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1. Les formes secondairement progressives de SEP

Author: D. Brassat
Subjects: 0301 basic medicine, Gynecology, Progressive multiple sclerosis, 03 medical and health sciences, medicine.medical_specialty, 030104 developmental biology, 0302 clinical medicine, business.industry, Medicine, Neurology (clinical), Anti cd20, business, 030217 neurology & neurosurgery
Abstract: Resume La sclerose en plaques secondairement progressive (SEP-SP) partage de nombreuses caracteristiques physiopathologiques, cliniques et therapeutiques avec la forme primitivement progressive. Cependant lors de la consultation SEP, ces formes SEP-SP posent des problemes specifiques notamment sur la facon d’en faire le diagnostic et la decision de traiter ou non. Dans cette presentation nous esperons lister les problemes rencontres lors d’une consultation pour y apporter quelques reponses avec les moyens a notre disposition en 2017.
Published: 2017

2. 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

3. 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

4. Histoire naturelle de la sclérose en plaques

Author: Gilles Defer, Marc Debouverie, I. Bardou, M. Benamar, R. Bernard-Valnet, P. Branger, D. Brassat, N. Benallègue, F. Calocer, V. Damotte, O. Dejardin, A. Dejean, N. Derache, F. Docagne, C. Donzé, A.-L. Dubessy, B. Fontaine, G. Fournié, A. Fromont, A. Garcia, P. Hautecœur, L. Lanotte, D. Laplaud, B. Le Mauff, H. Lebas, E. Leray, G. Mathey, D. Merkler, L. Michel, M. Michieletto, J. Morille, B. Nicol, C. Pierrot-Deseilligny, S. Pittion-Vouyovitch, I. Rebeix, A. Saoudi, D. Seilhean, B. Stankoff, O. Toutirais, D. Vivien, and S. Vukusic
Published: 2019

5. Mécanismes d’actions des biothérapies dans la SEP

Author: R. Bernard-Valnet and D. Brassat
Published: 2019

6. Diagnostic positif de la sclérose en plaques

Author: Bruno Brochet, Christine Lebrun-Frénay, Jérôme de Sèze, Hélène Zéphir, E. Allart, B. Audoin, X. Ayrignac, C. Bensa, A. Blanchard-Dauphin, D. Brassat, C. Carra-Dallière, P. Clavelou, M. Cohen, A. Créange, N. Collongues, M. Debouverie, G. Defer, M. de Sèze, C. Donzé, G. Edan, A. Fromont, X. Gamé, O. Gout, C. Guillon, C. Harand, B. Jenny, P. Labauge, P.-H. Lalive, E. Le Page, P. Marque, L. Michel, X. Moisset, J.-C. Ouallet, O. Outteryck, F. Pelé, J. Pelletier, S. Pittion-Vouyovitch, A.-L. Ramelli, A. Ruet, E. Thouvenot, D. Veillard, C. Vignal-Clermont, and S. Vukusic
Published: 2017

7. Physiopathologie de la spasticité

Author: D Brassat and P. Marque
Subjects: business.industry, Central nervous system, Spinal reflex, Pathophysiology, Tonic (physiology), Biomechanical Phenomena, medicine.anatomical_structure, Neurology, medicine, Reflex, In patient, Neurology (clinical), Spasticity, medicine.symptom, business, Neuroscience
Abstract: The term "spasticity" describes the velocity-dependent increase in tonic stretch reflexes. The symptom is commonly seen in patients with injury to the central nervous system. It is rarely isolated but, instead, part of a set of symptoms that is sometimes confusing. However, the pathophysiology of the symptom has evolved over the past three decades, and it is now considered part of a global process that includes not only spinal reflex loop modifications, but also changes in the biomechanical properties of muscle fibers. Finally, recent studies of changes in the membrane properties of motor neurons and the occurrence of plateau potential have opened new perspectives. This review aims to describe these new pathophysiological models.
Published: 2012

8. Season of birth and not vitamin D receptor promoter polymorphisms is a risk factor for multiple sclerosis

Author: D A, Fernandes de Abreu, M C, Babron, M C I, Babron, I, Rebeix, C, Rebeix, C, Fontenille, J, Fontenille, J, Yaouanq, D, Yaouanq, D, Brassat, B, Brassat, B, Fontaine, F, Fontaine, F, Clerget-Darpoux, F, Jehan, and F, Feron
Subjects: Parents, Risk, Multiple Sclerosis, Genotype, Season of birth, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Calcitriol receptor, Gene Frequency, Risk Factors, medicine, Vitamin D and neurology, Humans, Genetic Predisposition to Disease, Prospective Studies, Risk factor, Promoter Regions, Genetic, Allele frequency, Pregnancy, business.industry, Incidence, Multiple sclerosis, Parturition, medicine.disease, Neurology, Immunology, Receptors, Calcitriol, France, Seasons, Neurology (clinical), business
Abstract: Both genetic and environmental factors contribute to multiple sclerosis, the most common neurodegenerative disorder with onset in young adults. The objective of the current study is, based on the hypothesis that environmentally predisposed individuals are at risk for multiple sclerosis, to investigate whether they also carry genetic variants within the vitamin D machinery. Using medical files and DNA samples from 583 trios (a patient and both parents) of the French Multiple Sclerosis Genetics Group as well as data from the French Statistics Bureau, we aimed to assess whether: (1) a seasonality of birth was observed in French multiple sclerosis patients; (2) three single nucleotide polymorphisms within the promoter region of the vitamin D receptor were associated with multiple sclerosis susceptibility; and (3) the combination of a high risk month of birth and vitamin D receptor polymorphisms were correlated to multiple sclerosis incidence. We observed a significantly reduced number of individuals born in November who were later diagnosed as multiple sclerosis patients. However, we found no association between the three studied vitamin D receptor polymorphisms and multiple sclerosis. In conclusion, our data suggest that high levels of vitamin D during the third trimester of pregnancy could be a protective factor for multiple sclerosis.
Published: 2009

9. Journées d’enseignement supérieur de neurologie – Toulouse 2017

Author: D. Brassat
Subjects: Neurology (clinical)
Published: 2017

10. [Cerebrotendinous xanthomatosis: a multicentric retrospective study of 15 adults, clinical and paraclinical typical and atypical aspects]

Author: C, Lionnet, C, Carra, X, Ayrignac, T, Levade, D, Gayraud, G, Castelnovo, G, Besson, G, Androdias, S, Vukusic, C, Confavreux, C, Zaenker, J, De Seze, N, Collongues, F, Blanc, C, Tranchant, D, Wallon, D, Hannequin, A, Gerdelat-Mas, D, Brassat, M, Clanet, H, Zephir, O, Outteryck, P, Vermersch, and P, Labauge
Subjects: Adult, Male, Mutation, Missense, Brain, Genes, Recessive, Xanthomatosis, Cerebrotendinous, Middle Aged, Chenodeoxycholic Acid, Magnetic Resonance Imaging, Amino Acid Substitution, Cholestanetriol 26-Monooxygenase, Humans, Female, Age of Onset, Symptom Assessment, Aged, Retrospective Studies
Abstract: Cerebrotendinous xanthomatosis, a metabolic leukodystrophy with an autosomal recessive inheritance, is secondary to deficiency of sterol 27-hydroxylase, an enzyme involved in cholesterol catabolism. Classical symptoms include clinical or infraclinical xanthomas affecting the skin and tendons, early cataracts, neurological signs and diarrhea. Brain imaging reveals involvement of the dentate nuclei and periventricular white matter hyperintensities. The diagnosis is based on an increased cholestanol level in serum, confirmed by the presence of a mutation in the CYP27A1 gene. Treatment is based on chenodeoxycholic acid.We report a retrospective multicentric study of 15 cases of cerebrotendinous xanthomatosis diagnosed in French adults. Clinical, molecular and MRI findings were recorded in all patients.The average age at diagnosis was 39years (range 27-65). Disease onset occurred in childhood in 73% of patients and in adulthood in 27%. All patients with a pediatric onset were diagnosed during adulthood (age range 28-65years). Clinical symptoms variably associated cerebellar syndrome, pyramidal syndrome, cognitive decline, epilepsy, neuropathy (sought in 10 of our patients, present in forms in 8), psychiatric disorders, cataract and xanthomas. One patient had an atypical presentation: monoparesis associated with xanthomas. Brain MRI was abnormal in all: findings consisted in T2-weighted hyperintensity of the dentate nuclei (47%), periventricular leuoencephalopathy (73%) which preferentially involved the posterior cerebral part (60%), leucoencephalopathy with a vascular pattern (7%), hyperintensity of the cortico-spinal tracts (53%), globi pallidi, corpus callosum and cerebral atrophy (33%). Serum cholestanol was elevated in 93% of patients. The most frequent mutation was 1183CT (n=5/15). Under treatment with chenodeoxycholic acid, eight patients improved initially, followed by stabilization in five of them, and worsening in the others. Four patients died.Patients with the xanthoma-neurological disorder association should be tested for cerebrotendinous xanthomatosis. The disease often begins in childhood with a diagnostic delay but also in adulthood. Involvement of the dentate nuclei is specific but not sensitive and the supratentorial leucoencephalopathy is not specific but with an antero-posterior gradient. A vascular distribution and involvement of the corpus callosum are possible. Serum cholestanol assay is very reliable: an elevated level provides the diagnosis, which must nevertheless be confirmed by molecular biology.
Published: 2013

11. [Nosology and etiologies of acute longitudinally extensive transverse myelitis]

Author: N, Collongues, C, Papeix, H, Zéphir, B, Audoin, F, Cotton, F, Durand-Dubief, S, Vukusic, D, Brassat, D, Laplaud, R, Marignier, and Hélène, Zéphir
Subjects: Consensus, Terminology as Topic, Acute Disease, Neuromyelitis Optica, Practice Guidelines as Topic, Humans, Myelitis, Transverse, Prognosis, Magnetic Resonance Imaging, Autoantibodies
Abstract: Acute transverse myelitis had many names and definitions, based primarily on clinical criteria. The role of MRI in the exploration of myelitis has increased recently after the individualization of neuromyelitis optica (NMO) in 2004. This approach has enabled clarification of the diagnostic and prognostic value of acute longitudinally extensive transverse myelitis (LETM), defined by an extensive T2 lesion affecting three vertebral segments in the sagittal plane. The limitations of this definition, the multiplicity of terms used to characterize it as well as the large number of etiologies associated with it led our group of experts to clarify its etiology and nosology. We conducted a national survey on this subject in order to propose a new definition of LETM. Additional first- and second-intention examinations were determined according to the clinical context. Infectious/para-infectious, inflammatory or paraneoplastic causes can thus be identified. To determine within a short time the cause of LETM is essential, since most of its causes are severe and require urgent treatment.
Published: 2013

12. [Pathophysiology of spasticity]

