Investigating the Presence of Neurodegeneration Independent of Relapses in MOGAD Compared to Relapsing-Remitting Multiple Sclerosis

Background and Objectives Neurodegeneration and progression independent of relapse activity (PIRA) are features of multiple sclerosis (MS), but their presence in myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) is unclear. The aim of this study was to investigate neurodegeneration in MOGAD, independent of relapses, by comparing clinical, cognitive, and advanced MRI markers in MOGAD, relapsing-remitting MS (RRMS), and healthy control (HC). Methods In this prospective study, participants with MOGAD, those with RRMS, and HC participants from the Oxford National Service and the Verona MS Centre were recruited and monitored between January 2018 and January 2024. Inclusion criteria included no attacks in the previous 6 months and during the study period, with a minimum 12-month interval between baseline and follow-up assessments. Participants underwent clinical Expanded Disability Status Scale (EDSS) assessment, cognitive Brief Repeatable Battery of Neuropsychological Tests (BRBNTs), and 3T brain structural and diffusion MRI evaluations. Clinical and cognitive PIRA events were defined as relapse-independent increases in EDSS scores and declines in cognitive function (a decrease of at least 1 SD in at least two BRBNTs). Annual percentage changes in brain volume, total cortical/deep gray matter (DGM)/white matter volumes, and cortical thickness were derived from structural MRI. Neurite orientation dispersion and density imaging metrics were calculated in lesional and nonlesional white matter from diffusion MRI. Results Twenty patients with MOGAD; 32 with RRMS, matched for age, sex, baseline EDSS score, and cognitive impairment; and 21 HCs were recruited. Over a median follow-up of 17 months (range 12–45) for RRMS and 16 months (range 12–56) for MOGAD, clinical PIRA occurred in 6.25% of patients with RRMS and 0% of patients with MOGAD and cognitive PIRA in 6.67% of patients with RRMS and 0% of patients with MOGAD. Compared with HCs, patients with RRMS showed greater annualized thalamic (β = −0.874; 95% CI −1.384 to −0.364; p = 0.001), hippocampal (β = −1.269; 95% CI −2.230 to −0.308; p = 0.010), and DGM (β = −0.920; 95% CI −0.920 to −0.099; p = 0.015) atrophy while no significant changes occurred in patients with MOGAD. Patients with RRMS also had greater annualized thalamic (β = −0.742; 95% CI −1.330 to −0.083; p = 0.011) and hippocampal (β = −1.078; 95% CI −1.960 to −0.197; p = 0.017) atrophy compared with patients with MOGAD. Longitudinal increases in free water content within white matter lesions were observed in the RRMS group (p = 0.008) but not in the MOGAD group. Discussion The absence of PIRA and progressive brain damage independent of attacks distinguished MOGAD from RRMS. Further research with larger cohorts and longer follow-ups is needed to validate these findings.