Search

The detection of contrast-enhancing lesions (CELs) is fundamental for the diagnosis and monitoring of patients with multiple sclerosis (MS). This task is time-consuming and suffers from high intra- and inter-rater variability in clinical practice. However, only a few studies proposed automatic approaches for CEL detection. This study aimed to develop a deep learning model that automatically detects and segments CELs in clinical Magnetic Resonance Imaging (MRI) scans. A 3D UNet-based network was trained with clinical MRI from the Swiss Multiple Sclerosis Cohort. The dataset comprised 372 scans from 280 MS patients: 162 showed at least one CEL, while 118 showed no CELs. The input dataset consisted of T1-weighted before and after gadolinium injection, and FLuid Attenuated Inversion Recovery images. The sampling strategy was based on a white matter lesion mask to confirm the existence of real contrast-enhancing lesions. To overcome the dataset imbalance, a weighted loss function was implemented. The Dice Score Coefficient and True Positive and False Positive Rates were 0.76, 0.93, and 0.02, respectively. Based on these results, the model developed in this study might well be considered for clinical decision support.

Blood-brain barrier (BBB) breakdown and immune cell infiltration into the CNS are early hallmarks of multiple sclerosis (MS). The mechanisms leading to BBB dysfunction are incompletely understood and generally thought to be a consequence of neuroinflammation. Here, we have challenged this view and asked if intrinsic alterations in the BBB of MS patients contribute to MS pathogenesis. To this end, we made use of human induced pluripotent stem cells derived from healthy controls and MS patients and differentiated them into brain microvascular endothelial cell (BMEC)-like cells as in vitro model of the BBB. MS-derived BMEC-like cells showed impaired junctional integrity, barrier properties and efflux pump activity when compared to healthy controls. Also, MS-derived BMEC-like cells displayed an inflammatory phenotype with increased adhesion molecule expression and immune cell interactions. Activation of Wnt/β-catenin signalling in MS-derived endothelial progenitor cells enhanced barrier characteristics and reduced the inflammatory phenotype. Our study provides evidence for an intrinsic impairment of BBB function in MS patients that can be modelled in vitro. Human iPSC-derived BMEC-like cells are thus suitable to explore the molecular underpinnings of BBB dysfunction in MS and will assist in the identification of potential novel therapeutic targets for BBB stabilization., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Early lymphopenia is a known side effect of dimethyl fumarate, a disease-modifying therapy for MS. However, the long-term effects on immune response and the impact on lymphocyte counts when another disease-modifying treatment is introduced, remain unknown. To better understand these specific aspects, we reviewed cases that develop prolonged grade 2 to 4 lymphopenia under dimethyl fumarate in Lausanne MS clinic., Method: Retrospective analysis of the 12 patients (10.1%) who discontinued dimethyl fumarate because of prolonged lymphopenia amongst the 119 patients treated with dimethyl fumarate. We reviewed their demographics, as well as their clinical, biological and MRI characteristics compared to the non-lymphopenic patients, during dimethyl fumarate therapy, and within a timeframe of up to 18 months after switching to another disease-modifying treatment. We also focused on lymphocyte subsets in a subgroup of patients., Results: Compared to non-lymphopenic patients, lymphopenic patients were older at dimethyl fumarate initiation (51.4 yo vs 39.7, p = 0.0003) and the majority were male (p = 0.037). Three of them (25%) developed delayed lymphopenia, more than one year after treatment onset. Despite persistent lymphopenia, three patients experienced disease activity. Amongst the nine patients (75%) who were switched to another therapy, five (55.6%) presented recurrent lymphopenia, predominantly with a CD8 + T cell decrease., Conclusions: Dimethyl fumarate has a long-term impact on lymphocyte biology, even after its discontinuation, with a sustained reduction in CD8+ T cells that may increase opportunistic infection risk, and should be taken in consideration when switching therapies after dimethyl fumarate., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The central vein sign (CVS) has been shown to help in the differential diagnosis of multiple sclerosis (MS), but most prior studies are retrospective., Objectives: To prospectively assess the diagnostic predictive value of the CVS in diagnostically difficult cases., Methods: In this prospective multicenter study, 51 patients with suspected MS who had clinical, imaging, or laboratory "red flags" (i.e. features atypical for MS) underwent 3T fluid-attenuated inversion recovery (FLAIR*) magnetic resonance imaging (MRI) for CVS assessment. After the diagnostic work-up, expert clinicians blinded to the results of the CVS assessment came to a clinical diagnosis. The value of the CVS to prospectively predict an MS diagnosis was assessed., Results: Of the 39 patients who received a clinical diagnosis by the end of the study, 27 had MS and 12 received a non-MS diagnosis that included systemic lupus erythematosus, sarcoidosis, migraine, Sjögren disease, SPG4-spastic-paraparesis, neuromyelitis optica, and Susac syndrome. The percentage of perivenular lesions was higher in MS (median = 86%) compared to non-MS (median = 21%; p  < 0.0001) patients. A 40% perivenular lesion cutoff was associated with 97% accuracy and a 96% positive/100% negative predictive value., Conclusion: The CVS detected on 3T FLAIR* images can accurately predict an MS diagnosis in patients suspected to have MS, but with atypical clinical, laboratory, and imaging features.

New studies confirm the possibility of late thrombolysis. Meta-analyses have confirmed that CGRP inhibitors are efficacious for migraines. Cladribine is a new oral treatment for relapsing-remitting multiple sclerosis. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a new clinical entity accounting for cognitive decline in old patients. The timing of levodopa introduction has no effect on the long-term course of idiopathic Parkinson's disease. Hypophosphatemia helps distinguish between seizures and syncopes in the emergency department. A second course of intravenous immunoglobulins provides no benefit for severe Guillain Barre syndrome. Outdoor therapy improves clinical scales in patients with disorder of consciousness. Ultrasound guided lumbar puncture improves the yield of the procedure., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Cerebellar pathology occurs in late multiple sclerosis (MS) but little is known about cerebellar changes during early disease stages. In this study, we propose a new multicontrast "connectometry" approach to assess the structural and functional integrity of cerebellar networks and connectivity in early MS., Methods: We used diffusion spectrum and resting-state functional MRI (rs-fMRI) to establish the structural and functional cerebellar connectomes in 28 early relapsing-remitting MS patients and 16 healthy controls (HC). We performed multicontrast "connectometry" by quantifying multiple MRI parameters along the structural tracts (generalized fractional anisotropy-GFA, T1/T2 relaxation times and magnetization transfer ratio) and functional connectivity measures. Subsequently, we assessed multivariate differences in local connections and network properties between MS and HC subjects; finally, we correlated detected alterations with lesion load, disease duration, and clinical scores., Results: In MS patients, a subset of structural connections showed quantitative MRI changes suggesting loss of axonal microstructure and integrity (increased T1 and decreased GFA, P < 0.05). These alterations highly correlated with motor, memory and attention in patients, but were independent of cerebellar lesion load and disease duration. Neither network organization nor rs-fMRI abnormalities were observed at this early stage., Conclusion: Multicontrast cerebellar connectometry revealed subtle cerebellar alterations in MS patients, which were independent of conventional disease markers and highly correlated with patient function. Future work should assess the prognostic value of the observed damage., (© 2014 Wiley Periodicals, Inc.)