Author: P, Marque and D, Brassat
Subjects: Feedback, Physiological, Motor Neurons, Multiple Sclerosis, Reflex, Abnormal, Muscle Relaxation, Muscle Fibers, Skeletal, Motor Cortex, Pyramidal Tracts, Autonomic Nervous System, Models, Biological, Biomechanical Phenomena, Spinal Cord, Muscle Spasticity, Humans, Paralysis, Muscle, Skeletal, Spinal Cord Injuries, Muscle Contraction
Abstract: The term "spasticity" describes the velocity-dependent increase in tonic stretch reflexes. The symptom is commonly seen in patients with injury to the central nervous system. It is rarely isolated but, instead, part of a set of symptoms that is sometimes confusing. However, the pathophysiology of the symptom has evolved over the past three decades, and it is now considered part of a global process that includes not only spinal reflex loop modifications, but also changes in the biomechanical properties of muscle fibers. Finally, recent studies of changes in the membrane properties of motor neurons and the occurrence of plateau potential have opened new perspectives. This review aims to describe these new pathophysiological models.
Published: 2012

13. [Chronic headaches]

Author: G, Moulis, K, Delavigne, M, Alvarez, D, Brassat, F, Bonneville, P, Massip, and D, Adoue
Subjects: Diagnosis, Differential, Male, Epilepsy, Treatment Outcome, Adolescent, Headache Disorders, Humans, Meningitis, Optic Nerve, Hypertrophy, Hearing Loss, Glucocorticoids
Published: 2010

14. Epidemiologie und Genetik

Author: D. Brassat, B. Fontaine, M. Clanet, and C. Azais-Vuillemin
Abstract: Wie bei den meisten Autoimmunkrankheiten scheinen eine genetische Pra-disposition und Umweltfaktoren notwendig zu sein, damit eine multiple Sklerose entstehen kann. Ungewiss bleibt jedoch, wie stark sich die genannten Faktoren jeweils auswirken. Auf die Bedeutung der genetischen Faktoren wurde bereits vor uber hundert Jahren hingewiesen, als Eichhorst die multiple Sklerose als eine genetisch bedingte und vererbbare Krankheit identifizierte, nachdem er zwei mehrfach betroffene Familien [1] beobachtet hatte. Seit dem ersten Viertel des 20. Jahrhunderts wurde eine Fulle epidemiologischer Studien durchgefuhrt, die das Vorhandensein zahlreicher Unterschiede in der Verteilung der Krankheit auf einzelne Lander und Populationen sowie innerhalb eben dieser Populationen je nach dem Wohnort oder dem Alter zur Zeit eines Ortswechsels in breitem Umfang belegten. Die Verwendung von Tiermodellen, die Untersuchung anderer multifaktorieller Krankheiten mit komplexer genetischer Ubertragung, die Fortschritte der Populationsgenetik haben nachhaltig klar gemacht, dass die Beziehung zwischen dem genetischen Erbe und der Umwelt nicht so leicht gedeutet werden kann. So drangt sich der Gedanke auf, dass die multiple Sklerose geographisch ungleich verteilt ist, doch spiegelt dies fur die einen das Vorhandensein eines infektiosen Agens, fur die anderen hingegen den Einfluss eines Gens wider.
Published: 2003

15. Résultats d’une enquête évaluant la gestion chez les patients ayant une sclérose en plaques sous autosondage de l’examen cytobactériologique des urines par le neurologue

Author: X. Gamé, M. Clanet, D. Brassat, D. Peaureaux, Frédérique Viala, and Evelyne Castel-Lacanal
Subjects: Gynecology, medicine.medical_specialty, business.industry, Urology, Medicine, business
Published: 2012

16. [Therapeutic indications targeting etiology. (With the exception of primary progressive forms)]

Author: D, Brassat
Subjects: Clinical Trials as Topic, Multiple Sclerosis, Relapsing-Remitting, Treatment Outcome, Dose-Response Relationship, Drug, Adrenal Cortex Hormones, Humans, Multiple Sclerosis, Chronic Progressive, Drug Administration Schedule, Immunosuppressive Agents
Abstract: On the subject of the treatment of Multiple Sclerosis, JM Charcot stated in 1877 that "the time has not yet come when such a subject can be seriously considered". Fortunately such point of view is no more up to date. This chapter will review the available treatment for relapsing-remitting and secondary progressive Multiple Sclerosis. The immunosuppressive drugs and steroids have been used for many years. Immunomodulation appeared more recently. A review of the evidence on the use of those drugs will be performed.
Published: 2002

17. Marqueurs d’inflammation dans la sclérose en plaques

Author: D. Brassat
Subjects: Neurology, Neurology (clinical)
Published: 2014

18. The pathogenesis of lesions and normal-appearing white matter changes in multiple sclerosis: a serial diffusion MRI study

Author: D Brassat, Gareth J. Barker, C A Clark, D. G. MacManus, DH Miller, Mark R. Symms, Alan J. Thompson, David J. Werring, and A G Droogan
Subjects: Adult, Gadolinium DTPA, Male, Pathology, medicine.medical_specialty, Multiple Sclerosis, Contrast Media, White matter, Lesion, Reference Values, medicine, Enhancing Lesion, Image Processing, Computer-Assisted, Effective diffusion coefficient, Humans, Magnetization transfer, medicine.diagnostic_test, business.industry, Multiple sclerosis, Brain, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Disease Progression, Female, Neurology (clinical), medicine.symptom, business, Nuclear medicine, Diffusion MRI
Abstract: The idea that the initiating event in the formation of all new multiple sclerosis lesions is a focal blood-brain barrier (BBB) leakage associated with perivascular inflammation has been challenged recently by the observation of subtle abnormalities in some quantitative magnetic resonance (MR) parameters (including the magnetization transfer ratio) prior to lesion enhancement. MR diffusion imaging can non-invasively quantify the average apparent diffusion coefficient (ADC(av)), a measure of water molecule random motion that is sensitive to pathological change in multiple sclerosis lesions and to abnormalities in the normal-appearing white matter (NAWM). We therefore used MR diffusion imaging to investigate the dynamic evolution of water diffusion measurements in new enhancing multiple sclerosis lesions, in the NAWM from which they arise, and in anatomically matched contralateral NAWM regions from which no visible lesions develop. Gadolinium diethylenetriaminepentaacetic acid (Gd)-enhanced MRI and MR diffusion studies were performed monthly for 1 year in five multiple sclerosis patients with clinically and radiologically active disease. The ADC(av) was calculated at each time point of the study (before, during and after lesion appearance on Gd-enhanced scans) for each new enhancing lesion, and for regions matched for size and position in the contralateral NAWM. A steady and moderate increase in ADC(av) in prelesion NAWM was observed, which was followed by a rapid and marked increase at the time of Gd enhancement and a slower decay after the cessation of enhancement. In matched contralateral NAWM regions there was a significant but milder increase in ADC(av) at the time of the first noted lesion enhancement. These findings indicate that new focal lesions associated with frank BBB leakage are preceded by subtle, progressive alterations in tissue integrity beyond the resolution of conventional MRI. The increases in ADC(av) in anatomically matched contralateral regions after lesions have appeared supports the concept that structural damage in lesions causes damage or dysfunction in connected areas of NAWM.
Published: 2000

19. [Treatment of symptoms and relapses of multiple sclerosis]

Author: D, Brassat and M, Clanet
Subjects: Multiple Sclerosis, Recurrence, Disease Progression, Quality of Life, Humans, Pain, Pain Management, Urination Disorders, Fatigue
Abstract: Multiple sclerosis is a demyelinating disease of the central nervous system, with relapses. For more than 30 years steroids have been used in order to treat relapses. Available trials performed to determine which posology or administration route, and their efficacy, provided poor certitudes. Multiple sclerosis leads to symptoms that alter the quality of life. For fatigue, pain, spasticity and micturition disorder a treatment will be proposed.
Published: 1999

20. [Genetics of Parkinson disease]

Author: D, Brassat, A, Durr, Y, Agid, and A, Brice
Subjects: Ligases, Ubiquitin-Protein Ligases, Synucleins, alpha-Synuclein, Chromosome Mapping, Humans, Proteins, Chromosomes, Human, Pair 6, Nerve Tissue Proteins, Parkinson Disease, Chromosomes, Human, Pair 4, Phosphoproteins
Abstract: What is the role of genetic factors in the pathophysiology of idiopathic Parkinson's disease, one of the most frequent neurodegenerative disorders? In the past two years, identification of two genes and localization of a third one have supported the hypothesis that genetics factors are involved in idiopathic Parkinson's disease. We present arguments that support such hypothesis, and describe recent advances in genetic studies of idiopathic Parkinson's disease.The first gene identified on chromosome 4 encodes alpha-synuclein. It causes a rare form of autosomal dominant Parkinson's disease. A locus on the short arm of chromosome 2 was recently identified in families with autosomal dominant Parkinson's disease. More recently, the gene encoding Parkin (located on chromosome 6) has been described. It already appears to be an important locus for juvenile parkinsonism with autosomal recessive transmission.We now have to understand how mutations in these genes lead to selective degeneration of dopaminergic neurons, and to determine whether or not they participate in the genetic susceptibility of idiopathic Parkinson's disease.
Published: 1999

21. Familial factors influence disability in MS multiplex families. French Multiple Sclerosis Genetics Group

Author: D, Brassat, C, Azais-Vuillemin, J, Yaouanq, G, Semana, J, Reboul, I, Cournu, C, Mertens, G, Edan, O, Lyon-Caen, M, Clanet, and B, Fontaine
Subjects: Adult, Male, Disability Evaluation, Multiple Sclerosis, HLA Antigens, Humans, Female, Age of Onset
Abstract: Both genetic and environmental factors play a role in the pathophysiology of MS and may influence the clinical expression of the disease.To determine the contribution of familial factors to the clinical expression of MS.The French Multiple Sclerosis Genetics Group identified 87 sibling pairs. For each patient, sex, age at onset, duration of the disease, and disease course from onset were recorded. Disability was determined by the progression index (PI), defined as the ratio of the Expanded Disability Status Scale (EDSS) score disease duration when the latter exceeded 5 years. Statistical analyses were performed either with a group of patients (clinical features, relation between human leukocyte antigen and clinical features) or with a group of sibpairs (concordance for clinical features).The mean age at onset was 29.6 years, the ratio of women to men was 59:28, and the mean PI was 0.27. There was no correlation for disease course and age at onset between sibs with MS. In contrast, we observed a weak but significant correlation of the PI in MS sibpairs (r = 0.234, p = 0.03).This study revealed a concordance in MS sibling pairs for the disease severity, supporting the hypothesis that the degree of disability might be partly influenced by familial factors (environmental or genetic).
Published: 1999

22. A systematic study of oligodendrocyte growth factors as candidates for genetic susceptibility to MS. French Multiple Sclerosis Genetics Group

