Pediatric Onset Multiple Sclerosis (POMS): Exploring phenotypic characterization and pubertal influences in modulating the disease activity from the Danish MS Registry (DMSR).

Background: Pediatric-onset multiple sclerosis (POMS) constitutes ~5% of multiple sclerosis (MS) cases and presents distinct clinical and diagnostic challenges. Puberty, characterized by significant hormonal changes, may influence disease presentation, relapse rates, and long-term outcomes.

Objectives: To investigate the impact of pubertal stages on clinical characteristics, relapse activity and disability progression in POMS using data from the Danish MS Registry (DMSR).

Methods: A nationwide cohort of 185 POMS patients were included and categorized by pre- (<11 years), peri- (11-14 years), and post-pubertal (>14 years) onset. Demographics, presenting symptoms, magnetic resonance imaging (MRI) findings, relapse rates, and Expanded Disability Status Scale (EDSS) scores were compared. Patients transitioning across the three pubertal stages (n = 54) were analyzed longitudinally for relapse rate.

Results: Pre-pubertal onset was associated with severe symptoms (cerebellar involvement, p = 0.042), greater lesion burden, higher 10-year disability (EDSS median = 3.75, p = 0.039), and lower relapse rates (annualized relapse rate (ARR) = 0.200). Male sex reduced relapse rates (p = 0.013). Female-to-male ratio increased from 1:1 pre-puberty to ~2:1 after puberty. Patients with pre-pubertal onset transitioning to peri- or post-puberty showed increasing relapse rates, peaking during peri-puberty (ARR = 0.302).

Conclusions: Puberty significantly modulates disease course in POMS, emphasizing the need for early, sex-specific interventions, proactive monitoring, and further exploration of hormonal influences on disease progression and treatment response.