Clemence Boutiere

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.

Natalizumab is a highly effective therapy but may impair central nervous system (CNS) immune surveillance, leading to rare opportunistic infections. We report a fatal case of cerebral toxoplasmosis under natalizumab. A 61-year-old man with stable multiple sclerosis (MS) developed acute hemiparesis on natalizumab therapy. Magnetic resonance imaging (MRI) showed multiple ring-enhancing lesions. Brain biopsy and polymerase chain reaction (PCR) confirmed reactivated Toxoplasma gondii . A low-risk IgG κ monoclonal gammopathy of undetermined significance (MGUS) was identified. Despite antiparasitic therapy, the patient developed coma and died. Natalizumab-induced CNS immune compartmentalization, combined with subtle MGUS-related immune dysfunction and immunosenescence, may have facilitated intracerebral reactivation. Vigilance for opportunistic infections may be warranted in older patients with hematologic comorbidities receiving natalizumab.

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.

Data on the plasma exchange (PLEX) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are limited. Herein, we evaluate outcomes after PLEX in MOGAD. This international multicenter retrospective cohort study included patients from 18 tertiary care centers in 6 countries. Inclusion criteria included fulfillment of the 2023 International MOGAD panel criteria, receipt of at least 3 sessions of PLEX, and follow-up of ≥3 months after PLEX. Patients with coexisting neuroinflammatory disorders were excluded. We assessed the frequency of complete recovery (CR), clinically significant improvement (CSI), visual acuity (VA), and Expanded Disability Status Scale (EDSS). Logistic regression analyses were performed to identify predictors of CR and CSI. Of 234 patients, 135 (58%) were female. The median (interquartile range [IQR]) age at attack was 34 (IQR 22-49) years, and 42 (17%) were children. In 165 of 243 (68%), the attack treated with PLEX was the first attack. Attack phenotypes included 161 optic neuritis (235 eyes), 77 myelitis, 24 acute disseminated encephalomyelitis, 15 brainstem/cerebellar, 3 cerebral-cortical encephalitis attack, and 1 cerebral polyfocal deficit-36 with >1 core phenotypes. A total of 239 (99%) attacks were also treated with corticosteroids and 32 (13%) with IV immunoglobulins. VA in optic neuritis improved from 20/400 (20/70-hand motion) to 20/20 (20/20-20/30), p < 0.001, and EDSS decreased from a median of 4.0 (3.0-6.5) to 1.0 (0.0-2.5), p < 0.001. Of 229 attacks without subsequent attacks within 3 months, 100 (44%) achieved CR and 213 (93%) CSI. The probability of CR was decreased with advanced age (adjusted odd ratio [95% CI] 0.97 [0.96-0.99] per year), higher EDSS worsening from baseline (0.66 [0.54-0.81] per 0.5 increment) and delayed PLEX (0.98 [0.96-0.99] per day). Advanced age (0.97 [0.96-0.99] per year) and delayed PLEX (0.95 [0.94-0.96] per day) decreased the probability of CSI. We observed favorable outcomes after PLEX in MOGAD attacks. However, advanced age and delayed initiation of PLEX were associated with a reduced probability of improvement. The absence of a control group limits our ability to differentiate PLEX effects from spontaneous recovery, prior corticosteroid response, or long-term immunotherapy. Future prospective studies are needed to assess the impact of PLEX on improvement. This study provides Class IV evidence that PLEX is associated with favorable clinical outcomes in patients with MOGAD.

