) of the posterior columns and lateral corticospinal tracts as shown in this lumbar level.
      notion image

Investigation

  • EMG: sensory neuropathy
  • MRI
    • In the brain and spinal cord
      • May show thinning (reduction in AP diameter) of the cervical cord
      • Cerebral and cerebellar atrophy may also be evident
    • DWI
      • To quantify the extent of neurodegeneration in Friedreich ataxia, that appears more extended than previously reported, showing a microstructural involvement of structures such as optic radiation and middle cerebellar peduncles

Presentation

  • The typical age of onset is 10-15 years old with gait ataxia and scoliosis followed by progressive loss of neuromuscular function, with the patient wheelchair-bound 10-20 years after symptom onset.
  • Neurological features
    • Cerebellar ataxia
    • Optic atrophy
    • Spinocerebellar tract degeneration
    • Reflex
      • Loss of deep tendon reflex as loss of sensory ganglia
      • Up going plantars due to demyelination of corticospinal tracts
  • Systemic
    • Hypertrophic obstructive cardiomyopathy (90%, most common cause of death)
    • Diabetes mellitus (10-20%)
    • High-arched palate
    • Scoliosis

Prognosis

  • Loss of ambulation within 10 yrs after onset years
  • Life expectancy 30-40 yrs after onset
  • Coenzyme Q and vitamin E may slow disease progression
    • Ataxia with isolated vitamin E deficiency

Differential diagnosis

  • Other hereditary ataxias,
  • Hereditary spastic paraplegia,
  • Ataxia telangiectasia
  • Acquired ataxias.

Trinucleotide repeat expansion diseases

  • Huntington disease, myotonic dystrophy, fragile X syndrome, and Friedreich ataxia.
  • May show genetic anticipation (disease severity ⬆️ and age of onset ⬇️ in successive generations).
  • Try (trinucleotide) hunting for my fragile cage-free eggs (X).
      • Disease
      Trinucleotide repeat
      Mode of inheritance
      Mnemonic
      Huntington disease
      (CAG)ₙ
      AD
      Caudate has ↓ ACh and GABA
      Myotonic dystrophy
      (CTG)ₙ
      AD
      Cataracts, Toupee (early balding in men), Gonadal atrophy
      Fragile X syndrome
      (CGG)ₙ
      XD
      Chin (protruding), Giant Gonads
      Friedreich ataxia
      (GAA)ₙ
      AR
      Ataxic GAAit