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159 results on '"Gilles, Edan"'

1. Discontinuation of second- versus first-line disease-modifying treatment in middle-aged patients with multiple sclerosis

Author: Maëlle Chappuis, Chloé Rousseau, Emma Bajeux, Sandrine Wiertlewski, David Laplaud, Emmanuelle Le Page, Laure Michel, Gilles Edan, Anne Kerbrat, CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigation Clinique [Rennes] (CIC), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Multiple Sclerosis, Fingolimod Hydrochloride, Treatment discontinuation, [SDV]Life Sciences [q-bio], Natalizumab, Middle Aged, Age, Multiple Sclerosis, Relapsing-Remitting, Neurology, Recurrence, Humans, Neurology (clinical), Immunosuppressive Agents, Retrospective Studies
Abstract: International audience; Background and purpose: There has been scant research on the consequences of discontinuing second-line disease-modifying treatment (DMT) in middle-aged patients with multiple sclerosis (MS). The objective was therefore to examine the occurrence of focal inflammatory activity after the discontinuation of second versus first-line DMT in patients over 45 years.Methods: Patients who had been treated for at least 6 months with second (natalizumab, fingolimod, anti CD20) or first-line DMT and who stopped their DMT were retrospectively included. Kaplan-Meier survival curves were used to study the occurrence of relapse and MRI activity according to the type of DMT stopped. Proportional hazard Cox models were calculated to identify factors associated with focal inflammatory activity. The annualized relapse rate was calculated under treatment and for every 3 months after DMT discontinuation.Results: We included 232 patients (median age: 52.8 years), 49 of whom stopped second-line DMT. The probability of having a relapse within the year following discontinuation was 6% for first-line DMT, 9% for fingolimod and 43% for natalizumab. In multivariate analysis, the probability of relapse after DMT discontinuation was significantly increased with natalizumab compared to first-line DMT (HR = 3.24; 95% CI [1.52; 6.90]). A peak of relapse was observed at 0-3 months after stopping natalizumab or fingolimod.Conclusion: Our study suggests that the risk of inflammatory activity is greater after discontinuation of natalizumab compared to other DMT even in middle-aged patients. As for younger patients, natalizumab discontinuation should only be considered if there is an adequate substitution of a different therapy. .
Published: 2022

2. Disability progression in multiple sclerosis patients using early first‐line treatments

Author: Mathilde, Lefort, Sandra, Vukusic, Romain, Casey, Gilles, Edan, Emmanuelle, Leray, Chantal, Nifle, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Département Méthodes quantitatives en santé publique (METIS), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Lyon], CHU Lyon, Fondation Eugène Devic EDMUS, This work was funded by the Eugène Devic EDMUS Foundation against Multiple Sclerosis and by the ARSEP Foundation (Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: beta-interferon, disability progression, Neurology, [SDV]Life Sciences [q-bio], glatiramer acetate, early treatment, Neurology (clinical), multiple sclerosis, observational studies, propensity score
Abstract: International audience; BACKGROUND: Therapeutic management of relapsing-remitting multiple sclerosis (RRMS) has evolved towards early treatment. The objective was to assess the impact of early treatment initiation on disability progression among RRMS first-line treated patients. METHODS: This study included all incident RRMS cases starting interferon or glatiramer acetate for the first time from 1996/01/01 to 2012/31/12 (N=5,279) from ten MS expert OFSEP centers (Observatoire Français de la Sclérose en Plaques). The delay from treatment start to attain an irreversible Expanded Disability Status Scale score of 3.0 were compared between "Early" group (N= 1,882; treated within 12 months following MS clinical onset) and "Later" group using propensity score weighted Kaplan-Meier methods, overall and stratified by age. RESULTS: Overall, the restricted mean time before reaching EDSS 3.0 (RMST) from treatment start was 11 years and two months for patients treated within the year following MS clinical onset and 10 years and seven months for patients treated later. Thus, early treated patients gained 7 months (95% CI: [4-11] months) in the time to reach EDSS 3.0 compared to patients treated later (treatment start delayed by 28 months). The difference in RMST was respectively six months (95% CI: [1-10] months) and 14 months (95% CI: [4-24] months) in the "≤40 years" age group and in the ">40 years" age group, in favour of early group. . CONCLUSIONS: Early treatment initiation resulted in a significant reduction of disability progression among patients with RRMS, and also among older patients.
Published: 2022

3. Serum metabolic profile in early multiple sclerosis as predictor of long-term disease progression in BENEFIT (P5-3.013)

Author: Marianna Cortese, Xiaojing Peng, Kjetil Bjornevik, Clary B. Clish, Gilles Edan, Mark Freedman, Hans-Peter Hartung, Xavier Montalban, Rupert Sandbrink, Ernst-Wilhelm Radue, Frederik Barkhof, Eva-Maria Wicklein, Ludwig Kappos, Kassandra Munger, and Alberto Ascherio
Published: 2023

4. Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis

Author: Georgina Arrambide, Ingrid van der Mei, Raed Alroughani, Lars Forsberg, Rodden M. Middleton, Guilherme Sciascia do Olival, Nikola Lazovski, Rumen Ivanov, Alexander Stahmann, Tomas Kalincik, Helmut Butzkueven, Richard S. Nicholas, J. Hillert, Alice Estavo Dias, Edward De Brouwer, Amber Salter, Serkan Ozakbas, Nupur Nag, Doralina Guimarães Brum, Alexander Fidao, Anna Zabalza, Yves Moreau, Ricardo Alonso, Anneke Van Der Walt, Nick Rijke, Lotte Geys, Anibal Chertcoff, Arnfin Bergmann, Robert N. McBurney, Clare Walton, Anna Glaser, Tina Parciak, Gilles Edan, Clément Gautrais, Ashkan Pirmani, Maria Fernanda Mendes, Juan Ignacio Rojas, Melinda Magyari, Liesbet M. Peeters, Robert J. Fox, Hollie Schmidt, Amin Ardeshirdavanai, Steve Simpson-Yap, Stefan Braune, Giancarlo Comi, Johana Bauer, Tim Spelman, Zabalza, Ana/0000-0003-3860-5251, Simpson, Jr., Steve/0000-0001-6521-3056, Kalincik, Tomas/0000-0003-3778-1376, Simpson-Yap, Steve, DE BROUWER, Edward, Kalincik, Tomas, Rijke, Nick, Hillert, Jan A., Walton, Clare, Edan, Gilles, Moreau, Yves, Spelman, Tim, GEYS, Lotte, PARCIAK, Tina, Gautrais, Clement, Lazovski, Nikola, PIRMANI, Ashkan, Ardeshirdavanai, Amin, Forsberg, Lars, Glaser, Anna, McBurney, Robert, Schmidt, Hollie, Bergmann, Arnfin B., Braune, Stefan, Stahmann, Alexander, Middleton, Rodden, Salter, Amber, Fox, Robert J., van der Walt, Anneke, Butzkueven, Helmut, Alroughani, Raed, Ozakbas, Serkan, Rojas, Juan, I, van der Mei, Ingrid, Nag, Nupur, Ivanov, Rumen, do Olival, Guilherme Sciascia, Dias, Alice Estavo, Magyari, Melinda, Brum, Doralina, Mendes, Maria Fernanda, Alonso, Ricardo N., Nicholas, Richard S., Bauer, Johana, Chertcoff, Anibal Sebastian, Zabalza, Anna, Arrambide, Georgina, Fidao, Alexander, Comi, Giancarlo, PEETERS, Liesbet, Institut Català de la Salut, [Simpson-Yap S] Department of Medicine, and Neuroepidemiology Unit, Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia [De Brouwer E] University of Tasmania, Hobart, Australia. ESAT-STADIUS, KU Leuven, Belgium. [Kalincik T] Department of Neurology, Melbourne MS Centre, Royal Melbourne Hospital, Parkville, Australia. [Rijke N, Walton C] MS International Federation, London, UK. [Hillert JA] Department of Clinical Neuroscience, Swedish MS Registry, Stockholm, Sweden. [Zabalza A, Arrambide G] Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, and Neuroepidemiology Unit, Melbourne School of Population and Global Health, University of Tasmania, KU Leuven, Royal Melbourne Hospital, MS International Federation, Swedish MS Registry, CHU Pontchaillou, Karolinska Institutet, Hasselt University, University Medical Center, QMENTA, Molecular Unit, Accelerated Cure Project for MS, NeuroTransData, MS Forschungs- und Projektentwicklungs-gGmbH, Swansea University, COViMS, Washington University in St. Louis, Cleveland Clinic, Monash University, Kuwait City, Dokuz Eylul University, Hospital Universitario de CEMIC, RELACOEM, Bulgarian SmartMS COVID-19 Dataset, ABEM-Brazilian MS Patients Association, University Hospital Rigshospitalet, Universidade Estadual Paulista (UNESP), REDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders, Irmandade da Santa Casa de Misericórdia de São Paulo, Ramos Mejia Hospital-EMA, Imperial College, Mental Health Area, EMA, Cemcat, Vall d'Hebron Hospital Universitari, Universitat Autònoma de Barcelona, and Ospedale San Raffaele
Subjects: Male, Dimethyl Fumarate, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], chemistry.chemical_compound, 0302 clinical medicine, Natalizumab, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Medicine, 10. No inequality, COVID-19 (Malaltia) - Complicacions, B-Lymphocytes, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Middle Aged, 3. Good health, Hospitalization, enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Cohort, Female, Rituximab, Life Sciences & Biomedicine, Research Article, medicine.drug, Adult, medicine.medical_specialty, Multiple Sclerosis, Adolescent, Clinical Neurology, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Antibodies, Monoclonal, Humanized, Young Adult, 03 medical and health sciences, Internal medicine, Humans, Risk factor, Aged, 030203 arthritis & rheumatology, Science & Technology, Expanded Disability Status Scale, SARS-CoV-2, business.industry, COVID-19, Odds ratio, Respiration, Artificial, Cross-Sectional Studies, Siponimod, chemistry, Ocrelizumab, Neurosciences & Neurology, Neurology (clinical), business, Esclerosi múltiple - Tractament, 030217 neurology & neurosurgery, Other subheadings::Other subheadings::/complications [Other subheadings]
Abstract: Made available in DSpace on 2022-04-28T19:46:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-09 Background and ObjectivesPeople with multiple sclerosis MS are a vulnerable group for severe coronavirus disease 2019 COVID-19, particularly those taking immunosuppressive disease-modifying therapies DMTs. We examined the characteristics of COVID-19 severity in an international sample of people with MS.MethodsData from 12 data sources in 28 countries were aggregated sources could include patients from 1-12 countries. Demographic age, sex, clinical MS phenotype, disability, and DMT untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit ICU admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale EDSS score.ResultsSix hundred fifty-seven 28.1% with suspected and 1,683 61.9% with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02 and ICU admission aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89, although only rituximab was associated with higher risk of artificial ventilation aOR 4.00, 95% CI 1.54-10.39. Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07 and ICU admission aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23, but only rituximab was associated with artificial ventilation aOR 6.15, 95% CI 3.09-12.27. Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92 and ICU admission aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91, but only rituximab was associated with ventilation aOR 5.52, 95% CI 1.71-17.84. Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity.DiscussionUsing the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19. CORe Department of Medicine and Neuroepidemiology Unit Melbourne School of Population and Global Health Menzies Institute for Medical Research University of Tasmania ESAT-STADIUS KU Leuven Department of Neurology Melbourne MS Centre Royal Melbourne Hospital MS International Federation Department of Clinical Neuroscience Swedish MS Registry Department of Neurology CHU Pontchaillou Karolinska Institutet Biomedical Research Institute-Data Science Institute Hasselt University Department of Medical Informatics University Medical Center Department of Computer Science and AI KU Leuven QMENTA Medpace Reference Laboratories Molecular Unit IConquerMS People-Powered Research Network Accelerated Cure Project for MS NeuroTransData Study Group NeuroTransData German MS-Register by the National MS Society MS Forschungs- und Projektentwicklungs-gGmbH MS Register Swansea University COViMS Division of Biostatistics Washington University in St. Louis Mellen Center for Multiple Sclerosis Cleveland Clinic Department of Neuroscience Central Clinical School Monash University Al-Amiri Hospital Kuwait City Dokuz Eylul University Neurology Department Hospital Universitario de CEMIC RELACOEM Australian MS Longitudinal Study Menzies Institute for Medical Research University of Tasmania Bulgarian SmartMS COVID-19 Dataset ABEM-Brazilian MS Patients Association Danish Multiple Sclerosis Registry Department of Neurology University Hospital Rigshospitalet Universidade Estadual Paulista Unesp Faculdade de Medicina REDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders Irmandade da Santa Casa de Misericórdia de São Paulo Multiple Sclerosis University Center Ramos Mejia Hospital-EMA Imperial College Swansea University Mental Health Area MS and Demyelinating Diseases Hospital Británico de Buenos Aires EMA Servei de Neurologia-Neuroimmunologia Centre d'Esclerosi Múltiple de Catalunya Cemcat Vall d'Hebron Institut de Recerca Vall d'Hebron Hospital Universitari Universitat Autònoma de Barcelona Institute of Experimental Neurology Ospedale San Raffaele Universidade Estadual Paulista Unesp Faculdade de Medicina
Published: 2021

5. Switching from natalizumab administration at the day hospital to administration at home. A 1 year prospective study of patient experience and quality of life in 30 consecutive patients with multiple sclerosis (TYSAD-35)

Author: Simon Lamy, David Veillard, Hélène Doyen, Anne Kerbrat, Laure Michel, Emilie Chretien, Ahmad Ousmen, Gilles Edan, and Emmanuelle Le Page
Subjects: Neurology, Neurology (clinical), General Medicine
Published: 2023

6. Multiple sclerosis clinical decision support system based on projection to reference datasets

Author: Chadia Ed‐driouch, Florent Chéneau, Françoise Simon, Guillaume Pasquier, Benoit Combès, Anne Kerbrat, Emmanuelle Le Page, Sophie Limou, Nicolas Vince, David‐Axel Laplaud, Franck Mars, Cédric Dumas, Gilles Edan, Pierre‐Antoine Gourraud, Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Perception, Action, Cognition pour la Conception et l’Ergonomie (LS2N - équipe PACCE), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Nantes Université (Nantes Univ), Département Automatique, Productique et Informatique (IMT Atlantique - DAPI), IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Institut de Recherche Technologique b-com (IRT b-com), Neuroimagerie: méthodes et applications (EMPENN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAL, IMAGE ET LANGAGE (IRISA-D6), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), École Centrale de Nantes (Nantes Univ - ECN), Centre hospitalier universitaire de Nantes (CHU Nantes), Bourse Région Pays de la Loire number 2019_11235, ANR-21-RHUS-0014,Primus,Transforming the care of patients with Multiple Sclerosis using a multidimensional data-driven clinical decision support system(2021), European Project: 754995,EU-TRAIN, Team 3 : Integrative transplantation, HLA, Immunology and genomics of kidney injury (U1064 Inserm - CR2TI), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Team 1 : Mononuclear phagocytes, Immunopathology, Immunovirology (U1064 Inserm - CR2TI), Team 5 : Neuroinflammation, mechanisms, therapeutic options (NEMO) (U1064 Inserm - CR2TI), Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and This project has received funding from theEuropean Union’s Horizon 2020 Researchand Innovation Programme under GrantAgreement No. 754995, and the scholarship'Bourse Region Pays de la Loire' number2019_11235. MS Vista is part of the PRIMUSproject. This work was supported in part bythe French National Research Agency(Agence Nationale de la Recherche, ANR) asits 3rd PIA, integrated to France 2030 planunder reference [ANR-21-RHUS-0014].
Subjects: MESH: Humans, General Neuroscience, MESH: Magnetic Resonance Imaging / methods, MESH: Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging, [SDV]Life Sciences [q-bio], [SCCO]Cognitive science, MESH: Interferon beta-1a / therapeutic use, MESH: Decision Support Systems, Clinical, MESH: Multiple Sclerosis, Relapsing-Remitting / drug therapy, MESH: Multiple Sclerosis / drug therapy, [INFO]Computer Science [cs], Neurology (clinical), MESH: Multiple Sclerosis, Relapsing-Remitting / pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objective: Multiple sclerosis (MS) is a multifactorial disease with increasingly complicated management. Our objective is to use on-demand computational power to address the challenges of dynamically managing MS.Methods: A phase 3 clinical trial data (NCT00906399) were used to contextualize the medication efficacy of peg-interferon beta-1a vs placebo on patients with relapsing-remitting MS (RRMS). Using a set of reference patients (PORs), selected based on adequate features similar to those of an individual patient, we visualize disease activity by measuring the percentage of relapses, accumulation of new T2 lesions on MRI, and worsening EDSS during the clinical trial.Results: We developed MS Vista, a functional prototype of clinical decision support system (CDSS), with a user-centered design and distributed infrastructure. MS Vista shows the medication efficacy of peginterferon beta-1a versus placebo for each individual patient with RRMS. In addition, MS Vista initiated the integration of a longitudinal magnetic resonance imaging (MRI) viewer and interactive dual physician-patient data display to facilitate communication.Interpretation: The pioneer use of PORs for each individual patient enables personalized analytics sustaining the dialog between neurologists, patients and caregivers with quantified evidence.
Published: 2022

