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1. Cost-utility of oral methylprednisolone in the treatment of multiple sclerosis relapses: Results from the COPOUSEP trial

Author: M. Michel, E. Le Page, D.A. Laplaud, R. Wardi, C. Lebrun, F. Zagnoli, S. Wiertlewski, M. Coustans, G. Edan, K. Chevreul, D. Veillard, F. Lallement, M. Cohen, C. Blanchard, E. Sartori, O. Demarco, F. Rouhart, C. Papeix, G. Taurin, T. Anani, P. Kassiotis, C. Hamon, M.A. Lester, M. Merienne, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), 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 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), Centre hospitalier universitaire de Nantes (CHU Nantes), This study was funded by the French Health Ministry, the Ligue Française contre la SEP, and Teva. The funders had no role in the design and conduct of the study, data collection, management, analysis, or interpretation, preparation, review, or approval of the manuscript, decision to submit the manuscript for publication., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), 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), 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), and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: medicine.medical_specialty, Multiple Sclerosis, Cost-Benefit Analysis, [SDV]Life Sciences [q-bio], Methylprednisolone, 03 medical and health sciences, Indirect costs, 0302 clinical medicine, Recurrence, Health insurance, Medicine, Humans, Oral methylprednisolone, Reimbursement, health care economics and organizations, Cost–utility analysis, business.industry, 030503 health policy & services, Multiple sclerosis, Cost-utility analysis, medicine.disease, 3. Good health, Oral administration, Neurology, Cost utility, Emergency medicine, Neurology (clinical), 0305 other medical science, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; Background: Studies have shown that oral high-dose methylprednisolone (MP) is non-inferior to intravenous MP in treating multiple sclerosis relapses in terms of effectiveness and tolerance. In order to assist with resource allocation and decision-making, its cost-effectiveness must also be assessed. Our objective was to evaluate the cost-utility of per os high-dose MP as well as the cost-savings associated with implementing the strategy.Methods: A cost-utility analysis at 28 days was carried out using data from the French COPOUSEP multicenter, double-blind randomized controlled non-inferiority trial and the statutory health insurance reimbursement database. Costs were calculated using a societal perspective, including both direct and indirect costs. An incremental cost-effectiveness ratio was calculated and bootstrapping methods assessed the uncertainty surrounding the results. An alternative scenario analysis in which MP was administered at home was also carried out. A budgetary impact analysis was carried at five years.Results: In the conditions of the trial (hospitalized patients), there was no significant difference in utilities and costs at 28 days. The incremental cost-effectiveness ratio was €15,360 per quality-adjusted life-year gained. If multiple sclerosis relapses were treated at home, oral MP would be more effective, less costly and associated with annual savings up to 25 million euros for the French healthcare system.Conclusions: Oral MP is cost-effective in the treatment of multiple sclerosis relapses and associated with major savings.
Published: 2022
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2. Urinary tract infections and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society

Author: C. Donzé, C. Papeix, C. Lebrun-Frenay, C. Lebrun-Frénay, N. Collongues, M. de Seze, A. Dinh, A. Even, C. Scheiber-Nogueira, C. Bensa, B. Bourre, C. Carra-Dallière, J. Ciron, M. Cohen, A.M. Guennoc, C. Louapre, F. Lebreton, L. Michel, E. Maillart, B. Audoin, X. Ayrignac, P. Bernady, B. Brochet, P. Clavelou, R. Colamarino, A. Declemy, J. de Seze, N. Derache, J.-M. Faucheux, O. Heinzlef, P. Labauge, D. Laplaud, E. Lepage, E. Leray, L. Magy, G. Mathey, C. Mekies, V. Mondain, E. Planque, J. Pelletier, S. Pittion, B. Stankhof, P. Tournaire, E. Thouvenot, S. Vukusic, S. Wiertlevski, H. Zephir, H. Alchaar, G. Androdias, M. Benazet, D. Bensmail, D. Biotti, A. Blanchard-Dauphin, M. Bonnan, C. Boutière, P. Branger, S. Bresch, J.-P. Bru, J.-P. Camdessanché, E. Castel Canal, M. Coustans, O. Casez, B. Castan, A. Creange, E. Creisson, T. De Broucker, R. Depaz, X. Douay, C. Dulau, F. Durand-Dubief, O. Fagniez, M. Faucher, A. Floch, M. Fournier, A. Fromont, P. Gallien, X. Gamé, D. Gault, A. Gayou, M. Giroux, O. Gout, J. Grimaud, P. Hautecoeur, A. Kerbrat, L. Kremer, A. Kwiatkowski, C. Labeyrie, S. Lachaud, C. Lanctin-Garcia, L. Lanotte, E. Manchon, A. Maurousset, A.-M. Milor, X. Moisset, A. Mont-Cuquet, T. Moreau, J.-C. Ouallet, I. Patry, D. Peaureaux, M.-C. Pouget, V. Pourcher Martinez, C. Radot, A. Ruet, C. Saint-Val, A. Salmon, F. Taithe, P. Tatevin, M. Vaillant, J.-P. Stahl, F. Vuoto, C. Zaenker, Hôpital Saint Philibert [Lomme], Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Université Nice Sophia Antipolis (... - 2019) (UNS), 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Urinary system, Population, MESH: Urinary Tract Infections, urologic and male genital diseases, Practice guidelines, Hypogammaglobulinemia, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, MESH: Pregnancy, Health care, medicine, Urinary tracts infections, In patient, 030212 general & internal medicine, Intensive care medicine, education, Asymptomatic bacteriuria, Pregnancy, education.field_of_study, MESH: Humans, Disease modifying therapy, business.industry, MESH: Multiple Sclerosis, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, MESH: Recurrence, Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives Establish recommendations for the management of UTIs in MS patients. Background Urinary tract infections (UTIs) are common during multiple sclerosis (MS) and are one of the most common comorbidities potentially responsible for deaths from urinary sepsis. Methods The recommendations attempt to answer three main questions about UTIs and MS. The French Group for Recommendations in MS (France4MS) did a systematic review of articles from PubMed and universities databases (01/1980–12/2019). The RAND/UCLA appropriateness method, which has been developed to synthesize the scientific literature and expert opinions on health care topics, was used for reaching a formal agreement. 26 MS experts worked on the full-text review and a group of 70 multidisciplinary health care specialists validated the final evaluation of summarized evidences. Results UTIs are not associated with an increased risk of relapse and permanent worsening of disability. Only febrile UTIs worsen transient disability through the Uhthoff phenomenon. Some immunosuppressive treatments increase the risk of UTIs in MS patients and require special attention especially in case of hypogammaglobulinemia. Experts recommend to treat UTIs in patients with MS, according to recommendations of the general population. Prevention of recurrent UTIs requires stabilization of the neurogenic bladder. In some cases, weekly oral cycling antibiotics can be proposed after specialist advice. Asymptomatic bacteriuria should not be screened for or treated systematically except in special cases (pregnancy and invasive urological procedures). Conclusion Physicians and patients should be aware of the updated recommendations for UTis and MS.
Published: 2020
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3. Immunization and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society

Author: C. Lebrun, S. Vukusic, V. Abadie, C. Achour, F. Ader, H. Alchaar, A. Alkhedr, F. Andreux, G. Androdias, R. Arjmand, B. Audoin, D. Audry, D. Aufauvre, C. Autreaux, X. Ayrignac, M. Bailbe, M. Benazet, C. Bensa, D. Bensmail, E. Berger, P. Bernady, Y. Bertagna, D. Biotti, A. Blanchard-Dauphin, J. Bonenfant, M. Bonnan, B. Bonnemain, F. Borgel, E. Botelho-Nevers, S. Boucly, B. Bourre, C. Boutière, P. Branger, D. Brassat, S. Bresch, V. Breuil, B. Brochet, H. Brugeilles, P. Bugnon, P. Cabre, J.-P. Camdessanché, C. Carra-Dalière, O. Casez, J.-M. Chamouard, B. Chassande, P. Chataignier, M. Chbicheb, A. Chenet, J. Ciron, P. Clavelou, M. Cohen, R. Colamarino, N. Collongues, I. Coman, P.-R. Corail, S. Courtois, M. Coustans, A. Creange, E. Creisson, N. Daluzeau, C. Davenas, J. De Seze, M. Debouverie, R. Depaz, N. Derache, L. Divio, X. Douay, C. Dulau, F. Durand-Dubief, G. Edan, Z. Elias, O. Fagniez, M. Faucher, J.-M. Faucheux, M. Fournier, A. Gagneux-Brunon, P. Gaida, P. Galli, P. Gallien, J. Gaudelus, D. Gault, A. Gayou, M. Genevray, A. Gentil, J. Gere, L. Gignoux, M. Giroux, P. Givron, O. Gout, J. Grimaud, A.-M. Guennoc, N. Hadhoum, P. Hautecoeur, O. Heinzlef, M. Jaeger, S. Jeannin, L. Kremer, A. Kwiatkowski, P. Labauge, C. Labeyrie, S. Lachaud, I. Laffont, C. Lanctin-Garcia, J. Lannoy, L. Lanotte, D. Laplaud, D. Latombe, M. Lauxerois, E. Le Page, C. Lebrun-Frenay, P. Lejeune, P. Lejoyeux, B. Lemonnier, E. Leray, C.-M. Loche, C. Louapre, C. Lubetzki, A. Maarouf, B. Mada, L. Magy, E. Maillart, E. Manchon, R. Marignier, P. Marque, G. Mathey, A. Maurousset, C. Mekies, M. Merienne, L. Michel, A.-M. Milor, X. Moisset, A. Montcuquet, T. Moreau, N. Morel, M. Moussa, J.-P. Naudillon, M. Normand, P. Olive, J.-C. Ouallet, O. Outteryck, C. Pacault, C. Papeix, I. Patry, D. Peaureaux, J. Pelletier, B. Pichon, S. Pittion, E. Planque, M.-C. Pouget, V. Pourcher, C. Radot, I. Robert, F. Rocher, A. Ruet, C. Saint-Val, J.-Y. Salle, A. Salmon, E. Sartori, S. Schaeffer, B. Stankhof, F. Taithe, E. Thouvenot, C. Tizon, A. Tourbah, P. Tourniaire, M. Vaillant, P. Vermersch, S. Vidil, A. Wahab, M.-H. Warter, S. Wiertlewski, B. Wiplosz, B. Wittwer, C. Zaenker, H. Zephir, Université Côte d'Azur (UCA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (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), Hosp Civils Lyon, Serv Malad Infect, Lyon, France, Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, 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), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Pontchaillou [Rennes], CHU Saint-Etienne, Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), 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), Comité de Développement Horticole du Centre Val de Loire (CDHRC), Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Service d'Etudes du Comportement des Matériaux de Conditionnement (SECM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Galaxies, Etoiles, Physique, Instrumentation (GEPI), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Rennes] = Neurology [Rennes], Excitabilité nerveuse et thérapeutique (ENT), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-EA 4391, Service de Physiologie Explorations Fonctionnelles-Hôpital Henri Mondor, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-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), Combustion Research Facility, Sandia National Laboratories - Corporation, Service de Pédiatrie [Jean Verdier], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Kuriwa Observatory, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Laboratoire de Mécanique, Modélisation et Procédés Propres (M2P2), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Euromov (EuroMov), Université de Montpellier (UM), 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), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), 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), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Centre National de la Recherche Scientifique (CNRS), Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire d'automatique et de génie des procédés (LAGEP), Université de Lyon-Université de Lyon-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Haras National Suisse, Centre Hospitalier Universitaire de Reims (CHU Reims), Center for health studies, Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Hospices Civils de Lyon, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Biogéosciences [UMR 6282] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), 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 Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Hôpital Henri Mondor-EA 4391, Service de Physiologie Explorations Fonctionnelles-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS), 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), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Comité de développement horticole de la région Centre-Val-de-Loire (CDHR CENTRE-VAL-DE-LOIRE), 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), 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 de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), 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)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Service de Neurologie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Ecole Centrale de Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, 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, CHU Clermont-Ferrand, Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Vaccination schedule, MEDLINE, Scientific literature, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Risk Factors, Health care, Medicine, Humans, 030212 general & internal medicine, Immunization Schedule, Societies, Medical, Vaccines, business.industry, Risk of infection, Prevention, Vaccination, medicine.disease, 3. Good health, Neurology, Immunization, Family medicine, Evidence-Based Practice, Practice Guidelines as Topic, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), France, business, Infection, Vaccine, 030217 neurology & neurosurgery
Abstract: Objectives To establish recommendations on immunization for patients with multiple sclerosis (MS). Background Vaccines have been suspected in the past to trigger MS and relapses. With the extension of the immunoactive treatment arsenal, other concerns have been raised more recently about an increased risk of infection or a decreased effectiveness of immunization in immunosuppressed patients. Methods The French Group for Recommendations into Multiple Sclerosis (France4MS) performed a systematic search of papers in Medline and other university databases (January 1975–June 2018). The RAND/UCLA appropriateness method was chosen to review the scientific literature and to formalize the degree of agreement among experts on 5 clinical questions related to immunization and MS. Readers from the steering committee conducted a systematic analysis, wrote a critical synthesis and prepared a list of proposals that were evaluated by a rating group of 28 MS experts. The final version of the recommendations was finally reviewed by a reading group of 110 health care professionals and classified as appropriate, inappropriate or uncertain. Results Neurologists should verify the vaccination status as soon as MS is diagnosed and before disease-modifying treatments (DMTs) are introduced. The French vaccination schedule applies to MS patients and seasonal influenza vaccination is recommended. In the case of treatment-induced immunosuppression, MS patients should be informed about the risk of infection and the vaccination standards of the French High Council of Health should be applied. Live attenuated vaccines are contra-indicated in patients recently treated with immunosuppressive drugs, including corticosteroids; other vaccines can be proposed whatever the treatment, but their effectiveness may be partly reduced with some drugs. Conclusion Physicians and patients should be aware of the updated recommendations for immunizations of patients with MS.
Published: 2019
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4. Neuraxial analgesia is not associated with an increased risk of post-partum relapses in MS