Author: C, Mertens, D, Brassat, J, Reboul, S, Eichenbaum-Voline, C, Vuillemin-Azais, I, Cournu, M C, Babron, G, Semana, G, Edan, M, Clanet, F, Clerget-Darpoux, A, Baron-Van Evercooren, O, Lyon-Caen, R, Liblau, and B, Fontaine
Subjects: Adult, Male, Risk, Oligodendroglia, Multiple Sclerosis, Polymorphism, Genetic, Genotype, Genetic Linkage, Humans, Female, Receptors, Growth Factor, Disease Susceptibility, Growth Substances
Abstract: To test 23 genes coding for growth factors and their receptors as candidates for MS genetic susceptibility in 84 multiplex families of French origin by linkage analysis.Epidemiologic studies have indicated that genetic susceptibility in MS exists. To identify MS susceptibility genes, association and linkage studies were performed with candidate genes suggested by the pathology of MS. The most consistent result was genetic association and linkage of MS to human leukocyte antigen (HLA) DR15. Recent advances in the knowledge of MS pathology have suggested that the oligodendrocyte, the myelin-forming cell in the CNS, and its growth factors might play a crucial role in MS.Fifty-two polymorphic markers within or flanking 23 candidate genes were used. Data were analyzed with the maximum likelihood score (MLS) approach. We also searched for a genetic interaction with HLA.Negative results were obtained for all candidate genes. The lower limits of the relative risk (Xs) possibly excluded for any candidate gene ranged from 1.3 to 2.8. Positive MLS values (up to 0.93) were observed for transforming growth factor beta 3 (TGFbeta3) in HLA DR15-associated families, suggesting a possible role for this growth factor in interaction with HLA.Oligodendrocyte growth factors do not play a significant role in MS genetic susceptibility, at least in the tested sample. TGFbeta3, the only gene highlighted by this study, deserves further analysis.
Published: 1998

23. Pharmacovigilance du rituximab pour le traitement des maladies auto-immunes hors AMM : résultats de l’étude RITAI (rituximab-autoimmunité)

Author: N. Congy, D. Brassat, S. Madaule, J.-L. Montastruc, Y. Leveneur, Philippe Arlet, Leonardo Astudillo, Alain Cantagrel, Laurent Sailler, F. Brevet, C. Paul, and Grégory Pugnet
Subjects: business.industry, Gastroenterology, Internal Medicine, Medicine, business
Published: 2013

24. Therapy-related acute myeloblastic leukemia after mitoxantrone treatment in a patient with MS

Author: J. H. Jaster, H. B. Niell, F. C. Dohan, T. W. Smith, D. Brassat, C. Recher, F. Rigal-Huguet, G. Laurent, M. Clanet, E. Waubant, E. Le Page, and G. Edan
Subjects: medicine.medical_specialty, Mitoxantrone, Acute leukemia, Myeloid, Acute myeloblastic leukemia, business.industry, Multiple sclerosis, medicine.disease, Surgery, Leukemia, medicine.anatomical_structure, Internal medicine, Cohort, medicine, Neurology (clinical), business, medicine.drug, Cohort study
Abstract: The authors report a patient with severe secondary progressive MS who responded to mitoxantrone but developed a fatal acute myeloblastic leukemia 15 months after completion of mitoxantrone therapy. Therapy-related acute leukemia (TRAL) in relation with mitoxantrone is rare; this patient was the first case among a cohort of 802 French MS patients treated with mitoxantrone. Nevertheless, this case stresses the need to further evaluate the long-term risk of TRAL in patients with MS who receive mitoxantrone.
Published: 2003

25. Therapy-related acute myeloblastic leukemia after mitoxantrone treatment in a patient with MS

Author: D, Brassat, C, Recher, E, Waubant, E, Le Page, F, Rigal-Huguet, G, Laurent, G, Edan, and M, Clanet
Subjects: Adult, Cohort Studies, Leukemia, Myeloid, Acute, Multiple Sclerosis, Humans, Female, Neurology (clinical), Mitoxantrone
Abstract: The authors report a patient with severe secondary progressive MS who responded to mitoxantrone but developed a fatal acute myeloblastic leukemia 15 months after completion of mitoxantrone therapy. Therapy-related acute leukemia (TRAL) in relation with mitoxantrone is rare; this patient was the first case among a cohort of 802 French MS patients treated with mitoxantrone. Nevertheless, this case stresses the need to further evaluate the long-term risk of TRAL in patients with MS who receive mitoxantrone.
Published: 2002

26. Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels Reflect Different Mechanisms of Disease Progression under B-Cell Depleting Treatment in Multiple Sclerosis.

Author: Benkert P, Maleska Maceski A, Schaedelin S, Oechtering J, Zadic A, Vilchez Gomez JF, Melie-Garcia L, Cagol A, Galbusera R, Subramaniam S, Lorscheider J, Galli E, Mueller J, Fischer-Barnicol B, Achtnichts L, Findling O, Lalive PH, Bridel C, Uginet M, Müller S, Pot C, Mathias A, Du Pasquier R, Salmen A, Hoepner R, Chan A, Disanto G, Zecca C, D'Souza M, Hemkens LG, Yaldizli Ö, Derfuss T, Roth P, Gobbi C, Brassat D, Tackenberg B, Pedotti R, Raposo C, Oksenberg J, Wiendl H, Berger K, Hermesdorf M, Piehl F, Conen D, Buser A, Kappos L, Khalil M, Granziera C, Abdelhak A, Leppert D, Willemse EAJ, and Kuhle J
Abstract: Objective: To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B-cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events., Methods: A total of 362 pwMS (1,480 samples) starting BCDT in the Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP levels in 2,861 control persons (4,943 samples) provided normative data to calculate adjusted Z scores., Results: Elevated sGFAP levels (Z score >1) at 1 year were associated with a higher hazard for PIRA (hazard ratio [HR]: 1.80 [95% CI: 1.17-2.78]; p = 0.0079) than elevated sNfL levels (HR, 1.45 [0.95-2.24], p = 0.0886) in a combined model. Independent of PIRA events, sGFAP levels longitudinally increased by 0.49 Z score units per 10 years follow-up (estimate, 0.49 [0.29, 0.69], p < 0.0001). In patients experiencing PIRA, sGFAP Z scores were 0.52 Z score units higher versus stable patients (0.52 [0.22, 0.83], p = 0.0009). Different sNfL Z score trajectories were found in pwMS with versus without PIRA (interaction p = 0.0028), with an average decrease of 0.92 Z score units per 10 years observed without PIRA (-0.92 [-1.23, -0.60], p < 0.0001), whereas levels in patients with PIRA remained high., Interpretation: Elevated sGFAP and lack of drop in sNfL after BCDT start are associated with increased risk of future PIRA. These findings provide a rationale for combined monitoring of sNfL and sGFAP in pwMS starting BCDT to predict the risk of PIRA, and to use sGFAP as an outcome in clinical trials aiming to impact on MS progressive disease biology. ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Published: 2024
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27. Progressive multifocal leukoencephalopathy genetic risk variants for pharmacovigilance of immunosuppressant therapies.

Author: Hatchwell E, Smith EB 3rd, Jalilzadeh S, Bruno CD, Taoufik Y, Hendel-Chavez H, Liblau R, Brassat D, Martin-Blondel G, Wiendl H, Schwab N, Cortese I, Monaco MC, Imberti L, Capra R, Oksenberg JR, Gasnault J, Stankoff B, Richmond TA, Rancour DM, Koralnik IJ, Hanson BA, Major EO, Chow CR, and Eis PS
Abstract: Background: Progressive multifocal leukoencephalopathy (PML) is a rare and often lethal brain disorder caused by the common, typically benign polyomavirus 2, also known as JC virus (JCV). In a small percentage of immunosuppressed individuals, JCV is reactivated and infects the brain, causing devastating neurological defects. A wide range of immunosuppressed groups can develop PML, such as patients with: HIV/AIDS, hematological malignancies (e.g., leukemias, lymphomas, and multiple myeloma), autoimmune disorders (e.g., psoriasis, rheumatoid arthritis, and systemic lupus erythematosus), and organ transplants. In some patients, iatrogenic (i.e., drug-induced) PML occurs as a serious adverse event from exposure to immunosuppressant therapies used to treat their disease (e.g., hematological malignancies and multiple sclerosis). While JCV infection and immunosuppression are necessary, they are not sufficient to cause PML., Methods: We hypothesized that patients may also have a genetic susceptibility from the presence of rare deleterious genetic variants in immune-relevant genes (e.g., those that cause inborn errors of immunity). In our prior genetic study of 184 PML cases, we discovered 19 candidate PML risk variants. In the current study of another 152 cases, we validated 4 of 19 variants in both population controls (gnomAD 3.1) and matched controls (JCV+ multiple sclerosis patients on a PML-linked drug ≥ 2 years)., Results: The four variants, found in immune system genes with strong biological links, are: C8B , 1-57409459-C-A, rs139498867; LY9 (alias SLAMF3 ), 1-160769595-AG-A, rs763811636; FCN2 , 9-137779251-G-A, rs76267164; STXBP2 , 19-7712287-G-C, rs35490401. Carriers of any one of these variants are shown to be at high risk of PML when drug-exposed PML cases are compared to drug-exposed matched controls: P value = 3.50E-06, OR = 8.7 [3.7-20.6]. Measures of clinical validity and utility compare favorably to other genetic risk tests, such as BRCA1 and BRCA2 screening for breast cancer risk and HLA-B * 15:02 pharmacogenetic screening for pharmacovigilance of carbamazepine to prevent Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis., Conclusion: For the first time, a PML genetic risk test can be implemented for screening patients taking or considering treatment with a PML-linked drug in order to decrease the incidence of PML and enable safer use of highly effective therapies used to treat their underlying disease., Competing Interests: Authors CB and CC are employed by Emerald Lake Safety LLC. Authors EH, ES, PE, and SJ are employed by Population Bio, Inc. Author TR is employed by Richmond Bioinformatics Consulting and author DR is employed by Lytic Solutions, LLC. Authors HW, IK, NS, and RL received funding from PML Screening, LLC to partially offset the costs for collection, and clinical characterization of patient samples used in the research. Authors EH, ES, PE, and YT are inventors of genetic screening methods for PML risk and have issued and pending patents related to this work. Applicants/Assignees on issued patents are: PML Screening, LLC, Newport Beach, CA (US), a joint venture between Population Bio, Inc. and Emerald Lake Safety LLC; Université Paris-Saclay, Gif sur Yvette (FR); The Assistance Publique-Hôpitaux de Paris (APHP), Paris (FR); and The Institut National de la Santé et de la Recherche Médicale (INSERM), Paris (FR). Author IC is a shareholder in Keires AG, Nouscom AG, and PDC*line Pharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from PML Screening, LLC. The funders had the following involvement with the study: conception and design of the study, laboratory experiments, data analysis and interpretation, and wrote the manuscript., (Copyright © 2022 Hatchwell, Smith, Jalilzadeh, Bruno, Taoufik, Hendel-Chavez, Liblau, Brassat, Martin-Blondel, Wiendl, Schwab, Cortese, Monaco, Imberti, Capra, Oksenberg, Gasnault, Stankoff, Richmond, Rancour, Koralnik, Hanson, Major, Chow and Eis.)
Published: 2022
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28. Correction: Broader Epstein-Barr virus-specific T cell receptor repertoire in patients with multiple sclerosis.

