Objective: We aimed to prospectively study the natural history of probable multiple system atrophy (MSA) including autonomic testing, survival analysis; and assess whether serum alpha-synuclein can be a biomarker.

Background: MSA is a fatal movement disorder characterized by variable combinations of parkinsonism, autonomic and cerebellar dysfunction. We report results of the first prospective natural history study of probable MSA in India.

Method: We recruited 60 probable MSA patients(MSA-P=19; MSA-C=41) and 30 controls. The progression of disease severity was assessed using UPDRS-III, UMSARS-I,II,III,IV; cardiac autonomic dysfunction(CAD) using heart rate variability(HRV), baroreflex sensitivity, Ewing’s protocol and tilt table test; and serum alpha-synuclein using ELISA; at baseline, 6-month(6M-FU) and 12-month follow-up(12M-FU). Clinical milestones were determined using Kaplan-Meier analysis.

Results: Median age and disease duration were 55(11) and 2(1.5)years. Serum alpha-synuclein was higher in MSA than controls(p<0.001). There was severe CAD in MSA as evidenced by HRV analysis, baroreflex failure and high autonomic severity scores(p<0.001). A greater proportion of MSA-P patients(84vs29%) had dopaminergic benefit(p<0.001). CAD had positive correlation with serum alpha-synuclein, disease severity and global disability. There was significant increase in UPDRS-III, UMSARS-I,II scores at 6M and 12M FU(p<0.001). Autonomic dysfunction had significant progression at 12M-FU(p=0.003). MSA-C patients had higher rate of disease progression(p<0.001). There was high mortality(45%) in our cohort. Median time to one-person support, wheelchair dependency, bedbound state and death were 27, 48, 66 and 70 months respectively. The probability of needing one-person support and wheelchair was lower in MSA-P than MSA-C(p=0.005; p=0.03), while the probability of bedbound state and survival was similar.

Conclusion: Probable MSA has a malignant nature as evidenced by its rapid progression, autonomic failure and short survival. Survival was shorter in our Indian cohort compared to MSA cohorts worldwide. Previous studies have shown that either MSA-C has better prognosis or there is no difference. Our MSA-P patients had better prognosis as evidenced by significant dopaminergic benefit, slower progression and lesser probability of needing walking-aids. Elevated serum alpha-synuclein and its positive correlation with CAD may provide evidence for its role as a biomarker.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/natural-history-of-probable-msa-in-india-a-prospective-cohort-study/