Author: Caroline Lavie, Fabien Rollot, Françoise Durand-Dubief, Romain Marignier, Iuliana Ionescu, Romain Casey, Thibault Moreau, Patricia Tourniaire, Michael Hutchinson, Marie Béatrice D’Hooghe, David-Axel Laplaud, Pierre Clavelou, Jérôme De Sèze, Marc Debouverie, David Brassat, Jean Pelletier, Christine Lebrun-Frenay, Emmanuelle Le Page, Giovanni Castelnovo, Eric Berger, Patrick Hautecoeur, Olivier Heinzlef, Luca Durelli, Marinella Clerico, Maria Trojano, Francesco Patti, Sandra Vukusic, A. Alpérovitch, H. Carton, M.B. d’Hooghe, O. Hommes, M. Hutchinson, P. Adeleine, A. Biron, P. Cortinovis-Tourniaire, J. Grimaud, M. Hours, T. Moreau, S. Vukusic, C. Confavreux, G. Chauplannaz, D. Latombe, M. Clanet, G. Lau, L. Rumbach, J.Y. Goas, F. Rouhart, A. Mazingue, E. Roullet, M. Madigand, P. Hautecoeur, P. Brunet, G. Edan, C. Allaire, G. Riffault, J. Leche, T. Benoit, C. Simonin, F. Ziegler, J.C. Baron, Y. Rivrain, R. Dumas, D. Loche, J.C. Bourrin, B. Huttin, B. Delisse, I. Gibert, C. Boulay, M. Verceletto, G. Durand, G. Bonneviot, R. Gil, M.A. Hedreville, C. Belair, R.J. Poitevin, J.L. Devoize, P. Wyremblewski, F. Delestre, A. Setiey, G. Comi, M. Filippi, A. Ghezzi, V. Martinelli, P. Rossi, M. Zaffaroni, M.R. Tola, M.P. Amato, C. Fioretti, G. Meucci, M. Inglese, G.L. Mancardi, D. Gambi, A. Thomas, M. Cavazzuti, A. Citterio, A. Heltberg, H.J. Hansen, O. Fernandez, F. Romero, T. Arbizu, J.J. Hernandez, C. De Andres de Frutos, D. Geffner Sclarky, Y. Aladro Benito, P. Reyes Yanes, M Aguilar, J.A. Burguera, R. Yaya, W. Bonakim Dib, D. Arzua-Mouronte, C.J.M. Sindic, R. Medaer, H. Roose, K.M.J. Geens, D. Guillaume, M. Van Zandycke, J. Janssens, M. Cornette, L. Mol, F. Weilbach, P. Flachenecker, H.P. Hartung, J. Haas, I. Tendolkar, E. Sindrn, H.W. Kölmel, D. Reichel, M. Rauch, S. Preuss, S. Poser, E. Mauch, S. Strausser-Fuchs, H. Kolleger, S. Hawkins, S.J.L. Howell, J.E. Rees, A. Thompson, M. Johnson, M. Boggild, R.P. Gregory, D. Bates, I. Bone, C. Polman, S. Frequin, P. Jongen, J. Correia de Sa, M.E. Rio, S. Huber, J. Lechner-Scott, L. Kappos, I. Ionescu, C. Cornu, M. El-Etr, E.E. Baulieu, M Schumacher, D.H. Miller, M. Pugeat, C. d’Archangues, J. Conard, J. Ménard, R. Sitruk-Ware, C. Pelissier, S. Dat, J. Belaïsch-Allard, N. Athéa, D. Büschsenschutz, O. Lyon-Caen, R. Gonsette, J.P. Boissel, P. Ffrench, F. Durand-Dubief, F. Cotton, C. Pachai, L. Bracoud, G. Androdias, R. Marignier, D.A. Laplaud, S. Wiertlewski, C. Lanctin-Garcia, G. Couvreur, G. Madinier, P. Clavelou, F. Taithe, D. Aufauvre, N. Guy, A. Ferrier, J. De Sèze, N. Collongues, M. Debouverie, F. Viala, D. Brassat, A. Gerdelat-Mas, P. Henry, J. Pelletier, A. Rico-Lamy, C. Lebrun-Frenay, E. Lepage, V. Deburghraeve, G. Castelnovo, E. Berger, M. Blondiau, O. Heinzlef, M. Coustans, C. Clerc, L. Rieu, M. Lauxerois, G. Hinzelin, J.C. Ouallet, D. Minier, P. Vion, N. Gromaire-Fayolle, N. Derache, E. Thouvenot, M. Sallansonnet-Froment, P. Tourniaire, L. Toureille, F. Borgel, B. Stankoff, C. Moroianu, A.M. Guennoc, C.L. Tournier-Gervason, S. Peysson, M. Trojano, F. Patti, E. D’Amico, L. Motti, L. Durelli, A. Tavella, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Service de neurologie fonctionnelle et d'épileptologie [Hôpital Pierre Wertheimer-HCL], Hospices Civils de Lyon (HCL)-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), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Henri Duffaut (Avignon), National MS Center Melsbroek, Vrije Universiteit Brussel [Bruxelles] (VUB), Vrije Universiteit Brussel (VUB), 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), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Laboratoire de Neuroimagerie in Vivo (LNV), CHU Strasbourg-Centre National de la Recherche Scientifique (CNRS), Les Hôpitaux Universitaires de Strasbourg (HUS), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Neurologie vasculaire, pathologie neuro-dégénérative et explorations fonctionnelles du système nerveux [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), 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), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Neurologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL), centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Università degli studi di Torino = University of Turin (UNITO), University of Catania [Italy], Hospices Civils de Lyon, Departement de Neurologie (HCL), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Protéines membranaires transductrices d'énergie (PMTE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut des Géosciences de l’Environnement (IGE), Institut de Recherche pour le Développement (IRD)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Environnement Ville Société (EVS), École normale supérieure - Lyon (ENS Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), 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)-Université Jean Monnet [Saint-Étienne] (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Solvay (France), Laboratoire des Mécanismes et Transfert en Géologie (LMTG), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Institute of Evolutionary Biology, University of Edinburgh, Université de Lille, Sciences et Technologies, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Différenciation, interaction, activation et migration des sous-populations lymphocitaires humaines, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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), Motricité, interactions, performance EA 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), Laboratoire Ecologie Fonctionnelle et Environnement (ECOLAB), Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Chimie Physique D'Orsay (LCPO), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), RMN et optique : De la mesure au biomarqueur, 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), Department of Neurology, CHU Lyon, Institut de Recherche de Chimie Paris (IRCP), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Hôpital de Hautepierre [Strasbourg], Laboratoire de Réactivité des Surfaces et des Interfaces (LRSI), Département de Physico-Chimie (DPC), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, 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 (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), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques, European Leukodystrophies Association, PHRC National, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-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), Pierre Wertheimer, Département de Neurologie, Laboratoire de Mathématiques (LAMA), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Nottingham Scientific Limited, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Turin, Università degli studi di Torino (UNITO), University of Bari Aldo Moro (UNIBA), Department of Neurosciences, Università degli studi di Catania [Catania], Centre de recherche en neurosciences de Lyon (CRNL), Neuroépidémiologie, Institut de Physique du Globe de Paris (IPGP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut de Recherche pour le Développement (IRD)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École nationale supérieure d'architecture de Lyon (ENSAL)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Nationale des Travaux Publics de l'État (ENTPE)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ministère de la Culture (MC), 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), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lavie, Caroline, Rollot, Fabien, Durand-Dubief, Françoise, Marignier, Romain, Ionescu, Iuliana, Casey, Romain, Moreau, Thibault, Tourniaire, Patricia, Hutchinson, Michael, D’Hooghe, Marie Béatrice, Laplaud, David-Axel, Clavelou, Pierre, De Sèze, Jérôme, Debouverie, Marc, Brassat, David, Pelletier, Jean, Lebrun-Frenay, Christine, Le Page, Emmanuelle, Castelnovo, Giovanni, Berger, Eric, Hautecoeur, Patrick, Heinzlef, Olivier, Durelli, Luca, Clerico, Marinella, Trojano, Maria, Patti, Francesco, Vukusic, Sandra, on behalf of PRIMS and POPARTMUS, Investigator, Filippi, Massimo, 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), 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 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), 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), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire de glaciologie et géophysique de l'environnement (LGGE), Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire Motricité, Interactions, Performance, Université de Nantes (UN), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), CEA-Direction de l'Energie Nucléaire (CEA-DEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-CEA-Direction de l'Energie Nucléaire (CEA-DEN), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Service de neurologie [Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service de Neurologie [CHU Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Service de Neurologie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Clinical sciences, Neuroprotection & Neuromodulation, and Neurology
Subjects: relapses, Neurology, [SDV]Life Sciences [q-bio], MESH: Pregnancy Complications / physiopathology, 0302 clinical medicine, MESH: Pregnancy, Anesthesia, Conduction, Recurrence, MESH: Anesthesia, Conduction / adverse effects, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, reproductive and urinary physiology, relapse, Postpartum Period, post-partum, MESH: Follow-Up Studies, MESH: Multiple Sclerosis / physiopathology, Obstetrical Analgesia, MESH: Multiple Sclerosis / chemically induced, Anesthesia, Female, pregnancy, Adult, medicine.medical_specialty, Clinical Neurology, Multiple sclerosis, MESH: Postpartum Period, 03 medical and health sciences, medicine, Humans, Multiple sclerosi, Post partum, Retrospective Studies, Pregnancy, MESH: Humans, MESH: Pregnancy Complications / chemically induced, business.industry, Neurotoxicity, MESH: Adult, MESH: Retrospective Studies, neuraxial analgesia, medicine.disease, MESH: Recurrence, Multiple sclerosis, neuraxial analgesia, post-partum, pregnancy, Pregnancy Complications, Increased risk, Neurology (clinical), [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: Background: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses. Objective: To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy. Methods: We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992–1995 and 2005–2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis. Results: A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78). Conclusion: Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.
Published: 2019
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5. Inaugural tumor-like multiple sclerosis: clinical presentation and medium-term outcome in 87 patients

