Author: "Michel Clanet" - Searchworks@Jio Institute Digital Library Search Results

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1. MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis

Author: Antonio Uccelli, Alice Laroni, Lou Brundin, Michel Clanet, Oscar Fernandez, Seyed Massood Nabavi, Paolo A. Muraro, Roberto S. Oliveri, Ernst W. Radue, Johann Sellner, Per Soelberg Sorensen, Maria Pia Sormani, Jens Thomas Wuerfel, Mario A. Battaglia, Mark S. Freedman, and on behalf of the MESEMS study group
Subjects: Multiple sclerosis, Mesenchymal stem cells, Mesenchymal stromal cells, Clinical trial, Medicine (General), R5-920
Abstract: Abstract Background Multiple sclerosis (MS) is an inflammatory disease of the central nervous system with a degenerative component, leading to irreversible disability. Mesenchymal stem cells (MSC) have been shown to prevent inflammation and neurodegeneration in animal models of MS, but no large phase II clinical trials have yet assessed the exploratory efficacy of MSC for MS. Methods/design This is an academic, investigator-initiated, randomized, double-blind, placebo-compared phase I/II clinical trial with autologous, bone-marrow derived MSC in MS. Enrolled subjects will receive autologous MSC at either baseline or at week 24, through a cross-over design. Primary co-objectives are to test safety and efficacy of MSC treatment compared to placebo at 6 months. Secondary objectives will evaluate the efficacy of MSC at clinical and MRI levels. In order to overcome funding constraints, the MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study has been designed to merge partially independent clinical trials, following harmonized protocols and sharing some key centralized procedures, including data collection and analyses. Discussion Results will provide patients and the scientific community with data on the safety and efficacy of MSC for MS. The innovative approach utilized to obtain funds to support the MESEMS trial could represent a new model to circumvent limitation of funds encountered by academic trials. Trial registration Andalusia: NCT01745783, registered on Dec 10, 2012. Badalona: NCT02035514 EudraCT, 2010–024081–21. Registered on 2012. Canada: ClinicalTrials.gov, NCT02239393. Registered on September 12, 2014. Copenhagen: EudraCT, 2012–000518-13. Registered on June 21, 2012. Italy: EudraCT, 2011–001295-19, and ClinicalTrials.gov, NCT01854957. Retrospectively registered on May 16, 2013. London: Eudra CT 2012–002357-35, and ClinicalTrials.gov, NCT01606215. Registered on May 25, 2012. Salzburg: EudraCT, 2015–000137-78. Registered on September 15, 2015. Stockholm: ClinicalTrials.gov, NCT01730547. Registered on November 21, 2012. Toulouse: ClinicalTrials.gov, NCT02403947. Registered on March 31, 2015.
Published: 2019
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2. Geographical Heterogeneity of Multiple Sclerosis Prevalence in France.

Author: Diane Pivot, Marc Debouverie, Michel Grzebyk, David Brassat, Michel Clanet, Pierre Clavelou, Christian Confavreux, Gilles Edan, Emmanuelle Leray, Thibault Moreau, Sandra Vukusic, Guy Hédelin, and Francis Guillemin
Subjects: Medicine, Science
Abstract: INTRODUCTION:Geographical variation in the prevalence of multiple sclerosis (MS) is controversial. Heterogeneity is important to acknowledge to adapt the provision of care within the healthcare system. We aimed to investigate differences in prevalence of MS in departments in the French territory. METHODS:We estimated MS prevalence on October 31, 2004 in 21 administrative departments in France (22% of the metropolitan departments) by using multiple data sources: the main French health insurance systems, neurologist networks devoted to MS and the Technical Information Agency of Hospitalization. We used a spatial Bayesian approach based on estimating the number of MS cases from 2005 and 2008 capture-recapture studies to analyze differences in prevalence. RESULTS:The age- and sex-standardized prevalence of MS per 100,000 inhabitants ranged from 68.1 (95% credible interval 54.6, 84.4) in Hautes-Pyrénées (southwest France) to 296.5 (258.8, 338.9) in Moselle (northeast France). The greatest prevalence was in the northeast departments, and the other departments showed great variability. DISCUSSION:By combining multiple data sources into a spatial Bayesian model, we found heterogeneity in MS prevalence among the 21 departments of France, some with higher prevalence than anticipated from previous publications. No clear explanation related to health insurance coverage and hospital facilities can be advanced. Population migration, socioeconomic status of the population studied and environmental effects are suspected.
Published: 2016
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3. Excess Mortality in Patients with Multiple Sclerosis Starts at 20 Years from Clinical Onset: Data from a Large-Scale French Observational Study.

Author: Emmanuelle Leray, Sandra Vukusic, Marc Debouverie, Michel Clanet, Bruno Brochet, Jérôme de Sèze, Hélène Zéphir, Gilles Defer, Christine Lebrun-Frenay, Thibault Moreau, Pierre Clavelou, Jean Pelletier, Eric Berger, Philippe Cabre, Jean-Philippe Camdessanché, Shoshannah Kalson-Ray, Christian Confavreux, and Gilles Edan
Subjects: Medicine, Science
Abstract: Recent studies in multiple sclerosis (MS) showed longer survival times from clinical onset than older hospital-based series. However estimated median time ranges widely, from 24 to 45 years, which makes huge difference for patients as this neurological disease mainly starts around age 20 to 40. Precise and up-to-date reference data about mortality in MS are crucial for patients and neurologists, but unavailable yet in France.Estimate survival in MS patients and compare mortality with that of the French general population.We conducted a multicenter observational study involving clinical longitudinal data from 30,413 eligible patients, linked to the national deaths register. Inclusion criteria were definite MS diagnosis and clinical onset prior to January, 1st 2009 in order to get a minimum of 1-year disease duration.After removing between-center duplicates and applying inclusion criteria, the final population comprised 27,603 MS patients (F/M sex ratio 2.5, mean age at onset 33.0 years, 85.5% relapsing onset). During the follow-up period (mean 15.2 +/- 10.3 years), 1569 deaths (5.7%) were identified; half related to MS. Death rates were significantly higher in men, patients with later clinical onset, and in progressive MS. Overall excess mortality compared with the general population was moderate (Standardized Mortality Ratio 1.48, 95% confidence interval [1.41-1.55]), but increased considerably after 20 years of disease (2.20 [2.10-2.31]).This study revealed a moderate decrease in life expectancy in MS patients, and showed that the risk of dying is strongly correlated to disease duration and disability, highlighting the need for early actions that can slow disability progression.
Published: 2015
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4. A case report of simultaneous PML-IRIS during corticosteroids tapering in a patient with an anti-synthetase syndrome [v1; ref status: indexed, http://f1000r.es/2l6]

Author: Guillaume Martin-Blondel, David Brassat, Hervé Dumas, Emmanuelle Uro-Coste, Daniel Adoue, Hans Lassmann, and Michel Clanet
Subjects: Clinical Immunology, Medicine, Science
Abstract: We report a case of simultaneous progressive multifocal leukoencephalopathy-associated immune reconstitution inflammatory syndrome (PML-IRIS) during corticosteroid tapering in a patient with an anti-synthetase syndrome. We describe the challenges associated with the diagnosis and the management of this emerging inflammatory neurological condition in this immunocompromised patient with a severe rheumatic disease. We highlight that, in the setting of IRIS, the low-level of the JC virus viral load requires a sensitive PCR assay before excluding PML.
Published: 2013
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5. Safety, tolerability, and activity of mesenchymal stem cells versus placebo in multiple sclerosis (MESEMS): a phase 2, randomised, double-blind crossover trial

Author: Antonio Uccelli, Alice Laroni, Rehiana Ali, Mario Alberto Battaglia, Morten Blinkenberg, Lou Brundin, Michel Clanet, Oscar Fernandez, James Marriott, Paolo Muraro, Seyed Massood Nabavi, Roberto S Oliveri, Ernst Radue, Cristina Ramo Tello, Irene Schiavetti, Johann Sellner, Per Soelberg Sorensen, Maria Pia Sormani, Jens Thomas Wuerfel, Mark S Freedman, Naser Aghdami, Eduardo Agüera-Morales, David Allan, Leila Arab, Mario Battaglia, Isabelle Berry, Bruno Bonetti, Chiara Capelli, Lucio Castellan, Maria Cellerino, Maria Teresa Cencioni, Giancarlo Comi, David Courtman, Francesco Dazzi, Anne Fischer-Nielsen, Victoria Fernandez, Mark S. Freedman, Roberto Furlan, Mario Gimona, Francesca Gualandi, Qingdong Guan, Ellen Iacobaeus, Matilde Inglese, Martino Introna, Guillermo Izquierdo, Shahedeh Karimi, Katarina Le Blanc, Sandra Loaiza, Shahrukh Mallik, Stephen Marley, Ruth Ann Marrie, James Marriot, Gianvito Martino, David Miller, Paolo A. Muraro, Richard Nicholas, Giovanni Orengo, Renuka Palanicawande, Matteo Pardini, Ernst W Radue, Carolina Rush, Luc Sensebe, Dirk Strunk, David Szwajcer, and Claire Thalamas
Subjects: Adult, medicine.medical_specialty, Multiple Sclerosis, Adolescent, Placebo, Young Adult, Double-Blind Method, Internal medicine, Clinical endpoint, Humans, Medicine, Adverse effect, Cross-Over Studies, Expanded Disability Status Scale, business.industry, Surrogate endpoint, Multiple sclerosis, Brain, Mesenchymal Stem Cells, Middle Aged, medicine.disease, Crossover study, Malformations of Cortical Development, Tolerability, Neurology (clinical), business
Abstract: Summary Background Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, have been proposed as a promising therapeutic option for people with multiple sclerosis on the basis of their immunomodulatory and neuroprotective properties. The MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study was devised to evaluate the safety, tolerability, and activity of autologous MSCs derived from bone marrow and infused intravenously in patients with active multiple sclerosis. Methods MESEMS is a randomised phase 2 trial done at 15 sites in nine countries. Patients (aged 18–50 years) with active relapsing-remitting or progressive multiple sclerosis were included if they had a disease duration of 2–15 years since onset of multiple sclerosis and an Expanded Disability Status Scale score of 2·5–6·5. Patients were randomly assigned (1:1), according to a crossover design, to receive a single intravenous dose of autologous bone marrow-derived MSCs followed by placebo at week 24, or to receive placebo followed by autologous MSCs at week 24, with a follow-up visit at week 48. Primary objectives were to test safety and activity of MSC treatment. The primary safety endpoint was to assess the number and severity of adverse events within each treatment arm. The primary efficacy endpoint was the number of gadolinium-enhancing lesions (GELs) counted over week 4, 12, and 24 compared between treatment groups. The primary efficacy endpoint was assessed in the full analyis set, after all participants completed the week 24 visit. Efficacy endpoints were evaluated using a predefined statistical testing procedure. Safety was monitored throughout the study by recording vital signs and adverse events at each visit. Findings From July 16, 2012, until July 31, 2019, 144 patients were randomly assigned to first receive early intravenous infusion of autologous bone marrow-derived MSCs (n=69) or placebo (n=75). MSC treatment did not meet the primary endpoint of efficacy on the total number of GELs accumulated from baseline to week 24 (rate ratio [RR] 0·94, 95% CI 0·58–1·50; p=0·78). 213 adverse events were recorded, similarly distributed between groups (93 cases recorded in 35 [51%] of 69 patients treated first with MSCs vs 120 cases in 42 [56%] of 75 patients infused first with placebo). The most frequent adverse events reported were infection and infestations, with a total of 54 (25%) of 213 adverse events (18 [19%] of 93 in the early-MSC group and 36 [30%] of 120 in the delayed-MSC group). Nine serious adverse events were reported in seven patients treated with placebo versus none in the MSC group. All serious adverse events were considered to be unrelated to the treatment infusion. No deaths were reported during the study. Interpretation Bone marrow-derived MSC treatment was safe and well tolerated but did not show an effect on GELs, an MRI surrogate marker of acute inflammation, in patients with active forms of multiple sclerosis, at week 24. Thus, this study does not support the use of bone marrow-derived MSCs to treat active multiple sclerosis. Further studies should address the effect of MSCs on parameters related to tissue repair. Funding Fondazione Italiana Sclerosi Multipla (FISM), the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), and the Multiple Sclerosis International Federation (MSIF) for centralised activities. Individual trials participating in the MESEMS network are funded by the following agencies: FISM and Compagnia di San Paolo (Italy); The Danish Multiple Sclerosis Society, The Toyota Foundation, and Danish Blood Donors’ Research Foundation (Denmark); the Spanish Health Research Institute Carlos 3 and the Andalusian Public Foundation Progreso y Salud (Spain); the Royan Institute for Stem Cell Biology and Technology (Iran); the Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, and Salzburg (Austria); the Fondation pour l’aide a la recherche sur la sclerose en plaques (ARSEP), French Muscular Dystrophy Association (AFM)-Telethon (France); the UK Multiple Sclerosis Society and the UK Stem Cell Foundation (UK); and the Multiple Sclerosis Society of Canada and The Multiple Sclerosis Scientific Research Foundation and Research Manitoba (Canada).
Published: 2021
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6. Basket clinical trial design for targeted therapies for cancer: a French National Authority for Health statement for health technology assessment

