Sarah Demortiere

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.

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.

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.

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.

Background Progression independent of relapse activity (PIRA) has been described since the early stage of relapsing multiple sclerosis (RMS). However, little is known about the relation between PIRA and inflammatory activity that is particularly important at this stage of the disease. Method We included 110 patients in a prospective study within 18 months of RMS onset. MRI examinations and clinical visits were scheduled on the same day for months 0, 6, 12, 24, 36, 60, 84, 120, 180 and 240. Results The mean (SD) age of patients was 30 (6.7) years at inclusion and median (range) follow-up 15 (9–20) years. Analysis of 1118 between-visit intervals revealed 93 confirmed disability accumulation events in 68 (62%) patients: 50 (54%) events related to relapse activity worsening and 43 (46%) PIRA events, including 17 (18%) with MRI activity. The risk of PIRA between two visits (stable event as the reference category) was associated with Expanded Disability Status Scale (EDSS) score (HR: 1.41; 95% CI: 1.18 to 1.69; pConclusion This study evidenced that inflammatory activity increases the risk of PIRA in early RMS, arguing that a significant part of PIRA is accessible to treatment targeting inflammation in these patients.

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.