Paramagnetic Rim Lesions in Pediatric Multiple Sclerosis and Their Association With Brain Tissue Atrophy

Background and objectives: Paramagnetic rim lesions (PRLs), visible on susceptibility-based imaging (SbI), reflect chronic active inflammation in multiple sclerosis (MS). In adult-onset MS, PRLs are associated with a more aggressive disease course.The objectives of this study were to assess the prevalence of PRLs in children with MS and to examine how baseline PRL count relates to clinical disability and brain tissue volume loss, both cross-sectionally and over short-term follow-up. Methods: We retrospectively analyzed pediatric patients from 4 UK tertiary neuroimmunology centers who met the 2017 McDonald diagnostic criteria and had 3D T1-weighted, T2-weighted, fluid-attenuated inversion recovery, and SbI MRI available. PRLs were identified per North American Imaging in MS criteria and anatomically classified. Brain volumes were segmented using Mindglide, with z-scores derived from NIH normative data. Associations between baseline PRL burden, clinical variables, and brain volumes were assessed using univariable and multivariable stepwise regression. Linear mixed-effects models evaluated the predictive value of baseline PRL burden on longitudinal brain volume changes. Results: Fifty-four patients (mean age 14.0 ± 2.2 years; 75.9% female) were included. At least 1 PRL was seen in 74.1% of patients, with a median number of 2 PRLs (interquartile range [IQR] = 0-6), predominantly in periventricular regions, and accounting for 25% of total T2-weighted hyperintense lesions. In multivariable Poisson regression, at baseline, shorter disease duration (incidence rate ratio [IRR] = 0.987, 95% CI 0.975-0.999, p = 0.035), and greater number (IRR 1.045, 95% CI 1.035-1.054, p < 0.001) and volume (IRR 1.018, 95% CI 1.004-1.032, p = 0.012) of T2-hyperintense lesions were associated with higher PRL count. Cross-sectionally, a higher PRL count was associated with lower cortical (β = -0.139, 95% CI -0.231 to -0.047, p = 0.016) and deep (β = -0.096, 95% CI -0.166 to -0.026, p = 0.032) gray matter volume z-scores. No significant association was observed between clinical disability and PRL count. In 45 patients followed up for a median 17 months (IQR 12-24), a higher baseline PRL count predicted greater deep gray matter volume loss over time (β = -0.020, 95% CI -0.034 to -0.006, p = 0.036). Discussion: PRLs are common in pediatric MS and are linked to greater lesion burden and gray matter atrophy. These findings suggest that PRLs are promising imaging biomarkers of more severe brain tissue damage although their ability to predict future disability requires confirmation in longer term studies.