Author: Sandrine Wiertlewski, Christine Lebrun, M. Coustans, Pierre Labauge, Gilles Edan, Société Francophone de la Sclérose en Plaques, Pascal Derkinderen, Mikael Cohen, C Carra-Dallieres, Patrick Devos, F Lefrere, B Daumas-Duport, Patrick Vermersch, Hélène Zéphir, Eric Berger, Jean Pelletier, C Brosset, E Auffray-Calvier, Lucien Rumbach, P. Lejeune, Romain Deschamps, Emeline Duhin, J-B N'Kendjuo, David-Axel Laplaud, G Balloy, Olivier Gout, Laure Michel, L Suchet, E. Le Page, J. de Seze, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), 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), Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Université de Genève (UNIGE), Fondation Ophtalmologique Adolphe de Rothschild [Paris], 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), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], CHU de Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Transduction du Signal et Plasticite Dans Le Systeme Nerveux, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Neuroimagerie in Vivo (LNV), CHU Strasbourg-Centre National de la Recherche Scientifique (CNRS), 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), Université de Genève = University of Geneva (UNIGE), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Demyelinating disease, Neurology, Pseudo-tumoral form, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, 030218 nuclear medicine & medical imaging, Lesion, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Balo, 10. No inequality, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Neuroradiology, medicine.diagnostic_test, business.industry, Brain, Diffuse Cerebral Sclerosis of Schilder, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Hemiparesis, Schilder, Acute disseminated encephalomyelitis, Disease Progression, Female, Neurology (clinical), Radiology, medicine.symptom, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Tumefactive demyelinating lesions of the central nervous system can be the initial presentation in various pathological entities [multiple sclerosis (the most common), Balo’s concentric sclerosis, Schilder’s disease and acute disseminated encephalomyelitis] with overlapping clinical presentation. The aim of our study was to better characterize these patients. Eighty-seven patients (62 women and 25 men) from different MS centers in France were studied retrospectively. Inclusion criteria were (1) a first clinical event (2) MRI showing one or more large demyelinating lesions (20 mm or more in diameter) with mass-like features. Patients with a previous demyelinating event (i.e. confirmed multiple sclerosis) were excluded. Mean age at onset was 26 years. The most common initial symptoms (67% of the patients) were hemiparesis or hemiplegia. Aphasia, headache and cognitive disturbances (i.e. atypical symptoms for demyelinating diseases) were observed in 15, 18 and 15% of patients, respectively. The mean largest diameter of the tumefactive lesions was 26.9 mm, with gadolinium enhancement in 66 patients (81%). Twenty-one patients (24%) had a single tumefactive lesion. During follow-up (median time 5.7 years) 4 patients died, 70 patients improved or remained stable and 12 worsened. 86% of patients received initial corticosteroid treatment, and 73% received disease-modifying therapy subsequently. EDSS at the end of the follow-up was 2.4 ± 2.6 (mean ± SD). This study provides further evidence that the clinical course of MS presenting with large focal tumor-like lesions does not differ from that of classical relapsing-remitting MS, once the noisy first relapsing occurred.
Published: 2018
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6. ‘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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7. Natalizumab and drug holiday in clinical practice: An observational study in very active relapsing remitting Multiple Sclerosis patients

Author: François Lallement, F. Rouhart, Gilles Edan, M. Coustans, David Laplaud, E. Sartori, Emmanuelle Leray, Anne Kerbrat, C. Guiziou, C. Desormeaux, R. Wardi, P. Kassiotis, E. Le Page, P. Diraison, Sandrine Wiertlewski, T. Anani, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], 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 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), and Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Time Factors, [SDV]Life Sciences [q-bio], Disease, Relapsing-Remitting, Antibodies, Monoclonal, Humanized, Antibodies, Drug Administration Schedule, Central nervous system disease, Young Adult, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Natalizumab, Internal medicine, Monoclonal, Activities of Daily Living, Secondary Prevention, Humans, Medicine, 030212 general & internal medicine, Young adult, Humanized, Retrospective Studies, business.industry, Multiple sclerosis, Retrospective cohort study, Drug holiday, Middle Aged, medicine.disease, 3. Good health, Surgery, Neurology, Female, Observational study, France, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; BACKGROUND: In order to reduce the risk of progressive multifocal leucoencephalopathy when using natalizumab for more than 12 months, a 6-month drug holiday has been discussed. However, the consequences on short term disease activity have been poorly assessed. OBJECTIVE: The aim of this study was to assess clinical and radiological disease activity within 6 months after stopping natalizumab in very active relapsing remitting Multiple Sclerosis (RRMS) patients. METHODS: In 8 hospitals from Western France, we retrospectively collected clinical and MRI data from consecutive RRMS patients treated with natalizumab for at least 6 months, and who stopped the drug for various reasons except therapeutic failure. Patients didn't receive any other disease modifying treatment after discontinuing natalizumab. RESULTS: A total of 27 patients with very active RRMS before natalizumab start (mean annualized relapse rate of 2.3, MRI activity in 21 of 27 patients) were studied. Within 6 months after discontinuing natalizumab, 18 patients (67%) experienced clinical relapse and 3 additional patients had radiological activity, without clinical relapse. Four patients (15%) experienced a rebound activity, with severe relapse and 20 or more gadolinium enhancing lesions on MRI. CONCLUSION: Such observational data didn't support the concept of drug holiday when using natalizumab in very active RRMS.
Published: 2011
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8. Evidence for a two-stage disability progression in multiple sclerosis

Author: Gilles Edan, J. Yaouanq, David Laplaud, M. Coustans, Emmanuelle Le Page, Emmanuelle Leray, and Joel Oger
Subjects: education.field_of_study, medicine.medical_specialty, Proportional hazards model, business.industry, Multiple sclerosis, Population, Neurodegeneration, Original Articles, Disease, multiple sclerosis, medicine.disease, Central nervous system disease, disability progression, age, Internal medicine, medicine, Physical therapy, prognosis, Neurology (clinical), Stage (cooking), Young adult, education, business, course
Abstract: It is well documented that disability accumulation in multiple sclerosis is correlated with axonal injury and that the extent of axonal injury is correlated with the degree of inflammation. However, the interdependence between focal inflammation, diffuse inflammation and neurodegeneration, and their relative contribution to clinical deficits, remains ambiguous. A hypothesis might be that early focal inflammation could be the pivotal event from which all else follows, suggesting the consideration of multiple sclerosis as a two-stage disease. This prompted us to define two phases in the disease course of multiple sclerosis by using two scores on the Kurtzke Disability Status Scale as benchmarks of disability accumulation: an early phase, ‘Phase 1’, from multiple sclerosis clinical onset to irreversible Disability Status Scale 3 and a late phase, ‘Phase 2’, from irreversible Disability Status Scale 3 to irreversible Disability Status Scale 6. Outcome was assessed through five parameters: Phase 1 duration, age at Disability Status Scale 3, time to Disability Status Scale 6 from multiple sclerosis onset, Phase 2 duration and age at Disability Status Scale 6. The first three were calculated among all patients, while the last two were computed only among patients who had reached Disability Status Scale 3. The possible influence of early clinical markers on these outcomes was studied using Kaplan–Meier estimates and Cox models. The analysis was performed in the Rennes multiple sclerosis database (2054 patients, accounting for 26 273 patient-years) as a whole, and according to phenotype at onset (1609 relapsing/445 progressive onset). Our results indicated that the disability progression during Phase 2 was independent of that during Phase 1. Indeed, the median Phase 2 duration was nearly identical (from 6 to 9 years) irrespective of Phase 1 duration (
Published: 2010
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9. Étude observationnelle de la mitoxantrone dans les formes rémittentes actives de sclérose en plaques: suivi à long terme d’une cohorte de 100 patients consécutifs