7. Severity of COVID19 infection among patients with multiple sclerosis treated with interferon-β

Author: Steve Simpson-Yap, Ashkan Pirmani, Edward De Brouwer, Liesbet M. Peeters, Lotte Geys, Tina Parciak, Anne Helme, Jan Hillert, Yves Moreau, Gilles Edan, Tim Spelman, Sifat Sharmin, Robert McBurney, Hollie Schmidt, Arnfin Bergmann, Stefan Braune, Alexander Stahmann, Rodden Middleton, Amber Salter, Bruce Bebo, Anneke van der Walt, Helmut Butzkueven, Serkan Ozakbas, Rana Karabudak, Cavit Boz, Raed Alroughani, Juan I Rojas, Ingrid van der Mei, Guilherme Sciascia do Olival, Melinda Magyari, Ricardo Alonso, Richard Nicholas, Anibal Chertcoff, Ana Zabalza, Georgina Arrambide, Nupur Nag, Annabel Descamps, Lars Costers, Ruth Dobson, Aleisha Miller, Paulo Rodrigues, Vesna Prčkovska, Giancarlo Comi, and Tomas Kalincik
Subjects: Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Neurology, Dimethyl Fumarate, COVID-19, Humans, Neurology (clinical), General Medicine, Glatiramer Acetate, Interferon-beta, Acetates, Immunosuppressive Agents
Abstract: Interferon-β, a disease-modifying therapy (DMT) for MS, may be associated with less severe COVID-19 in people with MS.Among 5,568 patients (83.4% confirmed COVID-19), interferon-treated patients had lower risk of severe COVID-19 compared to untreated, but not to glatiramer-acetate, dimethyl-fumarate, or pooled other DMTs.In comparison to other DMTs, we did not find evidence of protective effects of interferon-β on the severity of COVID-19, though compared to the untreated, the course of COVID19 was milder among those on interferon-β. This study does not support the use of interferon-β as a treatment to reduce COVID-19 severity in MS.
Published: 2022

8. Untreated patients with multiple sclerosis: A study of French expert centers

Author: Xavier Moisset, Bruno Stankoff, Pierre Clavelou, Karolina Hankiewicz, Bruno Brochet, Olivier Casez, Bruno Pereira, Chantal Nifle, Thibault Moreau, Sandra Vukusic, Christine Lebrun-Frenay, Eric Thouvenot, Alain Créange, Olivier Gout, Corinne Pottier, Olivier Heinzlef, Caroline Papeix, Gilles Defer, Eric Berger, David Laplaud, Audrey-Anne Fouchard, S. Bakchine, Alexis Montcuquet, Jean Pelletier, Jérôme De Seze, Dalia Dimitri Boulos, Jean-Philippe Camdessanché, Pierre Labauge, Bertrand Bourre, Philippe Cabre, Abdullatif Al-Khedr, Aude Maurousset, Frederic Taithe, Gilles Edan, Jonathan Ciron, Nicolas Maubeuge, Guillaume Mathey, Patrick Vermersch, Jonchère, Laurent, Cohortes - Observatoire Français de la Sclérose en Plaques - - OFSEP2010 - ANR-10-COHO-0002 - COHO - VALID, CHU Clermont-Ferrand, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Bordeaux (UB), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, Hôpital Lapeyronie [Montpellier] (CHU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Pasteur [Nice] (CHU), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Saint-Antoine [AP-HP], Fondation Ophtalmologique Adolphe de Rotschild, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHI Poissy-Saint-Germain, CHU Amiens-Picardie, CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de la Martinique [Fort de France], CHU Limoges, CHU Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Bicêtre, Centre Hospitalier Versailles, 78000 Le Chesnay, France, parent, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Agence Nationale de la Recherche French National Research Agency (ANR) European Commission [ANR-10-COHO-002], ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Université Paul-Valéry - Montpellier 3 (UPVM), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor [Créteil], and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Adult, medicine.medical_specialty, Multiple Sclerosis, Multivariate analysis, untreated, [SDV]Life Sciences [q-bio], progressive, Unmet needs, Primary progressive, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, 10. No inequality, Retrospective Studies, unmet medical needs, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Retrospective cohort study, Odds ratio, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, relapsing-remitting, Confidence interval, [SDV] Life Sciences [q-bio], Neurology, Neurology (clinical), Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery
Abstract: International audience; Background and purpose: Disease-modifying therapies (DMTs) have an impact on relapses and disease progression. Nonetheless, many patients with multiple sclerosis (MS) remain untreated. The objectives of the present study were to determine the proportion of untreated patients with MS followed in expert centers in France and to determine the predictive factors of nontreatment. Methods: We conducted a retrospective cohort study. Data were extracted from the 38 centers participating in the European Database for Multiple Sclerosis (EDMUS) on December 15, 2018, and patients with MS seen at least once during the study period (from June 15, 2016 to June 14, 2017) were included. Results: Of the 21,189 patients with MS (age 47.1 +/- 13.1 years; Expanded Disability Status Scale (EDSS) score 3.4 +/- 2.4), 6,631 (31.3%; 95% confidence interval [CI] 30.7-31.9) were not receiving any DMT. Although patients with a relapsing-remitting course (n = 11,693) were the most likely to receive DMT, 14.8% (95% CI 14.2-15.4) were still untreated (6.8% never treated). After multivariate analysis among patients with relapsing-remitting MS, the main factors explaining never having been treated were: not having >= 9 lesions on brain magnetic resonance imaging (odds ratio [OR] 0.52 [95% CI 0.44-0.61]) and lower EDSS score (OR 0.78 [95% CI 0.74-0.82]). Most patients with progressive MS (50.4% for secondary and 64.2% for primary progressive MS) did not receive any DMT during the study period, while 11.6% of patients with secondary and 34.0% of patients with primary progressive MS had never received any DMT. Conclusion: A significant proportion of patients with MS did not receive any DMT, even though such treatments are reimbursed by the healthcare system for French patients. This result highlights the unmet need for current DMTs for a large subgroup of patients with MS.
Published: 2021

9. Neurologic manifestations associated with COVID-19: a multicentre registry

Author: Elodie Meppiel, Nathan Peiffer-Smadja, Alexandra Maury, Imen Bekri, Cécile Delorme, Virginie Desestret, Lucas Gorza, Geoffroy Hautecloque-Raysz, Sophie Landre, Annie Lannuzel, Solène Moulin, Peggy Perrin, Paul Petitgas, François SellaI, Adrien Wang, Pierre Tattevin, Thomas de Broucker, Sophie Abgrall, Fanny Alby-Laurent, Thibault Allou, Joséphine Amevigbe, Hanifa Amarguellay, Nabil Alloussi, Guillaume Baille, Mathilde Barbaz, Lamia Bencherif, Samia Bensaadi, Guillaume Beraud, Alexandra Bizot, Laure Bottin, Fabrice Bruneel, Jean-Philippe Camdessanche, Jeanne Chauffier, Jean-Philippe Csajaghy, Chloé De Broucker, Thomas De Broucker, Luc Defebvre, Elodie Dembloque, Nathalie Derache, Olivier Dereeper, Céline Derollez, Cécile Descotes-Genon, Mathilde Devaux, Lydie Dubuc, Gilles Edan, Andréa Fickl, Thibault Fraisse, Michel Gugenheim, Karolina Hankiewicz, Yves Hansmann, Carole Henry, Stéphanie Jobard, Fanny Jouan, Arnaud Kwiatkowski, Thibault Lalu, Johan Leguilloux, Camille Lejeune, Clémence Liegeois, Sophie Mahy, Jonathan Marey, Laure Michel, Rita Mitri, Chloé Moulin, Asma Omarjee, Canan Ozsancak, Fernando Pico, Marie Poupard, Valérie Rabier, Camille Rizzato, Caroline Roos, Julien Saison, Naomi Sayre, Nicolas Sedillot, François Sellal, Jérôme Servan, Caroline Storey, Laurent Suchet, Paul Tarteret, Mathilde Thiebaut, Claudia Vaduva, David Varlan, Virginie Zarrouk, Centre Hospitalier de Saint-Denis [Ile-de-France], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre Hospitalier de Versailles André Mignot (CHV), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Hôpital Foch [Suresnes], Hôpitaux Civils de Colmar, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Centre Hospitalier Universitaire de Reims (CHU Reims), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Pontchaillou [Rennes], Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Jonchère, Laurent, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]
Subjects: Male, 0301 basic medicine, Microbiology (medical), Registry, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030106 microbiology, Encephalopathy, Nervous System, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Humans, Registries, 030212 general & internal medicine, Pleocytosis, Aged, Retrospective Studies, medicine.diagnostic_test, SARS-CoV-2, business.industry, Mortality rate, Brain, COVID-19, Retrospective cohort study, Magnetic resonance imaging, General Medicine, Neurologic manifestations, Middle Aged, medicine.disease, Thrombosis, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Neurological manifestations, Female, Original Article, France, Nervous System Diseases, business, Encephalitis
Abstract: International audience; OBJECTIVES: To provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March-April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible. RESULTS: We included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53-72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19-associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19-associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischaemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). CONCLUSIONS: Clinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.
Published: 2021

10. PRIMUS-Alpha : prototype de médecine de précision dans la sclérose en plaques contextualisant l’évolution des patients dans des données de référence multi-sources

Author: Stanislas Demuth, Chadia Ed-Driouch, Olivia Rousseau, Jérôme De Sèze, David-Axel Laplaud, Gilles Edan, and Pierre-Antoine Gourraud
Subjects: Neurology, Neurology (clinical)
Published: 2023

11. COPP-MS: COrticosteroids during the Post-Partum in relapsing Multiple Sclerosis patients

Author: Soizic Leguy, Mathilde Lefort, Lucile Lescot, Audrey Michaud, Sandra Vukusic, Emmanuelle Le Page, Gilles Edan, Anne Kerbrat, Christine Lebrun-Frenay, Jérôme De Sèze, David-Axel Laplaud, Sandrine Wiertlewski, Emmanuelle Leray, Laure Michel, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), Recherche sur les services et le management en santé (RSMS), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation Eugène Devic EDMUS, Centre Hospitalier Universitaire de Nice (CHU Nice), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Collectif de recherche handicap, autonomie et société inclusive (CoRHASI), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work has been granted by the Eugene Devic EDMUS Foundation against Multiple Sclerosis and by the Aide à la Recherche sur la Sclérose en Plaques (ARSEP) foundation., and EHESP, SCD
Subjects: Disability, Preventive corticosteroids, Multiple Sclerosis, Postpartum Period, Pregnancy Complications, Multiple Sclerosis, Relapsing-Remitting, Neurology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Adrenal Cortex Hormones, Pregnancy, Recurrence, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), Post-partum, Relapses
Abstract: International audience; Background: No specific treatment has demonstrated its effectiveness to prevent post-partum relapses for multiple sclerosis (MS) women.Objective: To assess the effectiveness of preventive high-dose corticosteroids in the post-partum period by comparing two strategies: (1) no preventive treatment and (2) standardized preventive treatment.Methods: We selected five French Multiple Sclerosis centers using the same post-partum strategy for their patients-either high-dose steroids (treating centers TC) or no treatment (non-treating centers NTC). We included relapsing-remitting multiple sclerosis women who delivered between January 2007 and January 2017. Our primary outcomes were the time from delivery to first relapse, EDSS progression and MRI activity between patients of treating centers and non-treating centers, after propensity-score weighting.Results: 350 patients were included (116 from treating centers, 234 from non-treating centers). For both groups, the annualized relapse rate decreased during pregnancy (0.28 in treating centers and 0.34 in non-treating centers during the third trimester) and increased during the first post-partum trimester (0.45 and 0.69, respectively) with 11% and 14% (NS) of patients facing at least one relapse, respectively. Our primary outcomes were not statistically different between both groups.Conclusion: This study provides class III evidence that systematic high-dose corticosteroids are not associated with a reduced inflammatory activity during the post-partum period in multiple sclerosis patients.
Published: 2022

12. Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability

Author: Bertrand Audoin, Tobias Granberg, Yasuhiko Tachibana, Massimo Filippi, Charley Gros, Xavier Ayrignac, Masaaki Hori, Francesca Galassi, Gilles Edan, Julien Cohen-Adad, Govind Nair, Nicolas Collongues, Lydia Chougar, Anne Kerbrat, Jennifer Lefeuvre, Leszek Stawiarz, Renxin Chu, Daniel S. Reich, Rohit Bakshi, Russell Ouellette, Adil Maarouf, Clarisse Carra-Dalliere, Jean Pelletier, Jan Hillert, Jérôme De Seze, Benoît Combès, Atef Badji, Pierre Labauge, Elise Bannier, Paola Valsasina, Maria A. Rocca, Jason F. Talbott, Kouhei Kamiya, Josefina Maranzano, Raphaël Chouteau, Virginie Callot, École Polytechnique de Montréal (EPM), Unité de Neuroimagerie Fonctionnelle [Montréal] (UNF-CRIUGM), Université de Montréal (UdeM)-Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Empenn, Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Université de Rennes (UNIV-RENNES)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Université de Rennes (UNIV-RENNES), Département de Radiologie [CHU de Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Neurologie [CHU Rennes], CHU Pontchaillou [Rennes], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Université du Québec à Trois-Rivières (UQTR), Department of Clinical Neuroscience [Sotckholm], Karolinska Institutet [Stockholm], Department of Radiology and Biomedical Imaging [San Francisco], University of California [San Francisco] (UCSF), University of California-University of California, National Institute of Radiological Sciences (NIRS), Toho University Omori Medical Center [Tokyo], Service de Neuroradiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, National Institutes of Health [Bethesda] (NIH), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (BMNST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Vetenskapsrådet, Hjärnfonden, Doctoral TransMedTech, French Hospital Program of Clinical Research, PHRC, Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Neuroimagerie: méthodes et applications (Empenn), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Université de Rennes (UR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Università degli Studi di Brescia = University of Brescia (UniBs), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Jonchère, Laurent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Kerbrat, A., Gros, C., Badji, A., Bannier, E., Galassi, F., Combes, B., Chouteau, R., Labauge, P., Ayrignac, X., Carra-Dalliere, C., Maranzano, J., Granberg, T., Ouellette, R., Stawiarz, L., Hillert, J., Talbott, J., Tachibana, Y., Hori, M., Kamiya, K., Chougar, L., Lefeuvre, J., Reich, D. S., Nair, G., Valsasina, P., Rocca, M. A., Filippi, M., Chu, R., Bakshi, R., Callot, V., Pelletier, J., Audoin, B., Maarouf, A., Collongues, N., De Seze, J., Edan, G., and Cohen-Adad, J.
Subjects: Adult, Male, corticospinal tract, Pathology, medicine.medical_specialty, Cord, Pyramidal Tracts, multiple sclerosis, 030218 nuclear medicine & medical imaging, Lesion, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 10. No inequality, Retrospective Studies, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Clinically isolated syndrome, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Brain, Cervical Cord, Original Articles, Middle Aged, Spinal cord, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, disability, Corticospinal tract, Disease Progression, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Neurology (clinical), Brainstem, medicine.symptom, business, 030217 neurology & neurosurgery, MRI
Abstract: Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P
Published: 2020

13. Vitamin D, smoking, EBV, and long-term cognitive performance in MS

Author: Marianna, Cortese, Kassandra L, Munger, Elena H, Martínez-Lapiscina, Christian, Barro, Gilles, Edan, Mark S, Freedman, Hans-Peter, Hartung, Xavier, Montalbán, Frederick W, Foley, Iris Katharina, Penner, Bernhard, Hemmer, Edward J, Fox, Sven, Schippling, Eva-Maria, Wicklein, Ludwig, Kappos, Jens, Kuhle, Alberto, Ascherio, and Henry F., McFarland
Subjects: Male, 0301 basic medicine, Epstein-Barr Virus Infections, medicine.medical_specialty, Paced Auditory Serial Addition Test, Antibodies, Viral, Logistic regression, Time, 03 medical and health sciences, chemistry.chemical_compound, Cognition, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Adjuvants, Immunologic, Double-Blind Method, Neurofilament Proteins, Risk Factors, Internal medicine, Vitamin D and neurology, Humans, Medicine, Vitamin D, Cotinine, Clinically isolated syndrome, medicine.diagnostic_test, business.industry, Multiple sclerosis, Smoking, medicine.disease, Confidence interval, 030104 developmental biology, chemistry, Female, Neurology (clinical), business, Body mass index, Biomarkers, 030217 neurology & neurosurgery, Demyelinating Diseases, Follow-Up Studies, Interferon beta-1b
Abstract: ObjectiveTo investigate whether vitamin D, smoking, and anti-Epstein-Barr virus (EBV) antibody concentrations predict long-term cognitive status and neuroaxonal injury in multiple sclerosis (MS).MethodsThis study was conducted among 278 patients with clinically isolated syndrome who participated in the clinical trial BENEFIT (Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment) and completed the 11-year assessment (BENEFIT-11). We measured serum 25-hydroxyvitamin-D (25(OH)D), cotinine (smoking biomarker), and anti-Epstein-Barr virus nuclear antigen 1 (EBNA-1) immunoglobulin G (IgG) at baseline and at months 6, 12, and 24 and examined whether these biomarkers contributed to predict Paced Auditory Serial Addition Test (PASAT)-3 scores and serum neurofilament light chain (NfL) concentrations at 11 years. Linear and logistic regression models were adjusted for sex, baseline age, treatment allocation, steroid treatment, multifocal symptoms, T2 lesions, and body mass index.ResultsHigher vitamin D predicted better, whereas smoking predicted worse cognitive performance. A 50-nmol/L higher mean 25(OH)D in the first 2 years was related to 65% lower odds of poorer PASAT performance at year 11 (95% confidence intervals [95% CIs]: 0.14–0.89). Standardized PASAT scores were lower in smokers and heavy smokers than nonsmokers (ptrend = 0.026). Baseline anti–EBNA-1 IgG levels did not predict cognitive performance (ptrend = 0.88). Associations with NfL concentrations at year 11 corroborated these findings—a 50-nmol/L higher mean 25(OH)D in the first 2 years was associated with 20% lower NfL (95% CI: −36% to 0%), whereas smokers had 20% higher NfL levels than nonsmokers (95% CI: 2%–40%). Anti–EBNA-1 antibodies were not associated with NfL.ConclusionsLower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS.
Published: 2020

