Subtyping relapsing-remitting multiple sclerosis using structural MRI

Background and purpose Subtyping relapsing-remitting multiple sclerosis (RRMS) patients may help predict disease progression and triage patients for treatment. We aimed to subtype RRMS patients by structural MRI and investigate their clinical significances. Methods 155 relapse-remitting MS (RRMS) and 210 healthy controls (HC) were retrospectively enrolled with structural 3DT1, diffusion tensor imaging (DTI) and resting-state functional MRI. Z scores of cortical and deep gray matter volumes (CGMV and DGMV) and white matter fractional anisotropy (WM-FA) in RRMS patients were calculated based on means and standard deviations of HC. We defined RRMS as "normal" (- 2 < z scores of both GMV and WM-FA), DGM (z scores of DGMV < - 2), and DGM-plus types (z scores of DGMV and [CGMV or WM-FA] < - 2) according to combinations of z scores compared to HC. Expanded disability status scale (EDSS), cognitive and functional MRI measurements, and conversion rate to secondary progressive MS (SPMS) at 5-year follow-up were compared between subtypes. Results 77 (49.7%) patients were "normal" type, 37 (23.9%) patients were DGM type and 34 (21.9%) patients were DGM-plus type. 7 (4.5%) patients who were not categorized into the above types were excluded. DGM-plus type had the highest EDSS. Both DGM and DGM-plus types had more severe cognitive impairment than "normal" type. Only DGM-plus type showed decreased functional MRI measures compared to HC. A higher conversion ratio to SPMS in DGM-plus type (55%) was identified compared to "normal" type (14%, p < 0.001) and DGM type (20%, p = 0.005). Conclusion Three MRI-subtypes of RRMS were identified with distinct clinical and imaging features and different prognosis.