Lesion-level correspondence and longitudinal properties of paramagnetic rim and slowly expanding lesions in multiple sclerosis

Background: Paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs) have been posited as markers of chronic active lesions (CALs). Objective: To assess the lesion-level concordance of PRLs and SELs in MS and to characterize changes in brain tissue integrity in CALs over time. Methods: MRIs were analyzed from a substudy of AFFINITY [NCT03222973], a phase 2 trial of opicinumab in relapsing MS. Assessments included (1) identification of SELs based on longitudinal MRIs over 72 weeks, and identification of PRLs on susceptibility-weighted imaging (SWI) filtered phase images at week 72; (2) evaluation of subject-level correlation of SEL and PRL counts, volumes, and degree of lesion-level overlap between SELs and PRLs; and (3) characterization of tissue integrity over time in overlapping and non-overlapping SELs and PRLs. Results: In 41 subjects, 119 chronic PRLs and 267 SELs were detected. Of 119 (39.5%) chronic PRLs, 47 co-localized with a SEL; 46/267 (17.2%) SELs co-localized with a PRL. PRLs co-localized with SELs showed expansion and worsening microstructural damage over time. SELs with and without co-localization with PRLs showed ongoing tissue damage. Conclusions: Chronic MS lesions identified as both PRL and SEL were associated with the most severe accumulation of tissue damage.

Automated summary

This study aimed to assess the lesion-level concordance between paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs) in chronic active lesions (CALs) of multiple sclerosis (MS), and to characterize changes in brain tissue integrity in CALs. The results showed that co-localization of PRLs and SELs was associated with rapid expansion and worsening of microstructural damage over time, and both SELs with and without co-localization with PRLs showed ongoing tissue damage. Therefore, the coexistence of PRLs and SELs is associated with severe accumulation of tissue damage.