14. Updated Results of the COVID-19 in MS Global Data Sharing Initiative: Anti-CD20 and Other Risk Factors Associated With COVID-19 Severity

Author: Steve Simpson-Yap, Ashkan Pirmani, Tomas Kalincik, Edward De Brouwer, Lotte Geys, Tina Parciak, Anne Helme, Nick Rijke, Jan A. Hillert, Yves Moreau, Gilles Edan, Sifat Sharmin, Tim Spelman, Robert McBurney, Hollie Schmidt, Arnfin B. Bergmann, Stefan Braune, Alexander Stahmann, Rod M. Middleton, Amber Salter, Bruce Bebo, Anneke Van der Walt, Helmut Butzkueven, Serkan Ozakbas, Cavit Boz, Rana Karabudak, Raed Alroughani, Juan I. Rojas, Ingrid A. van der Mei, Guilherme Sciascia do Olival, Melinda Magyari, Ricardo N. Alonso, Richard S. Nicholas, Anibal S. Chertcoff, Ana Zabalza de Torres, Georgina Arrambide, Nupur Nag, Annabel Descamps, Lars Costers, Ruth Dobson, Aleisha Miller, Paulo Rodrigues, Vesna Prčkovska, Giancarlo Comi, Liesbet M. Peeters, Institut Català de la Salut, [Simpson-Yap S] CORe, Department of Medicine, and Neuroepidemiology Unit, Melbourne School of Population & Global Health, The University of Melbourne, Menzies Institute for Medical Research, University of Tasmania, Australia. [Pirmani A, Geys L, Parciak T] ESAT-STADIUS, KU Leuven, Biomedical Research Institute–Data Science Institute, Hasselt University, Belgium. [Kalincik T] CORe, Department of Medicine, The University of Melbourne, MS Centre, Department of Neurology, Royal Melbourne Hospital, Australia. [De Brouwer E] ESAT-STADIUS, KU Leuven, Belgium. [Zabalza de Torres A, Arrambide G] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Male, Multiple Sclerosis, COVID-19 (Malaltia) - Factors de risc, Clinical Neurology, Esclerosi múltiple, técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Risk Factors, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Humans, Science & Technology, Information Dissemination, Natalizumab, Neurosciences, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], COVID-19, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Glatiramer Acetate, Multiple Sclerosis, Chronic Progressive, Antigens, CD20, Neurology, enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Neurology (clinical), Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Neurosciences & Neurology, Rituximab, Life Sciences & Biomedicine, Immunosuppressive Agents
Abstract: 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. 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.
Published: 2022

15. 1298Associations of DMT therapies with COVID-19 severity in multiple sclerosis

Author: Lotte Geyes, Nikola Lazovski, Ingrid van der Mei, Ricardo Alonso, Anna Glaser, Tomas Kalincik, Tina Parciak, Rumen Ivanov, Richard Nicholas, Arnfin Bergmann, Gilles Edan, Ashkan Pirmani, Hollie Schmidt, Amber Salter, Robert J. Fox, Steve Simpson-Yap, Johana Bauer, Jan Hillert, Liesbet Peeters, Giancarlo Comi, Amin Ardeshirdavani, Helmut Butzkueven, Alexander Fidao, Anibal Chertcoff, Alice Estavo Dias, Robert N. McBurney, Melinda Magyari, Lars Forsberg, Ana Zabalza, Georgina Arrambide, Alexander Stahmann, Rodden M. Middleton, Nupur Nag, Doralina Guimarães Brum, Nick Rijke, Guilherme Sciascia do Olival, Tim Spelman, Juan Ignacio Rojas, Edward De Brouwer, Clare Walton, Anneke van der Walt, Clément Gautrais, Maria Fernandes Mendes, and Stefan Braune
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Multiple sclerosis, General Medicine, medicine.disease, Intensive care unit, law.invention, chemistry.chemical_compound, Siponimod, Natalizumab, chemistry, law, Internal medicine, medicine, Alemtuzumab, Ocrelizumab, Rituximab, Risk factor, business, medicine.drug
Abstract: Background People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods Data from 12 data-sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl-fumarate, glatiramer-acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other) covariates were queried, alongside COVID-19 hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression, adjusted for age, sex, MS phenotype, and EDSS. Results 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Among suspected+confirmed/confirmed-only COVID-19, 20.9%/26.9% were hospitalised, 5.4%/7.2% were admitted to ICU, 4.1%/5.4% required artificial ventilation, and 3.2%/3.9% died. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl-fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Conclusions Despite the cross-sectional design of this study, the internal and external consistency of these results with prior studies suggests their use may be a risk factor for more severe COVID-19. Key messages Anti-CD20 DMTs may be associated with worse COVID-19 severity amongst people with multiple sclerosis.
Published: 2021

16. Disease reactivation after fingolimod cessation in Multiple Sclerosis patients with pregnancy desire: A retrospective study

Author: Alix Callens, Soline Leblanc, Emmanuelle Le Page, Gilles Edan, Aurore Jourdain, Marc Coustans, Sandrine Wiertlewski, David Laplaud, Dorothée Videt, Francois Lallement, Emmanuelle Leray, Laure Michel, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), Recherche sur les services et le management en santé (RSMS), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Intercommunal de Cornouaille [Quimper] (CHI Cornouaille [Quimper]), Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), CH Vannes, CHU de Saint-Brieuc, and École des Hautes Études en Santé Publique [EHESP] (EHESP)
Subjects: Multiple Sclerosis, Fingolimod Hydrochloride, General Medicine, Multiple Sclerosis, Relapsing-Remitting, Neurology, Pregnancy, Recurrence, Humans, Fingolimod-disease reactivation, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Pregnancy desire, Immunosuppressive Agents, Retrospective Studies
Abstract: International audience; Reactivation of Multiple Sclerosis (MS) activity has been described after fingolimod cessation. Because of its contra indication during pregnancy, switch towards lower efficacy treatments are frequent in MS patients with childbearing desire but expose them to a risk of disease reactivation. In this retrospective study including 44 women with MS, a significant increase of the median annualized relapse rate was found in the year following fingolimod discontinuation compared to the period before (p < 0.0001), and 57% of women experienced at least one relapse. When considering to start fingolimod, particular attention should be paid to women with a short-term pregnancy desire
Published: 2022

17. A Clinically-Compatible Workflow for Computer-Aided Assessment of Brain Disease Activity in Multiple Sclerosis Patients

Author: Benoit, Combès, Anne, Kerbrat, Guillaume, Pasquier, Olivier, Commowick, Brandon, Le Bon, Francesca, Galassi, Philippe, L'Hostis, Nora, El Graoui, Raphael, Chouteau, Emmanuel, Cordonnier, Gilles, Edan, and Jean-Christophe, Ferré
Subjects: computer aided diagnosis, Multiple Sclerosis, lesion activity, health services administration, education, Medicine, radiology, Original Research, MRI
Abstract: Over the last 10 years, the number of approved disease modifying drugs acting on the focal inflammatory process in Multiple Sclerosis (MS) has increased from 3 to 10. This wide choice offers the opportunity of a personalized medicine with the objective of no clinical and radiological activity for each patient. This new paradigm requires the optimization of the detection of new FLAIR lesions on longitudinal MRI. In this paper, we describe a complete workflow—that we developed, implemented, deployed, and evaluated—to facilitate the monitoring of new FLAIR lesions on longitudinal MRI of MS patients. This workflow has been designed to be usable by both hospital and private neurologists and radiologists in France. It consists of three main components: (i) a software component that allows for automated and secured anonymization and transfer of MRI data from the clinical Picture Archive and Communication System (PACS) to a processing server (and vice-versa); (ii) a fully automated segmentation core that enables detection of focal longitudinal changes in patients from T1-weighted, T2-weighted and FLAIR brain MRI scans, and (iii) a dedicated web viewer that provides an intuitive visualization of new lesions to radiologists and neurologists. We first present these different components. Then, we evaluate the workflow on 54 pairs of longitudinal MRI scans that were analyzed by 3 experts (1 neuroradiologist, 1 radiologist, and 1 neurologist) with and without the proposed workflow. We show that our workflow provided a valuable aid to clinicians in detecting new MS lesions both in terms of accuracy (mean number of detected lesions per patient and per expert 1.8 without the workflow vs. 2.3 with the workflow, p = 5.10−4) and of time dedicated by the experts (mean time difference 2′45″, p = 10−4). This increase in the number of detected lesions has implications in the classification of MS patients as stable or active, even for the most experienced neuroradiologist (mean sensitivity was 0.74 without the workflow and 0.90 with the workflow, p-value for no difference = 0.003). It therefore has potential consequences on the therapeutic management of MS patients.
Published: 2021

18. Joint assessment of brain and spinal cord motor tract damage in patients with early RRMS: predominant impact of spinal cord lesions on motor function

Author: Haykel Snoussi, Gilles Edan, Anne Kerbrat, Elise Bannier, Jean-Christophe Ferré, Raphaël Chouteau, Benoît Combès, Christian Barillot, Paul Sauleau, Neuroimagerie: méthodes et applications (Empenn), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Service de Neurologie [CHU Rennes], CHU Pontchaillou [Rennes], Département de Radiologie [CHU de Rennes], Université de Rennes (UR), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurophysiologie [Rennes] = Neurophysiology [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques, Empenn, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-Institut des Neurosciences Cliniques de Rennes (INCR), Bannier, Elise, and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR)
Subjects: Adult, Male, Pyramidal Tracts, Fluid-attenuated inversion recovery, Motor function, Cohort Studies, Multiple sclerosis, Lesion, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, T2 lesions, medicine, Humans, In patient, Longitudinal Studies, 030212 general & internal medicine, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Spinal cord, business.industry, Brain, Cervical Cord, Evoked Potentials, Motor, Magnetic Resonance Imaging, White Matter, Electrophysiology, medicine.anatomical_structure, Neurology, Motor Skills, Corticospinal tract, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Neurology (clinical), medicine.symptom, Nuclear medicine, business, human activities, 030217 neurology & neurosurgery, MRI, Tractography
Abstract: International audience; BACKGROUND: In patients with MS, the effect of structural damage to the corticospinal tract (CST) has been separately evaluated in the brain and spinal cord (SC), even though a cumulative impact is suspected.OBJECTIVE: To evaluate CST damages on both the cortex and cervical SC, and examine their relative associations with motor function, measured both clinically and by electrophysiology.METHODS: We included 43 patients with early relapsing-remitting MS. Lesions were manually segmented on SC (axial T2*) and brain (3D FLAIR) scans. The CST was automatically segmented using an atlas (SC) or tractography (brain). Lesion volume fractions and diffusion parameters were calculated for SC, brain and CST. Central motor conduction time (CMCT) and triple stimulation technique amplitude ratio were measured for 42 upper limbs, from 22 patients.RESULTS: Mean lesion volume fractions were 5.2% in the SC portion of the CST and 0.9% in the brain portion. We did not find a significant correlation between brain and SC lesion volume fraction (r = 0.06, p = 0.68). The pyramidal EDSS score and CMCT were both significantly correlated with the lesion fraction in the SC CST (r = 0.39, p = 0.01 and r = 0.33, p = 0.03), but not in the brain CST.CONCLUSION: Our results highlight the major contribution of SC lesions to CST damage and motor function abnormalities.
Published: 2019

19. Pathologic and MRI analysis in acute atypical inflammatory demyelinating lesions

Author: Thierry Vincent, A.-M. Guennoc, Pierre Labauge, Anne Kerbrat, François Cotton, Stéphane Kremer, Béatrice Carsin-Nicol, Mahmoud Charif, Sandra Vukusic, Thibaut Allou, Jérôme De Seze, Aurélie Ruet, Laurent Magy, Nicolas Menjot de Champfleur, Clarisse Carra-Dalliere, Guido Ahle, Eric Thouvenot, Françoise Durand-Dubief, Hélène Oesterle, Valérie Rigau, Denis Sablot, Romain Marignier, Nicolas Collongues, Gilles Edan, Mikael Cohen, Sonia Hebbadj, Benoit Lhermitte, Frederic Taithe, M. P. Boncoeur-Martel, Xavier Ayrignac, Grelier, Elisabeth, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'Anatomie Pathologique Générale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Département d’Immunologie, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Service de radiologie [Strasbourg], Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Hôpitaux Civils de Colmar, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pierre Wertheimer, Département de Neurologie, Service de Neurologie [Lyon], CHU Lyon, Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Pasteur [Nice] (CHU), Service de Neurologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Service de neurologie [Rennes], Université de Rennes (UR), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Neuroinflammation: imagerie et thérapie de la sclérose en plaques, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de Radiologie et Imagerie Médicale [CHU Limoges], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Atypical inflammatory demyelinating syndrome, medicine.medical_specialty, Pathology, Multiple Sclerosis, Histopathology, Context (language use), Immunopathology, Cohort Studies, Lesion, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Pathological, Aged, Retrospective Studies, Neuroradiology, Aquaporin 4, medicine.diagnostic_test, business.industry, Multiple sclerosis, Brain biopsy, Neuromyelitis Optica, food and beverages, Magnetic resonance imaging, Middle Aged, medicine.disease, Atypical demyelinating lesions, Magnetic Resonance Imaging, 3. Good health, Neurology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Acute Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), medicine.symptom, business, Aquaporin-4, 030217 neurology & neurosurgery, Demyelinating Diseases
Abstract: The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and multiple sclerosis and NMOSD is not clear. Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions. We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed. Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Balo-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1–12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD. Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate.
Published: 2019