Author: Sylvie Chevret, Pierre Cochat, François Gueyffier, Antoine Vanier, Etienne Lengliné, Françoise Degos, Michel Clanet, Serge Kouzan, Hugues Blondon, Mathilde Grande, Patrick Dufour, Jade Putzolu, Julien Peron, and Bernard Guillot
Subjects: Clinical Trials as Topic, medicine.medical_specialty, Multiple tumours, Technology Assessment, Biomedical, business.industry, Clinical study design, Health technology, Cancer, Antineoplastic Agents, medicine.disease, Transparency (behavior), National authority, Clinical trial, Government Agencies, Treatment Outcome, Oncology, Research Design, Neoplasms, Family medicine, medicine, Humans, France, Molecular Targeted Therapy, business, Reimbursement
Abstract: Summary During the past decade, health technology assessment bodies have faced new challenges in establishing the benefits of new drugs for individuals and health-care systems. A topic of increasing importance to the field of oncology is the so-called agnostic regulatory approval of targeted therapies for cancer (independent of tumour location and histology) granted on the basis of basket trials. Basket trials in oncology offer the advantage of simultaneously evaluating treatments for multiple tumours, even rare cancers, in a single clinical trial. To address the novel challenges introduced by these trials, an interdisciplinary panel was convened on behalf of the Transparency Committee of the French National Authority for Health to clarify an approach designed to guarantee a transparent, reproducible, and fair assessment of histology-agnostic treatments for reimbursement by the French National Health Insurance Fund. The requirements of this approach include the need for randomisation, clinically relevant endpoints, appropriate correction for multiple significance testing, characterisation of subgroup heterogeneity, and validation of underlying biomarker assays. A prospectively designated external control is encouraged when the implementation of a direct comparison is deemed infeasible. We also underline the importance of recording outcomes from basket trials in a registry for use as future external controls.
Published: 2021
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7. Aquaporin 4 distribution in the brain and its relevance for the radiological appearance of neuromyelitis optica spectrum disease

Author: Roxana Ameli, Charles R.G. Guttmann, Juan Carlos Prieto, Fabien Rollot, Miklos Palotai, Sandra Vukusic, Romain Marignier, François Cotton, René Anxionnat, Jean-Paul Armspach, Bertrand Audoin, Christian Barillot, Isabelle Berry, Fabrice Bonneville, Claire Boutet, Giovanni Castelnovo, Frédéric Cervenanski, Mikael Cohen, Olivier Commowick, Jerome De Seze, Vincent Dousset, Francoise Durand-Dubief, Gilles Edan, Jean-Christophe Ferre, Damien Galanaud, Tristan Glattard, Sylvie Grand, Justine Guillaumont, Rémy Guillevin, Salem Hannoun, Fabrice Heitz, Alexandre Krainik, Stéphane Kremer, Pierre Labauge, Nicolas Menjot De Champfleur, Jean-Philippe Ranjeva, Jean-Amédée Roch, Dominique Sappey-Marinier, Julien Savatovsky, Bruno Stankoff, Ayman Tourbah, Thomas Tourdias, Bruno Brochet, Michel Clanet, Nathalie Dufay, David Laplaud, Marie-Claire Maze, Thibault Moreau, Cédric Trolliet, Bernard Frangoulis, Javier Olaiz, Jean Pelletier, Bertrand Bourre, David Brassat, Philippe Cabre, Jean-Philippe Camdessanche, William Camu, Olivier Casez, Pierre Clavelou, Nicolas Collongues, Alain Creange, Gilles Defer, Marc Debouverie, Olivier Gout, Christine Lebrun-Frenay, Catherine Lubetzki, Caroline Papeix, Patrick Vermersch, Hélène Zephir, Service de Radiologie [Hôpital Femme Mère Enfant - HCL], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Department of Radiology [Boston], Brigham and Women's Hospital [Boston], Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Service de Neurologie [Lyon], CHU Lyon, 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), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-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), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Neuroimagerie: méthodes et applications (Empenn), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Service de Médecine Nucléaire - Pierre-Paul Riquet [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Radiologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Strasbourg, Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neuroradiologie [Grenoble], CHU Grenoble, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Institut d’Imagerie Fonctionnelle Humaine [CHU Montpellier] (I2FH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital privé Jean Mermoz [Lyon], CHU Rothschild [AP-HP], CHU Tenon [AP-HP], Université de Reims Champagne-Ardenne (URCA), Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Neurologie Vasculaire [Toulouse], Service de neurochirurgie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Fondation Eugène Devic EDMUS, Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hôpital Albert Clarac [CHU de la Martinique], CHU de la Martinique [Fort de France], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut de Biologie Computationnelle (IBC), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de neurologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital de Hautepierre [Strasbourg], Département de neurosciences (CHU Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-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), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Empenn, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Service de Médecine Nucléaire [Toulouse], CHU Toulouse [Toulouse], Pôle neurosciences [Hôpital de Purpan - Toulouse], Service de radiologie [Saint-Etienne], CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Service de neurochirurgie [Nantes], Hôpital Nord (Saint Etienne), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Male, Pathology, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Myelitis, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Clinical significance, Retrospective Studies, Aquaporin 4, Neuromyelitis optica, Radiological and Ultrasound Technology, business.industry, Incidence (epidemiology), Neuromyelitis Optica, Brain, Human brain, Middle Aged, medicine.disease, Spinal cord, Magnetic Resonance Imaging, medicine.anatomical_structure, Cohort, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: International audience; Background and purposeTo determine the precise incidence of lesions at sites of high Aquaporin-4 expression (hAQP4) and their possible association with known neuromyelitis optica spectrum disease (NMOSD) lesions patterns.Materials and methodsA retrospective analysis of brain and, when available, spinal cord MRI scans of 54 NMOSD patients recruited among the French NMOSD cohort was performed. Brain lesions were annotated as MS-like, non-specific, or evocative of NMOSD. The topography of hAQP4 was reassessed by human brain atlas. The incidence of lesions in hAQP4 and their association with lesions evocative of NMOSD was estimated.ResultsAmong those included (41/54 female, mean age: 45 years) 47/54 (87%) presented brain lesions. Twenty-six/47 (55%) had lesions in hAQP4. Thirty-two/54 patients (60%) had lesions considered evocative of NMOSD. The majority of them also presented lesions in hAQP4 (65%, 21/32). Patients with lesions in hAQP4 and lesions evocative of NMOSD demonstrated more extensive myelitis compared to the other patients (7 [6–10] versus 4 [3–5] vertebral segments, P = 0.009).ConclusionThe coexistence of lesions evocative of NMOSD and in hAQP4 is associated with significantly more extensive myelitis, and might have pathophysiological and clinical significance.
Published: 2021
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8. A case report of simultaneous PML-IRIS during corticosteroids tapering in a patient with an anti-synthetase syndrome [version 1; referees: 2 approved, 1 approved with reservations]

Author: Guillaume Martin-Blondel, David Brassat, Hervé Dumas, Emmanuelle Uro-Coste, Daniel Adoue, Hans Lassmann, and Michel Clanet
Subjects: Case Report, Articles, Clinical Immunology, JC virus, Progressive multifocal leukoencephalopathy, Immune reconstitution inflammatory syndrome, Antisynthetase syndrome, Corticosteroids.
Abstract: We report a case of simultaneous progressive multifocal leukoencephalopathy-associated immune reconstitution inflammatory syndrome (PML-IRIS) during corticosteroid tapering in a patient with an anti-synthetase syndrome. We describe the challenges associated with the diagnosis and the management of this emerging inflammatory neurological condition in this immunocompromised patient with a severe rheumatic disease. We highlight that, in the setting of IRIS, the low-level of the JC virus viral load requires a sensitive PCR assay before excluding PML.
Published: 2013
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9. Association of Central Hypersomnia and Fatigue in Patients With Multiple Sclerosis: A Polysomnographic Study

Author: Bruno Stankoff, Michel Tiberge, Rana Assouad, Michel Clanet, Isabelle Arnulf, Catherine Lubetzki, Sophie Tezenas du Montcel, Caroline Papeix, Frédérique Viala, and Anne-Laure Dubessy
Subjects: Adult, Male, medicine.medical_specialty, Aging, Multiple Sclerosis, medicine.medical_treatment, Polysomnography, Rest, Sleep, REM, Disorders of Excessive Somnolence, Bed rest, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Cognition, Sleep Apnea Syndromes, Interquartile range, Internal medicine, Restless Legs Syndrome, Outpatients, medicine, Humans, Effects of sleep deprivation on cognitive performance, Depression (differential diagnoses), Fatigue, medicine.diagnostic_test, business.industry, Depression, Multiple sclerosis, Sleep apnea, 030229 sport sciences, Middle Aged, Sleep Latency, medicine.disease, Female, Neurology (clinical), Sleep Stages, business, 030217 neurology & neurosurgery, Psychomotor Performance, Narcolepsy
Abstract: ObjectiveTo evaluate sleepiness and central hypersomnia in multiple sclerosis (MS)–associated fatigue, we performed long-term polysomnography in patients with MS and healthy controls.MethodsPatients with MS and healthy controls completed questionnaires on sleep, fatigue, sleepiness, and depression. They underwent nocturnal polysomnography, multiple sleep latency tests, and bed rest 24-hour polysomnography. Patients were divided into 3 groups (fatigue and sleepiness, fatigue and no sleepiness, neither fatigue nor sleepiness).ResultsAmong 44 patients with MS, 19 (43.2%) had fatigue and sleepiness, 15 (34%) had only fatigue, and 10 (22.7%) had neither fatigue nor sleepiness. Compared to 24 controls, patients with fatigue and sleepiness had higher REM sleep percentages (median [interquartile range] 20.5% [19.6–24.7] vs 18.1% [12.6–20.6]), lower arousal indexes (12.7 [7.5–17.0] vs 22.4 [14.3–34.4]), and shorter daytime mean sleep latencies (8.6 [6.3–14.3] vs 16.6 [12.6–19.5] min). Restless leg syndrome, periodic leg movements, and sleep apnea had similar frequencies between groups. Central hypersomnia was found in 10 (53%) patients with fatigue and sleepiness (narcolepsy type 2, n = 2), in 2 (13%) patients with fatigue only, and in 3 (30%) patients with neither fatigue nor sleepiness. Patients with central hypersomnia were younger and sleepier than those without hypersomnia, but had similar levels of fatigue, disability, depression, cognitive performance, and frequencies of the human leukocyte antigen DQB1*0602 genotype. The severity of fatigue increased with higher depression scores, higher sleepiness severity, and lower sleep efficacy.ConclusionCentral hypersomnias are frequent in MS when fatigue and sleepiness are present. Screening them through polysomnography studies is recommended.
Published: 2020

10. Observatoire Français de la Sclérose en Plaques (OFSEP): A unique multimodal nationwide MS registry in France

Author: Romain Casey, David-Axel Laplaud, Fabien Rollot, François Cotton, Bertrand Fontaine, Thibault Moreau, Jérôme De Seze, Bruno Stankoff, Francis Guillemin, Michel Clanet, Bruno Brochet, Sandra Vukusic, Jean Pelletier, Marc Debouverie, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], 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), Université de Lyon, Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut François Magendie, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre 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 [Strasbourg], CHU Strasbourg-Hopital Civil, RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CIC 1433 Epidémiologie clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherche en Myologie, and Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Databases, Factual, registry, Multiple sclerosis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Humans, Registries, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, database, business.industry, Middle Aged, medicine.disease, University hospital, 3. Good health, Neurology, quality, Female, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Neurology (clinical), Medical emergency, business, 030217 neurology & neurosurgery
Abstract: The care of multiple sclerosis (MS) in France is based on two complementary interlinked networks: MS expert centers in university hospitals and regional networks of neurologists. The routine use of European database for multiple sclerosis (EDMUS) in all those centers has paved the way for the constitution of a national registry, designated as Observatoire Français de la Sclérose En Plaques (OFSEP). It promotes a prospective, standardized, high-quality, and multimodal collection of data. On June 2018, there were 68.097 files, with 71.1% females, representing 761,185 person-years. This huge database is open to the scientific community and might contribute exploring unresolved issues and unmet needs in MS.
Published: 2018
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11. Préface. Une approche éthique des maladies neuro-évolutives

Author: Michel Clanet
Published: 2019
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12. Assessment of a program to encourage the multidisciplinary management of urinary disorders in multiple sclerosis

Author: Evelyne Castel-Lacanal, Xavier Gamé, Michel Clanet, Xavier de Boissezon, Pascal Rischmann, David Brassat, and Philippe Marque
Subjects: Pediatrics, medicine.medical_specialty, business.industry, Urology, Multiple sclerosis, Urinary system, 030232 urology & nephrology, Urination disorder, Retrospective cohort study, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, medicine, Neurology (clinical), Urinary Complication, Disease management (health), Medical prescription, Young adult, business, 030217 neurology & neurosurgery
Abstract: Aims Urinary disorders (UD) secondary to multiple sclerosis (MS) are common and can be responsible for complications. Since 2004, we organized in our region their management through a neuro-urological activity and a care network that established and distributed an algorithm for screening and first line care. The objective was to assess the effects of this organization on the management of UD and its impact for patients. Methods Between January 2004 and December 2009, 328 patients were seen in neuro-urological consultation. The data of a group of 168 patients consulting during the deployment of our organization (before January 2007: group 1) were compared to those of 160 patients taken when the organization was well established (from January 2007: group 2). In parallel, the modification of the prescription rate of the first-line examination patients was evaluated. Results The two groups were significantly different concerning age, duration of MS, EDSS score (Group 1 vs. Group 2 respectively 51.6 ± 12.6 vs. 48 ± 11.8 years, P = 0.008; 19 ± 9.7 vs. 13.8 ± 10.5 years, P
Published: 2016
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13. Late-onset neutropenia and neurological relapse, during long-term rituximab therapy in myelin oligodendrocyte glycoprotein-antibody spectrum disorder

