MRI activity in pre-symptomatic multiple sclerosis: the role of paramagnetic rim lesions beyond the 2024 McDonald diagnostic criteria.

BACKGROUND: The 2024 McDonald criteria allow multiple sclerosis (MS) diagnosis in pre-symptomatic individuals but their association with MRI activity remains uncertain. We assessed whether paramagnetic rim lesions (PRL) predict future MRI activity beyond the 2024 McDonald criteria. METHODS: We retrospectively included individuals with incidental MRI findings suggestive of MS, ≥6 months of radiological follow-up, 3D T2*-weighted echo-planar-imaging MRI. Clinico-radiological data included PRL, central vein sign (CVS) Select-6, cerebrospinal fluid positivity, optic nerve, spinal cord involvement and disease-modifying treatment. Time to first MRI activity and annualised lesion rate (ALR) were analysed using multivariable-penalised Cox and mixed-effects Poisson models. RESULTS: Among 68 patients (mean age 38 years; 79.4% female; mean follow-up 55.7 months), 21 showed MRI activity. PRL were associated with shorter time to first MRI activity (HR 5.66, 95% CI 1.33 to 28.39, p=0.019). PRL (RR 3.45, 95% CI 1.40 to 8.47, p=0.007) and CVS positivity (RR 4.09, 95% CI 1.17 to 14.27, p=0.027) predicted higher ALR. Fulfilment of the 2024 McDonald criteria associated with increased risk of future MRI activity (HR=11.95, 95% CI 2.77 to 51.51, p=0.001; Cox regression). Adding PRL presence to the criteria changed classification performance (χ2=18, p<0.001; McNemar's test), improving specificity and accuracy while reducing sensitivity. CONCLUSIONS: PRL are associated with subsequent radiological activity in pre-symptomatic MS, featuring complementary predictive value beyond biomarkers currently included in the 2024 McDonald criteria.