Author: Emmanuelle Leray, Gilles Edan, Gregory Taurin, J. Chaperon, E. Le Page, and M. Coustans
Subjects: Neurology, Neurology (clinical)
Abstract: Resume Introduction Nous rapportons une etude observationnelle de 100 patients consecutifs ayant une SEP remittente agressive, traites par mitoxantrone (MITOX) selon les criteres de l’AMM obtenue en octobre 2003 (ELSEP ® ). Methode Cent patients ayant une SEP remittente agressive ont ete traites par MITOX 20 mg IV associee a 1 g de methylprednisolone IV par mois pendant 6 mois, suivie pour 57 d’entre eux par un traitement d’entretien par immunosuppresseur ou immunomodulateur. Les poussees et les scores EDSS ont ete recueillis prospectivement tous les 6 mois. L’activite IRM a ete evaluee avant et apres traitement par MITOX. Resultats Le suivi median etait de 3,8 ans. Avant MITOX, le taux annuel de poussees (TAP) etait de 3,2, l’EDSS moyen augmentait de 2,2 ± 1 points et 85 p. 100 des patients avaient une IRM active. A 1 an de suivi, le TAP etait reduit de 91 p. 100, 76 p. 100 des patients etaient indemnes de nouvelle poussee, l’EDSS moyen diminuait d’1,2 points (p 6 ), l’activite IRM etait reduite de 89 p. 100. Le benefice etait maintenu jusqu’a 5 ans sur les poussees et jusqu’a 4 ans sur le handicap. Conclusion Cet impact rapide et franc sur les marqueurs de l’inflammation suggere que la MITOX en cures mensuelles pendant 6 mois pourrait etre utilisee dans une strategie therapeutique plus globale en traitement d’induction.
Published: 2006
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10. Facteurs associés à l’acceptance d’un traitement par interféron β-1a intramusculaire chez des patients souffrants de sclérose en plaques : résultats de l’étude ADOPTE

Author: Marc Debouverie, M. Coustans, Claude Mekies, Sophie Bourée, Yann Bourhis, and Sandrine Nouet
Subjects: Gynecology, medicine.medical_specialty, Neurology, business.industry, Interferon beta-1a, medicine, Neurology (clinical), business, medicine.drug
Abstract: Introduction ACCEPT est un auto-questionnaire valide mesurant l’acceptance des patients pour leur traitement. L’acceptance est definie comme la balance entre avantages et inconvenients d’un traitement, evaluee par le patient lui-meme. Objectifs L’objectif etait de determiner l’acceptance de patients atteints de sclerose en plaques (SEP) pour leur traitement par interferon β-1a intramusculaire (IM IFNβ-1a) et d’en etudier les facteurs associes. Patients et methodes Etude observationnelle prospective longitudinale menee en France par 105 neurologues et sur 397 adultes atteints de SEP et initiant un traitement par IM IFNβ-1a. Les caracteristiques cliniques et therapeutiques etaient collectees a l’inclusion. Les questionnaires ACCEPT (patient/aidant), MMAS (Medication-taking Adherence Scale), MSKQ (Multiple Sclerosis Knowledge Questionnaire) et Alliance Therapeutique (AT) etaient completes lors du suivi. Les determinants de l’acceptance ont ete recherches par analyses de covariance. Resultats L’âge moyen des patients etait de 38,4 ans et la proportion de femmes de 77,9 %. L’anciennete moyenne du diagnostic de SEP etait de 3,4 ans. Le score moyen d’acceptance generale (AG) etait respectivement de 44,9 et 50,0 a 3 et 24 mois (0–100 : faible - forte AG). L’AG a 12 mois etait significativement associee a la persistance au traitement a 24 mois ( p Discussion Les scores moyens d’AG pour l’IM INFβ-1a restaient stables entre 3 et 24 mois, avec une concordance forte avec l’AG evaluee par l’aidant. Aucun impact de l’AG sur l’adhesion au traitement n’a ete observe, en revanche, une association significative entre acceptance precoce et persistance au traitement a ete mise en evidence. Le niveau d’alliance therapeutique entre le medecin et son patient restait eleve tout le long du suivi. Conclusion Les resultats de l’etude ADOPTE mettent en evidence une forte association entre acceptance et persistance au traitement par IM IFNβ-1a ainsi que le role determinant des aidants et des medecins. Informations complementaires L’etude ADOPTE a ete financee par Biogen.
Published: 2017
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11. Enquête de satisfaction sur le programme de formation à l’auto-injection d’AVONEX® PEN™, Facil’AVO

Author: S. Nouet, J. Servan, Thibault Moreau, M. Coustans, F. Borgel, and Claude Mekies
Subjects: Neurology, Neurology (clinical)
Published: 2014
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12. COPOUSEP : corticoïdes à forte dose par voie orale versus intraveineuse dans le traitement des poussées de sclérose en plaques : un essai randomisé en double insu : résultats du critère majeur d’efficacité à 1 mois

Author: Véronique Deburghgraeve, Christine Lebrun, R. Wardi, David-Axel Laplaud, M. Coustans, V. David, and E. Le Page
Subjects: Neurology, Neurology (clinical)
Published: 2014
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13. Acute urinary retention due to a novel collagen COL4A1 mutation

Author: Pierre Labauge, Manuelle Mine, Gilles Edan, Véronique Deburghgraeve, T. Rouaud, M. Coustans, and E. Tournier Lasserve
Subjects: Brain Infarction, Collagen Type IV, Male, Pathology, medicine.medical_specialty, Physical examination, Leukoencephalopathy, White matter, Type IV collagen, Young Adult, Leukoencephalopathies, medicine, Humans, Genetic Predisposition to Disease, Cerebral Hemorrhage, Intracerebral hemorrhage, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Urinary Retention, medicine.disease, Hyperintensity, Surgery, medicine.anatomical_structure, Amino Acid Substitution, Acute Disease, Mutation, Neurology (clinical), Brainstem, business
Abstract: The gene COL4A1 encodes the α1 chain of type IV collagen, a basement-membrane protein implying vascular parietal strength. Mutations in the gene COL4A1 have been described in families with diffuse small-vessel disease of the brain, resulting in perinatal stroke, congenital porencephaly, extensive leukoencephalopathy, intracerebral hemorrhage, and retinal arteriolar tortuosity.1–4 Our observation extends the clinical and magnetic resonance (MR) phenotype of COL4A1 mutation. ### Case reports. A 21-year-old man without neurologic medical history presented with acute urinary retention. He had a right amblyopia due to a congenital strabismus surgically treated in childhood. Clinical examination showed brisk lower limb reflexes and a left Babinski sign. Blood pressure was normal. The Mini-Mental State Examination score was strictly normal. The patient declined further neuropsychological testing. Brain CT showed diffuse leukoencephalopathy and multiple supratentorial microcalcifications (figure, A). Brain MRI revealed widespread white matter hyperintensities on T2 and fluid-attenuated inversion recovery sequences, dilated perivascular spaces, and lacunar infarctions. Leukoencephalopathy involved the cerebral periventricular and cerebellar deep white matter (figure, B). Multiple microbleeds were seen on gradient echo sequences, involving brainstem and supratentorial white matter (figure, C). MR angiography of cervical and intracranial arteries was normal, as was spinal …
Published: 2010

14. Mitoxantrone as induction treatment in aggressive relapsing remitting multiple sclerosis: treatment response factors in a 5 year follow-up observational study of 100 consecutive patients

Author: Emmanuelle Le Page, Gilles Edan, Gregory Taurin, M. Coustans, Emmanuelle Leray, Jacques Chaperon, and Sean Patrick Morrissey
Subjects: Adult, Male, medicine.medical_specialty, Azathioprine, Antineoplastic Agents, Observation, Asymptomatic, Antiviral Agents, Methylprednisolone, Disability Evaluation, Multiple Sclerosis, Relapsing-Remitting, Maintenance therapy, Recurrence, Internal medicine, medicine, Prevalence, Humans, Glatiramer acetate, Demography, Mitoxantrone, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Brain, Glatiramer Acetate, Interferon-beta, medicine.disease, Magnetic Resonance Imaging, Surgery, Psychiatry and Mental health, Methotrexate, Drug Therapy, Combination, Female, Neurology (clinical), medicine.symptom, business, Peptides, Immunosuppressive Agents, medicine.drug, Follow-Up Studies
Abstract: Background: Mitoxantrone was approved by the French health authority (AFSAPPS) in October 2003 to treat patients with aggressive multiple sclerosis (MS). Objective: To report the long term effectiveness and safety of mitoxantrone as induction therapy in patients with aggressive relapsing–remitting MS, and to assess treatment response factors. Material and methods: 100 consecutive patients with aggressive relapsing–remitting MS received mitoxantrone 20 mg monthly combined with methylprednisolone 1 g for 6 months. Relapses, Expanded Disability Status Scale (EDSS) and drug safety were assessed every 6 months for up to at least 5 years. Within 6 months after induction, 73 patients received maintenance therapy (mitoxantrone every 3 months (n = 21); interferon beta (n = 25); azathioprine (n = 15); methotrexate (n = 7); glatiramer acetate (n = 5)). Results: During the 12 months following initiation of mitoxantrone, the annual relapse rate (ARR) was reduced by 91%, 78% of patients remained relapse free, MRI activity was reduced by 89%, the mean EDSS decreased by 1.2 points (p −6 ) and 64% of patients improved by 1 point or more on the EDSS. In the longer term, the ARR reduction was sustained (0.29–0.42 for up to 5 years), the median time to the first relapse was 2.8 years and disability remained improved after 5 years. Younger age and lower EDSS score at the start of mitoxantrone treatment were predictive of better treatment response. Three patients presented with an asymptomatic decrease in left ventricular ejection fraction to less than 50% (one reversible). One patient was diagnosed with acute myeloid leukaemia (remission 5 years after diagnosis). Conclusion: Mitoxantrone monthly for 6 months as induction therapy followed by maintenance treatment showed sustained clinical benefit for up to 5 years with an acceptable adverse events profile in patients with aggressive relapsing–remitting MS.
Published: 2007

15. Long-term survival of patients with multiple sclerosis in West France

Author: Gilles Edan, J. Yaouanq, M. Coustans, E. Le Page, J. Chaperon, Emmanuelle Leray, Sean Patrick Morrissey, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], CHU de Pontchaillou, Service de Neurologie [Rennes], Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Survival, Population, Kaplan-Meier Estimate, Standardized mortality rates, Clinical onset, Central nervous system disease, Multiple sclerosis, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Cause of Death, Long term survival, Medicine, Humans, 030212 general & internal medicine, 10. No inequality, education, Cause of death, Aged, education.field_of_study, business.industry, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Prognosis, 3. Good health, Surgery, Neurology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), France, business, 030217 neurology & neurosurgery, Sex ratio
Abstract: In France no data have been published about comparing survival in multiple sclerosis (MS) patients with the general French population. We estimated survival probabilities in MS patients from a major centre for MS in West France. We also compared MS survival with the general population and assessed prognostic parameters. All patients with MS onset after January 1976 and classified as dead or alive on 1 January 2004 were included. One thousand eight-hundred and seventy-nine patients (sex ratio W: M 2.3; relapsing/progressive onset 77.4%/22.6%) fulfilled these criteria, disease duration ranged from one to 28 years. By 2004, 68 patients died (51 due to MS) and the 15 and 25-year survival probabilities were 96% and 88%. Male gender, progressive course (either primary or secondary), polysymptomatic onset, and increased annual relapse rate during the first two years of MS were related to a worse prognosis. After a mean follow-up duration of 12.7 years since clinical onset, MS increased the number of deaths compared with the general population. However taking into account disability status, we found that less disabled MS patients had a better survival and highly disabled patients a worse survival (eight-fold increase of mortality) compared with the French population. Multiple Sclerosis 2007; 13: 865—874. http://msj.sagepub.com
Published: 2007
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16. Taux de conversion en sclérose en plaques (SEP) à 2ans et prise en charge d’une cohorte française de 231 patients ayant présenté un syndrome cliniquement isolé (SCI)

