Neurodegeneration correlates of iron-related lesions and leptomeningeal inflammation in multiple sclerosis clinical subtypes.

Objective: The aim of this study was to investigate the significant implications of different types of lesions as assessed by QSM (quantitative-susceptibility-mapping) as well as leptomeningeal contrast-enhancement in a cohort of Relapsing-Remitting (RR) and Primary Progressive (PP) MS patients and to assess their association with clinical disability and MRI-measures of brain structural damage.

Methods: Different types of white-matter lesions were identified and quantified using QSM in 24 RRMS and 15 PPMS (11 patients with follow-up MRI). Leptomeningeal contrast-enhancement (LMCE; foci) was assessed on 3D-FLAIR post-gadolinium.

Results: Both RRMS and PPMS presented PRL (paramagnetic-rim lesions) and LMCE, with PPMS showing a trend towards more LMCE (RRMS 37%, PPMS 53%). In QSM RRMS patients showed more hyperintense white-matter lesions with greater lesion volume. In RRMS PRL correlated with disease duration and lesion burden especially the volume of juxtacortical Flair-hyperintense lesions. Besides, the presence of PRL lesions in PPMS was associated with subcortical atrophy mainly thalamus and pallidum volumetry. In all MS-cohort, patients with more than 3-PRLs exhibited reduced regional cortical thickness in specific temporal areas and post/para central gyrus. Forest-analysis selected age, increased NAWM (normal appearing white-matter) QSM intensity, total lesion volume and the presence of LMCE as informative predictors of cortical thickness. After anti-CD20 treatment, no significant change was observed regarding the number of PRL and LMCE, but the percentage of PRL lesions over the total lesion types and the QSM rim intensity increased.

Conclusions: Our findings suggest that QSM-lesion types and leptomeningeal inflammation capture different aspects of progressive disease biology in both RRMS and PPMS.