Association of Diagnosis Age with Clinical Characteristics and MRI Findings in Multiple Sclerosis

Background: Age at multiple sclerosis (MS) diagnosis may be associated with clinical course, inflammatory activity, and disability accrual, but evidence across the full age spectrum remains limited. We compared clinical and radiological features, phenotype distribution, and time to first post-diagnosis relapse across early-onset MS (EOMS), adult-onset MS (AOMS), and late-onset MS (LOMS). Methods: This observational study included patients with MS treated at two tertiary centers in Isfahan, Iran, combining a retrospective review of clinical records with a cross-sectional assessment at the most recent study visit. Patients were categorized as EOMS (MS diagnosis at ≤18 years), AOMS, or LOMS (diagnosis at or after 50 years) according to age at diagnosis. Demographic, clinical, MRI, and comorbidity data were compared across groups. Time to first post-diagnosis relapse was analyzed in RRMS using Cox regression, and continuous age effects were explored with spline models. Results: Among 3994 patients, 257 had EOMS, 3587 had AOMS, and 150 had LOMS. EOMS had a higher hazard of first post-diagnosis relapse (adjusted HR: 1.27, 95% CI: 1.05–1.54) and more frequent enhancing brain lesions. LOMS had a more progressive phenotype, higher EDSS at diagnosis and qualitative brain atrophy, and more age-associated comorbidities. The adjusted LOMS relapse estimate (HR: 0.58, 95% CI: 0.34–0.99) was borderline significant. Progressive MS became more common with increasing diagnosis age, largely reflecting PPMS, although unequal follow-up and last-visit classification limit causal interpretation. Female predominance persisted across all groups but was less pronounced in LOMS. Conclusions: Age at diagnosis was associated with clinical and radiological differences across the MS spectrum from a more relapsing phenotype to a more progressive, disability-associated phenotype. These findings should be verified in prospective studies based on symptomatic onset age.