Paramagnetic Rim Lesions in Highly Active Multiple Sclerosis at the Time of Disease Diagnosis: Prevalence Data and Clinical Implications

Background: Paramagnetic rim lesions (PRLs) are emerging MRI biomarkers of smoldering inflammation in multiple sclerosis with prognostic relevance1. However, their prevalence in the early stages of the disease remains underexplored. Objective: This prospective cohort study investigated the prevalence, anatomical distribution, and clinical significance of PRLs in newly diagnosed relapsing MS patients with high disease activity and explored their associations with conventional and non-conventional MRI measures, serum neurofilament light chain (sNfL), and clinical outcomes. Methods: We enrolled treatment-naïve patients who had received an MS diagnosis in the previous 12 months. Patients underwent 3 T brain and spinal MRI including susceptibility-weighted imaging at baseline, 6, and 12 months, along with neurological and cognitive assessments and sNfL sampling. Results: The cohort consisted of 21 patients, with a mean age of 31 and median disease duration of 9 months (IQR 4-17). Median EDSS score was 1.5. All patients presented with spinal cord lesions and 38% showed Gd + lesions. PRLs were detected in 76%, with a mean of 4.9 lesions per subject. Higher PRL burden correlated with greater T2 lesion volume and cortical lesion count, higher EDSS, reduced SDMT scores, and elevated baseline sNfL. PRLs remained stable over 12 months despite treatment; two new PRLs emerged at month 12. sNfL levels were higher in patients with ≥ 4 PRLs and decreased in all during follow-up. Conclusions: Paramagnetic rim lesions (PRLs) are detectable early in RMS and correlate with a more severe clinical and radiological profile. The combined assessment of PRLs and CLs may improve disease monitoring and guide personalized treatment.