Author: Fleur Lerebours, Fabrice Bonneville, Michel Clanet, David Brassat, Damien Biotti, and Jonathan Ciron
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Neutropenia, Autoantigens, Myelin oligodendrocyte glycoprotein, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, immune system diseases, Recurrence, medicine, Humans, Immunologic Factors, Spectrum disorder, Autoantibodies, 030203 arthritis & rheumatology, biology, business.industry, Multiple sclerosis, Neuromyelitis Optica, Middle Aged, medicine.disease, Neurology, chemistry, Absolute neutrophil count, biology.protein, Rituximab, Female, Myelin-Oligodendrocyte Glycoprotein, Neurology (clinical), Complication, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Late-onset neutropenia after rituximab therapy (LONART) is defined as a fall in the absolute neutrophil count below 500/mm3 at least 3 weeks after rituximab infusion, in the absence of any other explanation. LONART is rare during dysimmune conditions but can be life-threatening. We report on two patients with LONART and associated neurological relapse occurring in myelin oligodendrocyte glycoprotein (MOG)-antibody spectrum disorders. Rituximab was reintroduced in one patient, while the second patient was switched to tocilizumab. LONART can occur during anti-MOG spectrum disorders. Neurologists should be aware of this rare and treatable complication. Regular monitoring of blood cell counts is needed, and patients should be informed of the need to consult their physician if symptoms of infection appear.
Published: 2018

14. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis

Author: Ludwig Kappos, Roland S. Liblau, Krzysztof Selmaj, Giancarlo Comi, Per Soelberg Sørensen, Bernhard Hemmer, Elena Marcus, David Miller, Michel Clanet, Dhia Chandraratna, Eva Havrdova, Frauke Zipp, Tomas Olsson, Ralf Gold, Aksel Siva, Heinz Wiendl, Christoph Thalheim, Maria Pia Sormani, Maria Pia Amato, Xavier Montalban, Franz Fazekas, Catherine Lubetzki, Tobias Derfuss, Alan J. Thompson, Hans-Peter Hartung, Stephen Pilling, Susana Otero-Romero, Montalban, X., Gold, R., Thompson, A. J., Otero-Romero, S., Amato, M. P., Chandraratna, D., Clanet, M., Comi, G., Derfuss, T., Fazekas, F., Hartung, H. P., Havrdova, E., Hemmer, B., Kappos, L., Liblau, R., Lubetzki, C., Marcus, E., Miller, D. H., Olsson, T., Pilling, S., Selmaj, K., Siva, A., Sorensen, P. S., Sormani, M. P., Thalheim, C., Wiendl, H., and Zipp, F.
Subjects: medicine.medical_specialty, Consensus, Multiple Sclerosis, demyelinating, Complex disease, disease-modifying therapies, GRADE methodology, guideline, Multiple sclerosis, Neurology, Neurology (clinical), Outcome (game theory), Pharmacological treatment, Immunomodulation, 03 medical and health sciences, 0302 clinical medicine, Intervention (counseling), GRADE methodology, Agency (sociology), Nominal group technique, medicine, Immunologic Factors, Relevance (law), Humans, 030212 general & internal medicine, neurological disorder, disease-modifying therapies, Intensive care medicine, Societies, Medical, disease, Evidence-Based Medicine, business.industry, Multiple sclerosis, disease-modifying treatment, Guideline, medicine.disease, research method, Europe, Neurology, multiple sclerosi, Family medicine, Practice Guidelines as Topic, Neurology (clinical), business, guideline, 030217 neurology & neurosurgery
Abstract: Background and purpose: Multiple sclerosis (MS) is a complex disease of the central nervous system. As new drugs are becoming available, knowledge on diagnosis and treatment must continuously evolve. There is therefore a need for a reference tool compiling current data on benefit and safety, to aid professionals in treatment decisions and use of resources across Europe. The European Committee of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have joined forces to meet this need. The objective was to develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS to guide healthcare professionals in the decision-making process. Methods: This guideline has been developed using the GRADE methodology and following the recently updated EAN recommendations for guideline development. Clinical questions were formulated in PICO format (patient, intervention, comparator, outcome) and outcomes were prioritized according to their relevance to clinical practice. An exhaustive literature search up to December 2016 was performed for each question and the evidence is presented narratively and, when possible, combined in a meta-analysis using a random-effects model. The quality of evidence for each outcome was rated into four categories – very high, high, low and very low − according to the risk of bias. GRADE evidence profiles were created using GRADEprofiler (GRADEpro) software (Version 3.6). The recommendations with assigned strength (strong, weak) were formulated based on the quality of evidence and the risk−benefit balance. Consensus between the panellists was reached by use of the modified nominal group technique. Results: A total of 10 questions have been agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency at the time of publication. A total of 20 recommendations were agreed by the guideline working group members after three rounds of consensus.
Published: 2017

15. [Towards a national strategy on the diagnosis of neurocognitive disorders. A shared approach among the French National College of General Practitioners and specialists of neurocognitive disorders]

Author: Pierre, Krolak-Salmon, Laurent, Letrilliart, Mathieu, Ceccaldi, Sandrine, Andrieu, Olivier, Guérin, Bruno, Dubois, Bruno, Brochet, Pierre, Vandel, Claude, Jeandel, Armelle, Leperre-Desplanques, Michel, Clanet, and Pierre-Louis, Druais
Subjects: Aged, 80 and over, Neurologic Examination, Health Policy, Mental Disorders, General Practice, Neurocognitive Disorders, Neuroimaging, Mental Status and Dementia Tests, Diagnosis, Differential, Activities of Daily Living, Humans, Medicine, Dementia, Interdisciplinary Communication, France, Algorithms, Biomarkers, Societies, Medical
Abstract: Neurocognitive disorders leading to progressive cognitive, functional and behavioural impairment are often undiagnosed or diagnosed lately. But tailored care and therapeutics help in implementing secondary and tertiary prevention dynamics aiming at preserving quality of life and delaying, anticipating or preventing behavioural crisis and severe stages of dementia. Moreover, the diagnosis of numerous diseases induces specific care and therapeutics, as well access to research and clinical trials. For the first time, the representatives of the National College of General Practitioners, the French Federation of Memory Centres, the French Federation of Gerontology and Geriatrics, the French Federation of Neurology, the French Society of Psychogeriatrics and the national plan on neurodegenerative diseases propose a graduated and tailored diagnosis strategy involving primary care and specialists of neurocognitive disorders. This strategy has been built in the context of the national plan on neurodegenerative diseases, the European Joint Action "Act on dementia", and has been consensually agreed after a seminar animated by the National College of General Practitioners in March 2017.
Published: 2017

16. Cervical dysplasia in a patient with multiple sclerosis treated with natalizumab

Author: Michel Clanet, Quentin Dardonville, Geneviève Durrieu, and Jean-Louis Montastruc
Subjects: Pharmacology, medicine.medical_specialty, business.industry, Multiple sclerosis, HPV infection, medicine.disease, 030226 pharmacology & pharmacy, Dermatology, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Dysplasia, medicine, Pharmacology (medical), In patient, business, 030217 neurology & neurosurgery, Adverse drug reaction, medicine.drug
Abstract: We describe one report of a cervical dysplasia in a patient receiving natalizumab for multiple sclerosis. Other cases were identified in the WHO's global individual case safety report database, VigiBase® . These data underline the importance of monitoring HPV infection in patients with MS treated with natalizumab.
Published: 2018
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17. Urinary complications and risk factors in symptomatic multiple sclerosis patients. Study of a cohort of 328 patients

Author: David Gasq, Xavier Gamé, Michel Clanet, Julien Guillotreau, Philippe Marque, Frédérique Viala, Evelyne Castel-Lacanal, V. Bourg, Pascal Rischmann, and Xavier de Boissezon
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, Urology, Urinary system, Renal function, Retrospective cohort study, Urine, Surgery, Cystography, Internal medicine, Epidemiology, Cohort, medicine, Neurology (clinical), Urinary Complication, business
Abstract: Aims Lower urinary tract dysfunctions (LUTD) are very common in Multiple Sclerosis (MS), have a significant social impact, while the organic impact is discussed. We studied urinary complications and their risk factors in our cohort of MS patients, in order to improve the management of LUTD in MS. Methods Between 2004 and 2009, all patients affected by MS and managed for LUTD were included in a retrospective study. We studied the epidemiological data (age, gender), the clinical data (duration of MS, EDSS score, progression of MS) and the paraclinical data (urinary creatinine clearance, urine culture, urinary tract ultrasonography and in some cases urodynamic assessment and cystography). We then identified the urinary complications and their risk factors. Results Three hundred twenty eight patients, mean age 49.9 ± 12.3 years, with a MS for 14.3 ± 10 years on average and with a median EDSS score equal to 6 (1–9), were managed for LUTD. One hundred seventy eight (54%) patients developed one or more urinary complications. We identified duration of MS greater than 8.5 years and an EDSS above 7 as risk factors. Conclusion Urinary complications are common in symptomatic MS, these results imply screening and specialized care to limit the impact on the quality of life but also to prevent urinary complications. Neurourol. Urodynam. 34:32–36, 2015. © 2013 Wiley Periodicals, Inc.
Published: 2013
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18. A prospective observational post-marketing study of natalizumab-treated multiple sclerosis patients: clinical, radiological and biological features and adverse events. The BIONAT cohort

Author: Giovanni Castelnovo, Patrick Vermersch, B. Fontaine, William Camu, Audrey Rico, Nathalie Derache, Catherine Lubetzki, Marc Debouverie, Nicolas Couturier, Agnès Fromont, Eric Berger, Pierre Labauge, Bruno Brochet, Jean-Christophe Ouallet, C. Papeix, Eric Thouvenot, N Bohossian, Mikael Cohen, Thibault Moreau, Hélène Zéphir, Gilles-Louis Defer, David Brassat, David-Axel Laplaud, Christine Lebrun-Frenay, Olivier Outteryck, Pierre Clavelou, Cfsep, Ayman Tourbah, J. de Seze, Philippe Cabre, Patrick Hautecoeur, Jean Pelletier, Lucien Rumbach, Olivier Casez, Michel Clanet, Sophie Pittion, Jean-Claude Ongagna, and Sandrine Wiertlewski
Subjects: Adult, Male, medicine.medical_specialty, Antibodies, Monoclonal, Humanized, Cohort Studies, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, Internal medicine, parasitic diseases, Product Surveillance, Postmarketing, medicine, Humans, Prospective Studies, Adverse effect, business.industry, Progressive multifocal leukoencephalopathy, Multiple sclerosis, medicine.disease, Surgery, Neurology, Radiological weapon, Cohort, Biomarker (medicine), Female, Observational study, Neurology (clinical), business, medicine.drug
Abstract: Background and purpose BIONAT is a French multicentric phase IV study of natalizumab (NTZ)-treated relapsing−remitting multiple sclerosis (MS) patients. The purpose of this study was to collect clinical, radiological and biological data on 1204 patients starting NTZ, and to evaluate the clinical/radiological response to NTZ after 2 years of treatment. Methods Patients starting NTZ at 18 French MS centres since June 2007 were included. Good response to NTZ was defined by the absence of clinical and radiological activity. Data analysed in this first report on the BIONAT study focus on patients who started NTZ at least 2 years ago (n = 793; BIONAT2Y). Results NTZ was discontinued in 17.78% of BIONAT2Y. The proportion of patients without combined disease activity was 45.59% during the first two successive years of treatment. Systematic dosage of anti-NTZantibodies (Abs) detected only two supplementary patients with anti-NTZ Abs compared with strict application of recommendations. A significant decrease of IgG,M concentrations at 2 years of treatment was found. Conclusions The efficacy of NTZ therapy on relapsing−remitting MS in a real life setting is confirmed in the BIONAT cohort. The next step will be the identification of biomarkers predicting response to NTZ therapy and adverse events.
Published: 2013
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19. Geographical Heterogeneity of Multiple Sclerosis Prevalence in France

