Romain Marignier

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. 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. 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). 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.

Background: Serum neurofilament‐light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are associated with multiple sclerosis (MS) activity. This study aimed to identify patient‐ and disease‐level determinants of sNfL and sGFAP and to evaluate their ability to support differential diagnosis in neuromyelitis optica (NMO). Methods: sNFL and sGFAP levels were measured in 640 patients from the OFSEP cohort (88 NMO spectrum disorder (NMOSD) with anti‐aquaporin‐4 antibodies [AQP4‐NMOSD], 28 double‐seronegative NMOSD [DN‐NMOSD], 61 myelin oligodendrocyte glycoprotein antibody–associated disease [MOGAD], 64 clinically isolated syndrome [CIS], 237 relapsing–remitting MS [RRMS], and 162 primary progressive MS [PPMS]). The association between log[sNFL] and log[sGFAP] and age, sex, time since relapse, EDSS, oligoclonal bands, and MRI characteristics was analyzed by multiple linear regression. The diagnostic performance of sNfL and sGFAP in discriminating between NMOSD and MS subgroups was evaluated using multivariable logistic regression and area under the curve (AUC). Results: For each group, specific associations of sNFL and sGFAP levels with patient characteristics were observed. Clearest associations were observed in AQP4‐NMOSD patients. After a recent attack (≤ 90 days), multivariate analysis revealed that sGFAP and age discriminated AQP4‐NMOSD from MOGAD (AUC = 0.939 [0.910;0.982]), AQP4‐NMOSD and DN‐NMOSD from MOGAD (AUC = 0.863 [0.776;0.977]), and AQP4‐NMOSD from all other groups (AUC = 0.950 [0.918;0.987]). Diagnostic probability heatmaps based on sGFAP and age illustrate the probability of each diagnosis relative to others for bedside interpretation. Conclusion: After an acute attack of NMOSD, risk score based on sGFAP and age may guide the management of patients before autoantibody status is available.

Antibody-mediated inflammatory diseases of the CNS, including aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-Ab NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated...

ObjectivesAquaporin 4-immunoglobulin G-seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are rare conditio...

This post hoc analysis examined the impact of prior immunosuppressants on the long‐term efficacy and safety of inebilizumab, a cluster of differentiation 19 ⁺ B‐cell–depleting monoclonal antibody, in participants with aquaporin‐4–seropositive neuromyelitis optica spectrum disorder from the N‐MOmentum trial (NTC02200770). Inebilizumab treatment resulted in a sustained low annualized attack rate relative to the pretrial annualized attack rate and a high probability of remaining attack‐free for up to 4 years among participants with and without prior immunosuppressant use. Based on modeling data, inebilizumab had greater long‐term efficacy than historical immunosuppressants. Inebilizumab was well tolerated regardless of prior immunosuppressant use.

The differential diagnosis between aquaporin-4-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), and multiple sclerosis (MS) can be complex. Kappa free light chain index (KFLC-Index) emerged as an effective biomarker for distinguishing patients with MS from patients with other conditions. The main aim of this study was to assess the diagnostic performance of KFLC-Index in differentiating MOGAD, AQP4-NMOSD, and MS and to compare it with CSF-restricted oligoclonal bands (OCB) performance. We conducted a retrospective case-control study involving 18 French centers through our national NOMADMUS database. Patients were eligible if they received MOGAD or AQP4-NMOSD diagnosis and if OCB status and KFLC-Index levels were available or could be measured retrospectively. As a comparator, we included a group of patients with MS from the Lyon center. We included 303 patients with 140 MOGAD, 37 AQP4-NMOSD, and 126 MS. The sex ratio F/M was 1/1 in the MOGAD group, 5/1 in the NMOSD group, and 4/1 in the MS group. The median age was 38 years in the MOGAD group, 52 in the NMOSD group, and 32 in the MS group. The median KFLC-Index (interquartile range) was the lowest in the MOGAD group (0.60 [0.33-2.09]) with 71% of undetectable CSF-KFLC, intermediate in the NMOSD group (8.85 [3.04-16.78]), and the highest in the MS group (49.90 [16.31-113.39]). KFLC-Index had very good diagnostic performance in differentiating MOGAD from MS (area under the curve [AUC] 0.93, 95% CI 0.9-0.96) with an optimal threshold of 5.7 (95% CI 4.74-6.85), a sensitivity of 0.89 (0.83-0.94), and a specificity of 0.89 (0.83-0.94). KFLC-Index had good performance in differentiating NMOSD from MS (AUC 0.82, 95% CI 0.74-0.88) and MOGAD from NMOSD (AUC 0.77, 95% CI 0.69-0.86). KFLC-Index did not significantly outperformed OCB in separating MOGAD from MS and NMOSD from MS; however, the combination of the 2 tests was more performant than used separately. KFLC-Index is a valuable tool in distinguishing MS from AQP4-NMOSD and MOGAD and provides additional information to that given by OCB. We suggest that KFLC-Index as an additional supporting criterion for the differential diagnosis between MOGAD and MS.

Recent revisions to multiple sclerosis (MS) diagnostic criteria include the optic nerve as a site of dissemination in space, enabling this diagnosis in patients with acute optic neuritis (ON) and a single additional MS-typical location on MRI if dissemination in time (DIT) is demonstrated. We aimed to assess the frequency of non-MS diagnoses in this context. We retrospectively analyzed consecutive patients with inaugural acute ON and at least 1 MS-typical lesion in a single brain location on baseline MRI across 3 French centers. All patients met DIT criteria and underwent aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing. Final diagnoses were based on clinical, radiologic, and follow-up data. Among 96 patients (mean age 35.8 years; 70.8% female), 73 (76.0%) were diagnosed with MS and 23 (24.0%) with MOG antibody-associated disease (n = 18) or neuromyelitis optica spectrum disorder. Longitudinally extensive lesions, bilateral involvement, chiasmal enhancement, or optic perineuritis were observed in 100% of non-MS patients and 24.6% of patients with MS (difference 75.4%, 95% CI: 64.3-86.6; p < 0.001). All patients without these patterns were ultimately diagnosed with MS. AQP4 and MOG antibody testing, along with careful orbital MRI interpretation, is recommended in patients with ON meeting minimal new MS criteria.