Author: Dominique Audry-Chaboud, Giovanni Castelnovo, M. Coustans, Brigitte Salin, Eric Thouvenot, Nicolas Lemaire, and Rabah Benrabah
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction Les nouveaux criteres (Polman, 2010) permettent un diagnostic de SEP des le SCI. La prescription des traitements de fond reste soumise a la dissemination temporelle definie par le suivi clinico-radiologique. Objectifs Decrire la prise en charge clinique, paraclinique et therapeutique des SCI en pratique liberale ou hospitaliere et estimer le taux de conversion en SEP a 2 ans chez ces patients. Methodes Deux cent cinquante-deux patients furent inclus prospectivement par 59 neurologues sur une periode de 9 mois apres un SCI avec une IRM disponible. Le recueil prospectif des donnees observationnelles pendant 24 mois apres l’inclusion avec au moins une visite par an a permis d’analyser la conversion en SEP selon les criteres diagnostiques de 2005 et de 2010, la survenue de poussees, l’evolution du score EDSS, les resultats des examens radiologiques et biologiques, l’instauration de traitements. Resultats Des donnees completes a 2 ans furent obtenues pour 231 patients (âge moyen : 37 ans, sex-ratio F/H : 2,8) ; 26,0 % des patients presenterent une SEP definie sur la premiere IRM (2010). Les taux de conversion selon les criteres de 2010, 2005 ou SEP cliniquement definie furent respectivement de 48,6 %, 48,8 % et 38,4 % a 24 mois. Seize (14 % des 114 convertis) patients furent traites par un immunomodulateur avant la conversion selon les criteres de 2005. Discussion Les criteres diagnostiques de SEP de 2010 sont plus simples et plus sensibles que ceux de 2005 qui regissent la prescription des immunomodulateurs. Ces nouveaux criteres diagnostiques semblent accelerer la prescription des traitements de fond de la SEP pour un petit nombre de patients, qui voient leur taux de conversion clinique diminuer. Conclusion L’acceleration du diagnostic de SEP semble associee a une prescription precoce des traitements de fond apres un SCI et a une reduction du risque de conversion en SEP cliniquement definie.
Published: 2015
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17. Spontaneous resolution of arachnoid cysts: review and features of an unusual case

Author: P. Forlodou, R. Seizeur, P. Dam-Hieu, and M. Coustans
Subjects: Adult, Hematoma, Epidural, Cranial, Male, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Remission, Spontaneous, Epidural haematoma, Hematoma, Arachnoid cyst, parasitic diseases, medicine, Humans, Cyst, Neuroradiology, Unusual case, business.industry, Head injury, Anatomy, medicine.disease, nervous system diseases, body regions, Arachnoid Cysts, Radiography, Surgery, Neurology (clinical), Neurosurgery, business
Abstract: Most intra-cranial arachnoid cysts are quiescent and remain asymptomatic throughout life. Within the natural course of arachnoid cyst evolution, spontaneous resolution has been known to occur rarely, but its frequency is probably underestimated due to lack of systematic detection and long-term observation. We illustrate the spontaneous regression of arachnoid cysts with a patient which was conjointly diagnosed with an arachnoid cyst and a post-traumatic epidural haematoma. Cyst regression was observed 16 months later, upon examination following a second benign cranial trauma. Mechanisms underlying the resolution of the arachnoid cyst are discussed.
Published: 2006

18. Multiple sclerosis severity score: Using disability and disease duration to rate disease severity

Author: Maria José Sá, Justin P. Rubio, Bianca Miterski, S. R. Seaman, Jörg T. Epplen, Iuliana Achiti, Monica Marta, M. Coustans, Sandra Vukusic, G V McDonnell, Annette Bang Oturai, Richard Roxburgh, Maria Edite Rio, Pablo Villoslada, Bénédicte Dubois, Fabiana Tesser, Maurizio Leone, Christian Confavreux, T Masterman, Marcin P. Mycko, Gilles Edan, N. Téllez Lara, Ana Martins da Silva, Alexandra Weber, Stephen Sawcer, E. Le Page, Giuseppe Salemi, Giovanni Savettieri, P. Soelberg Sørensen, Anke Hensiek, Xavier Montalban, D. A. S. Compston, Maria Giovanna Marrosu, Helmut Butzkueven, Krzysztof Selmaj, Frauke Zipp, Maria Liguori, Isabel Leite, Stanley Hawkins, Elisabeth Gulowsen Celius, Jan Hillert, Maria Trojano, Trevor J. Kilpatrick, Eleonora Cocco, Chemical Biology 2, ROXBURGH RHSR, SEAMAN SR, MASTERMAN T, HENSIEK AE, SAWCER SJ, VUKUSIC S, ACHITI I, CONFAVREUX C, COUSTANS M, LE PAGE E, EDAN G, MCDONNELL GV, HAWKINS S, TROJANO M, LIGUORI M, COCCO E, MARROSU MG, TESSERE F, LEONE MA, WEBER A, ZIPP F, MITERSKI B, EPPLEN JT, OTURAI A, SOELBERG-SORENSEN P, CELIUS EG, TELLEZ LARA N, MONTALBAN X, VILLOSLADA P, SILVA AM, MARTA M, LEITE I, DUBOIS B, RUBIO J, BUTZKUEVEN H, KILPATRICK T, MYCKO MP, SELMAJ KW, RIO ME, SA M, SALEMI G, SAVETTIERI G, HILLERT J, and COMPSTON DAS
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Databases, Factual, Cross-sectional study, Models, Neurological, Disease, SUSCEPTIBILITY, Severity of Illness Index, Cohort Studies, Disability Evaluation, Predictive Value of Tests, Recurrence, Severity of illness, medicine, Humans, Longitudinal Studies, Age of Onset, Models, Statistical, Expanded Disability Status Scale, business.industry, Multiple sclerosis, OUTCOME MEASURE, Reproducibility of Results, NATURAL-HISTORY, Middle Aged, Prognosis, medicine.disease, Cross-Sectional Studies, Predictive value of tests, Disease Progression, Physical therapy, Female, France, Neurology (clinical), Age of onset, business, Cohort study
Abstract: Background: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease. Methods: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability. Results: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression. Conclusion: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.
Published: 2005

19. Mit Stoffwechselstörungen assoziierte Leukenzephalitiden

Author: G. Edan and M. Coustans
Abstract: )as klinische Bild einer zentralen pontinen Myelinolyse (ZPM) wurde 1949 geschrieben, als ein 38-jahriger Patient, der imBoston City Hospitalwegen)elirium tremensund einer Lungenerkrankung hospitalisiert war, eine Tetaplegie, Mutismus und Dysphagie entwickelte. Die Neurologen Maurice Tictor und Raymond Adams vermuteten eine Schadigung des Pons, die eilen bilateralen Befall der Pyramidenbahn erklaren wurde. Die Autopsie er-,ab eine Lasion im Bruckenfus, die im Wesentlichen das Myelin betraf ind Axone aussparte. Es bestand keine Gefasveranderung.
Published: 2003
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20. Maladie d’Erdheim-Chester : une cause rare d’insuffisance rénale aiguë obstructive

Author: Bassem Wehbe, V. Jean Michel, A. Fontaine, P. Siohan, and M. Coustans
Subjects: Nephrology
Abstract: Introduction La maladie d’Erdheim-Chester (MEC) est une histiocytose non langerhansienne, touchant les adultes jeunes. Depuis la description initiale en 1930, 400 cas ont ete rapportes. Il s’agit d’une maladie systemique a presentation heterogene amenant a de possibles errances diagnostiques. Patients et methodes M. T, 44 ans est suivi depuis 2005 pour des troubles du langage rapportes a une sclerose en plaques. Il est hospitalise en mai 2012 pour insuffisance renale aigue (IRA), douleurs articulaires et asthenie. Il s’agit d’une IRA obstructive avec dilatation bilaterale et isolee des calices sans obstacle ou plaque retroperitoneale visibles au scanner non injecte. L’amelioration de la fonction renale apres pose de sondes JJ permet la realisation d’un scanner injecte qui montre une plaque retroperitoneale et un aspect de reins chevelus. La biopsie chirurgicale de la plaque permet le diagnostic de MEC : fibrose collagenique et histiocytes spumeux aux caracteristiques immuno-histochimiques et genetiques particulieres : CD1a negatif, CD68 positif, positivite inconstante pour la proteine S-100. Une mutation du gene BRAF (codon V600) est mise en evidence. En octobre 2013, la majoration de taille en IRM du pedoncule cerebelleux moyen, et une prise de contraste du centre semi-ovale droit associee a une alteration de l’etat general conduisent a debuter un traitement par vemurafenib (inhibiteur de BRAF). Ceci permet une amelioration de l’etat general et l’ablation des sondes JJ en janvier 2014. Discussion et conclusion La MEC a une expression clinique heterogene : douleurs osseuses, infiltration periaortique, atteinte du systeme nerveux central. Une infiltration perirenale peut generer une IRA obstructive avec, au scanner, une dilatation isolee des calices, un aspect de reins « chevelus ». Le diagnostic de certitude repose sur l’anatomopathologie : histiocytes spumeux exprimant le CD68, negatifs pour le CD1a et la proteine S-100. Une mutation de BRAF (V600E) est decrite dans 54 % des cas. Le vemurafenib, inhibiteur de BRAF peut etre propose en cas de non-reponse a l’interferon alpha, traitement classique de la MEC. En l’absence de traitement, 1 patient sur 2 decede dans les 3 mois suivant le diagnostic.
Published: 2014
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21. [Is immunosuppression a future therapeutic strategy for multiple sclerosis?]

