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-NMOSD were the proportion 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 RRMS over MOGAD were white matter lesions (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 combined with higher RNFL thickness best differentiated RRMS from MOGAD (accuracy/specificity/sensitivity: 84/92/77%, p < 0.001).
Discussion Cortical lesions, CVS, and optic nerve markers achieve a high accuracy in distinguishing RRMS from APQ4-NMOSD and MOGAD. This information may be useful in clinical practice, especially outside the acute phase and when serologic testing is ambiguous or not promptly available.
Classification of Evidence This study provides Class II evidence that selected conventional and advanced brain, cord, and optic nerve MRI and OCT markers distinguish adult patients with RRMS from AQP4-NMOSD and MOGAD.
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=
- susceptibility-weighted imaging;
- TWT=
- timed 25-foot walk test
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
The Article Processing Charge was funded by University College London.
Submitted and externally peer reviewed. The handling editor was Elizabeth Silbermann, MD.
Class of Evidence: NPub.org/coe
CME Course: NPub.org/cmelist
- Received January 18, 2022.
- Accepted in final form September 9, 2022.
- Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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