Author: Guy Hédelin, Sandra Vukusic, Emmanuelle Leray, David Brassat, Christian Confavreux, Michel Clanet, Thibault Moreau, Michel Grzebyk, Gilles Edan, Diane Pivot, Marc Debouverie, Francis Guillemin, Pierre Clavelou, Service d'Evaluation et Information Médicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de neurologie [CHRU Nancy], Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut national de recherche et de sécurité (Vandoeuvre lès Nancy) (INRS ( Vandoeuvre lès Nancy)), Neurologie vasculaire, pathologie neuro-dégénérative et explorations fonctionnelles du système nerveux [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Neurologie [Hospices civils de Lyon - Hôpital Pierre Wertheimer], Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), This work has been realized with the help of the Observatoire FrancËais de la ScleÂrose en Plaques (OFSEP), which is supported by a grant provided by the French State and handled by the 'Agence Nationale de la Recherche,' within the framework of the 'Investments for the Future' programme, under the reference ANR-10-COHO-002, and the Eugène Devic EDMUS Foundation against multiple sclerosis., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Commowick, Olivier, Cohortes - Observatoire Français de la Sclérose en Plaques - - OFSEP2010 - ANR-10-COHO-0002 - COHO - VALID, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut national de recherche et de sécurité (Vandoeuvre lès Nancy) ( INRS ( Vandoeuvre lès Nancy) ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Hospices Civils de Lyon ( HCL ) -Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon ( HCL ), Vision, Action et Gestion d'informations en Santé ( VisAGeS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE ( IRISA-D5 ), Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Service de Neurologie [Rennes], Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Département Méthodes quantitatives en santé publique ( METIS ), École des Hautes Études en Santé Publique [EHESP] ( EHESP ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CIC-Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), ANR-10-COHO-002-01/10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques ( 2010 ), Université Toulouse III - Paul Sabatier (UT3), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), and Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Pediatrics, Cross-sectional study, Economics, Social Sciences, lcsh:Medicine, Geographical Locations, 0302 clinical medicine, Geoinformatics, Credible interval, Medicine and Health Sciences, Prevalence, 030212 general & internal medicine, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, lcsh:Science, education.field_of_study, Multidisciplinary, Latitude, Geography, Age Factors, Neurodegenerative Diseases, Spatial Autocorrelation, humanities, 3. Good health, Hospitalization, Europe, Political Geography, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.IB]Life Sciences [q-bio]/Bioengineering, France, Research Article, Cartography, medicine.medical_specialty, Computer and Information Sciences, Multiple Sclerosis, Neural Networks, Political Science, Population, Immunology, MEDLINE, Autoimmune Diseases, 03 medical and health sciences, Sex Factors, Health Economics, Health insurance, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], education, Socioeconomic status, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, Multiple sclerosis, lcsh:R, Biology and Life Sciences, Bayes Theorem, medicine.disease, Metropolitan area, Demyelinating Disorders, Health Care, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], People and Places, Earth Sciences, Clinical Immunology, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Clinical Medicine, business, 030217 neurology & neurosurgery, Demography, Health Insurance, Neuroscience
Abstract: International audience; INTRODUCTION:Geographical variation in the prevalence of multiple sclerosis (MS) is controversial. Heterogeneity is important to acknowledge to adapt the provision of care within the healthcare system. We aimed to investigate differences in prevalence of MS in departments in the French territory.METHODS:We estimated MS prevalence on October 31, 2004 in 21 administrative departments in France (22% of the metropolitan departments) by using multiple data sources: the main French health insurance systems, neurologist networks devoted to MS and the Technical Information Agency of Hospitalization. We used a spatial Bayesian approach based on estimating the number of MS cases from 2005 and 2008 capture-recapture studies to analyze differences in prevalence.RESULTS:The age- and sex-standardized prevalence of MS per 100,000 inhabitants ranged from 68.1 (95% credible interval 54.6, 84.4) in Hautes-Pyrénées (southwest France) to 296.5 (258.8, 338.9) in Moselle (northeast France). The greatest prevalence was in the northeast departments, and the other departments showed great variability.DISCUSSION:By combining multiple data sources into a spatial Bayesian model, we found heterogeneity in MS prevalence among the 21 departments of France, some with higher prevalence than anticipated from previous publications. No clear explanation related to health insurance coverage and hospital facilities can be advanced. Population migration, socioeconomic status of the population studied and environmental effects are suspected.
Published: 2016
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20. A role for VAV1 in experimental autoimmune encephalomyelitis and multiple sclerosis

Author: Audrey Casemayou, Anu Kemppinen, Lucille Lamouroux, Pentti J. Tienari, Gilbert J. Fournié, Ingrid Dahlman, Ingrid Kockum, Olivier Papapietro, Rita Nohra, Lars Klareskog, Gilles Edan, George C. Ebers, Annette Bang Oturai, Louise K. Sjöholm, Dominique Lagrange, Michel Clanet, Mohsen Khademi, Anne Spurkland, Céline Colacios, Frida Lundmark, Leonid Padyukov, Helle Bach Soendergaard, Christine Duthoit, Abdelhadi Saoudi, Amennai Daniel Beyeen, Isabelle Bernard, Tomas Olsson, Anne Dejean, Dessa Sadovnick, Maja Jagodic, Maria Seddighzadeh, Jan Hillert, Janna Saarela, Bertrand Fontaine, Hanne F. Harbo, Sreeram V. Ramagopalan, and Lars Alfredsson
Subjects: CD4-Positive T-Lymphocytes, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, Tumor Necrosis Factor-alpha, Multiple sclerosis, Central nervous system, Experimental autoimmune encephalomyelitis, Haplotype, Quantitative Trait Loci, Congenic, Genome-wide association study, General Medicine, Odds ratio, Biology, medicine.disease, Polymorphism, Single Nucleotide, Proinflammatory cytokine, Rats, Interferon-gamma, medicine.anatomical_structure, Immunology, medicine, Animals, Proto-Oncogene Proteins c-vav
Abstract: Multiple sclerosis, the most common cause of progressive neurological disability in young adults, is a chronic inflammatory disease. There is solid evidence for a genetic influence in multiple sclerosis, and deciphering the causative genes could reveal key pathways influencing the disease. A genome region on rat chromosome 9 regulates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Using interval-specific congenic rat lines and association of single-nucleotide polymorphisms with inflammatory phenotypes, we localized the gene of influence to Vav1 , which codes for a signal-transducing protein in leukocytes. Analysis of seven human cohorts (12,735 individuals) demonstrated an association of rs2546133-rs2617822 haplotypes in the first VAV1 intron with multiple sclerosis (CA: odds ratio, 1.18; CG: odds ratio, 0.86; TG: odds ratio, 0.90). The risk CA haplotype also predisposed for higher VAV1 messenger RNA expression. VAV1 expression was increased in individuals with multiple sclerosis and correlated with tumor necrosis factor and interferon-γ expression in peripheral blood and cerebrospinal fluid cells. We conclude that VAV1 plays a central role in controlling central nervous system immune-mediated disease and proinflammatory cytokine production critical for disease pathogenesis.
Published: 2016

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

Author: Coles, Alasdair J., Twyman, Cary L., Arnold, Douglas L., Cohen, Jeffrey A., Christian, Confavreux, Fox, Edward J., Hans Peter Hartung, Eva, Havrdova, Selmaj, Krzysztof W., Weiner, Howard L., Tamara, Miller, Elizabeth, Fisher, Rupert, Sandbrink, Lake, Stephen L., Margolin, David H., Pedro, Oyuela, Panzara, Michael A., Compston, D Alastair S., Gupta, the CARE MS II investigators: Ajay S., Edward, Fox, Glyman, Steven A., Thoits, Timothy K., Sullivan, Herman C., Cascione, Mark C., Rammohan, Kottil W., Gazda, Suzanne K., Wynn, Daniel R., Wray, Sibyl E., Stanton, Elias, Ford, Corey C., Andrew, Goodman, Hughes, Bruce L., Omar Azhar Khan, Vaishnav, Anand G., Stephen, Kirzinger, Lynch, Sharon G., Mattson, David H., Braley, Tiffany J., Mikol, Daniel D., Stephen, Krieger, Tamara Ann Miller, Riskind, Peter N., Roberto, Bomprezzi, Wingerchuk, Dean M., Brian, Steingo, Jeffrey Alan Cohen, Crayton, Heidi J., Cooper, Joanna A., Weiner, Leslie P., Harold Moses, J. r., Agius, Mark A., Ann Doan Do Bass, Lallana, Enrico C., Mitchell, Galen W., Krolczyk, Stanley J., Alireza, Minagar, Burk, Jubelt, Evans, Bradley K., Hunter, Samuel F., Rizvi, Syed A., Sheppard, Christopher A., David Honeycutt, W. M., Joseph, Herbert, Lathi, Ellen S., Gabriel, Pardo, Lily Jung Ilenson, Rothstein, Ted L., Thrower, Ben W., Mary Ann Picone, Mariko, Kita, Grazioli, Erica M., Silliman, Scott L., Thomas, Giancarlo, Gottesman, Malcolm H., Abou Zeid, Nuhad E., Rowe, Vernon D., Boutwell, Christine M., Schaeffer, John D., Riley, Claire S., Edwards, Keith R., Wendt, Jeanette K., G. Kim Bigley J. r., Shubin, Richard A., Silva Markovic Plese, Jones, Davis E., Gary, Clauser, Freedman, Mark S., Francois, Grand’Maison, Jacques, Francois H., Traboulsee, Anthony L., Brunet, Donald G., Marcelo, Kremenchutzky, Charles, Ayotte, Lava, Neil S., Waldman, Stephen R., Janus, Todd J., Stephen Gerard Vincent, Mark, Gudesblatt, Michael, Rossen, Stein, Lee S., Bennett Irving Machanic, Timothy, Vollmer, Gitt, Jeffrey S., Jeffrey, Dunn, Donald, Negroski, Fletcher, Mark H., Adil, Javed, Frohman, Elliot M., Richard, Macdonell, John Owen King, Paine, Mark A., Karyn, Boundy, Simon, Broadley, Steve, Vucic, Stephen, Reddel, Dreyer, Michael D., Raymond, Schwartz, Pamela Ann McCombe, Suzanne, Hodgkinson, Charles, Tilbery, Ferreira, Maria Lucia B., Dagoberto, Callegaro, Marcio Mena Barreto Martins, Jesus Arturo Violante Villanueva, Noemi Santos Caballero, Claudia Venzor Mendoza, Norma Haydee Deri, Alasdair, Coles, Neil James Scolding, Gavin, Giovannoni, Basil, Sharrack, Rog, David J., Giancarlo, Comi, Angelo, Ghezzi, Mancardi, Giovanni L., Durelli, Luca, Antonio, Bertolotto, Ruggero, Capra, Carlo, Pozzilli, Maria Giovanna Marrosu, Hupperts, Raymond M. M., Erik van Munster, Xavier, Montalbán, Rafael Arroyo González, Guillermo Izquierdo Ayuso, Óscar Fernández Fernández, Patrick, Vermersch, Jerome de Seze, Thibault, Moreau, Pierre, Clavelou, Catherine, Lubetzki, Michel, Clanet, Marc, Debouverie, Gilles, Edan, Judith, Haas, Martin, Stangel, Tjalf, Ziemssen, Bernhard, Hemmer, Karl, Baum, Klaus Zettl, U., Herrlinger, U., Wolfgang, Köhler, Gunter, Ochs, Patrick, Oschmann, Klaus Tiel Wilck, Hayrettin, Tumani, Urban, Peter P., Jan, Lycke, Anders, Svenningsson, Ivana, Kovarova, Marta, Vachova, Ivan, Rektor, Radomir, Talab, Krzysztof, Selmaj, Zbigniew, Stelmasiak, Wojciech, Kozubski, Dubois, Benedicte D. P., Dominique, Dive, Christian, Sindic, Karl, Vass, Per Soelberg Sørensen, Thor, Petersen, Mads, Ravnborg, Anat, Achiron, Adi Vaknin Dembinsky, Arnon, Karni, Gusev, Evgeny I., Stolyarov, Igor D., Zavalishin, Igor A., Skoromets, Alexander A., Boyko, Alexei N., Belova, Anna N., Malkova, Nadezhda A., Barantsevich, Evgeniy R., Yakupov, Eduard Z., Perfiliev, Semen V., Poverennova, Irina E., Voloshyna, Natalia P., Nehrych, Tetyana I., Kobys, Tetyana O., Mario, Habek, Vesna, Brinar, Zlatko, Trkanjec, Anton, Vladić, Spomenka Kidemet Piskać, Licia, Antonelli, Jelena, Drulović, Čongor, Nadj, Evica, Dinčić, Gordana, Tončev, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Klinische Neurowetenschappen, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Neurologie (9), RS: MHeNs School for Mental Health and Neuroscience, Radiology and nuclear medicine, and NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases
Subjects: Male, Adult, medicine.medical_specialty, Adolescent, CD52, multiple sclerosis, Administration, Cutaneous, Antibodies, Monoclonal, Humanized, law.invention, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Adjuvants, Immunologic, Randomized controlled trial, Recurrence, law, Internal medicine, Humans, Medicine, Glatiramer acetate, Infusions, Intravenous, Adverse effect, Alemtuzumab, disease, business.industry, Multiple sclerosis, Interferon beta-1a, Glatiramer Acetate, General Medicine, Middle Aged, medicine.disease, Treatment Outcome, Immunology, Female, Ocrelizumab, Peptides, business, Immunosuppressive Agents, medicine.drug
Abstract: The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment.In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18-55 years with relapsing-remitting multiple sclerosis and at least one relapse on interferon beta or glatiramer. Eligible participants were randomly allocated in a 1:2:2 ratio by an interactive voice response system, stratified by site, to receive subcutaneous interferon beta 1a 44 μg, intravenous alemtuzumab 12 mg per day, or intravenous alemtuzumab 24 mg per day. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and for 3 days at 12 months. The 24 mg per day group was discontinued to aid recruitment, but data are included for safety assessments. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability, comparing alemtuzumab 12 mg and interferon beta 1a in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00548405.202 (87%) of 231 patients randomly allocated interferon beta 1a and 426 (98%) of 436 patients randomly allocated alemtuzumab 12 mg were included in the primary analyses. 104 (51%) patients in the interferon beta 1a group relapsed (201 events) compared with 147 (35%) patients in the alemtuzumab group (236 events; rate ratio 0·51 [95% CI 0·39-0·65]; p0·0001), corresponding to a 49·4% improvement with alemtuzumab. 94 (47%) patients in the interferon beta 1a group were relapse-free at 2 years compared with 278 (65%) patients in the alemtuzumab group (p0·0001). 40 (20%) patients in the interferon beta 1a group had sustained accumulation of disability compared with 54 (13%) in the alemtuzumab group (hazard ratio 0·58 [95% CI 0·38-0·87]; p=0·008), corresponding to a 42% improvement in the alemtuzumab group. For 435 patients allocated alemtuzumab 12 mg, 393 (90%) had infusion-associated reactions, 334 (77%) had infections (compared with 134 [66%] of 202 patients in the interferon beta 1a group) that were mostly mild-moderate with none fatal, 69 (16%) had thyroid disorders, and three (1%) had immune thrombocytopenia.For patients with first-line treatment-refractory relapsing-remitting multiple sclerosis, alemtuzumab could be used to reduce relapse rates and sustained accumulation of disability. Suitable risk management strategies allow for early identification of alemtuzumab's main adverse effect of secondary autoimmunity.Genzyme (Sanofi) and Bayer Schering Pharma.
Published: 2012
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22. Étude observationnelle en vie réelle chez 15,039 patients atteints de (SEP) en France