Author: Schneider-Hohendorf T, Gerdes LA, Pignolet B, Gittelman R, Ostkamp P, Rubelt F, Raposo C, Tackenberg B, Riepenhausen M, Janoschka C, Wünsch C, Bucciarelli F, Flierl-Hecht A, Beltrán E, Kümpfel T, Anslinger K, Gross CC, Chapman H, Kaplan I, Brassat D, Wekerle H, Kerschensteiner M, Klotz L, Lünemann JD, Hohlfeld R, Liblau R, Wiendl H, and Schwab N
Published: 2022
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29. Broader Epstein-Barr virus-specific T cell receptor repertoire in patients with multiple sclerosis.

Author: Schneider-Hohendorf T, Gerdes LA, Pignolet B, Gittelman R, Ostkamp P, Rubelt F, Raposo C, Tackenberg B, Riepenhausen M, Janoschka C, Wünsch C, Bucciarelli F, Flierl-Hecht A, Beltrán E, Kümpfel T, Anslinger K, Gross CC, Chapman H, Kaplan I, Brassat D, Wekerle H, Kerschensteiner M, Klotz L, Lünemann JD, Hohlfeld R, Liblau R, Wiendl H, and Schwab N
Subjects: CD8-Positive T-Lymphocytes, Herpesvirus 4, Human, Humans, Receptors, Antigen, T-Cell, alpha-beta genetics, Epstein-Barr Virus Infections complications, Multiple Sclerosis
Abstract: Epstein-Barr virus (EBV) infection precedes multiple sclerosis (MS) pathology and cross-reactive antibodies might link EBV infection to CNS autoimmunity. As an altered anti-EBV T cell reaction was suggested in MS, we queried peripheral blood T cell receptor β chain (TCRβ) repertoires of 1,395 MS patients, 887 controls, and 35 monozygotic, MS-discordant twin pairs for multimer-confirmed, viral antigen-specific TCRβ sequences. We detected more MHC-I-restricted EBV-specific TCRβ sequences in MS patients. Differences in genetics or upbringing could be excluded by validation in monozygotic twin pairs discordant for MS. Anti-VLA-4 treatment amplified this observation, while interferon β- or anti-CD20 treatment did not modulate EBV-specific T cell occurrence. In healthy individuals, EBV-specific CD8+ T cells were of an effector-memory phenotype in peripheral blood and cerebrospinal fluid. In MS patients, cerebrospinal fluid also contained EBV-specific central-memory CD8+ T cells, suggesting recent priming. Therefore, MS is not only preceded by EBV infection, but also associated with broader EBV-specific TCR repertoires, consistent with an ongoing anti-EBV immune reaction in MS., (© 2022 Schneider-Hohendorf et al.)
Published: 2022
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30. BEST-MS: A prospective head-to-head comparative study of natalizumab and fingolimod in active relapsing MS.

Author: Cohen M, Mondot L, Bucciarelli F, Pignolet B, Laplaud DA, Wiertlewski S, Brochet B, Ruet A, Defer G, Derache N, Vermersch P, Zephir H, Debouverie M, Mathey G, Berger E, Cappé C, Labauge P, Carra C, De Seze J, Bigaut K, Brassat D, and Lebrun-Frenay C
Subjects: Humans, Natalizumab therapeutic use, Neoplasm Recurrence, Local, Prospective Studies, Fingolimod Hydrochloride therapeutic use, Multiple Sclerosis
Abstract: Background: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS)., Objective: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing-remitting MS., Method: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity., Results: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group ( p = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p = 0.029)., Conclusion: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing-remitting MS. Our results suggest a superiority of NTZ over FTY.
Published: 2021
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31. Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study.

Author: Vukusic S, Ionescu I, Cornu C, Bossard N, Durand-Dubief F, Cotton F, Durelli L, Marignier R, Gignoux L, Laplaud DA, Moreau T, Clavelou P, De Seze J, Debouverie M, Brassat D, Pelletier J, Lebrun-Frenay C, Le Page E, Castelnovo G, Berger E, Hautecoeur P, Heinzlef O, Trojano M, Patti F, Baulieu EE, Remontet L, and El-Etr M
Subjects: Female, Humans, Megestrol, Norpregnadienes, Postpartum Period, Pregnancy, Recurrence, Estradiol, Multiple Sclerosis drug therapy
Abstract: Background: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy., Objective: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo., Methods: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo., Results: Recruitment was stopped prematurely due to slow inclusions ( n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58-1.39), placebo = 0.97 (0.63-1.50) ( p = 0.79))., Conclusion: POPARTMUS failed showing efficacy of a NOMAc-E2 combination in preventing post-partum relapses.
Published: 2021
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32. Identification of Umbre Orthobunyavirus as a Novel Zoonotic Virus Responsible for Lethal Encephalitis in 2 French Patients with Hypogammaglobulinemia.

Author: Pérot P, Bielle F, Bigot T, Foulongne V, Bolloré K, Chrétien D, Gil P, Gutiérrez S, L'Ambert G, Mokhtari K, Hellert J, Flamand M, Tamietti C, Coulpier M, Huard de Verneuil A, Temmam S, Couderc T, De Sousa Cunha E, Boluda S, Plu I, Delisle MB, Bonneville F, Brassat D, Fieschi C, Malphettes M, Duyckaerts C, Mathon B, Demeret S, Seilhean D, and Eloit M
Subjects: Animals, Europe, France epidemiology, Humans, Agammaglobulinemia, Encephalitis, Orthobunyavirus genetics, Viruses
Abstract: Background: Human encephalitis represents a medical challenge from a diagnostic and therapeutic point of view. We investigated the cause of 2 fatal cases of encephalitis of unknown origin in immunocompromised patients., Methods: Untargeted metatranscriptomics was applied on the brain tissue of 2 patients to search for pathogens (viruses, bacteria, fungi, or protozoans) without a prior hypothesis., Results: Umbre arbovirus, an orthobunyavirus never previously identified in humans, was found in 2 patients. In situ hybridization and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) showed that Umbre virus infected neurons and replicated at high titers. The virus was not detected in cerebrospinal fluid by RT-qPCR. Viral sequences related to Koongol virus, another orthobunyavirus close to Umbre virus, were found in Culex pipiens mosquitoes captured in the south of France where the patients had spent some time before the onset of symptoms, demonstrating the presence of the same clade of arboviruses in Europe and their potential public health impact. A serological survey conducted in the same area did not identify individuals positive for Umbre virus. The absence of seropositivity in the population may not reflect the actual risk of disease transmission in immunocompromised individuals., Conclusions: Umbre arbovirus can cause encephalitis in immunocompromised humans and is present in Europe., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Published: 2021
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33. Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity.

Author: Longbrake EE, Mao-Draayer Y, Cascione M, Zielinski T, Bame E, Brassat D, Chen C, Kapadia S, Mendoza JP, Miller C, Parks B, Xing D, and Robertson D
Subjects: Anti-Inflammatory Agents therapeutic use, Humans, Immunity, Humoral, Immunosuppressive Agents therapeutic use, Neoplasm Recurrence, Local, Prospective Studies, Dimethyl Fumarate therapeutic use, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract: Background: Delayed-release dimethyl fumarate (DMF) demonstrates sustained efficacy and safety for relapsing forms of MS. Absolute lymphocyte count (ALC) is reduced initially, then stabilizes on treatment., Objective: PROCLAIM, a 96-week, prospective, open-label, phase 3b study, assessed lymphocyte subsets and immunoglobulin (Ig) levels during 48 and 96 weeks (W) of DMF treatment., Methods: Patients received 240 mg DMF BID. Endpoints: lymphocyte subset count changes (primary); Ig isotypes and ALC changes (secondary); adverse events and relationship between ALC changes and ARR/EDSS (exploratory); and neurofilament assessment (ad hoc)., Results: Of 218 patients enrolled, 158 (72%) completed the study. Median ALC decreased 39% from baseline to W96 (BL-W96), stabilizing above the lower limit of normal (baseline: 1.82 × 10 9 /L; W48: 1.06 × 10 9 /L; W96: 1.05 × 10 9 /L). CD4 + and CD8 + T cells correlated highly with ALC from BL-W96 ( p < 0.001). Relative to total T cells, naive CD4 + and CD8 + T cells increased, whereas CD4 + and CD8 + central and effector memory T cells decreased. Total IgA, IgG, IgM, and IgG1-4 subclass levels remained stable. Adverse event rates were similar across ALC subgroups. ARR, EDSS, and neurofilament were not correlated with ALCs., Conclusion: Lymphocyte decreases with DMF were maintained over treatment, yet immunoglobulins remained stable. No increase in infection incidence was observed in patients with or without lymphopenia., Support: Biogen.
Published: 2021
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34. Serum Neurofilament Levels and PML Risk in Patients With Multiple Sclerosis Treated With Natalizumab.

Author: Fissolo N, Pignolet B, Rio J, Vermersch P, Ruet A, deSèze J, Labauge P, Vukusic S, Papeix C, Martinez-Almoyna L, Tourbah A, Clavelou P, Moreau T, Pelletier J, Lebrun-Frenay C, Bourre B, Defer G, Montalban X, Brassat D, and Comabella M
Subjects: Adult, Female, Follow-Up Studies, Humans, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting blood, Multiple Sclerosis, Relapsing-Remitting diagnosis, Multiple Sclerosis, Relapsing-Remitting drug therapy, Prognosis, Sensitivity and Specificity, Young Adult, Immunologic Factors administration & dosage, Leukoencephalopathy, Progressive Multifocal blood, Leukoencephalopathy, Progressive Multifocal diagnosis, Multiple Sclerosis blood, Multiple Sclerosis diagnosis, Multiple Sclerosis drug therapy, Natalizumab administration & dosage, Neurofilament Proteins blood
Abstract: Objectives: The study aimed to assess the potential for serum neurofilament light chain (NFL) levels to predict the risk of progressive multifocal leukoencephalopathy (PML) in natalizumab (NTZ)-treated patients with multiple sclerosis (MS) and to discriminate PML from MS relapses., Methods: NFL levels were measured with single molecule array (Simoa) in 4 cohorts: (1) a prospective cohort of patients with MS who developed PML under NTZ therapy (pre-PML) and non-PML NTZ-treated patients (NTZ-ctr); (2) a cohort of patients whose blood was collected during PML; (3) an independent cohort of non-PML NTZ-treated patients with serum NFL determinations at 2 years (replication cohort); and (4) a cohort of patients whose blood was collected during exacerbations., Results: Serum NFL levels were significantly increased after 2 years of NTZ treatment in pre-PML patients compared with NTZ-ctr. The prognostic performance of serum NFL levels to predict PML development at 2 years was similar in the NTZ-ctr group and replication cohort. Serum NFL levels also distinguished PML from MS relapses and were 8-fold higher during PML compared with relapses., Conclusions: These results support the use of serum NFL levels in clinical practice to identify patients with relapsing-remitting MS at higher PML risk and to differentiate PML from clinical relapses in NTZ-treated patients., Classification of Evidence: This study provides Class I evidence that serum NFL levels can identify NTZ-treated patients with MS who will develop PML with a sensitivity of 67% and specificity of 80%., (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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35. Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity.

