Differentiating Multiple Sclerosis From AQP4-Neuromyelitis Optica Spectrum Disorder and MOG-Antibody Disease With Imaging

Abstract

Background and Objectives Relapsing-remitting multiple sclerosis (RRMS), aquaporin-4 antibody–positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) may have overlapping clinical features. There is an unmet need for imaging markers that differentiate between them when serologic testing is unavailable or ambiguous. We assessed whether imaging characteristics typical of MS discriminate RRMS from AQP4-NMOSD and MOGAD, alone and in combination. Methods Adult, nonacute patients with RRMS, APQ4-NMOSD, and MOGAD and healthy controls were prospectively recruited at the National Hospital for Neurology and Neurosurgery (London, United Kingdom) and the Walton Centre (Liverpool, United Kingdom) between 2014 and 2019. They underwent conventional and advanced brain, cord, and optic nerve MRI and optical coherence tomography (OCT). Results A total of 91 consecutive patients (31 RRMS, 30 APQ4-NMOSD, and 30 MOGAD) and 34 healthy controls were recruited. The most accurate measures differentiating RRMS from AQP4-NMOSDweretheproportion of lesions with the central vein sign (CVS) (84% vs 33%, accuracy/specificity/sensitivity: 91/88/93%, p < 0.001), followed by cortical lesions (median: 2 [range: 1–14] vs 1 [0–1], accuracy/specificity/sensitivity: 84/90/77%, p = 0.002) and white matter lesions (mean: 39.07 [±25.8] vs 9.5 [±14], accuracy/specificity/sensitivity: 78/84/73%, p = 0.001). The combination of higher proportion of CVS, cortical lesions, and optic nerve magnetization transfer ratio reached the highest accuracy in distinguishing RRMS from AQP4-NMOSD (accuracy/specificity/sensitivity: 95/92/97%, p < 0.001). The most accurate measures favoring RRMSoverMOGADwerewhitematterlesions(39.07[±25.8]vs 1 [±2.3], accuracy/specificity/sensitivity: 94/94/93%, p = 0.006), followed by cortical lesions (2 [1–14] vs 1 [0–1], accuracy/specificity/sensitivity: 84/97/71%, p = 0.004), and retinal nerve fiber layer thickness (RNFL) (mean: 87.54 [±13.83] vs 75.54 [±20.33], accuracy/specificity/sensitivity: 80/79/81%, p = 0.009). Higher cortical lesion number Glossary 9-HPT = 9-hole peg test; Ab = antibody; AQP4-NMOSD = aquaporin-4 antibody–positive neuromyelitis optica spectrum disorder; AUC = area under the curve; CBA = cell-based assay; CSA = cross-sectional area; CVS = central vein sign; DTI = diffusion tensor imaging; EDSS = Expanded Disability Status Scale; GCIPL = ganglion cell–inner plexiform layer; MOGAD = myelin oligodendrocyte glycoprotein antibody–associated disease; MTR = magnetization transfer ratio; OCT = optical coherence tomography; RC = regression coefficient; RRMS = relapsing-remitting multiple sclerosis; SWI = susceptibilityweighted imaging; TWT = timed 25-foot walk test.