20. Multiple sclerosis new lesions segmentation challenge

Author: Frédéric Cervenansky, Olivier Commowick, François Cotton, Michel Dojat, and Gilles Edan)
Subjects: Multiple sclerosis, clinical MS marker, segmentation, new lesions, new lesion detection
Abstract: MICCAI endorsed event Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system affecting more than half a million persons in Europe, with prevalence rate of 83 per 100 000 with higher rates in northern countries and a female:male ratio around 2.0 [1]. Today, conventional MRI is widely used for disease diagnosis [2], patient follow-up, monitoring of therapies, and more generally for the understanding of the natural history of MS. One of the major challenges in using MRI for MS is the segmentation of lesions whose number and appearance at a given time point are crucial indicators for diagnostic and treatment follow-up. To cope with inter- and intra-observer variability and remove the burden of manual segmentation from the clinicians, a large number of techniques have been proposed in the literature [3] towards automatically segmenting MS lesions. Several challenges have looked at the evaluation of these methods (e.g. [4,5] to cite the most recent ones). However, a growing literature is now interested in the delineation of new MS lesions on T2/FLAIR by comparing one time point to another. This marker is even more crucial than the total number and volume of lesions as the accumulation of new lesions allows clinicians to know if a given antiinflammatory DMD (disease modifying drug) works for the patient. The DMDs approved for MS can indeed only stop the accumulation of new T2 lesions in the cerebral tissue, and have no recognized impact on the compartmentalized neurodegenerative process within the CNS. The only indicator of drug efficacy is thus the absence of new T2 lesions within the CNS. Moreover, there is a direct link between accumulation of new lesions and increasing handicap [9]. Automating the detection of these new lesions would therefore be a major advance for evaluating the patient disease activity. To date, no challenge has looked at this specific task (assessing the number of new lesions). While [4] included a longitudinal part to their challenge, they were more evaluating consistency of the segmentation rather than trying to specifically evaluate the detection of new lesions. Based on the success of the first MSSEG challenge (Miccai 2016 [5]), we propose to organize a new challenge, this time on new MS lesions detection. This will allow to 1) estimate the progress performed during this period, 2) extend the number of patients, and 3) focus on this crucial clinical marker. We propose to perform the evaluation task on a large database (100 patients, each with two time points) compiled from the OFSEP cohort [8], the French MS registry, with 3D FLAIR images from different centers and scanners. We consider only FLAIR images as a consensus is growing in acquisition around MS [10] to avoid contrast agents (as Gadolinium is now known to accumulate in the brain) and go as fast as possible for acquisition, thus leading more and more to only 3D FLAIR acquisitions. As in our previous challenge, we propose to conduct the evaluation on a dedicated platform (FLIIAM) to automate the evaluation and remove the potential biases (e.g. challengers manually optimizing their parameters for each patient). References [1] M. Pugliatti, et al., The epidemiology of multiple sclerosis in Europe, Eur J Neurol, vol. 13, pp. 700-22, 2006. [2] Thompson, A. J. et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. The Lancet Neurol. 17, 162–173 (2018). [3] Llado, X. et al. Segmentation of multiple sclerosis lesions in brain MRI: A review of automated approaches. Inf. Sci. 186, 164 – 185 (2012). [4] Carass, A. et al. Longitudinal Multiple Sclerosis Lesion Segmentation: Resource & Challenge. Neuroimage 148, 77–102, (2017). [5] Commowick, O. et al. Objective evaluation of multiple sclerosis lesion segmentation using a data management and processing infrastructure. Sci. Reports 8, 13650 (2018). [6] Cotton, F., Kremer, S., Hannoun, S., Vukusic, S. & Dousset, V. OFSEP, a nationwide cohort of people with multiple sclerosis: Consensus minimal MRI protocol. J. Neuroradiol. 42, 133 – 140 (2015). [7] Akhondi-Asl A. and Warfield S.K. Simultaneous Truth and Performance Level Estimation Through Fusion of Probabilistic Segmentations. IEEE Transactions on Medical Imaging 32(10), 1840-1852 (2013). [8] Vukusic S., Casey R. et al. Observatoire Français de la Sclérose en Plaques (OFSEP): A unique multimodal nationwide MS registry in France. Multiple Sclerosis 26(1), 118-122 (2020). [9] Sormani M.P., Rio J. et al. Scoring treatment response in patients with relapsing multiple sclerosis. Multiple sclerosis journal 19 (5), 605-612 (2013). [10] Brisset J.-C., Kremer S. et al. New OFSEP recommendations for MRI assessment of multiple sclerosis patients: Special consideration for gadolinium deposition and frequent acquisitions. Journal of neuroradiology 47(4), 250- 258 (2020). [11] Commowick O., Wiest-Daesslé N. and Prima S. Block-Matching Strategies for Rigid Registration of Multimodal Medical Images. In 9th IEEE International Symposium on Biomedical Imaging (ISBI), 700–703 (2012). [12] Tustison N., Avants B. et al. N4ITK: Improved N3 Bias Correction. IEEE Transactions on Medical Imaging 29(6), 1310-1320 (2010). [13] Anima scripts open source software RRID:SCR_017072 https://anima.irisa.fr
Published: 2021
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21. Associations of DMT therapies with COVID-19 severity in multiple sclerosis

Author: Tomas Kalincik, Nick Rijke, Ingrid van der Mei, Clare Walton, Clément Gautrais, Stefan Braune, Yves Moreau, Tim Spelman, Robert McBurney, Georgina Arrambide, Guilherme Sciascia do Olival, Juan Ignacio Rojas, Edward De Brouwer, Jan Hillert, Amin Ardeshirdavani, Ashkan Pirmani, Giancarlo Comi, Lotte Geys, Anna Glaser, Alice Estavo Dias, Alexander Stahmann, Doralina Guimarães Brum, Alexander Fidao, Melinda Magyari, Rumen Ivanov, Lars Forsberg, Amber Salter, Rodden M. Middleton, Nikola Lazovski, Anneke van der Walt, R. Alroughani, Serkan Ozakbas, Liesbet M. Peeters, Helmut Butzkueven, Maria Fernanda Mendes, Anibal Chertcoff, Arnfin Bergmann, Hollie Schmidt, Nupur Nag, Tina Parciak, Richard Nicholas, Gilles Edan, Steve Simpson-Yap, Robert J. Fox, Johana Bauer, Ricardo Alonso, and Anna Zabalza
Subjects: Artificial ventilation, medicine.medical_specialty, business.industry, medicine.medical_treatment, Multiple sclerosis, Logistic regression, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Internal medicine, Cohort, Medicine, Ocrelizumab, Rituximab, 030212 general & internal medicine, Risk factor, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: BackgroundPeople with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS.MethodsData from 12 data-sources in 28 countries were aggregated. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression.Results657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29-2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36; aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death.ConclusionsUsing the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission, suggesting their use may be a risk factor for more severe COVID-19.
Published: 2021

22. Mass Cytometry Identifies Expansion of T-bet

Author: Laura, Couloume, Juliette, Ferrant, Simon, Le Gallou, Marion, Mandon, Rachel, Jean, Nadège, Bescher, Helene, Zephir, Gilles, Edan, Eric, Thouvenot, Aurelie, Ruet, Marc, Debouverie, Karin, Tarte, Patricia, Amé, Mikael, Roussel, and Laure, Michel
Subjects: Adult, Male, mass cytometry, B-Lymphocytes, B cells, Membrane Glycoproteins, Multiple Sclerosis, Immunology, B-Lymphocyte Subsets, Cell Separation, Brief Research Report, Flow Cytometry, multiple sclerosis, Monocytes, Cohort Studies, Young Adult, Humans, biomarker, Female, Receptors, Immunologic, T-Box Domain Proteins, monocytes, Biomarkers
Abstract: Multiple sclerosis (MS) is an immune-driven demyelinating disease of the central nervous system. Immune cell features are particularly promising as predictive biomarkers due to their central role in the pathogenesis but also as drug targets, even if nowadays, they have no impact in clinical practice. Recently, high-resolution approaches, such as mass cytometry (CyTOF), helped to better understand the diversity and functions of the immune system. In this study, we performed an exploratory analysis of blood immune response profiles in healthy controls and MS patients sampled at their first neurological relapse, using two large CyTOF panels including 62 markers exploring myeloid and lymphoid cells. An increased abundance of both a T-bet-expressing B cell subset and a CD206+ classical monocyte subset was detected in the blood of early MS patients. Moreover, T-bet-expressing B cells tended to be enriched in aggressive MS patients. This study provides new insights into understanding the pathophysiology of MS and the identification of immunological biomarkers. Further studies will be required to validate these results and to determine the exact role of the identified clusters in neuroinflammation.
Published: 2021

23. The introduction of new medications in pediatric multiple sclerosis: Open issues and challenges

Author: Maria Pia Amato, Eva Havrdova, Gilles Edan, Xavier Montalban, Patrich Vermersch, Angelo Ghezzi, Carlo Pozzilli, Maria Trojano, Ludwig Kappos, Hans-Peter Hartung, Giancarlo Comi, Per Soelber Sorensen, Ospedale di Gallarate, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Charles University [Prague] (CU), University Hospital Basel [Basel], Centre d'Esclerosi Múltiple de Catalunya (CemCat), University of Toronto, Azienda Ospedaliera Sant'Andrea [Roma], Copenhagen University Hospital, Rigshospitalet [Copenhagen], Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Bari Aldo Moro (UNIBA), and Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC))
Subjects: Adult, medicine.medical_specialty, Multiple Sclerosis, [SDV]Life Sciences [q-bio], disease-modifying drugs, law.invention, 03 medical and health sciences, 0302 clinical medicine, New medications, Randomized controlled trial, law, Clinical endpoint, Medicine, Humans, 030212 general & internal medicine, Intensive care medicine, Child, observational studies, clinical trials, Ethical issues, business.industry, Fingolimod Hydrochloride, Multiple sclerosis, medicine.disease, Fingolimod, 3. Good health, Clinical trial, Neurology, randomized controlled trials, Observational study, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, medicine.drug, Pediatric multiple sclerosis
Abstract: International audience; Disease-modifying drugs (DMDs) for multiple sclerosis (MS) have been evaluated in pediatric patients in observational studies demonstrating a similar, even better clinical effect compared to adults, with a similar safety. Only fingolimod has been tested in a randomized controlled trial (RCT) and is approved for pediatric multiple sclerosis (ped-MS). Numerous methodological, practical, and ethical issues underline that RCTs are difficult to conduct in ped-MS. This also creates a lack of safety information. To facilitate the availability of new agents in ped-MS, we encourage to develop a different approach based on pharmacokinetic/pharmacodynamic studies to yield information on optimal doses and implementation of obligatory registries to obtain information on safety as primary endpoint.
Published: 2020

24. Associations of DMT Therapies with COVID-19 Severity in Multiple Sclerosis: An International Cohort Study

Author: Liesbet Peeters, Lotte Geys, Anna Glaser, Nupur Nag, Welt Avd, Lars Forsberg, Ashkan Pirmani, Juan Ignacio Rojas, Alexander Stahmann, Tina Parciak, Ricardo Alonso, Amin Ardeshirdavani, Gilles Edan, Maria Fernanda Mendes, Alice Estavo Dias, Helmut Butzkueven, Doralina Guimarães Brum, Hollie Schmidt, J. Hillert, Mei Ivd, Yves Moreau, Rod Middleton, Anibal Chertcoff, Amber Salter, Arnfin Bergmann, Robert McBurney, Georgina Arrambide, Edward De Brouwer, Tim Spelman, Rumen Ivanov, Melinda Magyari, Clare Walton, Steve Simpson-Yap, Clément Gautrais, Nikola Lazovski, Stefan Braune, Olival GSd, Tomas Kalincik, Nick Rijke, Giancarlo Comi, Alexander Fidao, Anna Zabalza, Richard Nicholas, Robert J. Fox, and Johana Bauer
Subjects: Oncology, medicine.medical_specialty, Text mining, Coronavirus disease 2019 (COVID-19), business.industry, Internal medicine, Multiple sclerosis, medicine, medicine.disease, business, Cohort study
Published: 2020

25. High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice

Author: Laura Couloume, Laetitia Barbin, Emmanuelle Leray, Damien Le Port, Emmanuelle Le Page, Anne Kerbrat, Sandrine Wiertlewski, David-Axel Laplaud, Solenn Ory, L. Michel, Gilles Edan, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), École des Hautes Études en Santé Publique [EHESP] (EHESP), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [Rennes] = Neurology [Rennes], Etablissement Français du Sang Bretagne, EFS, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Association ANTARES, MedDay Pharma, Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and EHESP, SCD
Subjects: Adult, medicine.medical_specialty, secondary progressive multiple sclerosis, Multiple Sclerosis, primary progressive multiple sclerosis, effectiveness, Biotin, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Disability Evaluation, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Randomized controlled trial, law, Internal medicine, medicine, Humans, Prospective Studies, 10. No inequality, Prospective cohort study, Adverse effect, Progressive multiple sclerosis, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Multiple sclerosis, Magnetic resonance imaging, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Neurology, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Disease Progression, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), progression, business, 030217 neurology & neurosurgery
Abstract: Background: A recent controlled trial suggested that high-dose biotin supplementation reverses disability progression in patients with progressive multiple sclerosis. Objective: To analyze the impact of high-dose biotin in routine clinical practice on disability progression at 12 months. Methods: Progressive multiple sclerosis patients who started high-dose biotin at Nantes or Rennes Hospital between 3 June 2015 and 15 September 2017 were included in this prospective study. Disability outcome measures, patient-reported outcome measures, relapses, magnetic resonance imaging (MRI) data, and adverse events were collected at baseline, 6, and 12 months. Results: A total of 178 patients were included. At baseline, patients were 52.0 ± 9.4 years old, mean Expanded Disability Status Scale (EDSS) score was 6.1 ± 1.3, mean disease duration was 16.9 ± 9.5 years. At 12 months, 3.8% of the patients had an improved EDSS score. Regarding the other disability scales, scores either remained stable or increased significantly. In total, 47.4% of the patients described stability, 27.6% felt an improvement, and 25% described a worsening. Four patients (2.2%) had a relapse. Of the 74 patients (41.6%) who underwent an MRI, 20 (27.0%) had new T2 lesions, 8 (10.8%) had gadolinium-enhancing lesions. Twenty-five (14%) reported adverse event. Conclusion: In this study, high-dose biotin did not seem to be associated with a clear improvement in disability.
Published: 2019

26. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

Author: Ludwig Kappos, Amit Bar-Or, Bruce A C Cree, Robert J Fox, Gavin Giovannoni, Ralf Gold, Patrick Vermersch, Douglas L Arnold, Sophie Arnould, Tatiana Scherz, Christian Wolf, Erik Wallström, Frank Dahlke, Anat Achiron, Lutz Achtnichts, Kadriye Agan, Gulsen Akman-Demir, Alison B Allen, Jack P Antel, Alfredo Rodriguez Antiguedad, Michelle Apperson, Angela M Applebee, Guillermo Izquierdo Ayuso, Masayuki Baba, Ovidiu Bajenaru, Rodica Balasa, Belgin Petek Balci, Michael Barnett, Ann Bass, Veit U Becker, Mihaela Bejinariu, Florian Then Bergh, Arnfin Bergmann, Evanthia Bernitsas, Achim Berthele, Virender Bhan, Felix Bischof, Randall John Bjork, Gregg Blevins, Matthias Boehringer, Thomas Boerner, Robert Bonek, James D Bowen, Allen Bowling, Alexey N Boyko, Cavit Boz, Vera Bracknies, Stefan Braune, Vincenzo Brescia Morra, Bruno Brochet, Waldemar Brola, Paul Kenneth Brownstone, Miroslav Brozman, Donald Brunet, Ioan Buraga, Margaret Burnett, Mathias Buttmann, Helmut Butzkueven, Jonathan Cahill, Jonathan C Calkwood, William Camu, Mark Cascione, Giovani Castelnovo, Diego Centonze, Joao Cerqueira, Andrew Chan, Andrea Cimprichova, Stanley Cohan, Giancarlo Comi, Jill Conway, Joanna A Cooper, John Corboy, Jorge Correale, Brian Costell, David A Cottrell, Patricia K Coyle, Matthew Craner, Liying Cui, Luis Cunha, Anna Czlonkowska, Ana Martins da Silva, Joao de Sa, Jérôme de Seze, Marc Debouverie, Jan Debruyne, Danny Decoo, Gilles Defer, Tobias Derfuss, Norma H Deri, Bhupesh Dihenia, Peter Dioszeghy, Vladimir Donath, Benedicte Dubois, Martin Duddy, Pierre Duquette, Gilles Edan, Husnu Efendi, Stanton Elias, Peter J Emrich, Bonaventura Casanova Estruch, Evgeniy P Evdoshenko, Juergen Faiss, Alexander S Fedyanin, Wolfgang Feneberg, Jiske Fermont, Oscar Fernandez Fernandez, Francisco Coret Ferrer, Katharina Fink, Helen Ford, Corey Ford, Ada Francia, Mark Freedman, Benjamin Frishberg, Simonetta Galgani, George P Garmany, Klaus Gehring, Jeffrey Gitt, Claudio Gobbi, Lawrence P Goldstick, Rafael Arroyo Gonzalez, Francois Grandmaison, Nikolaos Grigoriadis, Olga Grigorova, Luigi Maria Edoardo Grimaldi, Jeffrey Gross, Katrin Gross-Paju, Mark Gudesblatt, Daniel Guillaume, Judith Haas, Viera Hancinova, Anca Hancu, Orla Hardiman, Arndt Harmjanz, Fedor R Heidenreich, G J D Hengstman, Joseph Herbert, Mark Herring, Suzanne Hodgkinson, Olaf M Hoffmann, Werner E Hofmann, William D Honeycutt, Le Hanh Hua, Dehui Huang, Yining Huang, DeRen Huang, Raymond Hupperts, Piroska Imre, Alan Keith Jacobs, Gabor Jakab, Elzbieta Jasinska, Kenichi Kaida, Jolanta Kalnina, Ara Kaprelyan, Guntis Karelis, Dimitrios Karussis, Amos Katz, Farit A Khabirov, Bhupendra Khatri, Takashi Kimura, Ilya Kister, Rasa Kizlaitiene, Eleonora Klimova, Juergen Koehler, Aparna Komatineni, Anselm Kornhuber, Krisztina Kovacs, Agnes Koves, Wojciech Kozubski, Georgi Krastev, Lauren B Krupp, Egon Kurca, Christoph Lassek, Guy Laureys, Liesly Lee, Eckart Lensch, Fritz Leutmezer, Hongzeng Li, Ralf A Linker, Michael Linnebank, Petra Liskova, Cristina Llanera, Jiahong Lu, Andreas Lutterotti, Jan Lycke, Richard Macdonell, Maciej Maciejowski, Mathias Maeurer, Rim V Magzhanov, Eva-Maria Maida, Lina Malciene, Yang Mao-Draayer, Girolama Alessandra Marfia, Clyde Markowitz, Vasileios Mastorodimos, Klotild Matyas, Jose Meca-Lallana, Juan Antonio Garcia Merino, Ioan Gheorghe Mihetiu, Ivan Milanov, Aaron E Miller, Andrejs Millers, Massimiliano Mirabella, Masanori Mizuno, Xavier Montalban, Lilina Montoya, Masahiro Mori, Stefanie Mueller, Jin Nakahara, Yuji Nakatsuji, Scott Newsome, Richard Nicholas, A Scott Nielsen, Esmaeil Nikfekr, Ugo Nocentini, Chiyoko Nohara, Kyoichi Nomura, Miroslav M Odinak, Tomas Olsson, B W van Oosten, Celia Oreja-Guevara, Patrick Oschmann, James Overell, Andrew Pachner, Gyula Panczel, Massimo Pandolfo, Caroline Papeix, Liliana Patrucco, Jean Pelletier, Raul Piedrabuena, Misha Pless, Udo Polzer, Krisztian Pozsegovits, Daiva Rastenyte, Sebastian Rauer, Gerd Reifschneider, Roberto Rey, Syed A Rizvi, Derrick Robertson, Jose Martinez Rodriguez, David Rog, Homayoun Roshanisefat, Vernon Rowe, Csilla Rozsa, Susan Rubin, Stanislaw Rusek, Francesco Saccà, Takahiko Saida, Antonio Vasco Salgado, Victoria Eugenia Fernandez Sanchez, Kalina Sanders, Maria Satori, Denis V Sazonov, Elio Angelo Scarpini, Eugen Schlegel, Myriam Schluep, Stephan Schmidt, Erich Scholz, H M Schrijver, Matthias Schwab, Raymond Schwartz, James Scott, Krzysztof Selmaj, Stuart Shafer, Basil Sharrack, Ivan A Shchukin, Yuko Shimizu, Penko Shotekov, Arno Siever, Karl-Otto Sigel, Scott Silliman, Magdolna Simo, Mihaela Simu, Vladimiro Sinay, Antonio Escartin Siquier, Aksel Siva, Ondrej Skoda, Andrew Solomon, Martin Stangel, Dusan Stefoski, Brian Steingo, Igor D Stolyarov, Pavel Stourac, Katrin Strassburger-Krogias, Erik Strauss, Olaf Stuve, Ivaylo Tarnev, Antonios Tavernarakis, Cristina Ramo Tello, Murat Terzi, Veronika Ticha, Marina Ticmeanu, Klaus Tiel-Wilck, Toomas Toomsoo, Niall Tubridy, Mark J Tullman, Hayrettin Tumani, Peter Turcani, Ben Turner, Antonio Uccelli, Francisco Javier Olascoaga Urtaza, Marta Vachova, Attila Valikovics, Silke Walter, Bart Van Wijmeersch, Ludo Vanopdenbosch, Joerg R Weber, Sara Weiss, Robert Weissert, Timothy West, Heinz Wiendl, Sandrine Wiertlewski, Brigitte Wildemann, Barbara Willekens, L H Visser, Galina Vorobeychik, Xianhao Xu, Takashi Yamamura, Yi N Yang, Sergio Martinez Yelamos, Michael Yeung, Alan Zacharias, Marvin Zelkowitz, Uwe Zettl, Meini Zhang, Hongyu Zhou, Ulf Zieman, Tjalf Ziemssen, Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital, University of Basel, Basel, Center for Neuroinflammation and Neurotherapeutics, and Multiple Sclerosis Division, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, Mellen Centre for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, Department of Neurology St. Josef-Hospital, Ruhr University Bochum, Germany, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Montreal Neurological Institute, McGill University, Montreal, QC, Canada, NeuroRx Research, Montreal, QC, Novartis Pharma AG, Lycalis, Brussels, AP-HM, CHU Timone, Pole de Neurosciences Cliniques, Department of Neurology, Marseille, France., Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Kappos, Ludwig, Bar-Or, Amit, Cree, Bruce A C, Fox, Robert J, Giovannoni, Gavin, Gold, Ralf, Vermersch, Patrick, Arnold, Douglas L, Arnould, Sophie, Scherz, Tatiana, Wolf, Christian, Wallström, Erik, Dahlke, Frank, Achiron, Anat, Achtnichts, Lutz, Agan, Kadriye, Akman-Demir, Gulsen, Allen, Alison B, Antel, Jack P, Antiguedad, Alfredo Rodriguez, Apperson, Michelle, Applebee, Angela M, Ayuso, Guillermo Izquierdo, Baba, Masayuki, Bajenaru, Ovidiu, Balasa, Rodica, Balci, Belgin Petek, Barnett, Michael, Bass, Ann, Becker, Veit U, Bejinariu, Mihaela, Bergh, Florian Then, Bergmann, Arnfin, Bernitsas, Evanthia, Berthele, Achim, Bhan, Virender, Bischof, Felix, Bjork, Randall John, Blevins, Gregg, Boehringer, Matthia, Boerner, Thoma, Bonek, Robert, Bowen, James D, Bowling, Allen, Boyko, Alexey N, Boz, Cavit, Bracknies, Vera, Braune, Stefan, Brescia Morra, Vincenzo, Brochet, Bruno, Brola, Waldemar, Brownstone, Paul Kenneth, Brozman, Miroslav, Brunet, Donald, Buraga, Ioan, Burnett, Margaret, Buttmann, Mathia, Butzkueven, Helmut, Cahill, Jonathan, Calkwood, Jonathan C, Camu, William, Cascione, Mark, Castelnovo, Giovani, Centonze, Diego, Cerqueira, Joao, Chan, Andrew, Cimprichova, Andrea, Cohan, Stanley, Comi, Giancarlo, Conway, Jill, Cooper, Joanna A, Corboy, John, Correale, Jorge, Costell, Brian, Cottrell, David A, Coyle, Patricia K, Craner, Matthew, Cui, Liying, Cunha, Lui, Czlonkowska, Anna, da Silva, Ana Martin, de Sa, Joao, de Seze, Jérôme, Debouverie, Marc, Debruyne, Jan, Decoo, Danny, Defer, Gille, Derfuss, Tobia, Deri, Norma H, Dihenia, Bhupesh, Dioszeghy, Peter, Donath, Vladimir, Dubois, Benedicte, Duddy, Martin, Duquette, Pierre, Edan, Gille, Efendi, Husnu, Elias, Stanton, Emrich, Peter J, Estruch, Bonaventura Casanova, Evdoshenko, Evgeniy P, Faiss, Juergen, Fedyanin, Alexander S, Feneberg, Wolfgang, Fermont, Jiske, Fernandez, Oscar Fernandez, Ferrer, Francisco Coret, Fink, Katharina, Ford, Helen, Ford, Corey, Francia, Ada, Freedman, Mark, Frishberg, Benjamin, Galgani, Simonetta, Garmany, George P, Gehring, Klau, Gitt, Jeffrey, Gobbi, Claudio, Goldstick, Lawrence P, Gonzalez, Rafael Arroyo, Grandmaison, Francoi, Grigoriadis, Nikolao, Grigorova, Olga, Grimaldi, Luigi Maria Edoardo, Gross, Jeffrey, Gross-Paju, Katrin, Gudesblatt, Mark, Guillaume, Daniel, Haas, Judith, Hancinova, Viera, Hancu, Anca, Hardiman, Orla, Harmjanz, Arndt, Heidenreich, Fedor R, Hengstman, G J D, Herbert, Joseph, Herring, Mark, Hodgkinson, Suzanne, Hoffmann, Olaf M, Hofmann, Werner E, Honeycutt, William D, Hua, Le Hanh, Huang, Dehui, Huang, Yining, Huang, Deren, Hupperts, Raymond, Imre, Piroska, Jacobs, Alan Keith, Jakab, Gabor, Jasinska, Elzbieta, Kaida, Kenichi, Kalnina, Jolanta, Kaprelyan, Ara, Karelis, Gunti, Karussis, Dimitrio, Katz, Amo, Khabirov, Farit A, Khatri, Bhupendra, Kimura, Takashi, Kister, Ilya, Kizlaitiene, Rasa, Klimova, Eleonora, Koehler, Juergen, Komatineni, Aparna, Kornhuber, Anselm, Kovacs, Krisztina, Koves, Agne, Kozubski, Wojciech, Krastev, Georgi, Krupp, Lauren B, Kurca, Egon, Lassek, Christoph, Laureys, Guy, Lee, Liesly, Lensch, Eckart, Leutmezer, Fritz, Li, Hongzeng, Linker, Ralf A, Linnebank, Michael, Liskova, Petra, Llanera, Cristina, Lu, Jiahong, Lutterotti, Andrea, Lycke, Jan, Macdonell, Richard, Maciejowski, Maciej, Maeurer, Mathia, Magzhanov, Rim V, Maida, Eva-Maria, Malciene, Lina, Mao-Draayer, Yang, Marfia, Girolama Alessandra, Markowitz, Clyde, Mastorodimos, Vasileio, Matyas, Klotild, Meca-Lallana, Jose, Merino, Juan Antonio Garcia, Mihetiu, Ioan Gheorghe, Milanov, Ivan, Miller, Aaron E, Millers, Andrej, Mirabella, Massimiliano, Mizuno, Masanori, Montalban, Xavier, Montoya, Lilina, Mori, Masahiro, Mueller, Stefanie, Nakahara, Jin, Nakatsuji, Yuji, Newsome, Scott, Nicholas, Richard, Nielsen, A Scott, Nikfekr, Esmaeil, Nocentini, Ugo, Nohara, Chiyoko, Nomura, Kyoichi, Odinak, Miroslav M, Olsson, Toma, van Oosten, B W, Oreja-Guevara, Celia, Oschmann, Patrick, Overell, Jame, Pachner, Andrew, Panczel, Gyula, Pandolfo, Massimo, Papeix, Caroline, Patrucco, Liliana, Pelletier, Jean, Piedrabuena, Raul, Pless, Misha, Polzer, Udo, Pozsegovits, Krisztian, Rastenyte, Daiva, Rauer, Sebastian, Reifschneider, Gerd, Rey, Roberto, Rizvi, Syed A, Robertson, Derrick, Rodriguez, Jose Martinez, Rog, David, Roshanisefat, Homayoun, Rowe, Vernon, Rozsa, Csilla, Rubin, Susan, Rusek, Stanislaw, Saccà, Francesco, Saida, Takahiko, Salgado, Antonio Vasco, Sanchez, Victoria Eugenia Fernandez, Sanders, Kalina, Satori, Maria, Sazonov, Denis V, Scarpini, Elio Angelo, Schlegel, Eugen, Schluep, Myriam, Schmidt, Stephan, Scholz, Erich, Schrijver, H M, Schwab, Matthia, Schwartz, Raymond, Scott, Jame, Selmaj, Krzysztof, Shafer, Stuart, Sharrack, Basil, Shchukin, Ivan A, Shimizu, Yuko, Shotekov, Penko, Siever, Arno, Sigel, Karl-Otto, Silliman, Scott, Simo, Magdolna, Simu, Mihaela, Sinay, Vladimiro, Siquier, Antonio Escartin, Siva, Aksel, Skoda, Ondrej, Solomon, Andrew, Stangel, Martin, Stefoski, Dusan, Steingo, Brian, Stolyarov, Igor D, Stourac, Pavel, Strassburger-Krogias, Katrin, Strauss, Erik, Stuve, Olaf, Tarnev, Ivaylo, Tavernarakis, Antonio, Tello, Cristina Ramo, Terzi, Murat, Ticha, Veronika, Ticmeanu, Marina, Tiel-Wilck, Klau, Toomsoo, Tooma, Tubridy, Niall, Tullman, Mark J, Tumani, Hayrettin, Turcani, Peter, Turner, Ben, Uccelli, Antonio, Urtaza, Francisco Javier Olascoaga, Vachova, Marta, Valikovics, Attila, Walter, Silke, Van Wijmeersch, Bart, Vanopdenbosch, Ludo, Weber, Joerg R, Weiss, Sara, Weissert, Robert, West, Timothy, Wiendl, Heinz, Wiertlewski, Sandrine, Wildemann, Brigitte, Willekens, Barbara, Visser, L H, Vorobeychik, Galina, Xu, Xianhao, Yamamura, Takashi, Yang, Yi N, Yelamos, Sergio Martinez, Yeung, Michael, Zacharias, Alan, Zelkowitz, Marvin, Zettl, Uwe, Zhang, Meini, Zhou, Hongyu, Zieman, Ulf, Ziemssen, Tjalf, and EXPAND Clinical Investigators
Subjects: Adult, Male, 0301 basic medicine, Relative risk reduction, medicine.medical_specialty, Adolescent, Placebo, law.invention, Cohort Studies, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, Multiple Sclerosis, Chronic Progressive / drug therapy, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Benzyl Compounds, Clinical endpoint, Humans, Medicine, ComputingMilieux_MISCELLANEOUS, Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA, Expanded Disability Status Scale, Dose-Response Relationship, Drug, business.industry, Hazard ratio, General Medicine, Middle Aged, Multiple Sclerosis, Chronic Progressive, Fingolimod, Treatment Outcome, Settore M-EDF/01 - METODI E DIDATTICHE DELLE ATTIVITÀ MOTORIE, 030104 developmental biology, Siponimod, chemistry, Disease Progression, Azetidines, Female, Settore MED/26 - Neurologia, Human medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, medicine.drug
Abstract: Summary Background No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding Novartis Pharma AG.
Published: 2018

27. Survey of diagnostic and treatment practices for multiple sclerosis in Europe

Author: G. Comi, Patrick Vermersch, Carlo Pozzilli, B. Tackenberg, P. S. Soerensen, Gilles Edan, H.-P. Hartung, M. Delvecchio, Ludwig Kappos, Oscar Fernández, G. Gionvannoni, Sten Fredrikson, Eva Havrdova, SDA Bocconi Scuola di Direzione Aziendale, Service de Neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Department of Clinical Neurosciences, Neurology Division, Karolinska Institutet, Queen Mary's School of Medicine and Dentistry, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Department of Neurological Sciences, University of Roma 'La Sapienza', Danish Multiple Sclerosis Research Centre, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Neurology, Philipps Universität Marburg, Hospital Regional Universitario Carlos Haya, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), departmet of Neurology, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Department of neurology, Charles University [Prague] (CU), Department of Neurology [Suisse], University Hospital Basel [Basel], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Philipps Universität Marburg = Philipps University of Marburg, CHU Lille, Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, European Charcot Foundation, Barillot, Christian, Fernã¡ndez, O., Delvecchio, M., Edan, G., Fredrikson, S., Gionvannoni, G., Hartung, H. . P., Havrdova, E., Kappos, L., Pozzilli, C., Soerensen, P. S., Tackenberg, B., Vermersch, P., Comi, Giancarlo, Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Université de Lille, Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CentraleSupélec-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)
Subjects: Male, MESH: Multiple Sclerosis, Relapsing-Remitting, Delphi Technique, Modified delphi, Disease, MESH: Health Care Surveys, Relapsing-Remitting, Spinal Puncture, MESH: Delphi Technique, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, Surveys and Questionnaires, relapsingâ remitting, 030212 general & internal medicine, clinically isolated syndrome, radiologically isolated syndrome, relapsingâremitting, Adult, Disease Progression, Europe, Female, Humans, Magnetic Resonance Imaging, Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Neurologists, Health Care Surveys, Neurology, Neurology (clinical), Clinically isolated syndrome, 3. Good health, Clinical Practice, MESH: Disease Progression, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.medical_specialty, Steering committee, MESH: Spinal Puncture, relapsing−remitting, Disease activity, 03 medical and health sciences, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Mild form, MESH: Neurologists, MESH: Surveys and Questionnaires, MESH: Humans, business.industry, Multiple sclerosis, MESH: Adult, MESH: Multiple Sclerosis, medicine.disease, MESH: Male, Family medicine, Physical therapy, MESH: Europe, business, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; Background and purpose - Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice. Methods - A steering committee of MS neurologists used a modified Delphi process to develop case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Case-based questions were developed for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) and RRMS with breakthrough disease. Results - Multiple sclerosis neurologists from 11 European countries responded to survey 1 (n = 233) and survey 2 (n = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first-line injectables and oral treatments for mild RRMS, and moved to second-line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented. Conclusions - Although there was general agreement on some aspects of treatment, responses to other management and clinical practice questions varied considerably. These results, which reflect current clinical practice patterns, highlight the need for additional MS treatment education and awareness and may help inform the development of MS practice guidelines in Europe.
Published: 2017

