Definition and Overview
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by a combination of autonomic failure with parkinsonism (MSA-P) or cerebellar ataxia (MSA-C). It is a synucleinopathy caused by accumulation of alpha-synuclein in oligodendrocytes (glial cytoplasmic inclusions) [1].
Incidence is 0.6-0.7 per 100,000 per year, with typical onset after age 50. Mean survival from symptom onset is 6-10 years [2].
Classification
MSA-P (parkinsonian predominant): rigidity, bradykinesia, and postural instability with poor levodopa response. Accounts for approximately 60% in Western countries.
MSA-C (cerebellar predominant): gait ataxia, limb ataxia, cerebellar dysarthria, and oculomotor dysfunction. More common in East Asia [1].
Symptoms
Autonomic failure is a hallmark and often the earliest manifestation:
- Orthostatic hypotension: often severe, with >30 mmHg systolic BP drop
- Urogenital dysfunction: urinary incontinence, erectile dysfunction (often earliest symptom in men)
- Constipation and gastroparesis
- Sweating abnormalities
Motor symptoms vary by subtype. Sleep disturbances including REM sleep behavior disorder (RBD) often precede motor symptoms by years [3].
Diagnosis
MRI findings: "hot cross bun sign" in the pons (characteristic of MSA-C), putaminal atrophy with slit-like hyperintensity (MSA-P). DaT scan may show reduced striatal uptake. Autonomic testing (tilt table, HRV, QSART) documents autonomic failure [4].
Key differentiators from Parkinson's disease: poor levodopa response, early severe autonomic failure, rapid progression, and absence of MIBG cardiac uptake reduction pattern (reduced in PD, variable in MSA).
Treatment
Treatment is symptomatic. Orthostatic hypotension: fludrocortisone, midodrine, droxidopa. Sleep apnea: CPAP. Parkinsonism: levodopa trial (modest response in 30-40%). Physical therapy and fall prevention are essential [5].
Prognosis
MSA is a progressive disease with no disease-modifying therapy currently available. Mean survival is 6-10 years from symptom onset. Respiratory stridor and aspiration pneumonia are common causes of death.