Author: G, Edan and M, Coustans
Subjects: Immunosuppression Therapy, Clinical Trials as Topic, Methotrexate, Multiple Sclerosis, Azathioprine, Humans, Mitoxantrone, Cyclophosphamide, Immunosuppressive Agents
Abstract: Although in previous studies no clear demonstration was found of the efficacy of azathioprine, cyclophosphamide and methotrexate as immunoprophylactic agents in cases of multiple sclerosis (MS), over the past five years a number of well-designed clinical trials utilizing immunosuppressive and immunomodulatory agents have shown partial efficacy regarding the drugs involved, but they have not been able to determine in what way these drugs can modify the natural course of this disease. Among the immunosuppressors, mitoxantrone is of particular interest as during the past two years three controlled trials have taken place in Europe and have demonstrated its efficacy both as regards clinical (frequency of symptoms, progression of the disease) and magnetic resonance imaging (MRI) criteria. Due to its potentially severe cardiotoxicity related to total cumulative dose, mitoxantrone is only prescribed for a limited period, and its use is limited to selected patients with a high relapse rate and incomplete remission, or to those who do not respond to beta-interferon treatment. The immunomodulatory agents have less immediate efficacy, but because they are well tolerated they can be used early in the course of the disease and over a prolonged period of time. The beta-interferons (1a or 1b) have been given market approval for use in the treatment of MS: three large, randomized, double-blind studies have demonstrated their capacity to reduce by 30% the frequency of symptoms and the appearance of disabilities associated with relapse and with the progression of the disease. Glatirameracetate or copolymer 1, which is available in France (ATU), has been found to reduce the frequency of relapse by 30%. It constitutes an alternative immunomodulatory treatment for relapsing-remitting patients without major functional disabilities and who suffer from severe side effects with beta-interferon treatment. In the future, the early use of immunomodulatory agents and therapeutic drug combinations may be introduced. Therapeutic trials are currently in progress to determine the viability of this approach.
Published: 2000

22. [Evolution and surveillance of multiple sclerosis]

Author: G, Edan and M, Coustans
Subjects: Central Nervous System, Diagnosis, Differential, Multiple Sclerosis, Disease Progression, Humans, Disabled Persons
Abstract: Multiple sclerosis is a highly complex disease due to the great diversity of symptoms and signs from disseminated demyelinating CNS lesions which lead to different levels of handicap, and to the different types of evolution (exacerbations or slow progression). Most of the patients with multiple sclerosis have a normal longevity. The main concern is the accumulation of disabilities. In order to follow accurately the progression of these disabilities, specific scales, especially EDSS, have been validated allowing more uniformity in method of collecting data from multiple sclerosis.
Published: 1999

23. Caractéristiques et prise en charge initiale des patients présentant un syndrome cliniquement isolé (SCI) en France en 2012

Author: Eric Thouvenot, M.-L. Camut, D. Audry-Chaboud, M. Hellet, Brigitte Salin, M. Coustans, and J.-P. Meunier
Subjects: Neurology, Epidemiology, Public Health, Environmental and Occupational Health, Neurology (clinical)
Abstract: Caracteristiques et prise en charge initiale des patients presentant un syndrome cliniquement isole (SCI) en France en 2012 E. Thouvenot , D. Audry-Chaboud , B. Salin , M.L. Camut , J.P. Meunier , M. Hellet , M. Coustans e a Service de neurologie, CHU de Nimes, Nimes, France b Cabinet de neurologie, Dijon, France c TEVA, Paris La Defense, Paris, France d AXONAL, Nanterre, France e Service de Neurologie, CHI de Cornouaille, Quimper, France
Published: 2014
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24. B2-4 - La sclérose en plaques de forme rémittente apparaît comme une maladie en deux phases, suggérant deux mécanismes consécutifs dans la progression du handicap : étude à propos de 1 609 patients du service de neurologie du CHU de Rennes

Author: M. Coustans, Gilles Edan, J. Chaperon, E. Le Page, and Emmanuelle Leray
Subjects: Epidemiology, Public Health, Environmental and Occupational Health
Published: 2006
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25. Progressive multifocal leukoencephalopathy in patients with chronic liver disease successfully treated with pembrolizumab.

Author: Jeantin L, Shor N, Coustans M, Roos-Weil D, Quintin-Roué I, Bellanger A, Le Garff-Tavernier M, Ben Jemaa R, Thabut D, Pourcher V, and Weiss N
Subjects: Humans, Antibodies, Monoclonal, Humanized, Brain, Leukoencephalopathy, Progressive Multifocal, Liver Diseases, JC Virus
Published: 2024
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26. Disease reactivation after fingolimod cessation in Multiple Sclerosis patients with pregnancy desire: A retrospective study.

Author: Callens A, Leblanc S, Le Page E, Edan G, Jourdain A, Coustans M, Wiertlewski S, Laplaud D, Videt D, Lallement F, Leray E, and Michel L
Subjects: Female, Fingolimod Hydrochloride adverse effects, Humans, Immunosuppressive Agents adverse effects, Pregnancy, Recurrence, Retrospective Studies, Multiple Sclerosis chemically induced, Multiple Sclerosis complications, Multiple Sclerosis drug therapy, Multiple Sclerosis, Relapsing-Remitting chemically induced
Abstract: 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., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)
Published: 2022
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27. Long-Term Effectiveness, Safety and Tolerability of Fingolimod in Patients with Multiple Sclerosis in Real-World Treatment Settings in France: The VIRGILE Study.

Author: Papeix C, Castelnovo G, Leray E, Coustans M, Levy P, Visy JM, Kobelt G, Lamy F, Allaf B, Heintzmann F, Chouette I, Raponi E, Durand B, Grevat E, Kamar D, Debouverie M, and Lebrun-Frenay C
Abstract: Introduction: It is important to confirm the effectiveness and tolerability of disease-modifying treatments for relapsing-remitting multiple sclerosis (RRMS) in real-world treatment settings. This prospective observational cohort study (VIRGILE) was performed at the request of the French health authorities. The primary objective was to evaluate the effectiveness of fingolimod 0.5 mg in reducing the annualised relapse rate (ARR) in patients with RRMS., Methods: Participating neurologists enrolled all adult patients with RRMS starting fingolimod treatment between 2014 and 2016, who were followed for 3 years. Follow-up consultations took place at the investigator's discretion. The primary outcome measure was the change in ARR at month 24 after fingolimod initiation. Relapses and adverse events were documented at each consultation; disability assessment (EDSS) and magnetic resonance imagery were performed at the investigator's discretion., Results: Of 1055 eligible patients, 633 patients were assessable at month 36; 405 (64.0%) were treated continuously with fingolimod for 3 years. The ARR decreased from 0.92 ± 0.92 at inclusion to 0.31 ± 0.51 at month 24, a significant reduction of 0.58 [95% CI - 0.51 to - 0.65] relapses/year (p < 0.001). Since starting fingolimod, 461 patients (60.9%) remained relapse-free at month 24 and 366 patients (55.5%) at month 36. In multivariate analysis, no previous disease-modifying treatment, number of relapses in the previous year and lower EDSS score at inclusion were associated with a greater on-treatment reduction in ARR. The mean EDSS score remained stable over the course of the study. Sixty-one out of 289 (21.1%) patients presented new radiological signs of disease activity. Treatment-related serious adverse events were lymphopenia (N = 21), bradycardia (N = 19), elevated transaminases (N = 9) and macular oedema (N = 9)., Conclusions: The effectiveness and tolerability of fingolimod in everyday clinical practice are consistent with findings of previous phase III studies. Our study highlights the utility of fingolimod for the long-term management of patients with multiple sclerosis., (© 2022. The Author(s).)
Published: 2022
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28. Cost-utility of oral methylprednisolone in the treatment of multiple sclerosis relapses: Results from the COPOUSEP trial.

Author: Michel M, Le Page E, Laplaud DA, Wardi R, Lebrun C, Zagnoli F, Wiertlewski S, Coustans M, Edan G, Chevreul K, and Veillard D
Subjects: Cost-Benefit Analysis, Humans, Methylprednisolone therapeutic use, Recurrence, Multiple Sclerosis drug therapy
Abstract: Background: Studies have shown that oral high-dose methylprednisolone (MP) is non-inferior to intravenous MP in treating multiple sclerosis relapses in terms of effectiveness and tolerance. In order to assist with resource allocation and decision-making, its cost-effectiveness must also be assessed. Our objective was to evaluate the cost-utility of per os high-dose MP as well as the cost-savings associated with implementing the strategy., Methods: A cost-utility analysis at 28 days was carried out using data from the French COPOUSEP multicenter, double-blind randomized controlled non-inferiority trial and the statutory health insurance reimbursement database. Costs were calculated using a societal perspective, including both direct and indirect costs. An incremental cost-effectiveness ratio was calculated and bootstrapping methods assessed the uncertainty surrounding the results. An alternative scenario analysis in which MP was administered at home was also carried out. A budgetary impact analysis was carried at five years., Results: In the conditions of the trial (hospitalized patients), there was no significant difference in utilities and costs at 28 days. The incremental cost-effectiveness ratio was €15,360 per quality-adjusted life-year gained. If multiple sclerosis relapses were treated at home, oral MP would be more effective, less costly and associated with annual savings up to 25 million euros for the French healthcare system., Conclusions: Oral MP is cost-effective in the treatment of multiple sclerosis relapses and associated with major savings., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
Published: 2022
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29. Longitudinally Extensive Myelitis Associated With Immune Checkpoint Inhibitors.

Author: Picca A, Berzero G, Bihan K, Jachiet V, Januel E, Coustans M, Cauquil C, Perrin J, Berlanga P, Kramkimel N, Garel B, Devic P, Ducray F, Benazra M, Bompaire F, Leclercq D, Michot JM, Ammari S, and Psimaras D
Subjects: Adolescent, Adult, Aged, Female, Glucocorticoids therapeutic use, Humans, Immunotherapy, Magnetic Resonance Imaging, Male, Middle Aged, Myelitis diagnosis, Neoplasms drug therapy, Retrospective Studies, Immune Checkpoint Inhibitors adverse effects, Myelitis drug therapy, Myelitis etiology
Abstract: Objective: To define the characteristics and the outcome of myelitis associated with immune checkpoint inhibitors (ICIs)., Methods: We performed a retrospective research in the databases of the French Pharmacovigilance Agency and the OncoNeuroTox network for patients who developed myelitis following treatment with ICIs (2011-2020). A systematic review of the literature was performed to identify similar cases., Results: We identified 7 patients who developed myelitis after treatment with ICIs (anti-PD1 [n = 6], anti-PD1 + anti-CTLA4 [n = 1]). Neurologic symptoms included paraparesis (100%), sphincter dysfunction (86%), tactile/thermic sensory disturbances (71%), and proprioceptive ataxia (43%). At the peak of symptom severity, all patients were nonambulatory. MRI typically showed longitudinally extensive lesions, with patchy contrast enhancement. CSF invariably showed inflammatory findings. Five patients (71%) had clinical and/or paraclinical evidence of concomitant cerebral, meningeal, caudal roots, and/or peripheral nerve involvement. Despite the prompt discontinuation of ICIs and administration of high-dose glucocorticoids (n = 7), most patients needed second-line immune therapies (n = 5) because of poor recovery or early relapses. At last follow-up, only 3 patients had regained an ambulatory status (43%). Literature review identified 13 previously reported cases, showing similar clinical and paraclinical features. All patients discontinued ICIs and received high-dose glucocorticoids, with the addition of other immune therapies in 8. Clinical improvement was reported for 10 patients., Conclusion: Myelitis is a rare but severe complication of ICIs that shows limited response to glucocorticoids. Considering the poor functional outcome associated with longitudinally extensive myelitis, strong and protracted immune therapy combinations are probably needed upfront to improve patient outcome and prevent early relapses., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Published: 2021
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30. Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis.

