Skip to content

Multisystem Atrophy - Cerebellar Type (MSA-C)

Summary

fleuron

  • MSA-C is a neurodegenerative disorder characterised by cerebellar ataxia, autonomic dysfunction, and parkinsonian features
  • Pathologically, it involves α-synuclein accumulation in oligodendrocytes and neuronal loss
  • Imaging shows cerebellar and pontine atrophy with characteristic 'hot cross bun' sign on MRI

Pathophysiology

  • Accumulation of α-synuclein in oligodendrocytes forming glial cytoplasmic inclusions (GCIs)
  • Neuronal loss and gliosis in multiple brain regions, particularly:
    • Cerebellum
    • Pons
    • Basal ganglia
    • Autonomic nuclei
  • Degeneration of olivopontocerebellar pathways
  • Mitochondrial dysfunction and oxidative stress contribute to neuronal death

Demographics

  • Typical onset between 50-60 years of age
  • Slightly more common in men (1.3:1 male-to-female ratio)
  • Estimated prevalence of 3-4 per 100,000 population
  • MSA-C subtype more common in Asian populations compared to Western countries

Diagnosis

  • Based on clinical presentation and neuroimaging findings
  • Key clinical features:
    • Progressive cerebellar ataxia
    • Autonomic dysfunction (e.g., orthostatic hypotension, urinary incontinence)
    • Parkinsonian features (less prominent than in MSA-P subtype)
  • Diagnostic criteria:
    • Probable MSA-C: cerebellar syndrome, autonomic failure, and additional features
    • Possible MSA-C: cerebellar syndrome and poorly levodopa-responsive parkinsonism

Imaging

  • MRI findings:
    • Cerebellar atrophy, particularly in the vermis
    • Pontine atrophy
    • 'Hot cross bun' sign in pons (T2-weighted images)
    • Middle cerebellar peduncle hyperintensities
    • Putaminal rim sign (T2 hypointensity of lateral putamen)
  • PET/SPECT:
    • Decreased glucose metabolism in cerebellum and brainstem
    • Reduced dopamine transporter binding in striatum

panels-1

  • 70 year old with marked pontine and middle cerebellar peduncle atrophy.
  • Cruciform T2-hyperintensity in the pons and T2-hyperintensity in the right middle cerebellar peduncle.

panels-1

  • 60-year-old patient presented with ataxia and dysarthria.
  • MRI showed marked pontine and moderate cerebellar volume loss. Cruciform high signal in the pons represented the hot cross bun sign.

panels-1

  • A 70-year-old patient presented with ataxia causing frequent falls.
  • MRI showed severe atrophy affecting the pons, middle cerebellar peduncles, and cerebellar hemispheres.
  • The hot cross bun sign was present on FLAIR.
  • DaTSCAN showed normal availability of the presynaptic dopamine transporters - as might be expected in MSA-P.

Treatment

  • No curative treatment available; management focuses on symptomatic relief
  • Pharmacological interventions:
    • Levodopa for parkinsonian symptoms (often with limited response)
    • Fludrocortisone or midodrine for orthostatic hypotension
    • Anticholinergics for urinary symptoms
  • Non-pharmacological approaches:
    • Physiotherapy and occupational therapy for ataxia and mobility
    • Speech therapy for dysarthria
    • Dietary modifications and gastrostomy for dysphagia
  • Supportive care and management of complications (e.g., aspiration pneumonia, falls)
  • Ongoing research into neuroprotective strategies and α-synuclein-targeted therapies

Differential diagnosis

Differential Diagnosis Distinguishing Feature
Spinocerebellar ataxia Variable patterns of cerebellar and brainstem atrophy depending on type; no "hot cross bun" sign; no putaminal rim
Multiple sclerosis Disseminated ovoid white matter lesions; Dawson's fingers on sagittal FLAIR; no hot cross bun sign
Parkinson's disease No cerebellar or pontine atrophy; preserved MCP; no hot cross bun sign; nigrosome-1 loss on SWI
Progressive supranuclear palsy Midbrain atrophy with "hummingbird" or "morning glory" sign; no hot cross bun sign; superior cerebellar peduncle atrophy
Alzheimer's disease Hippocampal and entorhinal cortex atrophy; posterior parietal hypometabolism; no cerebellar or pontine atrophy
Alcoholic cerebellar degeneration Superior vermis atrophy; preserved brainstem; no putaminal rim or hot cross bun
Paraneoplastic cerebellar degeneration Rapid progression; presence of anti-neuronal antibodies; underlying malignancy
Vitamin E deficiency Low serum vitamin E levels; improvement with supplementation
FXTAS (Fragile X-associated tremor/ataxia syndrome) Genetic testing positive for FMR1 premutation; intention tremor more prominent
Chronic inflammatory demyelinating polyneuropathy Prominent peripheral neuropathy; elevated CSF protein; nerve conduction studies abnormal