28. Decreasing impact of late relapses on disability worsening in secondary progressive multiple sclerosis

Author: Anne Kerbrat, Laure Michel, Emmanuelle Le Page, Emmanuelle Leray, Chloé Rousseau, Gilles Edan, Emma Bajeux, Kevin Ahrweiller, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre hospitalier universitaire de Nantes (CHU Nantes), Observatoire Français de la Sclérose en Plaques, and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Natural history, Severity of Illness Index, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, 030212 general & internal medicine, Secondary progressive, Long-term follow-up, Retrospective Studies, Expanded Disability Status Scale, business.industry, Hazard ratio, Age Factors, Retrospective cohort study, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Confidence interval, Neurology, Disease Progression, Secondary progressive multiple sclerosis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Neurology (clinical), business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Relapses, Follow-Up Studies
Abstract: Background: Changes in relapse activity during secondary progressive multiple sclerosis (SPMS) need to be accurately characterized in order to identify patients who might benefit from continuing disease-modifying therapies. Objective: To describe relapse occurrence in patients with SPMS during long-term follow-up and assess its impact on disability worsening. Methods: This retrospective cohort study included 506 patients. We assessed the influence of relapses on time from SPMS onset to an Expanded Disability Status Scale score of 6 (EDSS 6), and on irreversible worsening of EDSS scores across different periods. Results: The annualized relapse rate (ARR) decreased with patient’s age (mean reduction of 43% per decade) and SPMS duration (mean reduction of 46% every 5 years). Post-progression relapses were associated with shorter time from secondary progressive (SP) phase onset to EDSS 6 (hazard ratio (HR) = 1.29, 95% confidence interval (CI) = (1.01, 1.64)). Relapse occurrence during the first 3 years and 3–5 years after SP onset was associated with an increased risk of irreversible EDSS worsening (OR = 3.12 (1.54, 6.31) and 2.04 (1.16, 3.58)). This association was no longer significant after 5 years. Conclusion: The occurrence of relapses was a marker of short-term disability progression during early SPMS, but did not have decisive impact in later SPMS.
Published: 2019

29. Préface

Author: Gilles Edan
Published: 2019

30. Amélioration rapide de la fonction visuelle après corticothérapie orale à forte dose chez des patients atteints de neuropathie optique inflammatoire

Author: D Baudet, B Mortemousque, E. Le Page, F Mouriaux, Gilles Edan, and A Poujade
Subjects: 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, 030212 general & internal medicine, 030217 neurology & neurosurgery, 3. Good health
Abstract: Resume Objectif Etudier l’evolution de l’acuite visuelle et des parametres de la fonction visuelle des patients atteints de neuropathie optique inflammatoire (NOI) traites par corticotherapie orale a forte dose. Methode Neuf patients atteints de NOI traites par 1000 mg de methylprednisolone per os par jour pendant trois a cinq jours ont ete inclus dans cette etude retrospective descriptive monocentrique. Les visites de suivi ont ete effectuees aux 4 e (j4), 15 e (j15), 30 e (j30) et 90 e (j90) jours apres l’instauration du traitement. Le bilan initial (j0) et les visites comprenaient une mesure de l’acuite visuelle (AV) selon l’echelle de l’Early Treatment Diabetic Retinopathy Study, un test de la sensibilite au contraste (SC) et un champ visuel (CV) automatique 30,2 (indice Visual Field Index [VFI]). La tolerance subjective globale du traitement a ete evaluee sur une echelle de 0 a 10. Resultats Nous avons observe une amelioration de l’ensemble des parametres des j4. Entre j0 et j4, l’AV moyenne a progresse de 40,1 a 57,9 lettres, le VFI moyen de 40,9 % a 70,3 % et la SC globale moyenne de 7,7 a 11,3 dB. De j15 a j90, l’AV moyenne a progresse de 77 lettres a 80,3 lettres, le VFI moyen de 91,2 % a 97,9 % et la SC globale moyenne de 15,4 dB a 16,7 dB. Quatre patients ont qualifie la tolerance excellente (10), trois autres patients entre 8 et 9 et les deux derniers a 6. Conclusion Nous avons mis en evidence une amelioration rapide des parametres de la fonction visuelle des patients atteints de NOI apres corticotherapie orale a forte dose.
Published: 2016

31. Epidemiology of multiple sclerosis

Author: Thibault Moreau, Emmanuelle Leray, Gilles Edan, Agnès Fromont, Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Comportement et noyaux gris centraux [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université européenne de Bretagne ( UEB ) -CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), École des Hautes Études en Santé Publique [EHESP] ( EHESP ), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Vision, Action et Gestion d'informations en Santé ( VisAGeS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE ( IRISA-D5 ), Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Pathology, Multiple Sclerosis, [SDV]Life Sciences [q-bio], Population, Natural history, Disease, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Epidemiology, Prevalence, medicine, Humans, 030212 general & internal medicine, Mortality, education, education.field_of_study, [ SDV ] Life Sciences [q-bio], business.industry, Incidence, Multiple sclerosis, Incidence (epidemiology), medicine.disease, 3. Good health, Neurology, Cohort, Disease Progression, Life expectancy, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Demography
Abstract: International audience; Multiple sclerosis (MS) is the most frequently seen demyelinating disease, with a prevalence that varies considerably, from high levels in North America and Europe (> 100/100,000 inhabitants) to low rates in Eastern Asia and sub-Saharan Africa (2/100,000 population). Knowledge of the geographical distribution of the disease and its survival data, and a better understanding of the natural history of the disease, have improved our understanding of the respective roles of endogenous and exogenous causes of MS. Concerning mortality, in a large French cohort of 27,603 patients, there was no difference between MS patients and controls in the first 20 years of the disease, although life expectancy was reduced by 6–7 years in MS patients. In 2004, the prevalence of MS in France was 94.7/100,000 population, according to data from the French National Health Insurance Agency for Salaried Workers (Caisse nationale d’assurance maladie des travailleurs Salariés [CNAM-TS]), which insures 87% of the French population. This prevalence was higher in the North and East of France. In several countries, including France, the gender ratio for MS incidence (women/men) went from 2/1 to 3/1 from the 1950s to the 2000s, but only for the relapsing–remitting form. As for risk factors of MS, the most pertinent environmental factors are infection with Epstein-Barr virus (EBV), especially if it arises after childhood and is symptomatic. The role of smoking in MS risk has been confirmed, but is modest. In contrast, vaccines, stress, traumatic events and allergies have not been identified as risk factors, while the involvement of vitamin D has yet to be confirmed. From a genetic point of view, the association between HLA-DRB1*15:01 and a high risk of MS has been known for decades. More recently, immunogenetic markers have been identified (IL2RA, IL7RA) and, in particular thanks to studies of genome-wide associations, more than 100 genetic variants have been reported. Most of these are involved in the immune response and often associated with other autoimmune diseases. Studies of the natural history of MS suggest it is a two-phase disease: in the first phase, inflammation is focal with flares; and in the second phase, disability progresses independently of focal inflammation. This has clear implications for therapy. Age may also be a key factor in the phenotype of the disease. In conclusion, France is a high-risk country for MS, but it only slightly reduces life expectancy. MS is a multifactorial disease and the implications of immunogenetics are major. Preventative approaches might be derived from knowledge of the risk factors and natural history of the disease (smoking, vitamin D)
Published: 2016

32. Co-occurrence of MS and ALS: a clue in favor of common pathophysiological findings?

Author: Philippe Corcia, Damien Le Port, Emmanuelle Le Page, Rudolph Hergesheimer, A.-M. Guennoc, Maud Pallix-Guyot, Mathieu Daryabin, Gilles Edan, Ayman Tourbah, and Stéphane Beltran
Subjects: 0301 basic medicine, Adult, Male, Pediatrics, medicine.medical_specialty, Multiple Sclerosis, Disease, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Humans, Amyotrophic lateral sclerosis, Age of Onset, Chi-Square Distribution, business.industry, Multiple sclerosis, Amyotrophic Lateral Sclerosis, Middle Aged, medicine.disease, Databases, Bibliographic, Magnetic Resonance Imaging, Pathophysiology, 030104 developmental biology, Neurology, Cohort, Female, Neurology (clinical), Age of onset, business, 030217 neurology & neurosurgery
Abstract: Amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are two neurological disorders that seem, theoretically, completely divergent according to epidemiological, clinical, pathophysiological, and therapeutic data. However, some reports that have mentioned the occurrence of both conditions within the same patient underpin the suggestion that this co-occurrence might not be random. We report six co-occurrences of ALS and MS cases, focusing on epidemiological and clinical diseases findings. We then compare our cohort to those in the literature. Our cohort was composed of five females and one male. The age of onset for MS ranged from 27 to 54 years with either primary or secondary prominence while all being progressive. Both diseases occurred sequentially in all but one the cases. Concerning ALS, the age of onset ranged from 51 to 60 years and the site of onset was the legs in 5/6 cases. The disease lasted from four to 29 months. Although infrequent, this co-occurrence supports the hypothesis of common, pathophysiological mechanisms between ALS and MS. We discuss some arguments favoring a potential link between both conditions.
Published: 2018

33. Effect of HLA-DRB1 alleles and genetic variants on the development of neutralizing antibodies to interferon beta in the BEYOND and BENEFIT trials

Author: Christoph Pohl, Beyond, Bertram Müller-Myhsok, M. S. Freedman, Dorothea Buck, Stuart D. Cook, Till M.F. Andlauer, Frederik Barkhof, Frank Weber, Hans-Peter Hartung, Giancarlo Comi, Karl Köchert, Mark Mühlau, Ludwig Kappos, Bernhard Hemmer, Xavier Montalban, Benefit Study Groups, Douglas Jeffery, Massimo Filippi, Gilles Edan, Wilmar Igl, Eva-Maria Wicklein, Barry G. W. Arnason, Buck, Dorothea, Andlauer, Till FM, Igl, Wilmar, Wicklein, Eva-Maria, Mühlau, Mark, Weber, Frank, Köchert, Karl, Pohl, Christoph, Arnason, Barry, Comi, Giancarlo, Cook, Stuart, Filippi, Massimo, Hartung, Hans-Peter, Jeffery, Dougla, Kappos, Ludwig, Barkhof, Frederik, Edan, Gille, Freedman, Mark S, Montalbán, Xavier, Müller-Myhsok, Bertram, Hemmer, Bernhard, Radiology and nuclear medicine, and Amsterdam Neuroscience - Neuroinfection & -inflammation
Subjects: Adult, Male, Multiple Sclerosis, Genome-wide association study, Single-nucleotide polymorphism, Human leukocyte antigen, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Genetic variation, medicine, Humans, Immunologic Factors, Multiple sclerosi, 030212 general & internal medicine, Prospective Studies, Allele, interferon beta, HLA-DRB1, genome-wide association study, business.industry, Multiple sclerosis, Middle Aged, medicine.disease, Antibodies, Neutralizing, anti-drug antibodie, Neurology, Genetic marker, Immunology, genetic variation, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Genome-Wide Association Study, HLA-DRB1 Chains, Interferon beta-1b
Abstract: Background: Treatment of multiple sclerosis (MS) with interferon β can lead to the development of antibodies directed against interferon β that interfere with treatment efficacy. Several observational studies have proposed different HLA alleles and genetic variants associated with the development of antibodies against interferon β. Objective: To validate the proposed genetic markers and to identify new markers. Methods: Associations of genetic candidate markers with antibody presence and development were examined in a post hoc analysis in 941 patients treated with interferon β-1b in the Betaferon® Efficacy Yielding Outcomes of a New Dose (BEYOND) and BEtaseron®/BEtaferon® in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) prospective phase III trials. All patients were treated with interferon β-1b for at least 6 months. In addition, a genome-wide association study was conducted to identify new genetic variants. Results: We confirmed an increased risk for carriers of HLA-DRB1*04:01 (odds ratio (OR) = 3.3, p = 6.9 × 10−4) and HLA-DRB1*07:01 (OR = 1.8, p = 3.5 × 10−3) for developing neutralizing antibodies (NAbs). Several additional, previously proposed HLA alleles and genetic variants showed nominally significant associations. In the exploratory analysis, variants in the HLA region were associated with NAb development at genome-wide significance (OR = 2.6, p = 2.30 × 10−15). Conclusion: The contribution of HLA alleles and HLA-associated single-nucleotide polymorphisms (SNPs) to the development and titer of antibodies against interferon β was confirmed in the combined analysis of two multi-national, multi-center studies.
Published: 2018

34. Natalizumab in secondary progressive multiple sclerosis

Author: Gilles Edan, Edan, Gilles, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, medicine.medical_specialty, Multiple Sclerosis, MESH: Multiple Sclerosis, Relapsing-Remitting, education, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Double-Blind Method, Internal medicine, medicine, Humans, MESH: Double-Blind Method, 030212 general & internal medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Multiple Sclerosis, Chronic Progressive, MESH: Humans, business.industry, Multiple sclerosis, Disease progression, MESH: Natalizumab, MESH: Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, medicine.disease, humanities, 3. Good health, Disease Progression, Secondary progressive multiple sclerosis, MESH: Disease Progression, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Comment onEffect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension. [Lancet Neurol. 2018]; International audience
Published: 2018

35. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial

Author: Emmanuelle, Le Page, David, Veillard, David A, Laplaud, Stéphanie, Hamonic, Rasha, Wardi, Christine, Lebrun, Fabien, Zagnoli, Sandrine, Wiertlewski, Véronique, Deburghgraeve, Marc, Coustans, Gilles, Edan, and C, Lebrun Frenay
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Population, Administration, Oral, Placebo, Methylprednisolone, law.invention, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Double-Blind Method, Randomized controlled trial, law, Oral administration, Internal medicine, Clinical endpoint, Humans, Medicine, Infusions, Intravenous, Adverse effect, education, Glucocorticoids, Saline, education.field_of_study, business.industry, General Medicine, Middle Aged, 3. Good health, Surgery, Treatment Outcome, Female, France, business, medicine.drug
Abstract: SummaryBackground High doses of intravenous methylprednisolone are recommended to treat relapses in patients with multiple sclerosis, but can be inconvenient and expensive. We aimed to assess whether oral administration of high-dose methylprednisolone was non-inferior to intravenous administration. Methods We did this multicentre, double-blind, randomised, controlled, non-inferiority trial at 13 centres for multiple sclerosis in France. We enrolled patients aged 18–55 years with relapsing-remitting multiple sclerosis who reported a relapse within the previous 15 days that caused an increase of at least one point in one or more scores on the Kurtzke Functional System Scale. With use of a computer-generated randomisation list and in blocks of four, we randomly assigned (1:1) patients to either oral or intravenous methylprednisolone, 1000 mg, once a day for 3 days. Patients, treating physicians and nurses, and data and outcome assessors were all masked to treatment allocation, which was achieved with the use of saline solution and placebo capsules. The primary endpoint was the proportion of patients who had improved by day 28 (decrease of at least one point in most affected score on Kurtzke Functional System Scale), without need for retreatment with corticosteroids, in the per-protocol population. The trial was powered to assess non-inferiority of oral compared with intravenous methylprednisolone with a predetermined non-inferiority margin of 15%. This trial is registered with ClinicalTrials.gov, number NCT00984984. Findings Between Jan 29, 2008, and June 14, 2013, we screened 200 patients and enrolled 199. We randomly assigned 100 patients to oral methylprednisolone and 99 patients to intravenous methylprednisolone with a mean time from relapse onset to treatment of 7·0 days (SD 3·6) and 7·4 days (3·9), respectively. In the per-protocol population, 66 (81%) of 82 patients in the oral group and 72 (80%) of 90 patients in the intravenous group achieved the primary endpoint (absolute treatment difference 0·5%, 90% CI −9·5 to 10·4). Rates of adverse events were similar, but insomnia was more frequently reported in the oral group (77 [77%]) than in the intravenous group (63 [64%]). Interpretation Oral administration of high-dose methylprednisolone for 3 days was not inferior to intravenous administration for improvement of disability scores 1 month after treatment and had a similar safety profile. This finding could have implications for access to treatment, patient comfort, and cost, but indication should always be properly considered by clinicians. Funding French Health Ministry, Ligue Francaise contre la SEP, Teva
Published: 2015

36. Pixantrone: a B-cell-depleting immunosuppressant for multiple sclerosis patients with active disease

Author: Marc Debouverie, Christian Sindic, Richard Gonsette, Gilles Edan, Jean-Christophe Ferré, Cliniques Universitaires Saint-Luc [Bruxelles], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de Radiologie [CHU de Rennes], Université de Rennes (UR), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Sclérose Latérale Amyotrophique et maladies [CHRU Nancy], Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Université de Rennes (UNIV-RENNES)-CentraleSupélec-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), and Edan, Gilles
Subjects: Male, 0301 basic medicine, MESH: Topoisomerase II Inhibitors, MESH: Multiple Sclerosis, Relapsing-Remitting, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Outcome Assessment, Health Care, Topoisomerase II Inhibitors, active disease, disease-modifying therapies, pixantrone, B-Lymphocytes, immunosuppression, MESH: Middle Aged, Hematology, Pixantrone, B-cell depletion, medicine.diagnostic_test, Immunosuppression, Middle Aged, Multiple Sclerosis, Chronic Progressive, 3. Good health, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Immunosuppressive Agents, medicine.symptom, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Neurological examination, Multiple sclerosis, Lesion, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, MESH: B-Lymphocytes, Internal medicine, MESH: Isoquinolines, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Multiple Sclerosis, Chronic Progressive, MESH: Outcome Assessment, Health Care, Cardiotoxicity, Mitoxantrone, MESH: Humans, business.industry, MESH: Adult, Isoquinolines, medicine.disease, MESH: Male, Surgery, 030104 developmental biology, chemistry, Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery
Abstract: Background: Mitoxantrone has been approved for patients with worsening relapsing–remitting (RR) or secondary progressive multiple sclerosis (SPMS), but its long-term use is limited by its cardiotoxicity. Pixantrone (PIX) is an analog of mitoxantrone. Objectives: The aim of this open-label, multicenter, noncomparative Phase I/II trial was to explore the immunosuppressive effect of PIX, its impact on clinical disease activity and cerebral gadolinium-enhanced (Gd+) lesions, and its safety. Methods: Eighteen patients with active RRMS and SPMS (⩾ 1 cerebral Gd+ lesion) despite approved immunomodulatory therapy received four intravenous PIX injections every 21 days. A neurological examination, hematology, lymphocyte subsets, and biochemistry were performed at Day 1, Weeks 3, 6 and 9, and Months 3, 6, 9 and 12. Echocardiography was performed before each infusion, at Months 3, 6 and 12. Cerebral MRI was performed at baseline, and at Months 6 and 12. Results: CD19+ cells were reduced by 95% at Month 3 and by 47% at Month 12. Gd+ lesions were reduced by 86% at Month 12 ( p = 0.01). The annual relapse rate was reduced by 87% ( p < 10−4). Two patients experienced a transient reduction in left ventricular fraction. Conclusion: These preliminary data indicate the efficacy of PIX in active RRMS and SPMS.
Published: 2015