Author: Ostkamp P, Salmen A, Pignolet B, Görlich D, Andlauer TFM, Schulte-Mecklenbeck A, Gonzalez-Escamilla G, Bucciarelli F, Gennero I, Breuer J, Antony G, Schneider-Hohendorf T, Mykicki N, Bayas A, Then Bergh F, Bittner S, Hartung HP, Friese MA, Linker RA, Luessi F, Lehmann-Horn K, Mühlau M, Paul F, Stangel M, Tackenberg B, Tumani H, Warnke C, Weber F, Wildemann B, Zettl UK, Ziemann U, Müller-Myhsok B, Kümpfel T, Klotz L, Meuth SG, Zipp F, Hemmer B, Hohlfeld R, Brassat D, Gold R, Gross CC, Lukas C, Groppa S, Loser K, Wiendl H, and Schwab N
Subjects: B-Lymphocytes radiation effects, Cohort Studies, Female, Genetic Variation, Genotype, Humans, Interferon-beta pharmacology, Interferon-beta therapeutic use, Male, Middle Aged, Monocytes metabolism, Multiple Sclerosis pathology, Multiple Sclerosis radiotherapy, Phenotype, Phototherapy, Recurrence, Severity of Illness Index, Sunlight, T-Lymphocytes metabolism, T-Lymphocytes radiation effects, Transcriptome genetics, Monocytes radiation effects, Multiple Sclerosis blood, Multiple Sclerosis immunology, Receptor, Melanocortin, Type 1 genetics, Transcriptome radiation effects, Vitamin D blood
Abstract: Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies ( n NationMS = 946, n BIONAT = 990). Additionally, effect-modification by medication and photosensitivity-associated MC1R variants was assessed. High serum vitD was associated with a reduced MS severity score (MSSS), reduced risk for relapses, and lower disability accumulation over time. Low latitude was associated with higher vitD, lower MSSS, fewer gadolinium-enhancing lesions, and lower disability accumulation. The association of latitude with disability was lacking in IFN-β-treated patients. In carriers of MC1R :rs1805008(T), who reported increased sensitivity toward sunlight, lower latitude was associated with higher MRI activity, whereas for noncarriers there was less MRI activity at lower latitudes. In a further exploratory approach, the effect of ultraviolet (UV)-phototherapy on the transcriptome of immune cells of MS patients was assessed using samples from an earlier study. Phototherapy induced a vitD and type I IFN signature that was most apparent in monocytes but that could also be detected in B and T cells. In summary, our study suggests beneficial effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD, and disease severity. However, sun exposure might be detrimental for photosensitive patients. Furthermore, a direct induction of type I IFNs through sun exposure could be another mechanism of UV-mediated immune-modulation in MS., Competing Interests: Competing interest statement: H.W. received honoraria and consultation fees from Bayer Healthcare, Biogen, Fresenius Medical Care, GlaxoSmithKline, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi Genzyme, and Teva Pharma. K.L. is coinventor on patent no. US 2016/0158322 A1 entitled “NDP-MSH for treatment of inflammatory and/or neurodegenerative disorders of the CNS.” A.S. received speaker honoraria and/or travel compensation for activities with Almirall Hermal GmbH, Biogen, Merck, Novartis, Roche and Sanofi Genzyme, none related to this work. R.G. serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd. (Teva), Biogen Idec, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen Idec, Teva, Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases, and is on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives research support from Teva, Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis, none related to this work. L.K. receives honoraria for lecturing and travel expenses for attending meetings from Biogen, Merck, Sanofi Genzyme, Novartis and Roche; her research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Interdisciplinary Center for Clinical Studies (IZKF) Muenster, Biogen, Merck, and Novartis. M.A.F. received honoraria for consultation and travel expenses from Biogen, Merck KGaA, Novartis, and Roche; his research is funded by the BMBF, DFG, Landesforschungsförderung Hamburg, Gemeinnützige Hertie-Stiftung, and Else Kröner-Fresenius-Stiftung. S.G.M. receives honoraria for lecturing, and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS, and Teva; his research is funded by the BMBF, DFG, Else Kröner Fresenius Foundation, German Academic Exchange Service, Hertie Foundation, IZKF Muenster, German Foundation Neurology and Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, ONO Pharma, Roche, and Teva. R.H. has received grant support from Biogen, Genzyme-Sanofi, Merck Serono, Novartis, Teva, and personal fees from Actelion, Biogen, Genzyme-Sanofi, Medday, Merck Serono, Novartis, Roche, and Teva. T.K. has received travel expenses and personal compensation from Bayer Healthcare, Teva Pharma, Merck, Novartis Pharma, Sanofi-Aventis/Genzyme, Roche, and Biogen, as well as grant support from Bayer Schering AG, Novartis, and Chugai Pharma. U.Z. has received grants from DFG, BMBF, the European Research Council, Bristol Myers Squibb, Janssen Pharmaceuticals NV, Servier, and Biogen Idec, and personal consultation fees from Pfizer GmbH, Bayer Vital GmbH, and CorTec GmbH. F.Z. received funds for scientific consultation or research by DFG, BMBF, the Pharmaceutical Management Science Association, Novartis, Octapharma, Merck Serono, ONO Pharma, Biogen, Genzyme, Celgene, Roche, Sanofi Aventis. A.S.-M. received travel expenses and research support from Novartis. C.C.G. received speaker honoraria and travel expenses for attending meetings from Biogen, Euroimmun, Genzyme, MyLan, Novartis Pharma GmbH, and Bayer Health Care, none related to this study; her work is funded by Biogen, Novartis, the BMBF (01Gl1603A), the DFG (GR3946/3-1, SFB Transregio 128 A09), the European Union (Horizon2020, ReSToRE), the IZKF, and the Innovative Medizinische Forschung. D.B. receives lectures, congress invitation, board participation with Bayer, Biogen, Medday, Merck, Novartis, Roche, Sanofi Genzyme, and Teva. B.T. received personal speaker honoraria and consultancy fees as a speaker and advisor from Alexion, Bayer Healthcare, Biogen, CSL Behring, GILEAD, GRIFOLS, Merck Serono, Novartis, Octapharma, Roche, Sanofi Genzyme, Teva, and UCB Pharma; his university received unrestricted research grants from Biogen-Idec, Novartis, Teva, Bayer Healthcare, CSL-Behring, GRIFOLS, Octapharma, Sanofi Genzyme, and UCB Pharma. F.T.B. has received, through his institution, grant support and/or travel reimbursement to attend scientific meetings from Actelion, Bayer, Biogen, Merck, Novartis, Sanofi Genzyme, and Teva; he has received personal honoraria for speaking or advisory board activities from Actelion, Bayer, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme; his research is funded, in part, by the DFG and the BMBF. C.W. has received institutional support from Novartis, Sanofi Genzyme, Biogen, and Roche. H.-P.H. has received fees for consulting, speaking, and serving on steering committees from Bayer Healthcare, Biogen, GeNeuro, MedImmune, Merck, Novartis, Opexa, Receptos Celgene, Roche, Sanofi Genzyme, CSL Behring, Octapharma, and Teva, with approval by the Rector of Heinrich-Heine University. H.T. received speaker honoraria from Bayer, Biogen, Fresenius, Genzyme, Merck, Novartis, Roche, Siemens, and Teva; he serves as section editor for the Journal of Neurology, Psychiatry, and Brain Research; H.T. and his institution receives research support from the BMBF, DMSG, Fresenius, Genzyme, Merck, and Novartis, none related to this work. A.B. has received personal compensation from Merck, Biogen, Bayer Vital, Novartis, Teva, Roche, Celgene, Alexion, and Sanofi Genzyme, and grants for congress trips and participation from Biogen, Teva, Novartis, Sanofi Genzyme, Celgene, and Merck, none related to this work. C.L. received an endowed professorship supported by the Novartis foundation, has received consulting and speaker’s honoraria from Biogen-Idec, Bayer Schering, Novartis, Sanofi Genzyme, and Teva; and has received research scientific grant support from Merck-Serono and Novartis. B.W. received research grants and/or honoria from Merck Serono, Biogen, Teva, Novartis, Sanofi Genzyme, Bayer Healthcare, Roche, and research grants from the Dietmar Hopp Foundation, the Klaus Tschira Foundation, the BMBF, and the DFG. U.K.Z. received honoraria for lecturing and/or travel expenses for attending meetings from Almirall, Alexion, Bayer, Biogen, Celgene, Merck Serono, Novartis, Octapharma, Roche, Sanofi Genzyme, and Teva, as well as grant support from the BMBF and European Union, none related to this study; his research is funded by the BMBF, German Ministry of Economy, DFG, and European Union. S.B. has received honoria and compensation for travel from Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, and Roche. M.S. has received honoraria for scientific lectures or consultancy from Alexion, Bayer Healthcare, Biogen, CSL Behring, Grifols, MedDay, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva; his institution received research support from Biogen, Sanofi-Genzyme, and Merck-Serono. R.A.L. received personal compensation from Celgene, Bayer Healthcare, Teva Pharma, Merck, Novartis Pharma, Sanofi-Aventis/Genzyme, Roche, and Biogen, as well as grant support from Novartis and Merck. F.W. served on the scientific advisory board of Genzyme, Merck Serono, and Novartis; he has received travel funding and/or speaker honoraria from Bayer, Biogen, Teva, Merck Serono, Novartis, and Pfizer; he is employed by Sana and received research support from the BMBF, Merck Serono, and Novartis. F.P. reported other support from Bayer, Novartis, Biogen-Idec, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, Roche, and Shire outside the submitted work; he has a post as academic editor for PLoS One and is associate editor for Neurology: Neuroimmunology & Neuroinflammation; he has scientific advisory board membership for Novartis and consulting fees from Sanofi Genzyme, Biogen-Idec, MedImmune, Shire, and Alexion; and research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, the German Research Council, Werth Stiftung, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy Jackson Charitable Foundation, and National Multiple Sclerosis of the United States. B.H. has served on scientific advisory boards for Novartis; he has served as data monitoring and safety committee member for AllergyCare and TG therapeutics; he or his institution have received speaker honoraria from Desitin; he holds part of two patents, one for the detection of antibodies against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon. All conflicts are not relevant to the topic of the study. F.L. has served on the advisory board of Roche and received travel funding from Teva. M.M. received research support from Merck Serono and Novartis as well as travel expenses for attending meetings from Merck Serono. K.L.-H. has received research support (to Technische Universität München) from Novartis, honoraria from Novartis and F. Hoffmann-La Roche, and compensation for travel expenses from Merck Serono., (Copyright © 2021 the Author(s). Published by PNAS.)
Published: 2021
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36. Author response: Prospective validation of the PML risk biomarker l-selectin and influence of natalizumab extended intervals.

