Multiple System Atrophy

Pathogenesis

MSA is a neurodegenerative disorder of unknown causes. Pathologically it I characterised by:

Microscopic:

  • the presence of cytoplasmic inclusions containing alpha-synuclein within oligodendrocytes in the basal ganglia, cerebellum, and cerebellar connections
  • neuronal loss
  • intranuclear inclusions in neurons with variable composition

Macroscopic:

  • atrophy of the cerebellum and its brainstem connections.

There is pathological overlap with Parkinson’s Disease, Lewy Body Dementia, and Progressive Supranuclear Palsy. The most specific feature is atrophy of the posterolateral putamen.

Presentation

MSA presents with a combination of progressive motor dysfunction and autonomic dysfunction.

Motor symptoms

The motor symptoms broadly categorise into two groups of presentations:

  • MSA-C: cerebellar-predominant
  • MSA-P: parkinsonism-predominant

MSA-P:

  • Bradykinesia
  • Tremor: usually postural rather than rest
  • Rigidity
  • Postural instability
  • Early falls
  • Pyramidal weakness

MSA-C:

  • Cerebellar ataxia
  • Dysarthria
  • Nystagmus

 

Autonomic dysfunction

  • Postural hypotension >> falls
  • Urinary incontinence
  • Erectile dysfuntion

Other

  • REM sleep behaviour disorder

Investigation

The differential diagnosis depends on the presentation. Other disorders which may produce a similar clinical picture include:

  • Idiopathic PD
  • Lewy Body Dementia
  • Progressive Supranuclear Palsy
  • Corticobasal Degeneration
  • Normal Pressure Hydrocephalus
  • Vascular parkinsonism

Diagnosis is largely clinical based on the presentation and the response to levodopa – investigations help to exclude other disorders and add evidence for MSA.

  • L-Dopa responsiveness: MSA is poorly responsive to L-Dopa, whereas idiopathic PD responds very well. A poor response to a good dose (up to 1g / day) favours a diagnosis of MSA.
  • MRI: Atrophy of the putamen may be seen in MSA but is non-specific.

Only around 60% of people diagnosed with MSA in life have clear MSA pathology at autopsy.

MSA Idiopathic PD
Autonomic dysfunction Prominent

Early

Mild

Late

Falls Early Late
Tremor Jerky, postural Fine, rest
Response to L-Dopa Poor Excellent

Management

There is no specific treatment. Management is therefore symptomatic. Drugs which can be used to treat common symptoms include:

  • Postural hypotension:
  • Mineralocorticoids: e.g. fludrocortisone
  • Alpha-1 agonists: e.g. midodrine
  • Extrapyramidal symptoms:
    • L-dopa may be helpful
  • Erectile dysfunction
    • Sildenafil
  • Urinary incontinence
    • Muscarinic antagnosists: e.g. oxybutinin