Applying the 2024 McDonald Diagnostic Criteria Effective for Identifying Prodromal MS in Real-World Study

Applying the 2024 McDonald diagnostic criteria for multiple sclerosis (MS) was effective in identifying individuals with prodromal MS, according to data presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2025. Compared with individuals with clinically isolated syndrome (CIS) or radiologically isolated syndrome (RIS), those with prodromal MS showed higher neuroinflammatory and neurodegenerative burden. Additionally, compared with individuals with a definite diagnosis of MS according to the 2017 McDonald criteria, those with a prodromal MS diagnosis via the 2024 McDonald criteria showed lower paramagnetic rim lesion (PRL) counts.

The study included 41 individuals with a diagnosis of CIS or RIS, according to the 2017 McDonald criteria. These participants were evaluated according to the 2024 McDonald criteria, with 23 (56%) receiving a diagnosis of prodromal MS and 18 (43%) failing to meet the criteria for prodromal MS. Both groups were assessed for serum, imaging, and cerebrospinal fluid (CSF) measurements of neuroinflammation and neurodegeneration.

Compared with individuals who did not meet the 2024 McDonald diagnostic criteria, those diagnosed with prodromal MS showed:

• Significantly higher levels of serum neurofilament light chain (sNfL) after adjusting for age (marginal means, 15 pg/mL vs 11 pg/mL; P=.003)
• Reduced normalized thalamic volume (NTV) (.009 vs .01; P=.009)
• Higher T2 lesions load (7585 mm3 vs 2184 mm3; P=.001)
• Higher cortical lesion (CL) counts (5 vs 0; P<.001)
• Higher PRL counts (1 vs 0; P=.003)

Researchers also evaluated for differences in these outcome measures between the cohort of individuals diagnosed with prodromal MS according to the 2024 McDonald criteria (n=23) and a cohort of age- and sex-matched participants with definite MS according to the 2017 McDonald criteria (n=23). This analysis demonstrated no significant differences in measures of sNfL, NTV, T2 lesion load, or CL counts. However, PRL count was significantly higher in the definite MS cohort vs the prodromal MS cohort (5 vs 1; P=.018).