Impact of 2024 Revisions of Multiple Sclerosis Diagnostic Criteria in People With Radiologically Isolated Syndrome

BACKGROUND AND OBJECTIVES: The biological onset of multiple sclerosis (MS) precedes its clinical onset by years, as shown by MRI and CSF biomarkers. The 2024 revisions of the McDonald criteria extend, for the first time, MS diagnosis to selected cases of radiologically isolated syndrome (RIS), that is, to people with incidentally discovered CNS lesions suggestive of autoimmune inflammatory demyelination, in the absence of typical symptoms. The aim of this multicenter study was to assess the proportion of patients with RIS reclassified as MS, after applying the 2024 criteria. METHODS: Adult participants (≥18 years) fulfilling the 2023 Lebrun-Frénay RIS criteria were selected from 22 Italian MS tertiary centers. Real-world, registry-based data were retrospectively collected at both baseline and follow-up. Reclassification followed 2024 criteria, allowing a MS diagnosis in RIS cases with ≥1 T2-hyperintense lesion in ≥2 typical MS regions (i.e., dissemination in space [DIS]), plus either MRI evidence of dissemination in time (DIT), CSF positivity, or central vein sign (CVS) positivity. Descriptive statistics were used. RESULTS: Among 236 patients with RIS (mean age 38.9 ± 11.6 years; 70.3% female; median follow-up 3.0 years [interquartile range {IQR}: 1.1-6]), at baseline, 228 (96.6%) fulfilled DIS, 51 (21.6%) fulfilled radiologic DIT, and 152 of 201 individuals with available CSF data were CSF-positive (75.6%). CVS data were available for 5 of 236 individuals; none were CVS-positive. At baseline, the 2024 criteria resulted in a MS diagnosis in 159 of 236 patients with RIS (67.4%). Of 42 patients with RIS experiencing a clinical event during follow-up, 88.1% would have been reclassified as MS a median of 2 years earlier (IQR: 1.0-5.5). During follow-up, 18 of 236 additional participants (7.6%) met the diagnostic criteria through radiologic DIT. DISCUSSION: The introduction of the 2024 criteria results in an earlier diagnosis of MS, before clinical manifestations of focal CNS damage, in most people formerly classified as RIS. Study limitations include incomplete kappa free light chain index data and nonstandardized MRI acquisition protocols; particularly, retrospective CVS assessment was negligible in this real-life context. Future studies including the full spectrum of asymptomatic individuals with MRI abnormalities and available paraclinical diagnostic tools are needed to better define the impact of 2024 revised criteria in this population.