Author: Schwab N, Schneider-Hohendorf T, Pignolet B, Brassat D, and Wiendl H
Subjects: Biomarkers, Humans, Immunologic Factors adverse effects, Natalizumab adverse effects, Prospective Studies, L-Selectin, Leukoencephalopathy, Progressive Multifocal chemically induced
Published: 2020
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37. What is the Relevance of the Systematic Use of Gadolinium During the MRI Follow-Up of Multiple Sclerosis Patients Under Natalizumab?

Author: Bellanger G, Biotti D, Patsoura S, Ciron J, Ferrier M, Gramada R, Meluchova Z, Lerebours F, Catalaa I, Dumas H, Cognard C, Brassat D, and Bonneville F
Subjects: Adult, Female, France, Humans, Male, Middle Aged, Retrospective Studies, Contrast Media administration & dosage, Gadolinium administration & dosage, Immunologic Factors therapeutic use, Magnetic Resonance Imaging, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis drug therapy, Natalizumab therapeutic use
Abstract: Background: Multiple sclerosis (MS) patients represent a population potentially affected by the intracerebral accumulation of gadolinium-based contrast agents (GBCA) due to repeated magnetic resonance imaging (MRI) performed during their lifetime; however, MRI is still the best tool to monitor MS inflammatory activity., Objective: This study aimed to evaluate the relevance of GBCA injections during the MRI follow-up of MS patients under natalizumab (Tysabri) treatment., Methods: The MRI data results were retrospectively reviewed in a monocentric study (University Hospital of Toulouse, France) from all consecutive patients treated with natalizumab from January 2014 to January 2017. For each examination during the whole MRI follow-up, new lesions (enhancing and non-enhancing) were analyzed., Results: A total of 129 patients were included in this study (65% female, mean age = 41 years, mean treatment duration 6.5 years, 50% positive for John Cunningham virus) and benefited from 735 MRIs with GBCA. Only 3 MRIs showed a new enhancing lesion, systematically encountered after treatment discontinuation., Conclusion: According to this study based on the clinical and radiological practice, the systematic use of GBCA seems of limited relevance in the MRI follow-up of asymptomatic patients treated continuously with natalizumab.
Published: 2020
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38. Frequency and characteristics of short versus longitudinally extensive myelitis in adults with MOG antibodies: A retrospective multicentric study.

Author: Ciron J, Cobo-Calvo A, Audoin B, Bourre B, Brassat D, Cohen M, Collongues N, Deschamps R, Durand-Dubief F, Laplaud D, Maillart E, Papeix C, Zephir H, Bereau M, Brochet B, Carra-Dallière C, Derache N, Gagou-Scherer C, Henry C, Kerschen P, Mathey G, Maubeuge N, Maurousset A, Montcuquet A, Moreau T, Prat C, Taithe F, Thouvenot E, Tourbah A, Rollot F, Vukusic S, and Marignier R
Subjects: Adult, Aged, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prognosis, Retrospective Studies, Young Adult, Autoantibodies, Disease Progression, Myelin-Oligodendrocyte Glycoprotein immunology, Myelitis diagnosis, Myelitis immunology, Myelitis pathology, Myelitis physiopathology, Registries, Severity of Illness Index
Abstract: Objectives: We aim to (1) determine the frequency and distinctive features of short myelitis (SM) and longitudinally extensive transverse myelitis (LETM) in a cohort of adults with myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated myelitis and (2) determine baseline prognostic factors among MOG-Ab-positive patients whose disease started with myelitis., Material and Methods: We retrospectively analyzed clinical and paraclinical variables from a multicentric French cohort of adults with MOG-Ab-associated myelitis. At last follow-up, patients were classified into two groups according to the severity of the Expanded Disability Status Scale (EDSS) as ⩽2.5 or ⩾3.0., Results: Seventy-three patients with at least one episode of myelitis over disease course were included; among them, 28 (38.4%) presented with SM at the time of the first myelitis. Motor and sphincter involvement was less frequently observed in SM (51.9% and 48.2%, respectively) than in LETM patients (83.3% and 78.6%, respectively), p = 0.007 and p = 0.017; 61% of LETM patients displayed brain lesions compared to 28.6% in the SM group, p = 0.008, and the thoracic segment was more frequently involved in the LETM (82.2%) than in the SM group (39.3%), p < 0.001. EDSS at last follow-up was higher in LETM (median 3.0 (interquartile range: 2.0-4.0)) compared to SM patients (2.0, (1.0-3.0)), p = 0.042. Finally, a higher EDSS at onset was identified as the only independent risk factor for EDSS ⩾3.0 (odds ratio, 1.40, 95% confidence interval (CI): 1.01-1.95, p = 0.046)., Conclusion: SM in MOG-Ab-associated disease is not rare. The severity at onset was the only independent factor related to the final prognosis in MOG-Ab-associated myelitis.
Published: 2020
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39. Progressive Multifocal Leukoencephalopathy Incidence and Risk Stratification Among Natalizumab Users in France.

Author: Vukusic S, Rollot F, Casey R, Pique J, Marignier R, Mathey G, Edan G, Brassat D, Ruet A, De Sèze J, Maillart E, Zéphir H, Labauge P, Derache N, Lebrun-Frenay C, Moreau T, Wiertlewski S, Berger E, Moisset X, Rico-Lamy A, Stankoff B, Bensa C, Thouvenot E, Heinzlef O, Al-Khedr A, Bourre B, Vaillant M, Cabre P, Montcuquet A, Wahab A, Camdessanché JP, Tourbah A, Guennoc AM, Hankiewicz K, Patry I, Nifle C, Maubeuge N, Labeyrie C, Vermersch P, and Laplaud DA
Subjects: Adolescent, Adult, Female, France epidemiology, Humans, Immunocompromised Host, Incidence, JC Virus, Leukoencephalopathy, Progressive Multifocal immunology, Leukoencephalopathy, Progressive Multifocal prevention & control, Male, Registries, Risk Factors, Young Adult, Immunologic Factors adverse effects, Leukoencephalopathy, Progressive Multifocal epidemiology, Multiple Sclerosis, Relapsing-Remitting drug therapy, Natalizumab adverse effects
Abstract: Importance: Risk of developing progressive multifocal leukoencephalopathy (PML) is the major barrier to using natalizumab for patients with multiple sclerosis (MS). To date, the association of risk stratification with PML incidence has not been evaluated., Objective: To describe the temporal evolution of PML incidence in France before and after introduction of risk minimization recommendations in 2013., Design, Setting, and Participants: This observational study used data in the MS registry OFSEP (Observatoire Français de la Sclérose en Plaques) collected between April 15, 2007, and December 31, 2016, by participating MS expert centers and MS-dedicated networks of neurologists in France. Patients with an MS diagnosis according to current criteria, regardless of age, were eligible, and those exposed to at least 1 natalizumab infusion (n = 6318) were included in the at-risk population. A questionnaire was sent to all centers, asking for a description of their practice regarding PML risk stratification. Data were analyzed in July 2018., Exposures: Time from the first natalizumab infusion to the occurrence of PML, natalizumab discontinuation plus 6 months, or the last clinical evaluation., Main Outcomes and Measures: Incidence was the number of PML cases reported relative to the person-years exposed to natalizumab. A Poisson regression model for the 2007 to 2016 period estimated the annual variation in incidence and incidence rate ratio (IRR), adjusted for sex and age at treatment initiation and stratified by period (2007-2013 and 2013-2016)., Results: In total, 6318 patients were exposed to natalizumab during the study period, of whom 4682 (74.1%) were female, with a mean (SD [range]) age at MS onset of 28.5 (9.1 [1.1-72.4]) years; 45 confirmed incident cases of PML were diagnosed in 22 414 person-years of exposure. The crude incidence rate for the whole 2007 to 2016 period was 2.00 (95% CI, 1.46-2.69) per 1000 patient-years. Incidence significantly increased by 45.3% (IRR, 1.45; 95% CI, 1.15-1.83; P = .001) each year before 2013 and decreased by 23.0% (IRR, 0.77; 95% CI, 0.61-0.97; P = .03) each year from 2013 to 2016., Conclusions and Relevance: The results of this study suggest, for the first time, a decrease in natalizumab-associated PML incidence since 2013 in France that may be associated with a generalized use of John Cunningham virus serologic test results; this finding appears to support the continuation and reinforcement of educational activities and risk-minimization strategies in the management of disease-modifying therapies for multiple sclerosis.
Published: 2020
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40. Prospective validation of the PML risk biomarker l-selectin and influence of natalizumab extended intervals.

Author: Schwab N, Schneider-Hohendorf T, Pignolet B, Bucciarelli F, Scandella L, Ciron J, Biotti D, Lebrun-Frenay C, Mathey G, Clavelou P, Pelletier J, Ostkamp P, Meinl I, Windhagen S, Klotz L, Gross CC, Meuth SG, Deisenhammer F, Brassat D, and Wiendl H
Subjects: Biomarkers blood, Cohort Studies, Drug Administration Schedule, Humans, Leukoencephalopathy, Progressive Multifocal diagnosis, Prospective Studies, Reproducibility of Results, Immunologic Factors therapeutic use, L-Selectin blood, Leukoencephalopathy, Progressive Multifocal blood, Leukoencephalopathy, Progressive Multifocal drug therapy, Natalizumab therapeutic use
Published: 2019
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41. MRI features of demyelinating disease associated with anti-MOG antibodies in adults.

Author: Denève M, Biotti D, Patsoura S, Ferrier M, Meluchova Z, Mahieu L, Heran F, Vignal C, Deschamps R, Gout O, Champfleur NM, Ayrignac X, Dallière CC, Labauge P, Dulau C, Tourdias T, Dumas H, Cognard C, Brassat D, and Bonneville F
Subjects: Adolescent, Adult, Autoantibodies, Brain diagnostic imaging, Brain pathology, Demyelinating Diseases immunology, Encephalitis diagnostic imaging, Encephalitis immunology, Encephalitis pathology, Female, Humans, Male, Myelin-Oligodendrocyte Glycoprotein immunology, Myelitis diagnostic imaging, Myelitis immunology, Myelitis pathology, Optic Nerve diagnostic imaging, Optic Nerve pathology, Optic Neuritis diagnostic imaging, Optic Neuritis immunology, Optic Neuritis pathology, Spinal Cord diagnostic imaging, Spinal Cord pathology, Young Adult, Demyelinating Diseases diagnostic imaging, Demyelinating Diseases pathology, Magnetic Resonance Imaging
Abstract: The spectrum of Myelin Oligodendrocytes Glycoprotein (MOG) antibody disease constitutes a recently described challenging entity, referring to a relatively new spectrum of autoimmune disorders with antibodies against MOG predominantly involving the optic nerve and spinal cord. The purpose of this article is to describe MRI features of MOG-AD involvement in the optic nerves, spinal cord and the brain of adults., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)
Published: 2019
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42. Comparative effectiveness of teriflunomide vs dimethyl fumarate in multiple sclerosis.

