MSA is a neurodegenerative disorder of unknown causes. Pathologically it I characterised by:
- 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
- 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.
MSA presents with a combination of progressive motor dysfunction and autonomic dysfunction.
The motor symptoms broadly categorise into two groups of presentations:
- MSA-C: cerebellar-predominant
- MSA-P: parkinsonism-predominant
- Tremor: usually postural rather than rest
- Postural instability
- Early falls
- Pyramidal weakness
- Cerebellar ataxia
- Postural hypotension >> falls
- Urinary incontinence
- Erectile dysfuntion
- REM sleep behaviour disorder
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.
|Tremor||Jerky, postural||Fine, rest|
|Response to L-Dopa||Poor||Excellent|
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
- Urinary incontinence
- Muscarinic antagnosists: e.g. oxybutinin