Association of paramagnetic rim lesions with patient-reported neuropsychiatric symptoms in multiple sclerosis

Background: Paramagnetic rim lesions (PRLs) mark chronic active lesions in multiple sclerosis (MS) and have been linked to disability progression and objective cognitive decline, but their relationship with invisible symptoms such as fatigue, mood disturbance and perceived cognition remains unclear. Methods: We prospectively enrolled adults with MS who underwent 3T susceptibility-weighted imaging. Supratentorial PRLs were counted and participants were categorised into 0, 1–3 or > 3 PRLs. Neuro-QoL T-scores for fatigue, depression, anxiety and perceived cognition were collected at baseline and annually for up to five years (median 3.1 years, 419 person-visits). Cross-sectional associations were examined with multivariable linear regression; longitudinal change was modelled with linear mixed-effects models adjusted for age, sex, race and MS course, applying false-discovery-rate correction. Results: Among 92 adults with MS (mean age 51 ± 13 years; 78 % women), 41 participants (45 %) had no PRLs, 27 (29 %) had 1–3, and 24 (26 %) had > 3. At baseline, PRL burden did not correlate with fatigue, depression, anxiety, or cognition (all FDR-adjusted p > 0.70). During follow-up, PRL category did not influence trajectories of fatigue, depression, or cognition. Participants with >3 PRLs experienced a modest annual reduction in anxiety (−1.8 T-score points/year; 95 % CI -3.05 to −0.56; FDR p = 0.02). Conclusions: Supratentorial PRL burden is not a major determinant of common invisible symptoms in MS. The unexpected inverse association with anxiety may in part reflect regression to the mean or adaptive coping over time and needs replication in larger cohorts incorporating lesion volume, location, and treatment exposure.