Author: Michel Clanet, Marianne Payet, Anne-Sophie Jean Deleglise, Laurène Courouve, Gilles Defer, Jérôme De Seze, and Stephane Bouée
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction Depuis une dizaine d’annees, la strategie therapeutique de la SEP a evolue. En France, en 2013, le nombre de patients atteints de SEP etait de 99,123, pour la plupart suivis dans des centres experts. Objectifs Decrire les caracteristiques demographiques, les conditions d’utilisation des traitements, la persistance aux traitements et l’effet therapeutique en vie reelle. Patients et methodes Etude observationnelle en vie reelle menee dans 11 centres ayant collecte les donnees de patients SEP dans EDMUS (European Database for Multiple Sclerosis). Dix-huit virgule quatre cents douze fichiers de patients, avec une survenue de SEP entre 1970 et 2014, ont ete extraits. La population d’analyse diagnostiquee SEP remittente s’eleve a 15,039 patients dont 73,9 % de femmes, avec un âge moyen de survenue de la SEP de 31,6 ± 9,8 ans. Parmi les 71,8 % de patients traites, 79,3 % ont recu un immunomodulateur injectable (IMM) en 1ere intention. Resultats Le delai entre la prescription du 1e traitement de fond et la survenue de la SEP est de 8,8 ± 7,8 ans avant 2000, et de 0,69 ± 0,7 ans apres 2010. Pour les patients diagnostiques apres 2000 et traites par IMM de 1ere ligne, le risque relatif (RR) de poussee etait significativement plus faible chez les patients traites par Interferonβ1a en sous-cutanee (IFNβ1a sc) que pour les patients sous acetate de glatiramere (AG) (RR = 1,203 ; IC95 % 1,037–1,397) ou IFNβ1a en intramusculaire (im) (RR = 1,192 ; IC95 % 1,023–1,39), et similaire sous IFNβ1b. Discussion Les caracteristiques de la cohorte sont conformes aux donnees epidemiologiques nationales, avec une severite de la maladie de legere a moderee. Parmi les IMM, l’IFNβ1a sc et l’IFNβ1b apparaissent comme les plus efficaces sur le risque de survenue de poussee par rapport a AG et IFNβ1a im. Conclusion Compte-tenu des limites methodologiques des etudes observationnelles, il convient de rester prudent lors de l’interpretation de ces donnees. Informations complementaires L’etude a ete financee par Merck KGaA. Remerciements aux 11 centres participants.
Published: 2017
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23. Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring

Author: Mads Ravnborg, Olivier Lyon-Caen, Antonio Garcia-Merino, Gilles Edan, David W. Bates, Hans Peter Hartung, Christian Sindic, Ernst W. Radü, Hans H. Hirsch, Takahiko Saida, Eva Havrdova, Ralf Gold, Mefkure Eraksoy, Per Soelberg Sørensen, Marcelo Kremenchutzky, David B. Clifford, Paul O'Connor, Eugene O. Major, John King, Nikolaos Grigoriadis, Carlo Pozzilli, Jan Hillert, Karl Vass, Stephen L. Hauser, Howard L. Weiner, Reinhard Hohlfeld, Michel Clanet, Ludwig Kappos, Ariel Miller, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, and UCL - (SLuc) Service de neurologie
Subjects: medicine.medical_specialty, JC virus, Placebo-controlled study, Alpha interferon, Integrin alpha4beta1, Antibodies, Monoclonal, Humanized, medicine.disease_cause, Leukoencephalopathy, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, medicine, Animals, Humans, Intensive care medicine, Adverse effect, business.industry, Patient Selection, Progressive multifocal leukoencephalopathy, Multiple sclerosis, Leukoencephalopathy, Progressive Multifocal, Antibodies, Monoclonal, medicine.disease, Treatment Outcome, Practice Guidelines as Topic, Immunology, Neurology (clinical), Drug Monitoring, business, medicine.drug
Abstract: Natalizumab, a highly specific α4-integrin antagonist, is approved for treatment of patients with active relapsing-remitting multiple sclerosis (RRMS). It is generally recommended for individuals who have not responded to a currently available first-line disease-modifying therapy or who have very active disease. The expected benefits of natalizumab treatment have to be weighed against risks, especially the rare but serious adverse event of progressive multifocal leukoencephalopathy. In this Review, we revisit and update previous recommendations on natalizumab for treatment of patients with RRMS, based on additional long-term follow-up of clinical studies and post-marketing observations, including appropriate patient selection and management recommendations.
Published: 2011
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24. Tyrosine kinase 2 variant influences T lymphocyte polarization and multiple sclerosis susceptibility

Author: David Brassat, Peter Rieckmann, Marc Debouverie, Bertrand Fontaine, Thibault Moreau, Roland S. Liblau, Bertram Müller-Myhsok, Sandra Vukusic, Florence Bucciarelli, Christine Lebrun-Frenay, Frank Weber, Manuel Comabella, Isabelle Cournu-Rebeix, Gilles Edan, Uwe K. Zettl, Christian Confavreux, Gilles Defer, Nicolas Couturier, Ramil N. Nurtdinov, Lennart T. Mars, Jorge R. Oksenberg, Xavier Montalban, Robert Goertsches, Abdelhadi Saoudi, and Michel Clanet
Subjects: Adult, Male, Models, Molecular, Multiple Sclerosis, Time Factors, Adolescent, Genotype, T-Lymphocytes, GATA3 Transcription Factor, Polymorphism, Single Nucleotide, Tropomyosin receptor kinase C, Receptor tyrosine kinase, Young Adult, Humans, Genetic Predisposition to Disease, Cells, Cultured, Cell Proliferation, TYK2 Kinase, Chi-Square Distribution, Janus kinase 2, biology, JAK-STAT signaling pathway, Flow Cytometry, FLT4, Gene Expression Regulation, Tyrosine kinase 2, Case-Control Studies, Immunology, biology.protein, Cytokines, Female, France, Neurology (clinical), Janus kinase, Platelet-derived growth factor receptor, Signal Transduction
Abstract: The tyrosine kinase 2 variant rs34536443 has been established as a genetic risk factor for multiple sclerosis in a variety of populations. However, the functional effect of this variant on disease pathogenesis remains unclear. This study replicated the genetic association of tyrosine kinase 2 with multiple sclerosis in a cohort of 1366 French patients and 1802 controls. Furthermore, we assessed the functional consequences of this polymorphism on human T lymphocytes by comparing the reactivity and cytokine profile of T lymphocytes isolated from individuals expressing the protective TYK2 GC genotype with the disease-associated TYK2 GG genotype. Our results demonstrate that the protective C allele infers decreased tyrosine kinase 2 activity, and this reduction of activity is associated with a shift in the cytokine profile favouring the secretion of Th2 cytokines. These findings suggest that the rs34536443 variant effect on multiple sclerosis susceptibility might be mediated by deviating T lymphocyte differentiation toward a Th2 phenotype. This impact of tyrosine kinase 2 on effector differentiation is likely to be of wider importance because other autoimmune diseases also have been associated with polymorphisms within tyrosine kinase 2. The modulation of tyrosine kinase 2 activity might therefore represent a new therapeutic approach for the treatment of autoimmune diseases. * Abbreviations : IFNβ : interferon beta IFNλ : interferon lambda IL : interleukin JAKs : Janus kinase superfamily STAT : signal transducers and activators of transcription family TNF : tumour necrosis factor TYK2 : tyrosine kinase 2
Published: 2011
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25. Diagnostic Criteria for Multiple Sclerosis: 2010 Revisions to the McDonald Criteria

Author: Paul L. O’Connor, Brian G. Weinshenker, Ludwig Kappos, Kazuo Fujihara, Massimo Filippi, Michael Hutchinson, Eva Havrdova, Brenda Banwell, Magnhild Sandberg-Wollheim, Jeffrey A. Cohen, Fred D. Lublin, Alan J. Thompson, Michel Clanet, Xavier Montalban, Chris H. Polman, Emmanuelle Waubant, Jerry S. Wolinsky, Stephen C. Reingold, Neurology, NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases, Polman, Ch, Reingold, Sc, Banwell, B, Clanet, M, Cohen, Ja, Filippi, Massimo, Fujihara, K, Havrdova, E, Hutchinson, M, Kappos, L, Lublin, Fd, Montalban, X, O'Connor, P, Sandberg Wollheim, M, Thompson, Aj, Waubant, E, Weinshenker, B, and Wolinsky, Js
Subjects: medicine.medical_specialty, Multiple Sclerosis, Clinical Sciences, Neurodegenerative, Autoimmune Disease, Sensitivity and Specificity, Poser criteria, 03 medical and health sciences, 0302 clinical medicine, Tumefactive multiple sclerosis, 030225 pediatrics, medicine, Humans, Medical physics, screening and diagnosis, Clinically isolated syndrome, Expanded Disability Status Scale, Neurology & Neurosurgery, business.industry, Multiple sclerosis, Neurosciences, McDonald criteria, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Surgery, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Chronic cerebrospinal venous insufficiency, Detection, Early Diagnosis, Neurology, Multiple sclerosis functional composite, Neurology (clinical), business, 030217 neurology & neurosurgery, Rapid Communication, 4.2 Evaluation of markers and technologies
Abstract: New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use. Ann Neurol 2011
Published: 2011
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26. EFNS guidelines on diagnosis and management of neuromyelitis optica

Author: R. Du Pasquier, Per Soelberg Sørensen, Chris H. Polman, Johann Sellner, Bernhard Hemmer, Michel Clanet, Zsolt Illes, Rogier Q. Hintzen, Xavier Montalban, and Mike Boggild
Subjects: medicine.medical_specialty, Neuromyelitis optica, business.industry, Multiple sclerosis, MEDLINE, Disease, Guideline, Evidence-based medicine, medicine.disease, Transverse myelitis, Neurology, medicine, Physical therapy, Optic neuritis, Neurology (clinical), Intensive care medicine, business
Abstract: Background and purpose: Neuromyelitis optica (NMO) or Devic's disease is a rare inflammatory and demyelinating autoimmune disorder of the central nervous system (CNS) characterized by recurrent attacks of optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM), which is distinct from multiple sclerosis (MS). The guidelines are designed to provide guidance for best clinical practice based on the current state of clinical and scientific knowledge. Search strategy: Evidence for this guideline was collected by searches for original articles, case reports and meta-analyses in the MEDLINE and Cochrane databases. In addition, clinical practice guidelines of professional neurological and rheumatological organizations were studied. Results: Different diagnostic criteria for NMO diagnosis [Wingerchuk et al. Revised NMO criteria, 2006 and Miller et al. National Multiple Sclerosis Society (NMSS) task force criteria, 2008] and features potentially indicative of NMO facilitate the diagnosis. In addition, guidance for the work-up and diagnosis of spatially limited NMO spectrum disorders is provided by the task force. Due to lack of studies fulfilling requirement for the highest levels of evidence, the task force suggests concepts for treatment of acute exacerbations and attack prevention based on expert opinion. Conclusions: Studies on diagnosis and management of NMO fulfilling requirements for the highest levels of evidence (class I-III rating) are limited, and diagnostic and therapeutic concepts based on expert opinion and consensus of the task force members were assembled for this guideline.
Published: 2010
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27. La SEP en Haute-Garonne : une sous-estimation importante du nombre de cas

Author: Michel Clanet, F. Viala, C. Sagnes-Raffy, Hannon, M. C. Gaulene, P. A. Gourraud, R. Bourrel, and M. A. Laffontan
Subjects: Estimation, Linkage (software), Matching (statistics), medicine.medical_specialty, Epidemiology, Multiple sclerosis, Public Health, Environmental and Occupational Health, Social Welfare, medicine.disease, Regression, Geography, Statistics, medicine, Log-linear model
Abstract: INTRODUCTION In France, the prevalence of multiple sclerosis is estimated between 65 and 125 patients per 100,000 inhabitants with a South-West towards North-East gradient. Nevertheless, the epidemiology of multiple sclerosis remains still imperfectly known, the recent studies being realized, either in a region of France, or from a single data source and thus suscepted not to be exhaustive. OBJECTIVE Assessing the prevalence of the multiple sclerosis in 2005 in Haute-Garonne by matching several data sources completed by a capture-recapture method; estimating the exhaustivity of each of the sources. METHODS The data sources were hospital data (DRG for the hospitalization, data of consultation), data of public health insurance system (main health insurance, agricultural health insurance, social welfare for self employed), and data from the MIPSEP network. The linkage was based on name, maiden name, first name, date of birth and sex and allowed a first estimation of the number of cases. Models of loglinear regression allowed estimating the total number of case and the sensitivity of each source. RESULTS The total number of cases obtained by matching several sources of information amounted to 1549. The use of several data sources increased by 25.6 % the maximum number of patients identified with a single source of information (national health insurance, any insurance). According to the model used, the method of capture-recapture estimated the number of cases up to 1722. Therefore, this study estimated a prevalence of multiple sclerosis between 110 and 149 cases per 100,000 inhabitants in Haute-Garonne. CONCLUSION The prevalence of the multiple sclerosis is largely underestimated in Haute-Garonne and questions the magnitude over the so-called gradient. Matching several sources of information is indispensable to improve collection of the total number of cases.
Published: 2010
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28. Observance et impact sur la qualité de vie du cathétérisme intermittent chez les patients atteints de sclérose en plaques

