An eight-year follow-up of the CMSAR: assessing how the new MDS criteria and biomarkers impact diagnostic accuracy

Multiple system atrophy (MSA) is a rare, progressive neurodegenerative disorder with high mortality and diagnostic uncertainty. We re-evaluated 80 cases from the Catalan MSA Registry (CMSAR), applying the 2022 MDS diagnostic criteria and cerebrospinal fluid biomarkers, including α-synuclein seeding assays (asyn-SAA) and neurofilament light chain (NfL). Clinical and biomarker reassessment was performed in 2022-2023. At re-evaluation, 20 patients were alive; 14 were reclassified as non-MSA and three as unclassifiable. MSA cases had shorter survival (8.8 vs 14.8 years, p = 0.001), and dysphagia predicted poorer outcomes. The 2022 criteria showed higher specificity (94% for clinically established, 71% for probable) than the 2008 criteria. NfL levels were significantly higher in MSA (p = 0.005) and predicted mortality. Asyn-SAA was negative in confirmed MSA cases and positive in three suspected Parkinson's disease cases. These findings support the added diagnostic value of integrating updated criteria and CSF biomarkers to improve MSA classification and long-term monitoring.