Bertrand Audoin

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: In Susac syndrome, there is no standardized scoring system for the interpretation of fluorescein angiography (FA). The objective of this study was to standardize the angiographic evaluation of these patients by applying an angiographic score validated for uveitis to the specific context of Susac syndrome. Methods: Retrospective analysis of patients diagnosed with Susac syndrome was conducted. Angiograms were evaluated using a structured scoring system based on predefined angiographic features and their localization by retinal quadrants. The presence of these items was summed to generate a total score. Interobserver agreement was assessed between 2 independent graders for the angiographic scoring system. Results: From July 2015 to May 2024, 10 patients (mean age 32 ± 13 years; 60% male) were included. A total of 83 bilateral FA (166 eyes) were analyzed, with each patient undergoing between 2 and 17 examinations (median = 8) over a mean follow-up of 42.6 ± 30.2 months. Arterial leakage was present in 60% of patients, and capillary nonperfusion or arterial occlusion in 70% of patients at first visit. The development of new signs of arterial leakage and/or nonperfusion was documented in 33.13% of follow-up angiograms. Most items showed excellent interobserver agreement, with weighted Cohen kappa values above 0.8, and all but 1 item exceeding 0.7. Conclusions: This angiographic scoring system demonstrates validity and repeatability for assessing Susac syndrome. Further prospective studies are needed to assess its application in larger cohorts, explore treatment response, and evaluate its role in guiding therapy decisions.

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.

Recent developments in quantitative T1 have enabled simultaneous scanning of both the brain and the cervical spinal cord (cSC) using the magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE) sequence. However, the multicentre variability of such an approach has not yet been assessed. In this paper, we aim to evaluate multicentre variability (inter-scanner, between-session, between-participant) of T1 MP2RAGE measurements in the brain and cSC. A total of 52 MP2RAGE scans were acquired at two centres equipped with Siemens 3T MRI systems using an optimized MP2RAGE sequence. A subset of participants underwent scanning at both centres to evaluate inter-site variability. Between-session and inter-participant variability were assessed both globally and within specific regions, including brain white matter, cortical gray matter, deep gray matter, and cervical spinal cord vertebral levels using a linear mixed effect model. Mean intra-site/inter-site/between-participant coefficients of variation (COV) were 0.4/0.9/2.3% for the brain ROIs and 2.0/2.4/1.7% for the cSC. Our findings validate the consistency and reliability of the MP2RAGE brain and cervical spinal cord simultaneous acquisition in a multicentre setting. This approach has the potential to significantly impact the study of central nervous system pathologies, such as multiple sclerosis, by enabling fast, accurate, and reproducible quantitative imaging collection across multiple centres.

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

Objective: Corticospinal tract damage is common in people with MS, but the degree of clinical symptoms varies. We hypothesize that corticospinal tract lesions are more extensive and severe in people with MS with motor impairments in both upper and lower limbs. We compared three groups of patients: isolated hyperreflexia (A), motor deficits limited to the lower limbs (B), or in both upper and lower limbs (C). Methods: We included 100 people with MS in a prospective cross‐sectional study. Corticospinal tract lesions were segmented on 3D FLAIR (brain) and axial T2* and T2‐weighted images (cervical and thoracic spinal cord). MP2RAGE quantitative T1 was used to assess microstructural damage severity in the brain and cervical spinal cord corticospinal tract. Results: Ninety‐two people with MS were included in the analysis (A = 38, B = 31, C = 23). Lesion volume was higher in groups B and C than in group A in the brainstem and cervical corticospinal tract (all p < 0.001), and quantitative T1 was higher only in the cervical corticospinal tract (all p < 0.05). In the multivariate analysis, age, disease duration, lesion volume in the brainstem, and quantitative T1 in the cervical spinal cord distinguished group A from groups B and C, but no differentiating factors were identified between groups B and C. Interpretation: Our study suggests that motor deficit in pwMS was associated with brainstem and cervical spinal cord corticospinal tract damage. Differences between pwMS with lower limb deficits and those with both lower and upper limb deficits could not be established.

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.

Background/Objectives: Characterizing spinal cord multiple sclerosis (MS) lesions in MRI is critical for diagnosis, monitoring, and treatment evaluation. However, current automated approaches for lesion detection and segmentation are typically designed for specific MRI contrasts or acquisition sites, limiting their generalizability in real-world clinical settings where imaging protocols vary widely. This work proposes a robust multi-site, multi-contrast segmentation framework for spinal cord lesions. Methods: The segmentation model was trained and evaluated on a large-scale dataset comprising 4428 annotated images from 1849 persons with MS across 23 imaging centers, encompassing six MRI contrasts (T1w, T2w, T2*w, PSIR, STIR, and UNIT1) acquired at 1.5 tesla (T), 3 T, and 7 T. Results: Likert-type assessment performed by neuroradiologist ratings demonstrated superior generalization of the model compared to existing contrast-specific pipelines ( p < 0.01). Additional experiments evaluated robustness across spinal levels, acquisition resolutions, binarization thresholds, and quantitative evaluation on external labeled datasets. Conclusions: The proposed model can achieve accurate and reliable spinal cord MS lesion segmentation across heterogeneous MRI data, addressing a key barrier to clinical translation. The model is available in the Spinal Cord Toolbox v7.2 and higher. Code repository: https://github.com/ivadomed/seg-sc-ms-lesion-multicontrast

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.