Among subtypes with multiple sclerosis (MS), patients with myelin-oligodendrocytes-glycoprotein antibody-associated disease (MOGAD) were associated with gray matter damage and those with neuromyelitis optica spectrum disorder-aquaporin-4 positive (NMOSD-AQP4) with reduced nonlesional tissue fractional anisotropy. These findings were published in the Multiple Sclerosis Journal.

Healthy control group participants (n=18) and patients with MOGAD (n=20), NMOSD-AQP4 (n=19), and relapsing-remitting MS (n=18) were assessed via magnetic resonance imaging (MRI).

The MOGAD, NMOSD-AQP4, MS, and control cohorts had a mean age of 41.8±11.0, 55.6±13.2, 44.1±6.6, and 38.9±13.4 years at onset (P <.001), 50%, 68.4%, 55.5%, and 55.5% were women (P =.695), and 100%, 52.6%, 100%, and 83% were White (P =.001), respectively. The median Expanded Disability Status Scale was highest among NMOSD-AQP4 and lowest among MOGAD subgroups (P =.025), and average visual acuity was highest among NMOSD-AQP4 and lowest among MS subgroups (P =.022).

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No significant differences were observed for total brain volume, white/gray matter fraction, third/fourth ventricular volumes, cortical thickness and volumes, or optic chiasm volumes.

Compared with control group participants, MS (difference, -4092 mm3; P =.0001) and MOGAD (difference, -2609 mm3; P =.02) patient groups were associated with decreased total deep gray matter volumes and the NMOSD-AQP4 subgroup had significantly smaller brainstems (difference, -2575.8 mm3; P =.04). These patterns were driven by gray matter structures among the MS cohort and putamen atrophy among the MOGAD subgroup.

Compared with the NMOSD-AQP4 patients, those with MS had smaller caudate (difference, -650 mm3; P =.01).

Stratified by optic neuritis, patients with NMOSD-AQP4 who had an attack were associated with lower chiasmatic volumes compared with control group participants (P <.001), NMOSD-AQP4 with no attack (P <.001), and other patient groups with an attack (both P £.04).

Brain lesions were observed among 70% of the MOGAD, 100% of NMOSD-AQP4, 100% of MS, and 2 of the control group participants. Lesion volumes were increased among the MS group compared with the MOGAD subgroup (difference, 2.219 mm3; P =.0005) and with the NMOSD-AQP4 cohort (difference, 1.326 mm3; P =.03). Lesions occurred more frequently in the periventricular areas among patients with MS (P <.05).

Compared with control group participants, lesion fractional anisotropy (all P <.001), mean diffusivity (all P £.02), and radial diffusivity (all P <.001) were reduced among patients.

Lesion volume was correlated with total deep gray matter volume (MOGAD: r, -0.93; P <.001; MS: r, -0.65; P =.0034) and cortical thickness (MOGAD: r, -0.71; P =.005; MS: r, -0.64; P =.0042).

This study was limited by its small subgroup sample sizes.

These data indicated patients with NMOSD-AQP4 were spared deep gray matter atrophy despite the subtype association with greater disability whereas patients with MOGAD had deep gray matter atrophy. Additional studies are needed to measure the invisible symptoms of MS subtypes.

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original article for a full list of disclosures.


Messina S, Mariano R, Roca-Fernandez A, et al. Contrasting the brain imaging features of MOG-antibody disease, with AQP4-antibody NMOSD and multiple sclerosis. Mult Scler. Published online May 28, 2021. doi:10.1177/13524585211018987