37. A retrospective study on the efficacy and safety of intraveinous immunoglobulin (Tegeline®) in patients with chronic inflammatory demyelinating polyneuropathy

Author: Gilles Edan, Florence Robert, Jean-Christophe Antoine, Christophe Vial, Jean Pouget, Guillaume Nicolas, and Sophie Puget
Subjects: Male, medicine.medical_specialty, Chronic inflammatory demyelinating polyneuropathy, Placebo, Modified Rankin Scale, Internal medicine, Clinical endpoint, Humans, Medicine, In patient, Retrospective Studies, biology, business.industry, Immunoglobulins, Intravenous, Polyradiculoneuropathy, Retrospective cohort study, General Medicine, medicine.disease, Surgery, Treatment Outcome, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, biology.protein, Female, Immunotherapy, Antibody, business, Follow-Up Studies
Abstract: To assess the efficacy and safety of intraveinous immunoglobulin (IV Ig) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) at 4, 7 and 12months.A national multicenter retrospective study was conducted by LFB Biotehcnologies in patients with CIDP who had received at least one cycle of a 5% polyvalent IV Ig, Tegeline(®), from LFB biomédicaments between 1995 and 2004. The primary endpoint was the efficacy of IV Ig at 4 months, which was defined as the responder rate based on the modified Rankin scale. Several secondary endpoints were assessed: safety and efficacy (i.e., responders according to the investigators' overall assessment of the patients' status) at 4, 7 and 12 months. The analysis was performed at 7 months only (due to missing data for 12 months and few patients).A total of 26 patients were included who had received between 1 and 6 cycles of IV Ig (mean 3±2) with a median follow-up of 9.9 months. The responder rate at 4 months based on the modified Rankin scale was 52% (95% CI 0.313-0.722), whereas the responder rate with placebo reported in the literature (meta-analysis including results from van Schaik and an ICE study) is 18% (P0.001). Responder patients at 4 months were still responders at 7 months. The overall safety of IV Ig was good, with adverse events of mild to moderate severity, which resolved without sequelae and were expected adverse events of IV Ig.This retrospective study confirmed both the efficacy of IV Ig at 4 months in the treatment of chronic inflammatory demyelinating polyneuropathy and the favorable safety profile of the product.
Published: 2015

38. Criteria improving multiple sclerosis diagnosis at the first MRI

Author: Margaux Genevray, M.-P. Chaunu, Laurent Pierot, Ayman Tourbah, L. Daelman, Nathalie Caucheteux, Adil Maarouf, Jean Pelletier, Olivier Gout, Emmanuelle Leray, Gilles Edan, Jean-Christophe Ferré, Romain Deschamps, Service de neurologie [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Maison Blanche, CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), IFP Energies nouvelles (IFPEN), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Service de radiologie et imagerie médicale [Rennes] = Radiology [Rennes], Université Jean Moulin - Lyon 3 (UJML), Université de Lyon, Pôle de Neurosciences Cliniques, Department of Neurology, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA), Service de Neurologie [Rennes] = Neurology [Rennes], CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)
Subjects: Adult, Male, medicine.medical_specialty, Neurology, Severity of Illness Index, Asymptomatic, Multiple sclerosis, Lesion, Young Adult, Predictive Value of Tests, Diagnosis, Image Processing, Computer-Assisted, medicine, Humans, Relapsing-remitting, Prospective cohort study, Retrospective Studies, Neuroradiology, business.industry, Brain, McDonald criteria, Retrospective cohort study, Prognosis, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Surgery, Logistic Models, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Radiology, medicine.symptom, business
Abstract: International audience; The introduction of the McDonald criteria has enabled earlier diagnosis of multiple sclerosis (MS). However, even with the 2010 revised criteria, nearly 50 % of patients remain classified as “possible MS” following the first MRI. The present study aimed to demonstrate that time to MS diagnosis could be shorter than 2010 revised criteria, and established after a single early MRI in most patients with the association of the symptomatic lesion and at least one suggestive asymptomatic lesion. We also evaluated the short-term predictive capacity of an individual suggestive lesion on disease activity. We analyzed initial MRI results from 146 patients with MS from a multicenter retrospective study. Visualization of the symptomatic lesion was used as a primary criterion. Secondary criteria included one suggestive lesion (SL) aspect or topography on MRI, or one non-specific lesion associated with positive CSF. The proposed criteria led to a positive diagnosis of MS in 100 % of cases, from information available from the time of the first MRI for 145 patients (99.3 %). At least one SL was observed for 143 patients (97.9 %), and positive CSF for the 3 others. Compared to the McDonald criteria, the proposed criteria had 100 % sensitivity, with a significantly shorter mean time to reach a positive diagnosis. Furthermore, the simultaneous presence of corpus callosum, temporal horn, and ovoid lesions was associated with radiological or clinical activity after a year of follow-up. The proposed diagnostic criteria are easy to apply, have a good sensitivity, and allow an earlier diagnosis than the 2010 McDonald criteria. Nevertheless, prospective studies are needed to establish specificity and to confirm these findings. © 2015, Springer-Verlag Berlin Heidelberg.
Published: 2015

39. Survey of diagnostic and treatment practices for multiple sclerosis (MS) in Europe. Part 2: Progressive MS, paediatric MS, pregnancy and general management

Author: Patrick Vermersch, Sten Fredrikson, Oscar Fernandez, Ludwig Kappos, G. Comi, Eva Havrdova, H.-P. Hartung, M. Delvecchio, Gavin Giovannoni, Gilles Edan, Carlo Pozzilli, P. S. Soerensen, and B. Tackenberg
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Management, Paediatric MS, Primary progressive MS, Secondary progressive MS, Neurology, Neurology (clinical), Primary progressive, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Pregnancy, Medicine, Humans, Immunologic Factors, In patient, Neurologists, Glatiramer acetate, Practice Patterns, Physicians', Secondary progressive, Child, business.industry, Multiple sclerosis, Brain, Glatiramer Acetate, Management of multiple sclerosis, medicine.disease, Europe, Pregnancy Complications, 030104 developmental biology, Spinal Cord, Family medicine, Health Care Surveys, Disease Progression, Female, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background and purpose The European Charcot Foundation supported the development of a set of surveys to understand current practice patterns for the diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarizes survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric MS and overall patient management. Methods A steering committee of MS neurologists developed case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Results Respondents generally favoured changing rather than stopping disease-modifying treatment (DMT) in patients transitioning from relapsing-remitting MS to SPMS, particularly with active disease. Respondents would not initiate DMT in patients with typical PPMS symptoms, although the presence of ≥1 spinal cord or brain gadolinium-enhancing lesion might affect that decision. For patients considering pregnancy, respondents were equally divided on whether to stop treatment before or after conception. Respondents strongly favoured starting DMT in paediatric MS with active disease; recommended treatments included interferon, glatiramer acetate and, in John Cunningham virus negative patients, natalizumab. Additional results regarding practice-based questions and management are summarized. Conclusions Results of part 2 of the survey of diagnostic and treatment practices for MS in Europe largely mirror results for part 1, with neurologists in general agreement about the treatment and management of SPMS, PPMS, pregnancy and paediatric MS as well as the general management of MS. However, there are also many areas of disagreement, indicating the need for evidence-based recommendations and/or guidelines.
Published: 2017

40. Diagnostics différentiels de la sclérose en plaques

Author: Bruno Brochet, M. de Sèze, Olivier Gout, Pierre Labauge, Jean Pelletier, Agnès Fromont, X. Gamé, Béatrice Jenny, C. Vignal-Clermont, C. Harand, Cécile Donzé, P.-H. Lalive, Eric Thouvenot, Bertrand Audoin, Jérôme De Seze, Jean-Christophe Ouallet, Etienne Allart, Clarisse Carra-Dalliere, Xavier Ayrignac, Gilles Edan, L. Michel, Olivier Outteryck, F. Pelé, Anne Blanchard-Dauphin, Mikael Cohen, Pierre Clavelou, Nicolas Collongues, E. Le Page, Marc Debouverie, David Brassat, Alain Créange, Hélène Zéphir, S. Pittion-Vouyovitch, Aurélie Ruet, P. Marque, Xavier Moisset, Christine Lebrun-Frénay, David Veillard, C. Guillon, C. Bensa, Anne-Laure Ramelli, Sandra Vukusic, and Gilles-Louis Defer
Subjects: business.industry, Medicine, business
Published: 2017

41. Signes et symptômes de la sclérose en plaques

Author: P. Marque, Olivier Outteryck, Anne-Laure Ramelli, Sandra Vukusic, Gilles-Louis Defer, C. Guillon, Agnès Fromont, Jean Pelletier, Mikael Cohen, Cécile Donzé, Pierre Clavelou, Bruno Brochet, C. Vignal-Clermont, C. Harand, Eric Thouvenot, S. Pittion-Vouyovitch, L. Michel, X. Gamé, Alain Créange, Xavier Ayrignac, Olivier Gout, F. Pelé, Christine Lebrun-Frénay, Béatrice Jenny, Etienne Allart, C. Bensa, Aurélie Ruet, Xavier Moisset, Bertrand Audoin, David Veillard, Hélène Zéphir, Jérôme De Seze, Marc Debouverie, Gilles Edan, Jean-Christophe Ouallet, M. de Sèze, Pierre Labauge, Clarisse Carra-Dalliere, David Brassat, E. Le Page, Anne Blanchard-Dauphin, Nicolas Collongues, and P.-H. Lalive
Subjects: business.industry, Medicine, business
Published: 2017

42. Thérapeutiques et prise en charge de la sclérose en plaques

Author: C. Bensa, Jean-Christophe Ouallet, Mikael Cohen, Pierre Clavelou, Olivier Outteryck, Bruno Brochet, S. Pittion-Vouyovitch, Xavier Ayrignac, David Brassat, Cécile Donzé, C. Harand, X. Gamé, L. Michel, Marc Debouverie, Bertrand Audoin, F. Pelé, C. Guillon, Etienne Allart, Clarisse Carra-Dalliere, Eric Thouvenot, David Veillard, Anne-Laure Ramelli, Sandra Vukusic, Hélène Zéphir, Gilles Edan, Gilles-Louis Defer, E. Le Page, P. Marque, Jérôme De Seze, Alain Créange, Jean Pelletier, Olivier Gout, Agnès Fromont, Béatrice Jenny, C. Vignal-Clermont, Christine Lebrun-Frénay, P.-H. Lalive, M. de Sèze, Pierre Labauge, Xavier Moisset, Aurélie Ruet, Anne Blanchard-Dauphin, and Nicolas Collongues
Subjects: business.industry, Medicine, business
Published: 2017

43. Mesure du ratio de transfert d’aimantation (MTR) sur la moelle épinière cervicale : reproductibilité et variabilité en multicentrique

Author: Jean-Christophe Ferré, Elise Bannier, Christian Barillot, Anne Kerbrat, Laureline Monteau, Benoît Combès, and Gilles Edan
Subjects: Radiological and Ultrasound Technology, Radiology, Nuclear Medicine and imaging, Neurology (clinical)
Abstract: Contexte et objectif L’evaluation des variations du ratio de transfert d’aimantation (MTR) dans la moelle epiniere est une etape preliminaire a l’etude de son utilisation clinique, en particulier dans le contexte d’etudes multicentriques. Notre objectif etait d’analyser la variabilite du MTR en intra-patient, inter-patient et en inter-centre, dans un groupe de sujets sains. Materiel et methodes Les donnees de 17 sujets sains, dont six scannes deux fois, ont ete acquises de C1 a C7 sur cinq IRM 3T (deux modeles) d’un meme fabricant. Les valeurs moyennes de MTR ont ete calculees pour chaque niveau vertebral dans la totalite du cordon medullaire (CM) et dans les regions de substance blanche (SB) et substance grise (SG). Ces regions ont ete definies a l’aide de methodes de traitement automatiques. Les ecarts-types (ET) associes aux variations intra-patients, inter-patients, et inter-centres ont ensuite ete estimes. Resultats Les valeurs moyennes de MTR medullaires etaient significativement plus elevees pour les trois premiers etages cervicaux : 40,5 %, 37,5 % et 35,7 % en C1, C2 et C3 respectivement. De C4 a C6, la valeur moyenne de MTR etait de 34,6 ± 0,9 % dans CM. Les valeurs dans la SG etaient plus faibles que dans la SB (32,7 ± 1,1 % contre 35,9 % ± 1,1 % ; p = 4e−12). La plus grande variabilite residait dans les mesures intra-patients, avec un ET de 0,8 pu dans CM. En revanche, l’ET inter-centre etait de 0,5 pu, representant environ 30 % de variabilite globale. Aucune variabilite substantielle inter-patient n’a ete detectee. Conclusion Une bonne reproductibilite entre centres et une faible variabilite dans la population controle des mesures de MTR dans la moelle epiniere cervicale, ouvre la voie a des etudes multicentriques longitudinales des pathologies demyelinisantes.
Published: 2018

44. Treatment of relapsing-remitting multiple sclerosis

Author: Gilles Edan and Marie Théaudin
Subjects: Psychiatry and Mental health, Clinical Psychology, medicine.medical_specialty, Relapsing remitting, business.industry, Multiple sclerosis, medicine, Neurology (clinical), business, medicine.disease, Dermatology
Published: 2018

45. Formes cavitaires de sclérose en plaques : étude multicentrique sur vingt patients

Author: A Robinson, Emmanuel Touzé, Odile Boespflug-Tanguy, Alain Créange, Diane Dupuy, Véronique Deburghgraeve, Giovanni Castelnovo, Lucien Rumbach, Dimitri Renard, Bruno Brochet, Christine Lebrun-Frenay, Patrick Vermersch, Astrid Corlobé, Hélène Zéphir, Cyril Goizet, Eric Berger, Mikael Cohen, Pierre Labauge, and Gilles Edan
Subjects: Gynecology, medicine.medical_specialty, business.industry, Multiple sclerosis, Disease progression, medicine.disease, 3. Good health, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Neurology, Multicenter study, White Matter Diseases, medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Resume Introduction Les lesions cavitaires, definies par une degenerescence kystique de la substance blanche, ont ete decrites dans des atteintes hereditaires de la substance blanche (« leucodystrophies »). Cette atteinte est une des caracteristiques du childhood ataxia with central nervous system hypomyelination syndrome (CACH). Elles n’ont pas ete decrites dans la sclerose en plaques. Methodes Nous rapportons une serie retrospective multicentrique de 20 patients atteints de sclerose en plaques et presentant de larges lesions cavitaires. Les donnees cliniques, biologiques, electrophysiologiques, moleculaires et IRM ont ete collectees. Resultats Vingt patients ont ete inclus dans cette etude (6 hommes et 14 femmes). L’âge moyen au debut de la maladie etait de 37,6 ans (extremite 17–58 ans) et la duree moyenne d’evolution de 10 ans (extremite 2–20 ans). La moitie des patients (10/20) etait une forme primaire progressive. Le score EDSS moyen etait de 5,5 (extremite 2–8). Le score MMS moyen etait a 20/30. La recherche genetique de mutation du gene EIF2B codant pour le CACH syndrome a ete recherchee dans 7 cas et a toujours ete negative. Les lesions cavitaires etaient strictement supratentorielles et localisees au sein d’une leucopathie diffuse, avec une predominance posterieure chez la plupart des patients. Conclusion Les formes cavitaires de sclerose en plaques semblent representer un sous-groupe de patients caracterisee par une evolution clinique severe (forme primaire progressive, scores EDSS eleves et atteinte cognitive severe).
Published: 2013

46. L’IRM est-elle utile dans le suivi des patients atteints de sclérose en plaques ? Non

Author: Gilles Edan
Subjects: Drug, medicine.medical_specialty, media_common.quotation_subject, Disease, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Internal medicine, Epidemiology, medicine, Disability progression, In patient, 030304 developmental biology, media_common, 0303 health sciences, business.industry, Multiple sclerosis, medicine.disease, 3. Good health, Surgery, Clinical Practice, Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Is regular MRI monitoring useful in clinical practice in multiple sclerosis patients treated with disease modifying therapy (DMT) drugs? My answer is no. Tacking a DMT drug is not by itself a pertinent criterion for requiring a systematic MRI monitoring in MS patients. Five clinical criteria should be taken into consideration before prescribing regular MRI examinations. The clinical form of the disease: MRI monitoring in DMT treated patients, has been demonstrated as useful only in pure relapsing-remitting MS patients. Up to now, there is no convincing demonstration of therapeutic efficacy with any DMT drug, neither first-line nor second-line drugs in patients with primary or secondary progressive MS disease. The duration of the disease, epidemiological data leading to the concept of a two-stage disability progression in MS, emphasizes the importance of treating as early as possible RRMS patients in order to stop accumulation of new focal MRI CNS lesions. In this regard, an annual monitoring for the 5 first years of the disease looks reasonable in order to better personalize the treatment choice among the few approved DMT drugs. The duration of the treatment: a first MRI assessment at month 6 after initiating a new DMT drug is adequate in order to better distinguish responder versus no responder. The persistence of Gado+lesions at 6 months is a strong indication for considering alternative treatment. The disease activity: both criteria, clinical and MRI, are needed to recognized very active or aggressive relapsing MS patients, leading to decide a rapid use of second-line treatment therapy. The treatment choice: in JC positive MS patients treated with natalizumab, the risk of PML is as high as more than 1 % in those JC+MS patients that are treated continuously more than 24 months. A regular MRI monitoring (3 or 6months) is recommended in order to detect as early as possible MRI abnormalities suggesting PML.
Published: 2013

47. Manifestations neuropsychiatriques dans la sclérose en plaques : et si des symptômes psychotiques annonçaient le début de la maladie ?

