MRI volumetry shows promise as a progression endpoint in MSA trials

Researchers analyzed one-year MRI and clinical data from 129 participants in the placebo arm of the M-STAR Study (NCT03952806): 76 had MSA-cerebellar (MSA-C) and 53 had MSA-parkinsonism (MSA-P). A multisite cohort of 184 healthy controls was included for comparison. The investigators assessed 42 regional brain volumes, four combined volumetric indexes, nine clinical scales and serum neurofilament light chain as potential progression measures.

At baseline, infratentorial structures were most atrophic in MSA-C, while the putamen was most atrophic in MSA-P. Over one year, infratentorial regions had the greatest volume loss relative to controls in both subtypes. The annualized change in a combined cerebellum-pons-putamen volume index had the largest effect size in the overall MSA cohort (−1.81; 95% CI, −2.14 to −1.55). The investigators estimated that 55 participants per arm would be needed to detect a 30% treatment effect using this index; estimated sample size was 59.6% lower than for clinical measures.

The findings suggest that automated MRI volumetry could be a sensitive imaging endpoint for MSA clinical trials. They are based on a one-year analysis of a trial’s placebo group, and the estimated treatment effects and sample sizes do not establish that MRI changes predict clinical benefit.