Rapid Progression and Shorter Survival in Indians Affected with Probable MSA: A Prospective Cohort Study.

BACKGROUND

Multiple system atrophy (MSA) is a fatal alpha-synucleinopathy characterized by variable combinations of parkinsonism and autonomic and cerebellar dysfunctions.

OBJECTIVE

We aimed to prospectively study the natural history of probable MSA, including cardiovascular autonomic dysfunction (CAD) and serum alpha-synuclein.

METHODS

Sixty probable MSA patients (MSA-P = 19; MSA-C = 41) and 30 age-and-gender-matched healthy controls were recruited. Disease severity (UPDRS III, UMSARS I, II, IV), CAD, and serum alpha-synuclein (ELISA) were assessed at baseline, 6-month (6 M-FU), and 12-month (12 M-FU) follow-ups. Survival probabilities (Kaplan-Meir analysis) and prognostic factors (Cox proportional hazards analysis) were assessed at the study's end period.

RESULTS

Total serum alpha-synuclein was higher in MSA patients than controls (P < 0.001). There was severe CAD in MSA patients at baseline (P < 0.001), which further deteriorated at 12 M-FU (P < 0.01). A greater proportion of MSA-P patients had a dopaminergic benefit than MSA-C patients (P < 0.001). CAD had a positive correlation with serum alpha-synuclein and disease severity. UPDRS III and UMSARS II scores were higher at follow-ups (P < 0.001). Disease progression was more rapid in MSA-C patients than MSA-P patients (P < 0.001). The median time to one-person support for walking and activities of daily living (ADL), wheelchair support, bedbound state, and death were 27, 48, 66, and 70 months, respectively. The probabilities of needing one-person support and wheelchair support were lower in MSA-P patients than MSA-C (P = 0.005; P = 0.03), whereas the probabilities of bedbound state and death were similar.

CONCLUSIONS

Probable MSA patients had a rapid progression, autonomic failure, and a shorter survival of 5.8 years in this Asian-Indian cohort compared to the other MSA cohorts worldwide (9-10 years). MSA-P patients had a better prognosis than MSA-C. Elevated serum alpha-synuclein and its positive correlation with CAD provide evidence for its role as a potential biomarker.