Author: Nathalie Guernion, Emeline Le Cadet, Anne Tirel, Michel Walter, Gilles Edan, Mickaël Le Galudec, Commowick, Olivier, CHRU Brest - Psychiatrie Adulte (CHU - Brest- Psychiatrie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université de Brest (UBO), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Service de neurologie, centre hospitalier universitaire de Rennes, 2, rue Henri-le-Guilloux, 35000 Rennes, France., CHU Pontchaillou [Rennes], CHRU Brest - Psychiatrie Adulte ( CHU - Brest- Psychiatrie ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Université de Brest ( UBO ), Vision, Action et Gestion d'informations en Santé ( VisAGeS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE ( IRISA-D5 ), Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pediatrics, medicine.medical_specialty, Psychosis, Population, Neurological examination, Disease, Grey matter, 03 medical and health sciences, 0302 clinical medicine, Medicine, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Family history, Medical diagnosis, Psychiatry, education, ComputingMilieux_MISCELLANEOUS, [SDV.IB] Life Sciences [q-bio]/Bioengineering, education.field_of_study, medicine.diagnostic_test, business.industry, Multiple sclerosis, General Medicine, medicine.disease, 030227 psychiatry, 3. Good health, medicine.anatomical_structure, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, 030217 neurology & neurosurgery
Abstract: Key points Patients suffering from multiple sclerosis (MS) can often dysplay psychiatric symptoms throughout the disease. The frequency of those symptoms could be two or three times greater in MS patients compared to the general population. Psychotic symptoms could be an early sign of MS. At first, neurological symptoms can either be mild or altogether absent. MRI brain scans show cerebral lesions in frontal and temporal regions. New MRI sequencing techniques support the hypothesis that disseminated defects in the grey matter occur in MS. These defects could in turn be responsible for cognitive disorders. Patients presenting a first-episode psychosis must have a neurological examination. MS should be considered as an alternative diagnosis of psychosis, particularly in atypical cases where family history of psychosis is absent and where there is bad response to standard psychotropic treatment. Collaboration between neurologists and psychiatrists whilst caring for patients displaying neuropsychiatric manifestations of MS is crucial to enable more accurate diagnoses and try to improve treatment and overall prognosis.
Published: 2013

48. Induction Therapy for Patients with Multiple Sclerosis: Why? When? How?

Author: Gilles Edan, Emmanuelle Le Page, Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, medicine.medical_specialty, Multiple Sclerosis, Neurology, Clinical Neurology, Drug Administration Schedule, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Pharmacotherapy, Maintenance therapy, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Glatiramer acetate, Randomized Controlled Trials as Topic, Mitoxantrone, business.industry, Multiple sclerosis, Glatiramer Acetate, Induction Chemotherapy, Interferon-beta, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, 3. Good health, Observational Studies as Topic, Psychiatry and Mental health, Treatment Outcome, Current Opinion, Immunology, Alemtuzumab, Neurology (clinical), Peptides, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; The concept of induction treatment followed by long-term maintenance treatment in multiple sclerosis (MS) has attracted considerable attention. The combination of mitoxantrone as the induction therapy followed by an immunomodulatory drug (e.g., interferon beta or glatiramer acetate) as the maintenance therapy is of particular interest. This approach is suitable for patients with particularly aggressive disease, characterised by frequent relapses with incomplete recovery and the accumulation of focal lesions visible on magnetic resonance imaging. A long-term study has shown that a short (6 month) course of mitoxantrone followed by maintenance therapy with an immunomodulatory drug brings about a rapid reduction in disease activity and subsequent sustained disease control for at least 5 years. Furthermore, randomised studies have demonstrated that induction with mitoxantrone followed by maintenance treatment affords better disease control than monotherapy with an interferon beta. Natalizumab is also effective in patients with very active MS, but has a propensity to result in rebound inflammatory disease activity on withdrawal. More recently, a mere 5-day course of 12-mg intravenous perfusions of alemtuzumab was found to bring long-term clinical benefits in early relapsing MS patients at risk of developing severe systemic autoimmune disease within the space of a few years.
Published: 2013

49. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial

Author: Coles, Alasdair J., Twyman, Cary L., Arnold, Douglas L., Cohen, Jeffrey A., Christian, Confavreux, Fox, Edward J., Hans Peter Hartung, Eva, Havrdova, Selmaj, Krzysztof W., Weiner, Howard L., Tamara, Miller, Elizabeth, Fisher, Rupert, Sandbrink, Lake, Stephen L., Margolin, David H., Pedro, Oyuela, Panzara, Michael A., Compston, D Alastair S., Gupta, the CARE MS II investigators: Ajay S., Edward, Fox, Glyman, Steven A., Thoits, Timothy K., Sullivan, Herman C., Cascione, Mark C., Rammohan, Kottil W., Gazda, Suzanne K., Wynn, Daniel R., Wray, Sibyl E., Stanton, Elias, Ford, Corey C., Andrew, Goodman, Hughes, Bruce L., Omar Azhar Khan, Vaishnav, Anand G., Stephen, Kirzinger, Lynch, Sharon G., Mattson, David H., Braley, Tiffany J., Mikol, Daniel D., Stephen, Krieger, Tamara Ann Miller, Riskind, Peter N., Roberto, Bomprezzi, Wingerchuk, Dean M., Brian, Steingo, Jeffrey Alan Cohen, Crayton, Heidi J., Cooper, Joanna A., Weiner, Leslie P., Harold Moses, J. r., Agius, Mark A., Ann Doan Do Bass, Lallana, Enrico C., Mitchell, Galen W., Krolczyk, Stanley J., Alireza, Minagar, Burk, Jubelt, Evans, Bradley K., Hunter, Samuel F., Rizvi, Syed A., Sheppard, Christopher A., David Honeycutt, W. M., Joseph, Herbert, Lathi, Ellen S., Gabriel, Pardo, Lily Jung Ilenson, Rothstein, Ted L., Thrower, Ben W., Mary Ann Picone, Mariko, Kita, Grazioli, Erica M., Silliman, Scott L., Thomas, Giancarlo, Gottesman, Malcolm H., Abou Zeid, Nuhad E., Rowe, Vernon D., Boutwell, Christine M., Schaeffer, John D., Riley, Claire S., Edwards, Keith R., Wendt, Jeanette K., G. Kim Bigley J. r., Shubin, Richard A., Silva Markovic Plese, Jones, Davis E., Gary, Clauser, Freedman, Mark S., Francois, Grand’Maison, Jacques, Francois H., Traboulsee, Anthony L., Brunet, Donald G., Marcelo, Kremenchutzky, Charles, Ayotte, Lava, Neil S., Waldman, Stephen R., Janus, Todd J., Stephen Gerard Vincent, Mark, Gudesblatt, Michael, Rossen, Stein, Lee S., Bennett Irving Machanic, Timothy, Vollmer, Gitt, Jeffrey S., Jeffrey, Dunn, Donald, Negroski, Fletcher, Mark H., Adil, Javed, Frohman, Elliot M., Richard, Macdonell, John Owen King, Paine, Mark A., Karyn, Boundy, Simon, Broadley, Steve, Vucic, Stephen, Reddel, Dreyer, Michael D., Raymond, Schwartz, Pamela Ann McCombe, Suzanne, Hodgkinson, Charles, Tilbery, Ferreira, Maria Lucia B., Dagoberto, Callegaro, Marcio Mena Barreto Martins, Jesus Arturo Violante Villanueva, Noemi Santos Caballero, Claudia Venzor Mendoza, Norma Haydee Deri, Alasdair, Coles, Neil James Scolding, Gavin, Giovannoni, Basil, Sharrack, Rog, David J., Giancarlo, Comi, Angelo, Ghezzi, Mancardi, Giovanni L., Durelli, Luca, Antonio, Bertolotto, Ruggero, Capra, Carlo, Pozzilli, Maria Giovanna Marrosu, Hupperts, Raymond M. M., Erik van Munster, Xavier, Montalbán, Rafael Arroyo González, Guillermo Izquierdo Ayuso, Óscar Fernández Fernández, Patrick, Vermersch, Jerome de Seze, Thibault, Moreau, Pierre, Clavelou, Catherine, Lubetzki, Michel, Clanet, Marc, Debouverie, Gilles, Edan, Judith, Haas, Martin, Stangel, Tjalf, Ziemssen, Bernhard, Hemmer, Karl, Baum, Klaus Zettl, U., Herrlinger, U., Wolfgang, Köhler, Gunter, Ochs, Patrick, Oschmann, Klaus Tiel Wilck, Hayrettin, Tumani, Urban, Peter P., Jan, Lycke, Anders, Svenningsson, Ivana, Kovarova, Marta, Vachova, Ivan, Rektor, Radomir, Talab, Krzysztof, Selmaj, Zbigniew, Stelmasiak, Wojciech, Kozubski, Dubois, Benedicte D. P., Dominique, Dive, Christian, Sindic, Karl, Vass, Per Soelberg Sørensen, Thor, Petersen, Mads, Ravnborg, Anat, Achiron, Adi Vaknin Dembinsky, Arnon, Karni, Gusev, Evgeny I., Stolyarov, Igor D., Zavalishin, Igor A., Skoromets, Alexander A., Boyko, Alexei N., Belova, Anna N., Malkova, Nadezhda A., Barantsevich, Evgeniy R., Yakupov, Eduard Z., Perfiliev, Semen V., Poverennova, Irina E., Voloshyna, Natalia P., Nehrych, Tetyana I., Kobys, Tetyana O., Mario, Habek, Vesna, Brinar, Zlatko, Trkanjec, Anton, Vladić, Spomenka Kidemet Piskać, Licia, Antonelli, Jelena, Drulović, Čongor, Nadj, Evica, Dinčić, Gordana, Tončev, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Klinische Neurowetenschappen, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Neurologie (9), RS: MHeNs School for Mental Health and Neuroscience, Radiology and nuclear medicine, and NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases
Subjects: Male, Adult, medicine.medical_specialty, Adolescent, CD52, multiple sclerosis, Administration, Cutaneous, Antibodies, Monoclonal, Humanized, law.invention, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Adjuvants, Immunologic, Randomized controlled trial, Recurrence, law, Internal medicine, Humans, Medicine, Glatiramer acetate, Infusions, Intravenous, Adverse effect, Alemtuzumab, disease, business.industry, Multiple sclerosis, Interferon beta-1a, Glatiramer Acetate, General Medicine, Middle Aged, medicine.disease, Treatment Outcome, Immunology, Female, Ocrelizumab, Peptides, business, Immunosuppressive Agents, medicine.drug
Abstract: The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment.In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18-55 years with relapsing-remitting multiple sclerosis and at least one relapse on interferon beta or glatiramer. Eligible participants were randomly allocated in a 1:2:2 ratio by an interactive voice response system, stratified by site, to receive subcutaneous interferon beta 1a 44 μg, intravenous alemtuzumab 12 mg per day, or intravenous alemtuzumab 24 mg per day. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and for 3 days at 12 months. The 24 mg per day group was discontinued to aid recruitment, but data are included for safety assessments. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability, comparing alemtuzumab 12 mg and interferon beta 1a in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00548405.202 (87%) of 231 patients randomly allocated interferon beta 1a and 426 (98%) of 436 patients randomly allocated alemtuzumab 12 mg were included in the primary analyses. 104 (51%) patients in the interferon beta 1a group relapsed (201 events) compared with 147 (35%) patients in the alemtuzumab group (236 events; rate ratio 0·51 [95% CI 0·39-0·65]; p0·0001), corresponding to a 49·4% improvement with alemtuzumab. 94 (47%) patients in the interferon beta 1a group were relapse-free at 2 years compared with 278 (65%) patients in the alemtuzumab group (p0·0001). 40 (20%) patients in the interferon beta 1a group had sustained accumulation of disability compared with 54 (13%) in the alemtuzumab group (hazard ratio 0·58 [95% CI 0·38-0·87]; p=0·008), corresponding to a 42% improvement in the alemtuzumab group. For 435 patients allocated alemtuzumab 12 mg, 393 (90%) had infusion-associated reactions, 334 (77%) had infections (compared with 134 [66%] of 202 patients in the interferon beta 1a group) that were mostly mild-moderate with none fatal, 69 (16%) had thyroid disorders, and three (1%) had immune thrombocytopenia.For patients with first-line treatment-refractory relapsing-remitting multiple sclerosis, alemtuzumab could be used to reduce relapse rates and sustained accumulation of disability. Suitable risk management strategies allow for early identification of alemtuzumab's main adverse effect of secondary autoimmunity.Genzyme (Sanofi) and Bayer Schering Pharma.
Published: 2012

50. ‘Clinically definite benign multiple sclerosis’, an unwarranted conceptual hodgepodge: evidence from a 30-year observational study

Author: M. Coustans, E. Le Page, Gilles Edan, J. Yaouanq, Joel Oger, Emmanuelle Leray, Neurosciences Cliniques, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes]-CHU Pontchaillou [Rennes]-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], CHU Pontchaillou [Rennes]-CHU Pontchaillou [Rennes], University of British Columbia (UBC), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Service de Neurologie [Rennes] = Neurology [Rennes], Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Pediatrics, MESH: Multiple Sclerosis, Relapsing-Remitting, Long term follow up, MEDLINE, Outcome measurement, Clinical onset, Multiple sclerosis, Disability Evaluation, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, 030225 pediatrics, Benign multiple sclerosis, Humans, Medicine, Longitudinal Studies, MESH: Longitudinal Studies, 10. No inequality, Long-term follow-up, MESH: Humans, Benign form, business.industry, Disease progression, MESH: Disability Evaluation, MESH: Adult, Prognosis, medicine.disease, MESH: Male, 3. Good health, Surgery, Neurology, Disease Progression, Female, MESH: Disease Progression, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Observational study, Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery
Abstract: Background: Benign multiple sclerosis (BMS) is a controversial concept which is still debated. However identification of this kind of patients is crucial to prevent them from unnecessary exposure to aggressive and/or long term medical treatments. Objectives: To assess two definitions of ‘clinically definite benign multiple sclerosis’ (CDBMS) using long-term follow-up data, and to look for prognostic factors of CDBMS. Methods: In 874 patients with definite relapsing–remitting MS, followed up for at least 10 years, disability was assessed using the Disability Status Scale (DSS). CDBMS was defined by either DSS score≤2 (CDBMS1 group) or DSS score≤ 3 (CDBMS2 group) at 10 years. We estimated the proportion of patients who were still benign at 20 and 30 years after clinical onset. Results: CDBMS frequency estimates were 57.7% and 73.9% when using CDBMS1 and CDBMS2 definitions, respectively. In the CDBMS1 group, only 41.7% (105/252) of cases were still benign 10 years later, and 41.1% (23/56) after an additional decade, while there were 53.8% (162/301) and 59.5% (44/74) respectively in the CDBMS2 group. Conclusions: This 30-year observational study, which is one of the largest published series, indicates that favourable 10-year disability scores of DSS 2 or 3 fail to ensure a long-term benign course of multiple sclerosis. After every decade almost half of the CDBMS were no longer benign. CDBMS, as currently defined, is an unwarranted conceptual hodgepodge. Other criteria using new biomarkers (genetic, biologic or MRI) should be found to detect benign cases of MS.
Published: 2012

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