Author: Louapre C, Collongues N, Stankoff B, Giannesini C, Papeix C, Bensa C, Deschamps R, Créange A, Wahab A, Pelletier J, Heinzlef O, Labauge P, Guilloton L, Ahle G, Goudot M, Bigaut K, Laplaud DA, Vukusic S, Lubetzki C, De Sèze J, Derouiche F, Tourbah A, Mathey G, Théaudin M, Sellal F, Dugay MH, Zéphir H, Vermersch P, Durand-Dubief F, Françoise R, Androdias-Condemine G, Pique J, Codjia P, Tilikete C, Marcaud V, Lebrun-Frenay C, Cohen M, Ungureanu A, Maillart E, Beigneux Y, Roux T, Corvol JC, Bordet A, Mathieu Y, Le Breton F, Boulos DD, Gout O, Guéguen A, Moulignier A, Boudot M, Chardain A, Coulette S, Manchon E, Ayache SS, Moreau T, Garcia PY, Kumaran D, Castelnovo G, Thouvenot E, Taithe, Poupart J, Kwiatkowski A, Defer G, Derache N, Branger P, Biotti D, Ciron J, Clerc C, Vaillant M, Magy L, Montcuquet A, Kerschen P, Coustans M, Guennoc AM, Brochet B, Ouallet JC, Ruet A, Dulau C, Wiertlewski S, Berger E, Buch D, Bourre B, Pallix-Guiot M, Maurousset A, Audoin B, Rico A, Maarouf A, Edan G, Papassin J, and Videt D
Subjects: Adult, COVID-19, Cohort Studies, Female, France epidemiology, Humans, Male, Middle Aged, Pandemics, Registries, Retrospective Studies, SARS-CoV-2, Treatment Outcome, Betacoronavirus, Coronavirus Infections epidemiology, Coronavirus Infections therapy, Multiple Sclerosis epidemiology, Multiple Sclerosis therapy, Pneumonia, Viral epidemiology, Pneumonia, Viral therapy
Abstract: Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities., Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity., Design, Setting, and Participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020., Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms., Main Outcomes and Measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes., Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01)., Conclusions and Relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.
Published: 2020
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31. Inaugural tumor-like multiple sclerosis: clinical presentation and medium-term outcome in 87 patients.

Author: Balloy G, Pelletier J, Suchet L, Lebrun C, Cohen M, Vermersch P, Zephir H, Duhin E, Gout O, Deschamps R, Le Page E, Edan G, Labauge P, Carra-Dallieres C, Rumbach L, Berger E, Lejeune P, Devos P, N'Kendjuo JB, Coustans M, Auffray-Calvier E, Daumas-Duport B, Michel L, Lefrere F, Laplaud DA, Brosset C, Derkinderen P, de Seze J, and Wiertlewski S
Subjects: Adult, Brain diagnostic imaging, Diffuse Cerebral Sclerosis of Schilder diagnostic imaging, Disease Progression, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Multiple Sclerosis pathology, Multiple Sclerosis therapy, Retrospective Studies, Multiple Sclerosis diagnostic imaging
Abstract: Background: Tumefactive demyelinating lesions of the central nervous system can be the initial presentation in various pathological entities [multiple sclerosis (the most common), Balo's concentric sclerosis, Schilder's disease and acute disseminated encephalomyelitis] with overlapping clinical presentation. The aim of our study was to better characterize these patients., Methods: Eighty-seven patients (62 women and 25 men) from different MS centers in France were studied retrospectively. Inclusion criteria were (1) a first clinical event (2) MRI showing one or more large demyelinating lesions (20 mm or more in diameter) with mass-like features. Patients with a previous demyelinating event (i.e. confirmed multiple sclerosis) were excluded., Results: Mean age at onset was 26 years. The most common initial symptoms (67% of the patients) were hemiparesis or hemiplegia. Aphasia, headache and cognitive disturbances (i.e. atypical symptoms for demyelinating diseases) were observed in 15, 18 and 15% of patients, respectively. The mean largest diameter of the tumefactive lesions was 26.9 mm, with gadolinium enhancement in 66 patients (81%). Twenty-one patients (24%) had a single tumefactive lesion. During follow-up (median time 5.7 years) 4 patients died, 70 patients improved or remained stable and 12 worsened. 86% of patients received initial corticosteroid treatment, and 73% received disease-modifying therapy subsequently. EDSS at the end of the follow-up was 2.4 ± 2.6 (mean ± SD)., Conclusion: This study provides further evidence that the clinical course of MS presenting with large focal tumor-like lesions does not differ from that of classical relapsing-remitting MS, once the noisy first relapsing occurred.
Published: 2018
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32. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: The MOGADOR study.

Author: Cobo-Calvo A, Ruiz A, Maillart E, Audoin B, Zephir H, Bourre B, Ciron J, Collongues N, Brassat D, Cotton F, Papeix C, Durand-Dubief F, Laplaud D, Deschamps R, Cohen M, Biotti D, Ayrignac X, Tilikete C, Thouvenot E, Brochet B, Dulau C, Moreau T, Tourbah A, Lebranchu P, Michel L, Lebrun-Frenay C, Montcuquet A, Mathey G, Debouverie M, Pelletier J, Labauge P, Derache N, Coustans M, Rollot F, De Seze J, Vukusic S, and Marignier R
Subjects: Adolescent, Adult, Aged, Aquaporin 4 blood, Autoantibodies, Brain Diseases blood, Brain Diseases immunology, Brain Diseases pathology, Demyelinating Autoimmune Diseases, CNS blood, Demyelinating Autoimmune Diseases, CNS pathology, Female, Humans, Male, Middle Aged, Myelin-Oligodendrocyte Glycoprotein blood, Prognosis, Retrospective Studies, Spinal Cord Diseases blood, Spinal Cord Diseases immunology, Spinal Cord Diseases pathology, Young Adult, Brain Diseases diagnosis, Demyelinating Autoimmune Diseases, CNS diagnosis, Myelin-Oligodendrocyte Glycoprotein immunology, Spinal Cord Diseases diagnosis
Abstract: Objective: To describe clinical and radiologic features associated with myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) in a large French nationwide adult cohort, to assess baseline prognostic features of MOG-Ab-associated diseases after a first acute demyelinating syndrome, and to evaluate the clinical value of MOG-Ab longitudinal analysis., Methods: Clinical data were obtained from 197 MOG-Ab-positive patients ≥18 years of age. Complete imaging data were available in 108, and 54 serum samples were eligible for longitudinal evaluation. For survival analysis comparison, 169 aquaporin-4 antibody (AQP4-Ab)-positive patients from the NOMADMUS database were included., Results: Median age at onset was 36.46 (range 18.0-76.8) years, and patients were predominantly white (92.9%) with male:female ratio, 1.1. Clinical phenotype at onset included optic neuritis or myelitis in 90.86%, isolated brainstem or encephalopathy syndromes in 6.6%, and a combination of syndromes in 2.5%. Distinctive brain MRI findings in MOG-Ab-positive patients were thalamic and pontine lesions. Cortical and leptomeningeal lesions were found in 16.3% and 6.1%, respectively. The probability of reaching a first relapse after 2 and 5 years was 44.8% and 61.8%, respectively. MOG-Ab-positive patients were at lower risk at presentation of further clinical relapse (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.26-0.79) compared to AQP4-Ab-positive individuals. MOG-Ab-positive individuals had a lower risk of reaching Disability Status Scale score of 3.0 (HR 0.46, 95% CI 0.22-0.94) and visual acuity of 20/100 (HR 0.23, 95% CI 0.07-0.72). Finally, MOG-Ab titers were higher at relapse than in remission ( p = 0.009)., Conclusion: In adults, MOG-Ab-associated disease extends beyond clinical and radiologic abnormalities in the optic nerve and spinal cord. Despite the relapsing course, the overall visual and motor outcome is better compared with AQP4-Ab-positive patients., (© 2018 American Academy of Neurology.)
Published: 2018
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33. Treating asymptomatic bacteriuria before immunosuppressive therapy during multiple sclerosis: Should we do it?

Author: Rouzaud C, Hautecoeur P, Donze C, Heinzlef O, Dinh A, Creange A, Abdullatif A, Audouin B, Tourbah A, Berger E, Bourre B, Brochet B, Mekies C, Cabre P, Papeix C, Casez O, Brassat D, Defer G, Derache N, De Seze J, Dive D, LePage E, Fromont A, Gouider R, Edan G, Pelletier J, Grimaud J, Guennoc AM, Camdessanché JP, Kwiatkowski A, Laplaud D, Lebrun C, Debouverie M, Coustans M, Gout O, La Rochelle OA, Heinzlef O, Ouallet JC, Cavelou P, Hautecoeur P, Labauge P, Vermersch P, Wiertlewski S, Vukusic S, Marignier R, Schluep M, Seeldrayers P, Slassi I, Stankoff B, Thaite F, Moreau T, Thouvenot E, Zephir H, Ciron J, Collongues N, Kerschen P, Cohen M, Gueguen A, Mathey G, Carra C, Bernady P, Faucheux JM, Planque E, Donze C, Ruet A, Mouzawakh C, and Pittion S
Subjects: Anti-Bacterial Agents therapeutic use, Humans, Multicenter Studies as Topic, Multiple Sclerosis therapy, Bacteriuria therapy, Immunosuppressive Agents therapeutic use, Multiple Sclerosis complications
Published: 2017
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34. Erdheim Chester disease: A rare obstructive case of acute renal failure.

Author: Jean-Michel V, Coustans M, Wehbe B, Metes I, and Siohan P
Subjects: Acute Kidney Injury drug therapy, Adult, Diagnosis, Differential, Erdheim-Chester Disease drug therapy, Humans, Indoles adverse effects, Indoles therapeutic use, Male, Sulfonamides adverse effects, Sulfonamides therapeutic use, Ureteral Obstruction drug therapy, Vemurafenib, Acute Kidney Injury diagnostic imaging, Erdheim-Chester Disease diagnostic imaging, Tomography, X-Ray Computed, Ureteral Obstruction diagnostic imaging
Published: 2016
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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: Le Page E, Veillard D, Laplaud DA, Hamonic S, Wardi R, Lebrun C, Zagnoli F, Wiertlewski S, Deburghgraeve V, Coustans M, and Edan G
Subjects: Administration, Oral, Adolescent, Adult, Double-Blind Method, Female, France, Humans, Infusions, Intravenous, Male, Middle Aged, Treatment Outcome, Young Adult, Glucocorticoids administration & dosage, Methylprednisolone administration & dosage, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract: Background: 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 Française contre la SEP, Teva., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
Published: 2015
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36. [Intravascular large B-cell lymphoma revealed by a cerebral infarct and a mesenteric ischemia].