Author: X. Gamé, Evelyne Castel-Lacanal, Julien Guillotreau, V. Bourg, Michel Clanet, Philippe Marque, X. De Boissezon, and Christian-François Roques
Subjects: Gynecology, medicine.medical_specialty, business.industry, medicine, Obstetrics and Gynecology, Neurology (clinical), business
Abstract: Les troubles vesicosphincteriens dans la sclerose en plaques (SEP) sont frequents. La symptomatologie urinaire est polymorphe et le traitement le plus souvent medicamenteux. Le catheterisme intermittent (CI), traitement de reference chez le blesse medullaire, fait partie de l’arsenal therapeutique. Le but de cette etude etait d’evaluer prospectivement en intention de traiter l’observance, la satisfaction et l’impact sur la qualite de vie du CI chez les patients atteints d’une SEP. Nous avons suivi, entre 2004 et 2006, 170 patients atteints d’une SEP pour des troubles vesicosphincteriens. Les parametres etudies etaient l’incidence du CI, les caracteristiques des patients relevant du CI, la compliance et l’acceptation des patients au CI, le taux d’arret a moyen terme et l’impact du CI sur la qualite de vie des patients. L’indication de changement de mode mictionnel au profit du CI a ete retenue chez 55 patients (32 %). Cinq patients (9,1 %) ont refuse d’apprendre le CI, cinq patients (9,1 %) l’ont arrete au bout de 7 ± 4 mois. Pour un suivi moyen de 2,7 ± 4,7 ans, 45 patients pratiquent toujours le CI. Tous les patients qui pratiquaient le CI depuis au moins quatre mois etaient satisfaits, considerant que le CI ameliorait leur qualite de vie (Echelle numerique = 8/10). Le CI, chez les patients atteints d’une SEP, est bien accepte et ameliore la qualite de vie.
Published: 2009
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29. Ethics of placebo-controlled clinical trials in multiple sclerosis: A reassessment

Author: Jerry S. Wolinsky, Stephen C. Reingold, Alan J. Thompson, Frederik Barkhof, Gary Cutter, Henry F. McFarland, Maria Pia Sormani, Jeffrey A. Cohen, Aaron E. Miller, Paul O'Connor, Morris Freedman, Luanne M. Metz, Chris H. Polman, Peter A. Calabresi, John Petkau, J. R. Richert, Fred D. Lublin, Xavier Montalban, Michel Clanet, Brian G. Weinshenker, Steven R. Schwid, Ludwig Kappos, Hillel Panitch, Neurology, Radiology and nuclear medicine, and Neuroscience Campus Amsterdam 2008
Subjects: medicine.medical_specialty, Multiple Sclerosis, media_common.quotation_subject, education, Drug Resistance, Alternative medicine, MEDLINE, Placebo, Risk Assessment, Health Services Accessibility, Placebos, Natalizumab, Informed consent, medicine, Humans, Mental Competency, Intensive care medicine, Pharmaceutical industry, media_common, Clinical Trials as Topic, Informed Consent, business.industry, Placebo Effect, Clinical trial, Treatment Outcome, Neurology (clinical), business, Autonomy, medicine.drug, Clinical psychology
Abstract: The increasing number of established effective therapies for relapsing multiple sclerosis (MS) and emerging consensus for early treatment raise practical concerns and ethical dilemmas for placebo-controlled clinical trials in this disease. An international group of clinicians, ethicists, statisticians, regulators, and representatives from the pharmaceutical industry convened to reconsider prior recommendations regarding the ethics of placebo-controlled trials in MS. The group concluded that placebo-controlled trials can still be done ethically, with restrictions. For patients with relapsing MS for which established effective therapies exist, placebo-controlled trials should only be offered with rigorous informed consent if the subjects refuse to use these treatments, have not responded to them, or if these treatments are not available to them for other reasons (e.g., economics). Suggestions are provided to protect subject autonomy and improve informed consent procedures. Recommendations are tighter than previously suggested for placebo-controlled trials in "resource-restricted" environments where established therapies may not be available. Guidance is also provided on the ethics of alternative trial designs and the balance between study subject burden and risk, scientific rationale and interpretability of trial outcomes.
Published: 2008
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30. Is the early-onset torsion dystonia (EOTD) linked to TOR1A gene as frequent as expected in France?

Author: Christine Coubes, Bruno Barroso, Victor Chan, Yves Agid, Alexis Brice, Brigitte Chabrol, Sylvie Tuffery-Giraud, Fabienne Clot, Isabelle Vuillaume, Marie Vidailhet, Chrisophe Vial, Laurie J. Ozelius, Karine Nguyen, Mélissa Yana Frédéric, Caroline Davin, Déborah Méchin, Alain Destée, Michel Clanet, Laura Cif, Céline Saquet, Arnaud Blanchard, Francis Rousset, Bernard Sablonnière, Gaetan Lesca, Agathe Roubertie, Alain Calender, Philippe Coubes, Thomas Besnard, Delphine Thorel, Mireille Claustres, Gwenaëlle Collod-Béroud, Alexandre Kreisler, Alexandra Durr, Jing Xie, Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], 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), Neurochirurgie [Hôpital Gui de Chauliac], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Centre de Biologie-Pathologie, UF de Neurobiologie-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de Génétique Moléculaire et Clinique, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Noyaux gris centraux, Université de Lille, Sciences et Technologies-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Genetics and Genome Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Service de neurologie, CHU Pau, Service de Neuropédiatrie, CHU Marseille, Centre hospitalier de Valence, Service de Génétique Clinique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Electroneuromyographie et Pathologie Neuromusculaires, Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Guy de Chauliac, M.Y.F. is supported by a grant from Association Française contre les Myopathies (AFM). This work was supported by the LFCD-AMADYS and INSERM Dystonia National Network and Gis Maladies Rares., Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], and COLLOD-BEROUD, Gwenaëlle
Subjects: Male, Heterozygote, Movement disorders, Adolescent, Genetic Linkage, Population, Dystonia Musculorum Deformans, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Gene Frequency, Genetic linkage, Genetics, medicine, Humans, Age of Onset, Mutation frequency, Child, education, Allele frequency, Genetics (clinical), Sequence Deletion, 030304 developmental biology, Dystonia, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, education.field_of_study, Haplotype, medicine.disease, 3. Good health, Phenotype, Haplotypes, Case-Control Studies, Jews, Female, France, medicine.symptom, Age of onset, 030217 neurology & neurosurgery, Molecular Chaperones
Abstract: International audience; Early onset torsion dystonia are rare movement disorders. Molecular defect is known for only a subgroup, consisting of a unique and recurrent mutation in the TOR1A gene. We undertook a nationwide census of French TOR1A-mutation carriers and the assessment of clinical associated signs. Overall, 53 index cases and 104 relatives were studied and haplotypes linked to the mutation constructed. The previously reported Ashkenazi-Jewish haplotype was found in 11 families with the remainder carrying distinct haplotypes suggesting independent mutation events. This study demonstrates the scarcity of this disease in France with estimated disease frequency of 0.13:100,000 and mutation frequency of 0.17:100,000.
Published: 2008
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31. Natural History of Multiple Sclerosis with Childhood Onset

Author: Christel Renoux, Sandra Vukusic, Yann Mikaeloff, Gilles Edan, Michel Clanet, Bénédicte Dubois, Marc Debouverie, Bruno Brochet, Christine Lebrun-Frenay, Jean Pelletier, Thibault Moreau, Catherine Lubetzki, Patrick Vermersch, Etienne Roullet, Laurent Magy, Marc Tardieu, Samy Suissa, and Christian Confavreux
Subjects: Adult, Male, Multiple Sclerosis, Adolescent, Infant, Observation, Kaplan-Meier Estimate, General Medicine, Prognosis, Cohort Studies, Child, Preschool, Disease Progression, Humans, Female, Age of Onset, Child
Abstract: BACKGROUND: The course and prognosis of childhood-onset multiple sclerosis have not been well described. METHODS: We used data from 13 adult neurology departments affiliated with the European Database for Multiple Sclerosis (EDMUS) network to identify a cohort of 394 patients who had multiple sclerosis with an onset at 16 years of age or younger and a comparison group of 1775 patients who had multiple sclerosis with an onset after 16 years of age. We determined the initial clinical features, the dates of disease onset, and the occurrence of outcomes, including relapse, conversion to secondary progression, and irreversible disability as measured by scores of 4 (limited walking ability but ability to walk more than 500 m without aid or rest), 6 (ability to walk with unilateral support no more than 100 m without rest), and 7 (ability to walk no more than 10 m without rest while using a wall or furniture for support) on the Kurtzke Disability Status Scale (range, 0 to 10; higher scores indicate more severe disability). RESULTS: For patients with childhood-onset multiple sclerosis, the estimated median time from onset to secondary progression was 28 years, and the median age at conversion to secondary progression was 41 years. The median times from onset to disability scores of 4, 6, and 7 were 20.0, 28.9, and 37.0 years, respectively, and the corresponding median ages were 34.6, 42.2, and 50.5 years. In comparison with patients with adult-onset disease, those with childhood-onset disease were more likely to be female than male (female:male ratio, 2.8 vs. 1.8), were more likely to have an exacerbating-remitting initial course (98% vs. 84%), took approximately 10 years longer to reach secondary progression and irreversible disability, and reached these landmarks at an age approximately 10 years younger (P
Published: 2007
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32. Modafinil for the Treatment of Fatigue in Multiple Sclerosis

Author: Bruno Stankoff, Catherine Lubetzki, and Michel Clanet
Subjects: Clinical trial, Psychiatry and Mental health, medicine.medical_specialty, Physical medicine and rehabilitation, Neurology, business.industry, Multiple sclerosis, Modafinil, medicine, Neurology (clinical), medicine.disease, business, medicine.drug
Published: 2006
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33. Neutralizing antibodies and efficacy of interferon -1a: A 4-year controlled study

Author: Michel Clanet, Magnhild Sandberg-Wollheim, Susan Goelz, Alfred Sandrock, E. W. Radue, Reinhard Hohlfeld, J. Xu, Ludwig Kappos, H.-P. Hartung, and D. Bennett
Subjects: Adult, Central Nervous System, Male, medicine.medical_specialty, Multiple Sclerosis, Enzyme-Linked Immunosorbent Assay, Gastroenterology, Disability Evaluation, Internal medicine, Secondary Prevention, Humans, Medicine, Clinical significance, Neutralizing antibody, Autoantibodies, Expanded Disability Status Scale, Dose-Response Relationship, Drug, biology, business.industry, Multiple sclerosis, Incidence (epidemiology), Interferon beta-1a, Interferon-beta, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Titer, Treatment Outcome, Immunology, Disease Progression, biology.protein, Female, Neurology (clinical), Antibody, business, medicine.drug
Abstract: Objective: To determine the incidence and clinical significance of neutralizing antibody (NAb) formation in patients with relapsing multiple sclerosis ( MS) who participated in the European Interferon Beta-1a IM Dose-Comparison Study. Methods. Patients were randomized to treatment with interferon beta-1a (IFN beta-1a) 30 mu g or 60 mu g IM once weekly for up to 4 years. Serum samples obtained at baseline and every 3 months thereafter were screened for the presence of IFN binding antibodies by ELISA. Patients whose results were seropositive on ELISA were screened for the presence of NAbs using an antiviral cytopathic effect assay. Patients were considered to be positive for NAbs ( NAb+) if the baseline NAb titer was 0 and two or more consecutive postbaseline titers were >= 20. Patients were considered to be negative for NAbs ( NAb -) if the baseline NAb titer was 0 and all postbaseline NAb titers were < 5. Results: The proportion of patients who became NAb + was lower in patients who received 30 mu g of IFN beta-1a than in those who received 60 mu g (7/400 [1.8%] vs 19/395 [4.8%]; p = 0.02). The mean time to NAb + status was 14.5 +/- 6.2 months. Compared with patients who remained NAb -, NAb + patients showed the following: higher relapse rates from months 12 to 48 ( p = 0.04), higher rate of mean change ( worsening) in Expanded Disability Status Scale score from baseline to month 48 ( p = 0.01), greater number of T1 gadolinium-enhanced lesions at months 24 and 36 ( p = 0.02 and 0.03), and greater accrual of new or enlarging T2 lesions from month 12 to months 24 and 36 ( p = 0.05 and 0.09) Conclusions: Neutralizing antibodies ( NAbs) to interferon beta-1a (IFN beta-1a), as observed with other IFN beta s used in the treatment of multiple sclerosis, reduce the therapeutic benefits measured by relapses and MRI activity. Data from this study also suggest NAbs to IFN beta-1a reduce treatment benefits as measured by change in Expanded Disability Status Scale score. (Less)
Published: 2005
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34. Rate of brain atrophy in relapsing MS decreases during treatment with IFN -1a

