Paramagnetic rim lesions predict the development of clinical MS in radiologically isolated syndrome: results from a prospective cohort study (S27.003) (2023)

<h3>Objective:</h3> To determine the association of various MRI measures and subsequent development of clinical MS in people with radiologically isolated syndrome (pwRIS). <h3>Background:</h3> We previously found that most pwRIS have high proportions of white matter lesions positive for the central vein sign (CVS+L) and at least one paramagnetic rim lesion (PRL), representing perivenular and chronic active demyelination, respectively. Whether PRL and CVS+L relate to the risk of developing clinical MS in pwRIS prospectively is unknown. <h3>Design/Methods:</h3> PwRIS were recruited prospectively and underwent 3T-MRI, including 3D-FLAIR and T2*segmented EPI of the brain, and sagittal T1-PSIR of the cervical spinal cord(SC). MRIs were evaluated for presence of PRL,CVS+L, and SC lesions (SCL). <h3>Results:</h3> 36 pwRIS (median age 43 years, 70% women, median time of clinical follow-up 6.3 years) were included in the study. Clinical MS developed in 9 (25%) subjects with a median time to first clinical event of 5.2 years. 67% developed RRMS and 33% PPMS. At baseline, pwRIS who developed clinical MS vs those who did not had a higher median number of PRL (11 vs 1, p=0.01) and CVS+L(34 vs 10, p=0.04). Longitudinally, number of new brain lesions, PRL, CVS+L (all p&lt;0.01) and SCL (p=0.02) were higher in those who subsequently developed clinical MS. Multivariable logistic regression using backward stepwise selection identified baseline PRL count as the most predictive variable of MS development among baseline and follow-up imaging measures (p=0.01). <h3>Conclusions:</h3> In this prospective cohort of pwRIS, 25% developed MS within 5 years after initial diagnosis, with 33% diagnosed as PPMS. Baseline PRL count was the most predictive MRI measure for subsequent development of clinical MS in pwRIS, suggesting that PRLs may have prognostic utility. Continued follow-up of this cohort and validation in larger datasets will be important to confirm the clinical predictive value of PRL and CVS+L in pwRIS. <b>Disclosure:</b> Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. The institution of Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen-Idec. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD-Serono. Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Oh has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen-Idec. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Oh has received research support from Biogen-Idec. The institution of Dr. Oh has received research support from EMD-Serono. The institution of Dr. Oh has received research support from Biogen-Idec. Timothy R. Lim has nothing to disclose. Dr. Suthiphosuwan has nothing to disclose. Dr. Espiritu has nothing to disclose. Melanie Guenette has nothing to disclose. Dr. Bharatha has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. The institution of Dr. Sati has received research support from National Multiple Sclerosis Society. The institution of Dr. Sati has received research support from National Institutes of Health. Dr. Sati has received publishing royalties from a publication relating to health care. Dr. Absinta has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Absinta has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abata Therapeutics. The institution of Dr. Absinta has received research support from International MS Alliance. The institution of Dr. Absinta has received research support from FRRB Early Career Award. The institution of Dr. Absinta has received research support from Cariplo Foundation. Dr. Reich has received research support from NIH. The institution of Dr. Reich has received research support from Vertex Pharmaceuticals. The institution of Dr. Reich has received research support from Adelson Medical Research Foundation. The institution of Dr. Reich has received research support from Myelin Repair Foundation. The institution of Dr. Reich has received research support from Sanofi-Genzyme. The institution of Dr. Reich has received research support from Abata Therapeutics. The institution of Dr. Reich has received research support from National Multiple Sclerosis Society. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with PeerView. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with AcademicCME. Dr. Reich has a non-compensated relationship as a Advisor with Sanofi-Genzyme that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Board of Directors with ACTRIMS that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Abata Therapeutics that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Roche that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with American Brain Foundation that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with University of Basel RC2NB that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Multiple Sclerosis Society of Canada that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Tuscan Doctorate in Neuroscience that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Editorial Board with Multiple Sclerosis Journal that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Glaxo-Smith-Kline that is relevant to AAN interests or activities.