INTRODUCTIONRituximab (RTX) has been proven effective in managing refractory generalized myasthenia gravis (MG), and its use is increasing worldwide. MG stabilization may initially require oral ...corticosteroid (CS) therapy, but its long-term side effects require the shortest duration of treatment. We studied the clinical effectiveness and usefulness of corticosteroids associated with RTX compared to RTX alone on MG remission.METHODSIn a monocentric retrospective cohort in the Nice University Hospital, we compared naïve MG patients treated with RTX as first-line therapy alone (G1) or associated with CS (G2). After the RTX induction, we evaluated efficacy with the Osserman score (OS) and the requirement for any rescue therapy (IVIg or plasmapheresis).RESULTSSixty-eight patients were treated with RTX, of which 19 (27.94%) benefited from an association with at least 0.5 mg/kg of corticosteroids. RTX-CS patients were more severe than RTX alone (OS for G1: 74.1 and G2: 64.94, p = 0.044). However, OS at 3 (83.44 and 83.12, p = 0.993), 6 (88.69 and 86.36, p = 0.545), 9 (82.91 and 85.73, p = 0.563), and 12 months (86.6 and 88.69, p = 0.761) from the treatment induction were similar. Rescue therapy following RTX induction was significantly higher for the RTX-CS (20.41% and 47.37%, p = 0.037). Regarding safety, adverse event rates were similar in the two groups (0% and 14.29%, p = 0.178).CONCLUSIONWe suggest that RTX alone is as effective as RTX-CS in MG patients, indicating that avoiding steroids could reduce side effects, decrease rescue therapies, and not affect MG outcomes.
The radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS). Increasing evidence suggests that the central vein sign (CVS) enhances ...lesion specificity, allowing for greater MS diagnostic accuracy. This study evaluated the diagnostic performance of the CVS in RIS.
Patients were prospectively recruited in a single tertiary center for MS care. Participants with RIS were included and compared to a control group of sex and age-matched subjects. All participants underwent 3 Tesla magnetic resonance imaging, including postcontrast susceptibility-based sequences, and the presence of CVS was analyzed. Sensitivity and specificity were assessed for different CVS lesion criteria, defined by proportions of lesions positive for CVS (CVS+) or by the absolute number of CVS+ lesions.
180 participants (45 RIS, 45 MS, 90 non-MS) were included, representing 5285 white matter lesions. Among them, 4608 were eligible for the CVS assessment (970 in RIS, 1378 in MS, and 2260 in non-MS). According to independent ROC comparisons, the proportion of CVS+ lesions performed similarly in diagnosing RIS from non-MS than MS from non-MS (p = 0.837). When a 6-lesion CVS+ threshold was applied, RIS lesions could be diagnosed with an accuracy of 87%. MS could be diagnosed with a sensitivity of 98% and a specificity of 83%. Adding OCBs or Kappa index to CVS biomarker increased the specificity to 100% for RIS diagnosis.
This study shows evidence that CVS is an effective imaging biomarker in differentiating RIS from non-MS, with similar performances to those in MS.
Background:
Vaccination in patients with multiple sclerosis (MS) treated with immunosuppressive drugs is highly recommended. Regarding COVID-19 vaccination, no specific concern has been raised.
...Objectives:
We aimed to evaluate if COVID-19 vaccination or infection increased the risk of disease activity, either radiological or clinical, with conversion to MS in a cohort of people with a radiologically isolated syndrome (RIS).
Methods:
This multicentric observational study analyzed patients in the RIS Consortium cohort during the pandemic between January 2020 and December 2022. We compared the occurrence of disease activity in patients according to their vaccination status. The same analysis was conducted by comparing patients’ history of COVID-19 infection.
Results:
No difference was found concerning clinical conversion to MS in the vaccinated versus unvaccinated group (6.7% vs 8.5%, p > 0.9). The rate of disease activity was not statistically different (13.6% and 7.4%, respectively, p = 0.54). The clinical conversion rate to MS was not significantly different in patients with a documented COVID-19 infection versus non-infected patients.
Conclusion:
Our study suggests that COVID-19 infection or immunization in RIS individuals does not increase the risk of disease activity. Our results support that COVID-19 vaccination can be safely proposed and repeated for these subjects.
Le syndrome radiologique isolé (RIS) représente la phase pré-symptomatique de la sclérose en plaques (SEP). De plus en plus de preuves suggèrent que le signe de la veine centrale (SVC) améliore la ...spécificité des lésions, permettant ainsi meilleure précision du diagnostic de SEP.
