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Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)

Summary

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  • ARSACS is a rare neurodegenerative disorder characterised by early-onset cerebellar ataxia, spasticity, and peripheral neuropathy
  • Caused by mutations in the SACS gene, leading to progressive cerebellar and spinal cord degeneration
  • Imaging reveals cerebellar atrophy, particularly of the superior vermis, and linear hypointensities in the pons on T2-weighted MRI1

Pathophysiology

  • Autosomal recessive inheritance pattern
  • Mutations in the SACS gene on chromosome 13q12.12
  • SACS gene encodes sacsin protein, involved in protein folding and quality control
  • Loss of sacsin function leads to:
    • Mitochondrial dysfunction
    • Accumulation of neurofilaments
    • Progressive neurodegeneration, particularly in the cerebellum and spinal cord

Demographics

  • Originally described in the Charlevoix-Saguenay region of Quebec, Canada
  • Prevalence in this region: 1 in 1,932 individuals
  • Worldwide prevalence: rare, with cases reported in various populations
  • Typical age of onset: early childhood (12-18 months)
  • Equal gender distribution

Diagnosis

  • Clinical presentation:
    • Early-onset ataxia (unsteady gait)
    • Progressive spasticity
    • Peripheral neuropathy
    • Dysarthria
    • Nystagmus
  • Genetic testing:
    • Identification of biallelic pathogenic variants in the SACS gene
  • Electromyography and nerve conduction studies:
    • Evidence of axonal-demyelinating sensorimotor neuropathy

Imaging

  • MRI findings:
    • Cerebellar atrophy, particularly of the superior vermis
    • Linear hypointensities in the pons on T2-weighted images ("Tiger stripe" appearance)
    • Cervical spinal cord atrophy
    • Cerebral cortical atrophy (in advanced cases)
  • Spinal cord imaging:
    • Thinning of the cervical and thoracic spinal cord
  • Optical Coherence Tomography (OCT):
    • Thickening of the retinal nerve fibre layer

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  • Subtle symmetrical tigroid T2-hypointensity within the pons and severe superior cerebellar vermian atrophy.

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  • 35-year-old patient presented with ataxia.
  • MRI showed atrophy of the superior vermis, hyperintensity in the middle cerebellar peduncles and, most characteristically, tigroid T2-hypointensity within the pons.

Treatment

  • No curative treatment; management is supportive (anti-spasticity agents, physiotherapy, orthoses)
  • Genetic counselling for affected families

Differential diagnosis

Imaging differential Differentiating feature
Friedreich ataxia Cervical cord and dorsal-column atrophy without superior vermian atrophy or pontine stripes
Multiple system atrophy, cerebellar type "Hot cross bun" pontine T2 hyperintensity rather than linear T2 hypointensities
FXTAS Symmetric middle cerebellar peduncle T2 hyperintensity without the pontine tigroid hypointensity
Spinocerebellar ataxia Olivopontocerebellar atrophy without pontine tigroid hypointensity or superior vermian predominance

  1. Richter et al. Clinical and molecular genetic studies on autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). 1993. Advances in neurology - Open in new tab. ↩