Contrasting the brain imaging features of MOG-Antibody disease, with AQP4-Antibody NMOSD and Multiple Sclerosis

Neuromyelitis optica associated with aquaporin-4-antibodies (NMOSD-AQP4) and myelin oligodentrocyte-glycoprotein antibody-associated disorder (MOGAD) have been recently recognised as different from multiple sclerosis. Although conventional MRI may help distinguish multiple sclerosis from antibody-mediated diseases, the use of quantitative and non-conventional imaging may give more pathological information and explain the clinical differences. We compared, using non-conventional imaging, brain MRI findings in 75 subjects in remission with NMOSD-AQP4, MOGAD, multiple sclerosis or healthy controls (HC). Volumetrics, white matter and cortical lesions, and tissue integrity measures using diffusion imaging, were analysed in the four groups along with their association with disability (expanded disability status scale [EDSS] and visual acuity). The volumetric analysis showed that, deep grey matter volumes were significantly lower in multiple sclerosis (p=0.0001) and MOGAD (p=0.02), compared to HC. Relapsing MOGAD had lower white matter, pallidus and hippocampus volumes than in monophasic (p<0.05). Optic chiasm volume was reduced only in NMOSD-AQP4 who had at least one episode of optic neuritis (ON) (NMOSD-AQP4-ON vs NMOSD-AQP4 p<0.001, HC p<0.001, MOGAD-ON p=0.04, multiple sclerosis-ON p=0.02) likely reflecting the recognised posterior location of NMOSD-AQP4-ON and its severity. Lesion volume was greatest in multiple sclerosis followed by MOGAD and in these two diseases, the lesion volume correlated with disease duration (multiple sclerosis R=0.46, p=0.05, MOGAD R=0.81, p<0.001), cortical thickness (multiple sclerosis R=-0.64, p=0.0042, MOGAD=-0.71, p=0.005) and deep grey matter volumes (multiple sclerosis R=-0.65, p=0.0034, MOGAD R=-0.93, p<0.001). Lesional-fractional anisotropy (FA) was reduced and mean diffusivity increased in all patients, but overall, FA was only reduced in the non-lesional tissue in multiple sclerosis (p=0.01), although focal reductions were noted in NMOSD-AQP4, reflecting mainly optic nerve and corticospinal tract pathways. Cortical/juxtacortical lesions were seen in a minority of MOGAD, while cortical/juxtacortical and purely cortical lesions were identified in the majority of multiple sclerosis and in none of the NMOSD-AQP4. Non-lesional FA in NMOSD-AQP4, lower white-matter volume and female sex in multiple sclerosis, and lower brainstem volume in MOGAD were the best predictors of EDSS disability (accounting for 46%, 49% and 19% respectively). Worse visual acuity associated with lower optic chiasm volume in NMOSD-AQP4 and lower thalamus volume in MOGAD (accounting for 58% and 35% respectively). Although MOGAD patients had good outcomes, deep grey matter atrophy was present. In contrast, NMOSD-AQP4 patients showed a relative sparing of deep grey matter volumes, despite greater residual disability as compared with MOGAD patients. NMOSD-AQP4 but not MOGAD patients showed reduced FA in non-lesional tissue.