Cette étude a pour objectif d’évaluer les performances diagnostiques du SVC chez les sujets RIS.
Il s’agit d’une étude monocentrique, prospective. Les sujets RIS ont été inclus et comparés à des patients SEP et à des contrôles non-SEP. Tous les participants ont réalisé une IRM, comprenant une séquence de susceptibilité magnétique optimisée, et la présence du SVC a été analysée. La sensibilité et la spécificité ont été évaluées en utilisant différents critères basés sur des proportions de lésions positives pour le SVC (SVCL+) et sur un nombre absolu de SVCL+.
Au total, 45 RIS, 45 SEP et 90 non-SEP ont été inclus, représentant 4608 lésions de la substance blanche éligibles à l’évaluation du SVC. Selon des comparaisons de courbes ROC indépendantes, la proportion de SVCL+ montrent des performances diagnostiques similaires en comparant les RIS et les SEP aux non-SEP (p=0,837). Lorsqu’un seuil de 40 % de SVCL+ était appliqué, le RIS pouvait être diagnostiqué avec une sensibilité de 84 % et une spécificité de 90 %, et la SEP pouvait être diagnostiquée avec la même spécificité et une sensibilité de 93 % (Fig. 1 et 2).
À ce jour, il n’y a pas de biomarqueur exclusif permettant le diagnostic de SEP et par extension de RIS. Nos résultats renforcent l’importance du SVC dans l’identification de lésions démyélinisantes du système nerveux central.
Cette étude montre que le SVC est un biomarqueur d’imagerie efficace pour différencier les RIS des non-SEP, avec des performances similaires à celles de la SEP.
Le syndrome radiologique isolé (RIS) représente la phase pré-symptomatique de la sclérose en plaques (SEP). De plus en plus de preuves suggèrent que le signe de la veine centrale (SVC) améliore la ...spécificité des lésions, permettant ainsi une plus grande précision du diagnostic de SEP.
Cette étude a pour objectif d’évaluer les performances diagnostiques du SVC chez les sujets RIS.
Il s'agit d'une étude monocentrique, prospective. Les sujets RIS ont été inclus et comparés à un groupe de patients SEP et à un groupe de témoins non-SEP appariés en sexe et en âge (+/- 5 ans). Tous les participants ont réalisé une imagerie par résonance magnétique 3T, comprenant une séquence de susceptibilité magnétique optimisée (SWAN-veinule) après injection de gadolinium, et la présence du SVC a été analysée. La sensibilité et la spécificité ont été évaluées en utilisant différents critères, utilisant des proportions de lésions positives pour le SVC (SVC+) ou par un nombre absolu de lésions SVC+.
180 participants (45 RIS, 45 SEP, 90 non-SEP) ont été inclus, représentant 5 285 lésions de la substance blanche. Parmi elles, 4 608 étaient éligibles à l’évaluation du SVC (RIS : 970, SEP : 1 378, non-SEP : 2 260). Selon des comparaisons de courbes ROC indépendantes, la proportion de lésions SVC+ montrent des performances diagnostiques similaires en comparant les RIS aux non-SEP et les SEP aux non-SEP (p= 0,837). Lorsqu'un seuil de 40% de SVC+ était appliqué, le RIS pouvait être diagnostiqué avec une sensibilité de 84 % et une spécificité de 90 %, et la SEP pouvait être diagnostiquée avec une sensibilité de 93 % et une spécificité de 90 %.
A ce jour, il n'y a pas de biomarqueur exclusif permettant le diagnostic de SEP et par extension de RIS. Nos résultats renforcent l'importance du SVC dans l'identification de lésions démyélinisantes du système nerveux central.
Cette étude montre que le SVC est un biomarqueur d'imagerie efficace pour différencier les RIS des non-SEP, avec des performances similaires à celles de la SEP (fig. 1, tab 1,2).
Abstract
The radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the CNS within ...individuals lacking symptoms typical of multiple sclerosis (MS). The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown.
2009-RIS subjects, by definition, fulfil three to four of four criteria for 2005 dissemination in space (DIS) and subjects fulfilling only one or two lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated.
Seven hundred and forty-seven subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled one or two 2017 DIS criteria (designated as Groups 1 and 2, respectively), and 496 (66.4%) fulfilled three or four 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS group and were more likely to develop new T2 lesions over time (P < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to MS.