A simple, quick, and reproducible procedure for distinguishing multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD) at inaugural optic neuritis (ION) could be highly valuable in guiding early management. We included all adults admitted to the MS center of Marseille for ION between March 2016 and April 2024, with CSF analysis including the kappa free light chain (K-FLC) index. Receiver operating characteristic curves were used to measure the diagnostic ability of the K-FLC index. Two hundred twenty-seven adults were admitted for ION; 210 (93%) had a K-FLC index measurement. MS was diagnosed in 84 (40%); clinically isolated syndrome suggestive of MS in 77 (36.5%), including 20 with future conversion to MS (CISwc); MOGAD in 26 (12.5%); NMOSD in 13 (6%); and other inflammatory disorders in 10 (5%). A K-FLC index ≥6.7 differentiated MS/CISwc from other diagnoses with specificity 86% and sensitivity 95% (area under the curve [AUC] 0.94). A K-FLC index <4.9 differentiated MOGAD from other diagnoses with specificity 63% and sensitivity 92% (AUC 0.78) and MOGAD from MS/CISwc with specificity 96% and sensitivity 92% (AUC 0.97). Among all patients, 93 (44%) had a K-FLC index <4.9: 24 of these (26%) had MOGAD and 5 (5.5%) MS/CISwc. Among the remaining patients with a K-FLC index ≥4.9 (n = 117), 2 (1.7%) had MOGAD (K-FLC index of 7.9 and 16.2) and 99 (85%) MS/CISwc. Among patients with normal MRI (n = 96), 73 (76%) had a K-FLC index <4.9: 22 of these (30%) had MOGAD, and none showed conversion to MS. Among the remaining patients with a K-FLC index ≥4.9 (n = 23), 2 (8.5%) had MOGAD and 7 (30.5%) showed conversion to MS. The K-FLC index did not differentiate NMOSD from other diagnoses and only moderately differentiated NMO from MS/CISwc (AUC 0.80). The K-FLC index is an accessible biomarker to guide early diagnosis in patients with ION. The probability of MOGAD in patients with ION and a K-FLC index ≥4.9 is low even in case of normal brain/spinal cord MRI. This study provides Class II evidence that for patients with ION, the K-FLC index can distinguish between MS/CISwc and MOGAD.

To evaluate the sensitivity of fluorescein angiography (FA) in detecting disease activity in Susac syndrome. We conducted a blinded analysis of all FA, brain MRI, and audiogram examinations performed throughout the follow-up of patients with Susac syndrome. A total of 79 FA examinations, 85 brain MRI scans, and 49 audiograms were analyzed from 9 patients followed for a mean (SD) period of 6 (4) years. Disease activity was detected in 41.5% of FA examinations, 10.5% of MRI scans, and 25% of audiograms (FA vs MRI, p < 0.0001; FA vs audiogram, p = 0.06; audiogram vs MRI, p < 0.05). Within 3 months of clinical relapses, activity was observed in 57%, 24%, and 27% of FA, MRI, and audiogram examinations, respectively (FA vs MRI, p < 0.05; FA vs audiogram, p = 0.09; audiogram vs MRI, p = 1). Quantitative analysis of FA showed a mean (SD) of 2.5 (2.5) leakages (both eyes) during relapses compared with 1.2 (1.4) during remission (p < 0.05). FA, particularly arterial leakage, demonstrated the highest sensitivity in detecting disease activity and may be a valuable tool for treatment management in Susac syndrome. Future studies with larger samples should aim to identify the optimal threshold of FA changes associated with an increased risk of relapse.

Real-life studies noted that the risk of disease activity in multiple sclerosis (MS) after switching to rituximab (RTX) or ocrelizumab (OCR) may be unequal depending on prior disease-modifying therapy (DMT), with a higher risk associated with fingolimod (FING). We performed a retrospective analysis of a structured prospective data collection including all consecutive patients with relapsing MS who were prescribed RTX/OCR in the MS center of Marseille. Cox proportional hazards models were applied to clinical and MRI outcomes. We included 321 patients with a median (interquartile range [IQR]) follow-up of 3.5 years (1.5-5) after RTX/OCR initiation. At the first RTX/OCR infusion, the mean (SD) age of patients was 37 (10) years, and the median (IQR) disease duration was 8 years (3-15): 68 patients did not receive treatment before RTX/OCR and 108 switched from FING, 47 from low efficacy therapy, and 98 from natalizumab. For statistical analysis, the group "FING" was divided into "short-FING" and "long-FING" groups according to the median value of the group's washout period (27 days). On Cox proportional hazards analysis, for only the "long-FING" group, the risk of relapse within the first 6 months of RTX/OCR was increased as compared with patients without previous DMT (hazard ratio [HR]: 8.78; 95% CI 1.72-44.86; p < 0.01). Previous DMT and washout period duration of FING had no effect on B-cell levels at 6 months. Beyond the first 6 months of RTX/OCR, age p = 0.01), male sex with increased risk of new T2 lesions (HR: 2.26; 95% CI 1.08-4.74; p = 0.03), and EDSS ≥2 with increased risk of disability accumulation (HR: 3.01; 95% CI 1.34-6.74; p < 0.01). Previous DMT had no effect on the effectiveness of RTX/OCR beyond 6 months after initiation. For patients switching from FING to RTX/OCR, the risk of disease reactivation within the first 6 months of treatment was increased as compared with patients with other DMT or no previous DMT only when the washout period exceeded 26 days. Neither FING nor other previous DMT reduced the effectiveness of RTX/OCR beyond the first 6 months of treatment.