Search

Background: Diagnosis of multiple sclerosis (MS) frequently relies on MRI dissemination in time (DIT) and space (DIS), as codified in 2017 McDonald criteria (McD 2017). The central vein sign (CVS) is a proposed MS diagnostic biomarker, but its optimal incorporation into McD 2017 has not been extensively studied., Objective: Evaluate the diagnostic performance of several methods incorporating CVS into McD 2017 radiological DIS criteria., Methods: Data were obtained from the CAVS-MS Pilot, a cross-sectional, international multi-center study conducted by the North American Imaging in MS Cooperative (NAIMS) that recruited adults referred for suspicion/diagnosis of demyelinating disease. Diagnostic performance of methods incorporating CVS into McD 2017 radiological DIS were evaluated by comparing sensitivity, specificity, and accuracy., Results: 78 participants (37 MS, 41 others) were included. For MS diagnosis, sensitivity, specificity, and accuracy of DIS based on brain imaging (DIS-B) alone was 92 %, 69 %, and 78 %. Requiring at least one lesion with CVS in any brain location in addition to DIS-B increased specificity (sensitivity 92 %, specificity 81 %, accuracy 86 %). Presence of 2 deep white matter lesions with CVS as an additional topography for DIS-B had higher sensitivity (sensitivity 97 %, specificity 59 %, accuracy 77 %)., Conclusions: Incorporation of CVS in McD 2017 DIS criteria can be used to improve diagnostic accuracy. Validation in additional prospective studies is needed., Competing Interests: Declaration of competing interest MA: Received Novartis fellowship award NGC4474. KN: Received licensing fee from Biogen; received Research Support from Department of Defense, National Institutes of Health, Patient Centered Outcomes Research Institute, and Biogen. LD: None CMO: None QC: None PR: Employed by and holds stocks in QMENTA JD: None CA: Has received grant support from the National Multiple Sclerosis Society and the NIH. Has received consulting fees from Horizon Therapeutics, Genentech, Sanofi Genzyme, TG Therapeutics, and EMD Serono. Has received honoraria for serving on grant review committees for the Department of Defense and the NIH and for participation in unbranded CME activities from the American Academy of Neurology, Efficient LLC, Spire Learning, and Catamount Medical Education AB: Consulting and/or advisory board fees from Accure, Atara Biotherapeutics, Biogen, BMS/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, Sanofi-Genzyme. Grant support to the University of Pennsylvania from Biogen Idec, Roche/Genentech, Merck/EMD Serono and Novartis. Research funding from the National Institutes of Health (NIH), The National MS Society (NMSS), the Juvenile Diabetes Research Foundation (JDRF), the Canadian Institutes of Health Research, Multiple Sclerosis Society of Canada. EC: None PAC: PI on grants to JHU from Genentech. Serves on scientific advisory boards for Lilly, Novartis, Idorsia, and Project Efflux. BACC: Compensation for consulting from: Alexion, Atara, Autobahn, Avotres, Biogen, Boston Pharma, EMD Serono, Gossamer Bio, Hexal/Sandoz, Horizon, Immunic AG, Kyverna, Neuron23, Novartis, Sanofi, and TG Therapeutics and research support from Genentech. LF: Received fees for consultancy and/or advisory board participation from Genentech, Novartis, Celgene/Bristol Myers Squibb, EMD Serono, and TG Therapeutics; Received fees for educational activities from Medscape, LLC, and the MS Association of America; program sponsorship to UT from EMD Serono; and grant support to UT from NIH/NINDS, PCORI, Genentech, and EMD Serono. RGH: Research support from Roche, Genentech, Atara, Medday. Consulting for Novartis, Sanofi/Genzyme, Roche/Genentech, QIA, and Neurona. EEL: Grants: Genentech, Biogen. Consulting: EMD Serono, BMS, Genentech, Genzyme, Bristol Myers Squibb, TG Therapeutics, Janssen, NGM Bio JO: Research support from Biogen-Idec, Roche, and EMD-Serono; consulting compensation from EMD-Serono, Sanofi-Genzyme, Biogen-Idec, Roche, Celgene, and Novartis NP: Reports research support from the Race to Erase MS Foundation and from the National Center for Advancing Translational Sciences, National Institutes of Health, through a UCSF-CTSI grant DP: Consulting compensation from EMD-Serono, Sanofi Genzyme, Roche, and Novartis VP: Employed by and holds stocks in QMENTA PR: None MR: Employed by and holds stock options in QMENTA RDS: Advisory board participation (Biogen, EMD Serono, Sanofi Genzyme); Consulting (EMD Serono, Biogen) MKS: None ESS: Consulting for scientific advisory boards from Viela Bio and Genentech, Speaker honoraria from Viela Bio NLS: Research support from the National Institutes of Health, National Multiple Sclerosis Society, Patient Centered Outcomes Research Institute, Race to Erase MS Foundation and Biogen-Idec AJS: Consulting: EMD Serono, Biogen, Alexion, Celgene, Greenwich Biosciences, Octave Bioscience, TG Therapeutics, Sanofi; Non-promotional speaking: EMD Serono; Research Funding: Biogen, Bristol Myers Squibb; Contracted Research: Biogen, Novartis, Actelion, Genentech/Roche RTS: Supported NIH R01NS112274, R01MH112847, R01MH123550. Consulting income from Octave Bioscience. DSR: Research support from Sanofi-Genzyme and Abata Therapeutics, unrelated to the current study. PS: Research support from the National Institutes of Health, National Multiple Sclerosis Society, Department of Defense, Erwin Rautenberg fondation. DO: Received research support from the National Institutes of Health, National Multiple Sclerosis Society, Patient Centered Outcomes Research Institute, Race to Erase MS Foundation, Genentech, Genzyme, and Novartis. Consulting fees from Biogen Idec, Genentech/Roche, Genzyme, Novartis, and Merck., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives: Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed., Methods: Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab., Results: Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1-7] and 7% [95% CI 4-11]), ICU/artificial ventilation (2% [95% CI 0-4] and 4% [95% CI 2-6]), and death (1% [95% CI 0-2] and 2% [95% CI 1-4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2-8), 3% (95% CI 1-5), and 1% (95% CI 0-3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19., Discussion: Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing (e.g., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)