Applying the 2024-revised McDonald criteria for multiple sclerosis using conventional diagnostic tools: a single-centre prospective cohort study in Germany

Background The 2024-revised McDonald criteria may enable earlier diagnosis of multiple sclerosis (MS) through inclusion of optic nerve involvement as fifth neuroanatomical topography, novel MRI biomarkers, cerebrospinal fluid (CSF) kappa free light chains (KFLC), and classification of radiologically isolated syndrome (RIS) as MS. Their applicability in routine practice remained for evaluation. Methods In this prospective single-centre cohort study in Germany, adults presenting between October 1, 2020, and June 30, 2025, with a first demyelinating event or RIS were screened. Participants underwent conventional diagnostic work-up according to the 2017-revised McDonald criteria, including contrast-enhanced MRI, visual evoked potentials (VEP), and CSF analysis. Novel MRI markers and optical coherence tomography were not systematically available. Primary outcome was the proportion of individuals fulfilling the 2024-revised versus the 2017-revised McDonald criteria at baseline assessment. Findings Applying the 2024-revised criteria, 201/215 individuals (93.5%) fulfilled diagnostic criteria for MS versus 181/215 (84%) using the 2017 revision (p < 0.0001). Additional diagnoses resulted from optic nerve involvement (55%) and RIS reclassification (35%). VEP identified optic nerve lesions in 89% of cases. Overall, 102/201 (51%) individuals fulfilled diagnostic criteria based on MRI findings alone, whereas 99/201 (49%) additionally required inflammatory CSF findings and dissemination in time. Interpretation Application of selected components of the 2024-revised McDonald criteria increased the proportion of individuals fulfilling the diagnostic criteria, mainly through inclusion of optic nerve involvement and recognition of RIS. CSF analysis remained important for diagnosis and differential diagnostics. Further studies should evaluate the contribution of novel imaging biomarkers. Funding No external funding was received.