Author: Bailly P, Diraison P, Coustans M, Lamotte N, and Breuilly C
Subjects: Aged, Cerebral Hemorrhage diagnosis, Cerebral Hemorrhage etiology, Cerebral Infarction complications, Diagnosis, Differential, Female, Humans, Lymphoma, Large B-Cell, Diffuse complications, Magnetic Resonance Imaging, Mesenteric Ischemia complications, Vascular Neoplasms complications, Cerebral Infarction diagnosis, Lymphoma, Large B-Cell, Diffuse diagnosis, Mesenteric Ischemia diagnosis, Vascular Neoplasms diagnosis
Published: 2015
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37. Acute urinary retention due to a novel collagen COL4A1 mutation.

Author: Rouaud T, Labauge P, Tournier Lasserve E, Mine M, Coustans M, Deburghgraeve V, and Edan G
Subjects: Acute Disease, Amino Acid Substitution genetics, Brain Infarction etiology, Brain Infarction genetics, Brain Infarction metabolism, Cerebral Hemorrhage etiology, Cerebral Hemorrhage genetics, Cerebral Hemorrhage metabolism, Humans, Leukoencephalopathies etiology, Leukoencephalopathies genetics, Leukoencephalopathies metabolism, Male, Urinary Retention metabolism, Young Adult, Collagen Type IV genetics, Genetic Predisposition to Disease genetics, Mutation genetics, Urinary Retention etiology, Urinary Retention genetics
Published: 2010
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38. Mitoxantrone as induction treatment in aggressive relapsing remitting multiple sclerosis: treatment response factors in a 5 year follow-up observational study of 100 consecutive patients.

Author: Le Page E, Leray E, Taurin G, Coustans M, Chaperon J, Morrissey SP, and Edan G
Subjects: Adult, Antiviral Agents therapeutic use, Azathioprine therapeutic use, Brain pathology, Demography, Disability Evaluation, Drug Therapy, Combination, Female, Follow-Up Studies, Glatiramer Acetate, Humans, Immunosuppressive Agents therapeutic use, Interferon-beta therapeutic use, Magnetic Resonance Imaging, Male, Methotrexate therapeutic use, Methylprednisolone therapeutic use, Multiple Sclerosis, Relapsing-Remitting diagnosis, Observation, Peptides therapeutic use, Prevalence, Recurrence, Antineoplastic Agents therapeutic use, Mitoxantrone therapeutic use, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract: Background: Mitoxantrone was approved by the French health authority (AFSAPPS) in October 2003 to treat patients with aggressive multiple sclerosis (MS)., Objective: To report the long term effectiveness and safety of mitoxantrone as induction therapy in patients with aggressive relapsing-remitting MS, and to assess treatment response factors., Material and Methods: 100 consecutive patients with aggressive relapsing-remitting MS received mitoxantrone 20 mg monthly combined with methylprednisolone 1 g for 6 months. Relapses, Expanded Disability Status Scale (EDSS) and drug safety were assessed every 6 months for up to at least 5 years. Within 6 months after induction, 73 patients received maintenance therapy (mitoxantrone every 3 months (n = 21); interferon beta (n = 25); azathioprine (n = 15); methotrexate (n = 7); glatiramer acetate (n = 5))., Results: During the 12 months following initiation of mitoxantrone, the annual relapse rate (ARR) was reduced by 91%, 78% of patients remained relapse free, MRI activity was reduced by 89%, the mean EDSS decreased by 1.2 points (p<10(-6)) and 64% of patients improved by 1 point or more on the EDSS. In the longer term, the ARR reduction was sustained (0.29-0.42 for up to 5 years), the median time to the first relapse was 2.8 years and disability remained improved after 5 years. Younger age and lower EDSS score at the start of mitoxantrone treatment were predictive of better treatment response. Three patients presented with an asymptomatic decrease in left ventricular ejection fraction to less than 50% (one reversible). One patient was diagnosed with acute myeloid leukaemia (remission 5 years after diagnosis)., Conclusion: Mitoxantrone monthly for 6 months as induction therapy followed by maintenance treatment showed sustained clinical benefit for up to 5 years with an acceptable adverse events profile in patients with aggressive relapsing-remitting MS.
Published: 2008
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39. Long-term survival of patients with multiple sclerosis in West France.

Author: Leray E, Morrissey S, Yaouanq J, Coustans M, Le Page E, Chaperon J, and Edan G
Subjects: Adult, Aged, Cause of Death, Disability Evaluation, Female, France epidemiology, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Prognosis, Multiple Sclerosis, Chronic Progressive mortality, Multiple Sclerosis, Relapsing-Remitting mortality
Abstract: In France no data have been published about comparing survival in multiple sclerosis (MS) patients with the general French population. We estimated survival probabilities in MS patients from a major centre for MS in West France. We also compared MS survival with the general population and assessed prognostic parameters. All patients with MS onset after January 1976 and classified as dead or alive on 1 January 2004 were included. One thousand eight-hundred and seventy-nine patients (sex ratio W: M 2.3; relapsing/progressive onset 77.4%/22.6%) fulfilled these criteria, disease duration ranged from one to 28 years. By 2004, 68 patients died (51 due to MS) and the 15 and 25-year survival probabilities were 96% and 88%. Male gender, progressive course (either primary or secondary), polysymptomatic onset, and increased annual relapse rate during the first two years of MS were related to a worse prognosis. After a mean follow-up duration of 12.7 years since clinical onset, MS increased the number of deaths compared with the general population. However taking into account disability status, we found that less disabled MS patients had a better survival and highly disabled patients a worse survival (eight-fold increase of mortality) compared with the French population.
Published: 2007
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40. Spontaneous resolution of arachnoid cysts: review and features of an unusual case.

Author: Seizeur R, Forlodou P, Coustans M, and Dam-Hieu P
Subjects: Adult, Arachnoid Cysts complications, Hematoma, Epidural, Cranial complications, Hematoma, Epidural, Cranial diagnostic imaging, Hematoma, Epidural, Cranial surgery, Humans, Male, Radiography, Remission, Spontaneous, Arachnoid Cysts diagnostic imaging
Abstract: Most intra-cranial arachnoid cysts are quiescent and remain asymptomatic throughout life. Within the natural course of arachnoid cyst evolution, spontaneous resolution has been known to occur rarely, but its frequency is probably underestimated due to lack of systematic detection and long-term observation. We illustrate the spontaneous regression of arachnoid cysts with a patient which was conjointly diagnosed with an arachnoid cyst and a post-traumatic epidural haematoma. Cyst regression was observed 16 months later, upon examination following a second benign cranial trauma. Mechanisms underlying the resolution of the arachnoid cyst are discussed.
Published: 2007
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41. Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity.

Author: Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, Sawcer SJ, Vukusic S, Achiti I, Confavreux C, Coustans M, le Page E, Edan G, McDonnell GV, Hawkins S, Trojano M, Liguori M, Cocco E, Marrosu MG, Tesser F, Leone MA, Weber A, Zipp F, Miterski B, Epplen JT, Oturai A, Sørensen PS, Celius EG, Lara NT, Montalban X, Villoslada P, Silva AM, Marta M, Leite I, Dubois B, Rubio J, Butzkueven H, Kilpatrick T, Mycko MP, Selmaj KW, Rio ME, Sá M, Salemi G, Savettieri G, Hillert J, and Compston DA
Subjects: Adult, Age of Onset, Cohort Studies, Cross-Sectional Studies, Databases, Factual, Disease Progression, Female, France epidemiology, Humans, Longitudinal Studies, Male, Middle Aged, Models, Neurological, Models, Statistical, Multiple Sclerosis epidemiology, Multiple Sclerosis physiopathology, Predictive Value of Tests, Prognosis, Recurrence, Reproducibility of Results, Disability Evaluation, Multiple Sclerosis diagnosis, Severity of Illness Index
Abstract: Background: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease., Methods: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability., Results: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression., Conclusion: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.
Published: 2005
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42. [Is immunosuppression a future therapeutic strategy for multiple sclerosis?].

Author: Edan G and Coustans M
Subjects: Azathioprine therapeutic use, Clinical Trials as Topic, Cyclophosphamide therapeutic use, Humans, Immunosuppressive Agents therapeutic use, Methotrexate therapeutic use, Mitoxantrone therapeutic use, Immunosuppression Therapy, Multiple Sclerosis therapy
Abstract: Although in previous studies no clear demonstration was found of the efficacy of azathioprine, cyclophosphamide and methotrexate as immunoprophylactic agents in cases of multiple sclerosis (MS), over the past five years a number of well-designed clinical trials utilizing immunosuppressive and immunomodulatory agents have shown partial efficacy regarding the drugs involved, but they have not been able to determine in what way these drugs can modify the natural course of this disease. Among the immunosuppressors, mitoxantrone is of particular interest as during the past two years three controlled trials have taken place in Europe and have demonstrated its efficacy both as regards clinical (frequency of symptoms, progression of the disease) and magnetic resonance imaging (MRI) criteria. Due to its potentially severe cardiotoxicity related to total cumulative dose, mitoxantrone is only prescribed for a limited period, and its use is limited to selected patients with a high relapse rate and incomplete remission, or to those who do not respond to beta-interferon treatment. The immunomodulatory agents have less immediate efficacy, but because they are well tolerated they can be used early in the course of the disease and over a prolonged period of time. The beta-interferons (1a or 1b) have been given market approval for use in the treatment of MS: three large, randomized, double-blind studies have demonstrated their capacity to reduce by 30% the frequency of symptoms and the appearance of disabilities associated with relapse and with the progression of the disease. Glatirameracetate or copolymer 1, which is available in France (ATU), has been found to reduce the frequency of relapse by 30%. It constitutes an alternative immunomodulatory treatment for relapsing-remitting patients without major functional disabilities and who suffer from severe side effects with beta-interferon treatment. In the future, the early use of immunomodulatory agents and therapeutic drug combinations may be introduced. Therapeutic trials are currently in progress to determine the viability of this approach.
Published: 2000

43. [Evolution and surveillance of multiple sclerosis].

Author: Edan G and Coustans M
Subjects: Diagnosis, Differential, Persons with Disabilities classification, Disease Progression, Humans, Multiple Sclerosis diagnosis, Central Nervous System pathology, Multiple Sclerosis pathology
Abstract: Multiple sclerosis is a highly complex disease due to the great diversity of symptoms and signs from disseminated demyelinating CNS lesions which lead to different levels of handicap, and to the different types of evolution (exacerbations or slow progression). Most of the patients with multiple sclerosis have a normal longevity. The main concern is the accumulation of disabilities. In order to follow accurately the progression of these disabilities, specific scales, especially EDSS, have been validated allowing more uniformity in method of collecting data from multiple sclerosis.
Published: 1999

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