Author: Laplaud DA, Casey R, Barbin L, Debouverie M, De Sèze J, Brassat D, Wiertlewski S, Brochet B, Pelletier J, Vermersch P, Edan G, Lebrun-Frenay C, Clavelou P, Thouvenot E, Camdessanché JP, Tourbah A, Stankoff B, Al Khedr A, Cabre P, Lubetzki C, Papeix C, Berger E, Heinzlef O, Debroucker T, Moreau T, Gout O, Bourre B, Wahab A, Labauge P, Magy L, Defer G, Guennoc AM, Maubeuge N, Labeyrie C, Patry I, Nifle C, Casez O, Michel L, Rollot F, Leray E, Vukusic S, and Foucher Y
Subjects: Adult, Disease Progression, Female, Fingolimod Hydrochloride therapeutic use, Humans, Hydroxybutyrates, Male, Middle Aged, Nitriles, Recurrence, Treatment Outcome, Crotonates therapeutic use, Dimethyl Fumarate therapeutic use, Immunosuppressive Agents therapeutic use, Multiple Sclerosis drug therapy, Toluidines therapeutic use
Abstract: Objective: In this study, we compared the effectiveness of teriflunomide (TRF) and dimethyl fumarate (DMF) on both clinical and MRI outcomes in patients followed prospectively in the Observatoire Français de la Sclérose en Plaques., Methods: A total of 1,770 patients with relapsing-remitting multiple sclerosis (RRMS) (713 on TRF and 1,057 on DMF) with an available baseline brain MRI were included in intention to treat. The 1- and 2-year postinitiation outcomes were relapses, increase of T2 lesions, increase in Expanded Disability Status Scale score, and reason for treatment discontinuation. Propensity scores (inverse probability weighting) and logistic regressions were estimated., Results: The confounder-adjusted proportions of patients were similar in TRF- compared to DMF-treated patients for relapses and disability progression after 1 and 2 years. However, the adjusted proportion of patients with at least one new T2 lesion after 2 years was lower in DMF compared to TRF (60.8% vs 72.2%, odds ratio [OR] 0.60, p < 0.001). Analyses of reasons for treatment withdrawal showed that lack of effectiveness was reported for 8.5% of DMF-treated patients vs 14.5% of TRF-treated patients (OR 0.54, p < 0.001), while adverse events accounted for 16% of TRF-treated patients and 21% of DMF-treated patients after 2 years (OR 1.39, p < 0.001)., Conclusions: After 2 years of treatment, we found similar effectiveness of DMF and TRF in terms of clinical outcomes, but with better MRI-based outcomes for DMF-treated patients, resulting in a lower rate of treatment discontinuation due to lack of effectiveness., Classification of Evidence: This study provides Class III evidence that for patients with RRMS, TRF and DMF have similar clinical effectiveness after 2 years of treatment., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Published: 2019
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43. Focal and diffuse cervical spinal cord damage in patients with early relapsing-remitting MS: A multicentre magnetisation transfer ratio study.

Author: Combès B, Kerbrat A, Ferré JC, Callot V, Maranzano J, Badji A, Le Page E, Labauge P, Ayrignac X, Carra Dallière C, de Champfleur NM, Pelletier J, Maarouf A, de Seze J, Collongues N, Brassat D, Durand-Dubief F, Barillot C, Bannier E, and Edan G
Subjects: Adult, Cervical Cord diagnostic imaging, Female, Humans, Male, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging, Neuroimaging, Cervical Cord pathology, Magnetic Resonance Imaging methods, Multiple Sclerosis, Relapsing-Remitting pathology
Abstract: Background: Studies including patients with well-established multiple sclerosis (MS) have shown a significant and disability-related reduction in the cervical spinal cord (SC) magnetisation transfer ratio (MTR)., Objectives: The objectives are to (1) assess whether MTR reduction is already measurable in the SC of patients with early relapsing-remitting multiple sclerosis (RRMS) and (2) describe its spatial distribution., Methods: We included 60 patients with RRMS <12 months and 34 age-matched controls at five centres. Axial T2*w, sagittal T2w, sagittal phase-sensitive inversion recovery (PSIR), 3DT1w, and axial magnetisation transfer (MT) images were acquired from C1 to C7. Lesions were manually labelled and mean MTR values computed both for the whole SC and for normal-appearing SC in different regions of interest., Results: Mean whole SC MTR was significantly lower in patients than controls (33.7 vs 34.9 pu, p = 0.00005), even after excluding lesions (33.9 pu, p = 0.0003). We observed a greater mean reduction in MTR for vertebral levels displaying the highest lesion loads (C2-C4). In the axial plane, we observed a greater mean MTR reduction at the SC periphery and barycentre., Conclusion: Cervical SC tissue damage measured using MTR is not restricted to macroscopic lesions in patients with early RRMS and is not homogeneously distributed.
Published: 2019
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44. Paraneoplastic neuromyelitis optica and ovarian teratoma: A case series.

Author: Bernard-Valnet R, Cobo-Calvo A, Siegfried A, Marasescu R, Bonnan M, Ballan G, Ellie E, Bauer J, Uro-Coste E, Marignier R, and Brassat D
Subjects: Adolescent, Adult, Aquaporin 4 metabolism, Female, Humans, Neuromyelitis Optica diagnosis, Neuromyelitis Optica metabolism, Ovarian Neoplasms diagnosis, Ovarian Neoplasms metabolism, Teratoma diagnosis, Teratoma metabolism, Young Adult, Neuromyelitis Optica complications, Neuromyelitis Optica pathology, Ovarian Neoplasms complications, Ovarian Neoplasms pathology, Teratoma complications, Teratoma pathology
Abstract: Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory disease of the central nervous system, characterized by the presence of auto-antibodies directed against aquaporin-4 (AQP4) expressed on astrocyte end-feet. Despite NMOSD does not primarily belong to the spectrum of paraneoplastic neurological syndromes, rare cases of association with neoplasia have been outlined. Here, we report the association of NMOSD with ovarian teratoma in 3 cases. Pathological analysis of teratomas revealed glial component strongly expressing AQP4 and closely localized to immune infiltrates. Our series highlight the rare association of teratoma with NMOSD and the possible paraneoplastic mechanism., (Copyright © 2019. Published by Elsevier B.V.)
Published: 2019
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45. Efficacy of rituximab in refractory RRMS.

Author: Durozard P, Maarouf A, Boutiere C, Ruet A, Brochet B, Vukusic S, Carra-Dalliere C, Labauge P, Mathey G, Debouverie M, Papeix C, Maillart E, Lubetzki C, Bensa C, Gout O, Giannesini C, Stankoff B, Ciron J, Brassat D, Pelletier J, Rico Lamy A, and Audoin B
Subjects: Adult, Female, Humans, Immunologic Factors administration & dosage, Male, Middle Aged, Retrospective Studies, Rituximab administration & dosage, Young Adult, Disease Progression, Immunologic Factors pharmacology, Multiple Sclerosis, Relapsing-Remitting drug therapy, Outcome Assessment, Health Care, Rituximab pharmacology
Abstract: Objective: To investigate the efficacy of rituximab as rescue therapy in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent disease activity confirmed by magnetic resonance imaging (MRI) despite immunosuppressive disease-modifying therapy (DMT)., Methods: In this observational nationwide retrospective multicenter study, we first identified 351 off-label rituximab-treated patients through a cohort of 15,984 RRMS patients. In this group, we identified patients with disease activity prior to rituximab confirmed by MRI (one or more new T2 lesion and/or gadolinium-enhancing lesion) despite immunosuppressive DMT (fingolimod, natalizumab, or mitoxantrone) with a follow-up after rituximab initiation longer than 6 months. Outcome data were collected from the French Observatory of Multiple Sclerosis (OFSEP) register and medical charts., Results: A total of 50 patients were identified. Median rituximab treatment duration was 1.1 (0.5-6.4) year. Mean annualized relapse rate significantly decreased from 0.8 during last immunosuppressive DMT to 0.18 after rituximab ( p < 0.0001). While 72% of patients showed gadolinium-enhancing lesions on the last MRI performed during last immunosuppressive DMT, 8% of them showed gadolinium-enhancing lesions on the first MRI performed 6.1 (range 1.4-18.4) months after rituximab ( p < 0.0001)., Conclusion: This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT.
Published: 2019
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46. Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects.

Author: Klotz L, Eschborn M, Lindner M, Liebmann M, Herold M, Janoschka C, Torres Garrido B, Schulte-Mecklenbeck A, Gross CC, Breuer J, Hundehege P, Posevitz V, Pignolet B, Nebel G, Glander S, Freise N, Austermann J, Wirth T, Campbell GR, Schneider-Hohendorf T, Eveslage M, Brassat D, Schwab N, Loser K, Roth J, Busch KB, Stoll M, Mahad DJ, Meuth SG, Turner T, Bar-Or A, and Wiendl H
Subjects: Aerobiosis drug effects, Animals, Cell Proliferation drug effects, Cell Respiration drug effects, Crotonates pharmacology, Dihydroorotate Dehydrogenase, Electron Transport Complex III metabolism, Energy Metabolism drug effects, Gene Expression Regulation drug effects, Glycolysis drug effects, Humans, Hydroxybutyrates, Lymphocyte Activation drug effects, Lymphocyte Subsets drug effects, Lymphocyte Subsets immunology, Mitochondria drug effects, Multiple Sclerosis genetics, Multiple Sclerosis pathology, Multiple Sclerosis, Relapsing-Remitting immunology, Nitriles, Oxidative Phosphorylation drug effects, Oxidoreductases Acting on CH-CH Group Donors antagonists & inhibitors, Oxidoreductases Acting on CH-CH Group Donors metabolism, Receptors, Antigen, T-Cell metabolism, T-Lymphocytes drug effects, Toluidines pharmacology, Crotonates therapeutic use, Mitochondria metabolism, Multiple Sclerosis drug therapy, Multiple Sclerosis immunology, T-Lymphocytes immunology, Toluidines therapeutic use
Abstract: Interference with immune cell proliferation represents a successful treatment strategy in T cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis (MS). One prominent example is pharmacological inhibition of dihydroorotate dehydrogenase (DHODH), which mediates de novo pyrimidine synthesis in actively proliferating T and B lymphocytes. Within the TERIDYNAMIC clinical study, we observed that the DHODH inhibitor teriflunomide caused selective changes in T cell subset composition and T cell receptor repertoire diversity in patients with relapsing-remitting MS (RRMS). In a preclinical antigen-specific setup, DHODH inhibition preferentially suppressed the proliferation of high-affinity T cells. Mechanistically, DHODH inhibition interferes with oxidative phosphorylation (OXPHOS) and aerobic glycolysis in activated T cells via functional inhibition of complex III of the respiratory chain. The affinity-dependent effects of DHODH inhibition were closely linked to differences in T cell metabolism. High-affinity T cells preferentially use OXPHOS during early activation, which explains their increased susceptibility toward DHODH inhibition. In a mouse model of MS, DHODH inhibitory treatment resulted in preferential inhibition of high-affinity autoreactive T cell clones. Compared to T cells from healthy controls, T cells from patients with RRMS exhibited increased OXPHOS and glycolysis, which were reduced with teriflunomide treatment. Together, these data point to a mechanism of action where DHODH inhibition corrects metabolic disturbances in T cells, which primarily affects profoundly metabolically active high-affinity T cell clones. Hence, DHODH inhibition may promote recovery of an altered T cell receptor repertoire in autoimmunity., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Published: 2019
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47. Neuraxial analgesia is not associated with an increased risk of post-partum relapses in MS.