At 5 years, the cumulative probability for a clinical event was 29.0% for Groups 1 and 2 compared to 38.7% for 2009-RIS (P = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1–2 increased the risk of symptomatic MS evolution at 5 years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (P < 0.001). The 2009-RIS subjects or Groups 1 and 2 with at least two of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied.
This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria.
Lebrun-Frénay et al. show that individuals who do not meet the diagnostic criteria for radiologically isolated syndrome based on their number of white matter lesions nevertheless transition to symptomatic multiple sclerosis at a similar rate to individuals who do fulfil the criteria, when additional risk factors are present.
BACKGROUND AND OBJECTIVESTo evaluate whether the kappa free light chain index (K-index) can predict the occurrence of new T2-weighted MRI lesions (T2L) and clinical events in clinically isolated ...syndrome (CIS) and radiologically isolated syndrome (RIS). METHODSAll consecutive patients presenting for the diagnostic workup, including CSF analysis, of clinical and/or MRI suspicion of multiple sclerosis (MS) since May 1, 2018, were evaluated. All patients diagnosed with CIS and RIS with at least 1-year follow-up were included. Clinical events and new T2L were collected during follow-up. The K-index performances in predicting new T2L and a clinical event were evaluated using time-dependent ROC analyses. The time to clinical event or new T2L was estimated using survival analysis according to the binarized K-index using an independent cutoff of 8.9, and the ability of each variable to predict outcomes was compared using the Harrell c-index. RESULTSOne hundred and eighty two patients (146 CIS and 36 RIS, median age 39 30; 48 y-o, 70% females) were included with a median follow-up of 21 13, 33 months. One hundred five (58%) patients (85 CIS and 20 RIS) experienced new T2L, and 28 (15%; 21 CIS and 7 RIS) experienced a clinical event. The K-index could predict new T2L over time in CIS (area under the curve AUC ranging from 0.86 to 0.96) and in RIS (AUC ranging from 0.84 to 0.54) but also a clinical event in CIS (AUC ranging from 0.75 to 0.87). Compared with oligoclonal bands (OCBs), the K-index had a better sensitivity and a slight lower specificity in predicting new T2L and clinical events in both populations. In the predictive model, the K-index was the variable that best predict new T2L in both CIS and RIS but also clinical events in CIS (c-index ranging from 0.70 to 0.77), better than the other variables, including OCB. DISCUSSIONThis study provides evidence that the K-index predicts new T2L in CIS and RIS but also clinical attack in patients with CIS. We suggest adding the K-index in the further MS diagnosis criteria revisions as a dissemination-in-time biomarker.
Les lésions de la substance blanche (WML pour White Matter Lesions) sur l'imagerie par résonance magnétique (IRM) sont une constatation courante dans la pratique clinique1. Alors que l'IRM devient de ...plus en plus accessible, les praticiens sont confrontés à des patients qui ont réalisés une IRM pour différentes raisons, demandant une confirmation de diagnostic de sclérose en plaques (SEP) malgré la discordance de la présentation clinique. Des guidelines2 ont été élaborées pour afin de faciliter le diagnostic mais des erreurs diagnostic3 sont encore fréquentes.
L'objectif de cette étude est d'explorer et de mettre en évidence les difficultés diagnostiques face à la découverte de WML sur l'IRM.
L’étude est basée sur une enquête, distribuée en ligne aux praticiens, comportant seize analyses d'images pondérées en T2, dont 10 étaient guidées, 4 n'étaient pas guidées et 2 étaient associées à l'application des critères d'imagerie de dissémination dans l'espace (DIS) de McDonald.
364 participants ont répondu à l'enquête. Selon l'identification de la localisation des lésions guidées, 34,3 % et 16,9 % des participants ont correctement identifié les lésions juxtacorticales (JC) et périventriculaires (PV), respectivement, tandis que 56,3 % ont correctement identifié les lésions non-guidées. L'application des critères de DIS de McDonald 2017 était correcte pour 35,3% des participants. Selon un score global de l'ensemble des questions de l'enquête, les facteurs indépendamment associés aux réponses correctes étaient la sous-spécialité experte en SEP (p<0,001) et les jeunes cliniciens (p=0,02). A contrario, l'utilisation d'un smartphone pour répondre à l'enquête étaient corrélée à un mauvais score (p =0,03).
Nos résultats mettent en évidence les difficultés liées à l'analyse des WML dans la pratique clinique et suggèrent que les diagnostics de SEP doivent être effectués par des médecins expérimentés afin de limiter les erreurs de diagnostic.
