Contrasting patterns of gray matter damage across subtypes of MS

Among the multiple sclerosis (MS) subtypes, patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) were associated with gray matter damage and patients with neuromyelitis optica spectrum disorder-aquaporin-4 positive (NMOSD -AQP4) with reduced non-lesional tissue fractional anisotropy. These results 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 examined using magnetic resonance imaging (MRI).

The MOGAD, NMOSD-AQP4, MS, and control cohorts had mean ages of 41.8 ± 11.0, 55.6 ± 13.2, 44.1 ± 6.6, and 38.9 ± 13.4 years, respectively at baseline (p <0.001), 50%, 68.4%, 55.5 5% and 55.5% were women (P = 0.695) and 100%, 52.6%, 100% and 83% were white, respectively (P = 0.001). The median Extended Disability Status Scale was highest for NMOSD-AQP4 and lowest for MOGAD subgroups (P = 0.025), and mean visual acuity was highest for NMOSD-AQP4 and lowest for MS subgroups (P = 0.022).

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

Compared to the control group, the patient groups were MS (difference, -4092 mm3; P = 0.0001) and MOGAD (difference, -2609 mm3; P = 0.02) with a decreased total volume of deep gray matter and the NMOSD-AQP4-associated subgroup had significantly smaller brainstems (difference, -2575.8 mm3; P = .04). These patterns were driven by gray matter structures in the MS cohort and putamen atrophy in the MOGAD subgroup.

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

Stratified according to optic neuritis were patients with NMOSD-AQP4 who had a seizure, with lower chiasmatic volumes compared to the participants in the control group (P <.001), NMOSD-AQP4 without a seizure (P <.001) and other patient groups with an attack (both P £ .04).

Brain lesions were observed in 70% of the MOGAD, 100% of the NMOSD-AQP4, 100% of the MS, and 2 of the control group participants. The lesion volumes were increased in the MS group compared to the MOGAD subgroup (difference 2.219 mm3; P = 0.0005) and with the NMOSD-AQP4 cohort (difference 1.326 mm3; P = 0.03). Lesions were more common in the periventricular areas in patients with MS (P <.05).

Compared to the participants in the control group, the fractional lesion anisotropy (all P <0.001), the mean diffusivity (all P £ 0.02) and the radial diffusivity (all P <0.001) were reduced in the patients.

Lesion volume correlated with total deep gray matter volume (MOGAD: r, -0.93; P <0.001; MS: r, -0.65; P = 0.0034) and cortical thickness (MOGAD: r, -0 .71; P = 0.005; MS: r, -0.64; P = 0.0042.

This study was limited by the small sample size of the subgroups.

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

Disclosure: Some authors stated links with biotech, pharmaceutical, and / or device manufacturers. For a full list of the details, see the original article.


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

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