Author: Michel Clanet, Ludwig Kappos, P Freitag, RA Rudick, Elizabeth M. C. Fisher, Martin Hardmeier, Stefan Wagenpfeil, E. W. Radue, and Mariska F. Kooijmans
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Central nervous system, Gastroenterology, law.invention, Cohort Studies, Multiple Sclerosis, Relapsing-Remitting, Atrophy, Randomized controlled trial, law, Internal medicine, medicine, Humans, Immunologic Factors, medicine.diagnostic_test, business.industry, Multiple sclerosis, Interferon beta-1a, Brain, Magnetic resonance imaging, Interferon-beta, medicine.disease, Magnetic Resonance Imaging, Surgery, Europe, Treatment Outcome, medicine.anatomical_structure, Cohort, Disease Progression, Female, Neurology (clinical), business, Follow-Up Studies, Cohort study, medicine.drug
Abstract: Objective: To determine the time course of brain atrophy during treatment with once-weekly IM interferon β-1a (IFNβ-1a). Methods: The MRI cohort (n = 386) of the European IFNβ-1a dose comparison study in relapsing multiple sclerosis (MS) was analyzed. In addition to baseline and three annual scans, a frequent subgroup (n = 138) had two scans before treatment initiation and scans at months 4, 5, 6, 10, and 11. Brain parenchymal fraction (BPF), a normalized measure of whole-brain atrophy, and volume of Gd-enhancing lesions (T1Gd) and T2 hyperintense lesions (T2LL) were evaluated. Results: BPF decrease was −0.686% (first year), −0.377% (second year), and −0.378% (third year). Analysis of the frequent subgroup showed that 68% of the first-year BPF decrease occurred during the first 4 months of treatment. This change was paralleled by a drop in T1Gd and T2LL. In the frequent subgroup, an annualized atrophy rate was determined by a regression slope for the pretreatment period and from month 4 of treatment onward. Annualized pretreatment rate (−1.06%) was significantly higher than the under-treatment rate (−0.33%). Conclusions: In the first year of treatment with anti-inflammatory agents, atrophy measurements are possibly confounded by resolution of inflammatory edema or more remote effects of previous damage to the CNS. The atrophy rate reduction observed after treatment month 4 may reflect a beneficial but partial effect of interferon β-1a and was sustained over the 3-year study period.
Published: 2005
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35. Clinical–MRI correlations in the secondary progressive phase of MS: lessons from the treatment trials

Author: C. Manelfe, Michel Clanet, Emmanuelle Cassol, and Isabelle Berry
Subjects: Pathology, medicine.medical_specialty, Placebo, Sensitivity and Specificity, Central nervous system disease, Text mining, medicine, Humans, Magnetization transfer, Secondary progressive, Pathological, Clinical Trials as Topic, medicine.diagnostic_test, business.industry, Multiple sclerosis, Reproducibility of Results, Magnetic resonance imaging, Interferon-beta, Multiple Sclerosis, Chronic Progressive, medicine.disease, Magnetic Resonance Imaging, Neurology, Disease Progression, Neurology (clinical), Radiology, business
Abstract: Conventional MRI techniques are sensitive to detect MS lesions and their change overtime. In relapsing-remitting MS correlations with clinical measures are weak suggesting a pathological heterogeneity of these lesions. There are less data available in secondary progressive phase of the disease. The best source for clinical MRI correlations analysis is the placebo arm of the published interferon beta trials. This review presents the main clinical-MRI findings from these trials then focuses on recent promising observations obtained with non conventional MRI techniques in SP MS patients.
Published: 2003
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36. Description, utilisation et efficacité en vie réelle des traitements de fond de la sclérose en plaques (SEP)

Author: Gilles-Louis Defer, J. de Seze, A.-S. Jean Deleglise, Laurène Courouve, Michel Clanet, S Bouee, and Marianne Payet
Subjects: Epidemiology, Public Health, Environmental and Occupational Health
Abstract: Objectif Depuis une dizaine d’annees, la strategie therapeutique de la SEP a evolue. En France, en 2013, le nombre de patients atteints de SEP etait de 99 123, pour la plupart suivis dans des centres experts. Les objectifs de cette etude etaient de decrire les caracteristiques demographiques des patients atteints de sclerose en plaques (SEP) remittente, les conditions d’utilisation des traitements de fond de la SEP, leur persistance et leur efficacite en vie reelle. Patients et methodes Une etude observationnelle en vie reelle a ete menee dans 11 centres utilisant le logiciel EDMUS (« European Database for Multiple Sclerosis »). Les dossiers de 15 039 patients dont la SEP a debute entre 1970 et 2014 ont ete extraits. Les analyses d’efficacite et de persistance ont ete ajustees sur l’âge au debut de la maladie, le sexe, la duree entre le debut de la maladie et le 1er traitement, le nombre de traitements anterieur et le nombre de poussees entre le debut de la maladie et la prescription du traitement. Resultats La proportion de femmes etait de 73,9 %, l’âge moyen de survenue de la SEP etait de 31,6 ans (ecart type : 9,8). Parmi les 15 039 sujets, 10 800 (71,8 %) ont recu un traitement de fond, dont 8564 (79,3 %) ont recu un immunomodulateur injectable (IMM) en premiere ligne. Le delai entre la prescription du premier traitement de fond et la survenue de la SEP etait de 8,8 ans ± 7,8 ans avant l’annee 2000, et de 0,7 ans apres 2010. La duree mediane de persistance des traitements (en annees) etait de 3,9, 3,5, 3,3 et 2,9 respectivement pour l‘interferonβ1a en intramusculaire (IM), l’interferonβ1a en sous cutane, l’acetate de glatiramere (AG) et les interferonβ1b. Apres ajustement (modele de Cox) et comparativement a l’Interferonβ1a en sous-cutanee (SC), le risque d’arret du traitement etait significativement superieur chez les patients traites par IFNβ1b (HR = 1,17, IC95 % = [1,10 ;1,25])). Pour les patients diagnostiques apres 2000 et traites par IMM de 1re ligne et apres ajustement (modele de Poisson), le risque relatif (RR) ajuste de poussee etait significativement plus faible chez les patients traites par Interferonβ1a SC que pour les patients sous AG (RR = 1,20 ; IC95 % = [1,04 ; 1,40]) ou interferonβ1a en IM (RR = 1,19 ; IC95 % = [1,02 ; 1,40]), et similaire sous interferonβ1b (RR = 1,19 ; IC95 % = [0,99 ;1,39]). Conclusion Les caracteristiques de ces sujets sont conformes aux donnees epidemiologiques nationales. Parmi les IMM, l’interferonβ1a SC et l’Interferonβ1b apparaissent plus efficaces sur le risque de survenue de poussee par rapport a AG et interferonβ1a IM. Compte-tenu des limites methodologiques des etudes observationnelles, il convient de rester prudent lors de l’interpretation de ces donnees.
Published: 2017
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37. Adult-onset genetic leukoencephalopathies: a MRI pattern-based approach in a comprehensive study of 154 patients

Author: Gilles Edan, Nicolas Collongues, Frédéric Blanc, Eloi Magnin, Marc Bataillard, Mickael Cohen, Thierry Levade, David Brassat, Jean-Philippe Neau, Patrizia Amati-Bonneau, Xavier Ayrignac, Maurice Giroud, Patrick Vermersch, Eric Berger, Cyril Goizet, Celine Bellesme, Clarisse Carra-Dalliere, Jean Louis Devoize, Christophe Verny, Anne Marie Guennoc, Pierre Labauge, Marc Debouverie, Pierre Clavelou, Thibault Moreau, Jean Pelletier, Laurent Magy, Bruno Brochet, Christian Denier, Jean-Philippe Camdessanché, Sandrine Wiertlewski, Nicolas Menjot de Champfleur, Jean-Christophe Ouallet, Gilles Defer, Frédérique Taithe, Elsa Kaphan, Nathalie Derache, Françoise Durand-Dubief, Michel Clanet, Sandra Vukusic, Christine Lebrun-Frenay, Stéphane Mathis, Olivier Outteryck, Bertrand Audoin, Lucie Guyant-Maréchal, Odile Boespflug Tanguy, Elisabeth Tournier-Lasserve, Didier Hannequin, Hélène Zéphir, Jean-Baptiste Chanson, Emmanuelle Le Page, Patrick Aubourg, Sophie Pittion, Jérôme De Seze, Imen Dorboz, Véronique Deburghgraeve, Giovanni Castelnovo, Dominique Bonneau, Julien Masliah-Planchon, David-Axel Laplaud, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 (UM1), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Department of Neuroradiology, Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Marseille, 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), Service de neurologie [Strasbourg], CHU Strasbourg, Laboratoire d'imagerie et de neurosciences cognitives (Strasbourg), Laboratoire d'Imagerie et de Neurosciences Cognitives (LINC), Université Louis Pasteur - Strasbourg I-IFR37-Centre National de la Recherche Scientifique (CNRS)-Université Louis Pasteur - Strasbourg I-IFR37-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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), CHU Saint-Etienne, Centre Hospitalier Universitaire de Nice (CHU Nice), Pôle neurosciences [Hôpital de Purpan - Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gérontologie (BICETRE - Géronto), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique, PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Clermont-Ferrand, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Neurologie [CHU Limoges], CHU Limoges, Centre Hospitalier d'Angoulême (CH Angoulême), Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Université de Montpellier (UM), Institut des Neurosciences de Montpellier (INM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université Montpellier 1 ( UM1 ), Université Paris-Sud - Paris 11 ( UP11 ) -Hôpital Bicêtre, Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), 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 ), Laboratoire d'Imagerie et de Neurosciences Cognitives ( LINC ), Université Louis Pasteur - Strasbourg I-IFR37-Centre National de la Recherche Scientifique ( CNRS ) -Université Louis Pasteur - Strasbourg I-IFR37-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Nice, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Laboratoire d'Immunologie ( EA 2686 ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CIC-Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Vision, Action et Gestion d'informations en Santé ( VisAGeS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE ( IRISA-D5 ), Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Service de Neurologie [Rennes], Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Gérontologie ( BICETRE - Géronto ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Biologie Neurovasculaire et Mitochondriale Intégrée, Université d'Angers ( UA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université d'Angers ( UA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Angers, Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Neurologie [Caen], CHU Caen-Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHRU Tours, Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre Hospitalier d'Angoulême, Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux ( Inserm U745 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Promoting Research Oriented Towards Early Cns Therapies ( PROTECT ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Sorbonne Paris Cité ( USPC ), 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 Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Pathology, leukodystrophy, Adolescent, [SDV]Life Sciences [q-bio], White matter, Leukoencephalopathy, Young Adult, metabolic, Leukoencephalopathies, medicine, Humans, Age of Onset, 10. No inequality, CADASIL, Aged, Retrospective Studies, [ SDV ] Life Sciences [q-bio], medicine.diagnostic_test, business.industry, Leukodystrophy, Retrospective cohort study, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, White Matter, 3. Good health, Cerebrovascular Disorders, medicine.anatomical_structure, Cohort, Female, Neurology (clinical), France, Age of onset, genetic, business, MRI
Abstract: International audience; Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7]. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.
Published: 2014
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38. A central nervous system B-cell lymphoma arising two years after initial diagnosis of CLIPPERS

Author: Michel Clanet, Hans Lassmann, Emmanuelle Uro-Coste, Camille Laurent, Guillaume Taieb, David Brassat, Marie-Bernadette Delisle, Alexandra Benouaich-Amiel, and Pierre Labauge
Subjects: Inflammation, Male, Pathology, medicine.medical_specialty, Lymphoma, B-Cell, business.industry, Central nervous system, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Pathophysiology, medicine.anatomical_structure, Neurology, Primary CNS Lymphoma, Antigens, CD, Central Nervous System Diseases, Pons, Immunology, Chronic Disease, medicine, Disease Progression, Humans, Neurology (clinical), B-cell lymphoma, business
Published: 2014

39. Interferon-Beta in the Treatment of Multiple Sclerosis

Author: Michel Clanet
Subjects: Oncology, medicine.medical_specialty, Interferon beta, business.industry, Multiple sclerosis, Immunogenicity, General Medicine, Pharmacology, medicine.disease, Bioavailability, Clinical trial, Pharmacotherapy, Internal medicine, Medicine, Ceiling effect, Pharmacology (medical), business, Adverse effect
Abstract: Three interferon-beta (IFNβ) products (Betaferon®, Avonex® and Rebif®) have been shown to be effective in the treatment of relapsing forms of multiple sclerosis, but the optimal dose of each product has not been established. The lack of head-to-head trials comparing the different IFNβs directly has led to comparisons across clinical trials, despite known limitations of such an approach (e.g. differences between studies with regard to patients studied, design, duration and end-point definitions). Furthermore, IFNβ preparations are manufactured and formulated differently and are delivered by different routes of administration; they are thus different with respect to their bioavailability, immunogenicity and specific activities. Nevertheless, the results of a manual review of all major published dose-comparison studies on IFNβ preparations suggest that there may be a dose-response effect below a certain threshold dose for each product. However, once this threshold dose is attained, a ceiling effect exists; higher doses do not provide added clinical benefit, but may be associated with a higher incidence of adverse events. Hence, physicians should weigh the lack of additional clinical benefits of higher IFNβ doses with the increased risk of adverse events when deciding on the appropriate dose of IFNβ for their patients.
Published: 2001
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40. A Pharmacoeconomic Evaluation of Botulinum Toxin in the Treatment of Spasmodic Torticollis

