Clear Positive MOG Antibodies in Adults With Multiple Sclerosis Features: Diagnostic Challenges.

BACKGROUND AND

OBJECTIVES

Distinguishing multiple sclerosis (MS) from myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can be challenging because of some shared clinical and radiologic features. We aimed to describe adults with clear positive serum MOG antibodies (MOG-Abs) presenting with MS features and rethink their nosological framework.

METHODS

We conducted a retrospective longitudinal study within the French NOMADMUS cohort and included adults from 2015 to 2025 tested clear positive for MOG-Ab in the serum with at least 1 MS-suggestive feature: (1) biological (CSF-specific oligoclonal bands [OCBs] and/or kappa free light chain index [KFLCi] ≥5.7) or (2) radiologic (≥1 lesion among juxtacortical lesion, Dawson finger, or inferior temporal lobe lesion). All MRI scans were reviewed blindly by an expert neuroradiologist. Minimum clinical and radiologic follow-up was 6 months. We classified patients as (1) typical MS when fulfilling 2024 McDonald criteria, with OCB and/or KFLCi ≥5.7 and showing no MOGAD supporting features, or (2) equivocal in all other situations.

RESULTS

Among the 78 included patients (65% female, median age: 35 years), 23% were classified as typical MS and 77% as equivocal; all met MOGAD criteria, and 76% met 2024 McDonald criteria, without using central veinous sign or paramagnetic rim lesion, which have been rarely assessed. Myelitis followed by optic neuritis constituted the predominant clinical presentations in the whole cohort (45% and 32%, respectively) and in both groups. For typical MS cases, half of the patients did not receive maintenance therapy after the first MOG-Ab-positive event, 28% relapsed, 55% developed new silent lesions, and none showed lesion resolution (median follow-up: 1.9 years). For equivocal patients, 84% had OCB and 88% had ≥1 MOGAD supporting feature. After the first MOG-Ab-positive event, 72% initiated a maintenance therapy-mostly rituximab-15% relapsed, 46% developed silent new lesions, and 23% showed complete resolution of ≥1 lesion (median follow-up: 3 years).

DISCUSSION: Clear positive MOG-Ab may occur in patients with genuine MS, and their presence may lead to therapeutic inertia. The substantial proportion of equivocal cases highlights current diagnostic limitations and underscores the need for longitudinal clinical and radiologic reassessment.