Author: Lavie C, Rollot F, Durand-Dubief F, Marignier R, Ionescu I, Casey R, Moreau T, Tourniaire P, Hutchinson M, D'Hooghe MB, Laplaud DA, Clavelou P, De Sèze J, Debouverie M, Brassat D, Pelletier J, Lebrun-Frenay C, Le Page E, Castelnovo G, Berger E, Hautecoeur P, Heinzlef O, Durelli L, Clerico M, Trojano M, Patti F, and Vukusic S
Subjects: Adult, Female, Follow-Up Studies, Humans, Postpartum Period, Pregnancy, Recurrence, Retrospective Studies, Anesthesia, Conduction adverse effects, Multiple Sclerosis chemically induced, Multiple Sclerosis physiopathology, Pregnancy Complications chemically induced, Pregnancy Complications physiopathology
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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48. Single-arm study to assess comprehensive infusion guidance for the prevention and management of the infusion associated reactions (IARs) in relapsing-remitting multiple sclerosis (RRMS) patients treated with alemtuzumab (EMERALD).

Author: Vukusic S, Brassat D, de Seze J, Izquierdo G, Lysandropoulos A, Moll W, Vanopdenbosch L, Arque MJ, Kertous M, Rufi P, and Oreja-Guevara C
Subjects: Adult, Alemtuzumab administration & dosage, Anti-Inflammatory Agents administration & dosage, Antibodies, Monoclonal, Humanized administration & dosage, Antipyretics pharmacology, Drug Therapy, Combination, Female, Histamine Antagonists pharmacology, Humans, Immunologic Factors administration & dosage, Incidence, Male, Methylprednisolone administration & dosage, Middle Aged, Proton Pump Inhibitors pharmacology, Alemtuzumab adverse effects, Anti-Inflammatory Agents pharmacology, Antibodies, Monoclonal, Humanized adverse effects, Drug-Related Side Effects and Adverse Reactions drug therapy, Drug-Related Side Effects and Adverse Reactions epidemiology, Drug-Related Side Effects and Adverse Reactions etiology, Drug-Related Side Effects and Adverse Reactions prevention & control, Exanthema chemically induced, Exanthema drug therapy, Exanthema epidemiology, Exanthema prevention & control, Immunologic Factors adverse effects, Infusions, Intravenous adverse effects, Methylprednisolone pharmacology, Multiple Sclerosis, Relapsing-Remitting drug therapy, Outcome Assessment, Health Care
Abstract: Background: Alemtuzumab is a humanized IgG monoclonal antibody approved in more than 60 countries for patients with relapsing remitting multiple sclerosis (RRMS). In phase 2 and 3 clinical trials (CAMMS223 (NCT00050778), CARE-MS I (NCT00530348), and CARE-MS II (NCT00548405)), patients receiving alemtuzumab demonstrated significantly greater improvements on clinical and MRI outcomes versus SC IFNβ-1a; mild to moderate infusion-associated reactions (IARs) were the most frequently reported adverse events (AEs) associated with alemtuzumab. EMERALD (NCT02205489) was a phase 4, multicenter, multinational, single-arm study designed to assess an algorithm for the prevention and management of IARs in RRMS patients treated with alemtuzumab., Methods: Patients were treated with a study regimen of enhanced IAR prophylaxis relative to phase 2 and 3 studies. H 1 and/or H 2 antagonists or equivalent gastroprotection (proton pump inhibitors) were given 1 day before alemtuzumab infusion, 1 h prior to the infusion, and post-infusion. Methylprednisolone was given orally 1 day before infusion, 1 h prior to the infusion, and as needed post-infusion. Antipyretics were given 1 h before infusion and as needed post-infusion. Anti-emetics and normal saline were given as needed during and post-infusion., Results: Of the 61 patients screened, 58 (95.1%) were enrolled into the study. Of the 58 patients who received the first infusion of Period 1, 57 (98.3%) completed the 5 days of Course 1. A total of 54 patients received the first infusion of Period 2 and 53 completed the 3-day course. All patients (n = 58) completed the Month 6 visit and 54 the Month 12 visit. 93.1% of patients had at least one IAR (91.4% in Period 1 and 81.5% in Period 2), the majority of which were grade 1 (69.1%) or grade 2 (28.0%). The three most common IARs of headache, pyrexia, and rash occurred in 48.8%, 40.7%, and 24.1% of patients during the first course and 14.8%, 17.2%, and 5.6% of patients during the second course, respectively. The majority of IARs occurred within 6 h after the start of alemtuzumab infusion, with a peak during the first 2 h. The types and overall incidence of IARs were consistent with phase 2 and 3 trials. Frequency and distribution of rash were reduced in the EMERALD study compared with previous clinical trials. Serious IARs occurred in 15.5%, a higher rate than reported in clinical trials of alemtuzumab., Conclusion: Although most alemtuzumab-treated patients experienced IARs as in previous controlled clinical studies, there was an improvement in the frequency and distribution of alemtuzumab-associated rash, which may have been associated with this study's prophylaxis regimen., (Copyright © 2019 Elsevier B.V. All rights reserved.)
Published: 2019
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49. Oligoclonal bands increase the specificity of MRI criteria to predict multiple sclerosis in children with radiologically isolated syndrome.

Author: Makhani N, Lebrun C, Siva A, Narula S, Wassmer E, Brassat D, Brenton JN, Cabre P, Carra Dallière C, de Seze J, Durand Dubief F, Inglese M, Langille M, Mathey G, Neuteboom RF, Pelletier J, Pohl D, Reich DS, Ignacio Rojas J, Shabanova V, Shapiro ED, Stone RT, Tenembaum S, Tintoré M, Uygunoglu U, Vargas W, Venkateswaren S, Vermersch P, Kantarci O, Okuda DT, and Pelletier D
Abstract: Background: Steps towards the development of diagnostic criteria are needed for children with the radiologically isolated syndrome to identify children at risk of clinical demyelination., Objectives: To evaluate the 2005 and 2016 MAGNIMS magnetic resonance imaging criteria for dissemination in space for multiple sclerosis, both alone and with oligoclonal bands in cerebrospinal fluid added, as predictors of a first clinical event consistent with central nervous system demyelination in children with radiologically isolated syndrome., Methods: We analysed an international historical cohort of 61 children with radiologically isolated syndrome (≤18 years), defined using the 2010 magnetic resonance imaging dissemination in space criteria (Ped-RIS) who were followed longitudinally (mean 4.2 ± 4.7 years). All index scans also met the 2017 magnetic resonance imaging dissemination in space criteria., Results: Diagnostic indices (95% confidence intervals) for the 2005 dissemination in space criteria, with and without oligoclonal bands, were: sensitivity 66.7% (38.4-88.2%) versus 72.7% (49.8-89.3%); specificity 83.3% (58.6-96.4%) versus 53.9% (37.2-69.9%). For the 2016 MAGNIMS dissemination in space criteria diagnostic indices were: sensitivity 76.5% (50.1-93.2%) versus 100% (84.6-100%); specificity 72.7% (49.8-89.3%) versus 25.6% (13.0-42.1%)., Conclusions: Oligoclonal bands increased the specificity of magnetic resonance imaging criteria in children with Ped-RIS. Clinicians should consider testing cerebrospinal fluid to improve diagnostic certainty. There is rationale to include cerebrospinal fluid analysis for biomarkers including oligoclonal bands in planned prospective studies to develop optimal diagnostic criteria for radiologically isolated syndrome in children.
Published: 2019
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50. First clinical inflammatory demyelinating events of the central nervous system in a population aged over 70 years: A multicentre study.

Author: Lavandier N, Bonnan M, Carra-Dallière C, Charif M, Labauge P, Camdessanche JP, Edan G, Naudin A, Brassat D, Ciron J, Clavelou P, Dulau C, Moroso A, Brochet B, and Ouallet JC
Subjects: Age of Onset, Aged, Aged, 80 and over, Brain diagnostic imaging, Central Nervous System Diseases diagnosis, Central Nervous System Diseases therapy, Demyelinating Diseases diagnosis, Demyelinating Diseases therapy, Female, Follow-Up Studies, Humans, Inflammation diagnosis, Inflammation epidemiology, Inflammation therapy, Male, Retrospective Studies, Spinal Cord diagnostic imaging, Central Nervous System Diseases epidemiology, Demyelinating Diseases epidemiology
Abstract: Background: Few data are available regarding patients with very late-onset inflammatory demyelinating events. (VLO-IDE)., Objectives: The aim of this study was to describe the clinical, biological, and radiological characteristics and aetiological diagnosis of very late first inflammatory demyelinating events of the central nervous system., Methods: We conducted a national descriptive retrospective multicentre study on a case series of patients aged >70 years at the time of VLO-IDE. Patients were recruited from a national call on behalf of the 'Société Francophone de la Sclérose en Plaques' (French Multiple Sclerosis Society)., Results: Twenty-five patients were referred (F:M sex ratio 2.1:1). The most frequent clinical impairment was a spinal cord deficit (23/25), usually severe (disability score, median EDSS 4.5 [2-9.5]). Spinal cord lesions were usually extensive, spanning at least three segments (11/25), and large brain lesions were also observed (lesions >20 mm in 6/25). The final aetiological diagnoses comprised multiple sclerosis (9/25), neuromyelitis optica spectrum disorders (7/25), neurosystemic lupus erythematosus (2/25), transverse myelitis without aetiological diagnosis (6/25) and optic neuritis (1/25)., Conclusions: This study highlights a particular phenotype of first clinical inflammatory demyelinating events in predominantly female patients aged >70 years who have severe motor impairment with common longitudinal extensive myelitis and large and common very active radiological inflammatory lesions. Neuromyelitis optica spectrum disorders seem overrepresented., (Copyright © 2018 Elsevier B.V. All rights reserved.)
Published: 2019
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