Author: Jean-Louis Montastruc, Michel Clanet, Olivier Rascol, Christine Brefel-Courbon, Carine More, Maryse Lapeyre-Mestre, and Marion Simonetta-Moreau
Subjects: Adult, Male, medicine.medical_specialty, Botulinum Toxins, Posture, Spasmodic Torticollis, Cohort Studies, Central nervous system disease, Quality of life, Internal medicine, medicine, Humans, Pharmacology (medical), Prospective Studies, Cervical dystonia, Prospective cohort study, Torticollis, Aged, Pharmacology, business.industry, Middle Aged, medicine.disease, Botulinum toxin, Surgery, Clinical trial, Nottingham Health Profile, Costs and Cost Analysis, Quality of Life, Female, Neurology (clinical), business, medicine.drug
Abstract: We performed a prospective study in 21 patients to evaluate the cost of treatment of spasmodic torticollis (cervical dystonia) before and after botulinum toxin type A (BTA) treatment and to assess the impact of BTA treatment on quality of life. Data were recorded for the analysis over a period starting 8 months before and ending 7.2 +/- 0.2 months (mean +/- SEM) after the first injection of BTA. All patients received at least two BTA injections (2.9 +/- 0.2 injections per patient). We studied direct medical costs (drugs, outpatient and inpatient visits, diagnostic procedures, physiotherapy), clinical effects of BTA (clinical rating scale and patient's global assessment), quality of life (French version of the Nottingham Health Profile [NHP]), and adverse reactions. Costs associated with the treatment of spasmodic torticollis before the first BTA injection were 479 +/- 143 French Francs (FF)/patient/month (97 +/- 29 US $/pt/mo). During BTA treatment, costs were 1,126 +/- 147 FF/pt/mo (228 +/- 30 US $/pt/mo), including a mean cost of BTA of 771 +/- 131 FF/pt/mo (157 +/- 27 US $/pt/mo). Treatment with BTA significantly decreased clinical symptoms of spasmodic torticollis and improved the emotional, social, and pain-related domains of the quality of life assessment. Botulinum toxin type A treatment increases the cost of treating spasmodic torticollis but improves quality of life in terms of pain, social, and psychologic functioning in patients with spasmodic torticollis.
Published: 2000
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41. Involvement of de novo ceramide biosynthesis in lymphotoxin-induced oligodendrocyte death

Author: Anne-catherine Feutz, Isabelle Plo, Guy Laurent, Michel Clanet, Ali Bettaieb, and Saïd Ghandour
Subjects: Lymphotoxin alpha, Ceramide, Cell Survival, Carboxylic Acids, Biology, Ceramides, Fumonisins, Mice, chemistry.chemical_compound, medicine, Animals, Humans, Enzyme Inhibitors, Cytotoxicity, Lymphotoxin-alpha, Ceramide synthase, Cell Line, Transformed, Fumonisin B1, General Neuroscience, Lipid signaling, Molecular biology, Recombinant Proteins, Oligodendrocyte, Oligodendroglia, Lymphotoxin, medicine.anatomical_structure, Biochemistry, chemistry, Oxidoreductases
Abstract: Both experimental and clinical studies suggest that lymphotoxin (LT) plays an important role in multiple sclerosis (MS) by inducing oligodendrocyte (OL) depletion. However, the mechanism of LT cytotoxicity is unknown. Because of the role of ceramide as a cell death mediator for a large variety of cytotoxic molecules, we have investigated the possible role of this second messenger in LT-induced cytotoxicity on SV40 immortalized new-born mice OL. Human recombinant LT exposure (50 ng/ml) resulted in intracellular ceramide accumulation which peaked at 48 h (approximately 170% increase) and paralleled LT-induced cytotoxicity. Moreover, fumonisin B1, a potent and specific ceramide synthase inhibitor, not only inhibited ceramide accumulation but also protected OL from LT cytotoxicity. These results suggest that LT-induced ceramide synthase stimulation and subsequent increased intracellular ceramide concentration are implicated in oligodendrocyte death.
Published: 1999
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42. Magnetic resonance imaging in multiple sclerosis

Author: Isabelle Berry and Michel Clanet
Subjects: Magnetic Resonance Spectroscopy, Multiple Sclerosis, Gadolinium, Axonal loss, chemistry.chemical_element, Fluid-attenuated inversion recovery, Diffusion, Nuclear magnetic resonance, Predictive Value of Tests, medicine, Humans, Pathological, medicine.diagnostic_test, business.industry, Multiple sclerosis, Relaxation (NMR), Magnetic resonance imaging, Prognosis, medicine.disease, Magnetic Resonance Imaging, Neurology, Gliosis, chemistry, Neurology (clinical), medicine.symptom, business
Abstract: Conventional magnetic resonance imaging (MRI) techniques acquire signal mainly from differences in relaxation properties and density of free water protons. Thus, the sensitivity in depicting lesions is high but pathological specificity is poor. Efforts are being made to increase the diagnostic power of MRI; better correlation with the clinical presentation and the use of better MRI criteria have increased the specificity of the conventional T2 sequences. New sequences, such as fast spin echo, turbo spin echo (TSE) or those derived from inversion recovery (fluid attenuated inversion recovery), have improved the detection of lesions. Acute phase monitoring focuses on changes in disease activity (new, recurring, enlarging, gadolinium-enhancing lesions) and chronic phase monitoring allows appreciation of the burden of the disease. However, MRI is considered as a secondary outcome measure in phase III trials because of insufficient correlation with the clinical disability. There is a continuing search for techniques that correlate better with clinical measures of the disease, such as the quantification of 'black holes' on T1-weighted images or the cerebral and spinal atrophy. The basic aspects of the pathological lesions in multiple sclerosis such as oedema, membrane disruption, demyelination, gliosis, cellular infiltration and axonal loss, can be studied more precisely by the new magnetic resonance techniques, which should better describe the actual clinical impact of the destructive process. In the past year the importance of axonal loss has simultaneously been confirmed by magnetic resonance spectroscopy and pathological findings. However, magnetization transfer imaging, magnetic resonance diffusion imaging and functional MRI are under intensive investigation for a better analysis of these different factors that impact on the reversibility of the patients disability.
Published: 1998
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43. Defining the clinical course of multiple sclerosis The 2013 revisions

Author: Olaf Stüve, Frederik Barkhof, Xavier Montalban, Jeffrey A. Cohen, Michel Clanet, Emmanuelle Waubant, Per Soelberg Sørensen, John Petkau, Stephen C. Reingold, Catherine Lubetzki, Jerry S. Wolinsky, Richard A. Rudick, Andrew D. Goodman, Fred D. Lublin, Maria Pia Sormani, Robert J. Fox, Brenda Banwell, Matilde Inglese, Aaron E. Miller, Bernd C. Kieseier, John A. Lincoln, Alan J. Thompson, Chris H. Polman, Mark S. Freedman, Ludwig Kappos, Bruce F. Bebo, Giancarlo Comi, Gary Cutter, Paul O'Connor, Laura J. Balcer, Peter A. Calabresi, Carlo Pozzilli, Radiology and nuclear medicine, Neurology, NCA - Neuroinflamation, Lublin, Fd, Reingold, Sc, Cohen, Ja, Cutter, Gr, Sørensen, P, Thompson, Aj, Wolinsky, J, Balcer, Lj, Banwell, B, Barkhof, F, Bebo B., Jr, Calabresi, Pa, Clanet, M, Comi, Giancarlo, Fox, Rj, Freedman, M, Goodman, Ad, Inglese, M, Kappos, L, Kieseier, Bc, Lincoln, Ja, Lubetzki, C, Miller, Ae, Montalban, X, O'Connor, Pw, Petkau, J, Pozzilli, C, Rudick, Ra, Sormani, Mp, Stüve, O, Waubant, E, and Polman, C. H.
Subjects: Clinical Trials as Topic, medicine.medical_specialty, Consensus, Multiple Sclerosis, Biological correlates, Humans, Societies, Medical, Neurology (clinical), business.industry, Multiple sclerosis, Advisory committee, Clinical course, MEDLINE, Disease, Relapse rate, medicine.disease, 3. Good health, Clinical trial, Medical, medicine, Societies, business, Psychiatry, Intensive care medicine
Abstract: Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.
Published: 2014
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44. MRI of intramedullary sarcoidosis: follow-up of a case

Author: Isabelle Berry, Michel Clanet, C. Manelfe, Emmanuelle Waubant, and Alain Bonafe
Subjects: Systemic disease, Sarcoidosis, Spinal Cord Diseases, law.invention, Diagnosis, Differential, Lesion, Central nervous system disease, Intramedullary rod, law, medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Neuroradiology, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, Female, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, Nuclear medicine, business, Follow-Up Studies, Calcification
Abstract: Intramedullary lesions are infrequently the first manifestation of sarcoidosis. We present clinical and radiological follow-up of spinal cord sarcoidosis in a 68-year-old woman, mimicking an intramedullary tumour. MRI revealed an unusual area of low signal intensity on T2-weighted spin-echo images at the core of the lesion, consistent with calcification. Clinical and MRI follow-up showed progressive resolution of the intraspinal lesion, except for the calcification, with oral steroid therapy.
Published: 1997
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45. Evidence for Linkage Disequilibrium Between HLA-DRB1 Gene and Multiple Sclerosis

Author: Michel Clanet, E Quelvennec, S. Eichenbaum, Françoise Clerget-Darpoux, Gilles Edan, M.-P. Roth, Gilbert Semana, and J. Yaouanq
Subjects: Genetics, Linkage disequilibrium, Multidisciplinary, Multiple sclerosis, Haplotype, Disequilibrium, Biology, medicine.disease, Genome, Evolutionary biology, Genetic predisposition, medicine, medicine.symptom, Gene, HLA-DRB1
Abstract: In their Perspective “The future of genetic studies of complex human diseases ([13 Sept., p. 1516][1]), Neil Risch and Kathleen Merikangas emphasize that such studies might benefit greatly from approaches based on gametic disequilibrium. Recent genome scans ([1][2]) and our own data on human
Published: 1997
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46. Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria

Author: Isabelle Berry, H M Lai, Michel Clanet, J M Gandon, M.T. Iba-Zizen, Bruno Brochet, O Sabouraud, Y Rolland, Gilles Edan, E A Cabanis, I. F. Moseley, David Miller, Christian Confavreux, J C Froment, Catherine Lubetzki, and Olivier Lyon-Caen
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Exacerbation, medicine.drug_class, medicine.medical_treatment, Methylprednisolone, Gastroenterology, law.invention, Adjuvants, Immunologic, Randomized controlled trial, law, Internal medicine, medicine, Humans, Amenorrhea, Chemotherapy, Mitoxantrone, business.industry, Multiple sclerosis, Therapeutic effect, Alopecia, Leukopenia, medicine.disease, Magnetic Resonance Imaging, Surgery, Psychiatry and Mental health, Corticosteroid, Drug Therapy, Combination, Female, Neurology (clinical), business, Follow-Up Studies, Research Article, medicine.drug
Abstract: OBJECTIVE: To evaluate the efficiency of mitoxantrone in multiple sclerosis. METHODS: Forty two patients with confirmed multiple sclerosis, selected as having a very active disease on clinical and MRI criteria were randomised to receive either mitoxantrone (20 mg intravenously (IV) monthly) and methylprednisolone (1 g iv monthly) or methylprednisolone alone over six months. In the steroid alone group five patients dropped out due to severe exacerbation. RESULTS: Blinded analysis of MRI data showed significantly more patients with no new enhancing lesions in the mitoxantrone group compared with the steroid alone group, (90% v 31%, P < 0.001). In the mitoxantrone group there was a month by month decrease almost to zero in the number of new enhancing lesions, and in the total number of enhancing lesions, whereas both remained high in the steroid alone group. The differences were significant for both indices at all months from 1-6. Unblinded clinical assessments showed a significant improvement in change in EDSS at months 2-6 in the mitoxantrone group, with a final mean improvement of more than one point (-1.1 v + 0.3; P < 0.001). There was a significant reduction in the number of relapses (7 v 31; P < 0.01), and an increase in the number of patients free of exacerbation (14 v 7; P < 0.05). CONCLUSION: In this selected group of patients with multiple sclerosis with very active disease, mitoxantrone combined with methylprednisolone was effective in improving both clinical and MRI indices of disease activity over a period of six months whereas methylprednisolone alone was not. Further double blinded long term studies are needed to properly evaluate the effect of mitoxantrone on progression in disability.
Published: 1997
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47. Sclérose en plaques et vaccination contre l’hépatite B chez l’adulte : le point en 2004

Author: Cyrille B. Confavreux, Ludwig Kappos, T. Arbizu, Sandra Vukusic, Bruno Brochet, Gilles Edan, Samy Suissa, and Michel Clanet
Subjects: Central nervous system disease, Vaccination, Neurology, business.industry, Multiple sclerosis, Medicine, Viral hepatitis b, Neurology (clinical), Viral disease, business, medicine.disease, Virology
Published: 2005
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48. A case report of simultaneous PML-IRIS during corticosteroids tapering in a patient with an anti-synthetase syndrome

Author: David Brassat, Michel Clanet, Emmanuelle Uro-Coste, Guillaume Martin-Blondel, Daniel Adoue, Hervé Dumas, and Hans Lassmann
Subjects: General Immunology and Microbiology, medicine.drug_class, business.industry, Progressive multifocal leukoencephalopathy, viruses, JC virus, Tapering, Antisynthetase syndrome, Case Report, General Medicine, Articles, medicine.disease_cause, medicine.disease, General Biochemistry, Genetics and Molecular Biology, medicine.anatomical_structure, Immune reconstitution inflammatory syndrome, Immunology, medicine, Corticosteroid, Clinical Immunology, General Pharmacology, Toxicology and Pharmaceutics, Iris (anatomy), business, Viral load
Abstract: We report a case of simultaneous progressive multifocal leukoencephalopathy-associated immune reconstitution inflammatory syndrome (PML-IRIS) during corticosteroid tapering in a patient with an anti-synthetase syndrome. We describe the challenges associated with the diagnosis and the management of this emerging inflammatory neurological condition in this immunocompromised patient with a severe rheumatic disease. We highlight that, in the setting of IRIS, the low-level of the JC virus viral load requires a sensitive PCR assay before excluding PML.
Published: 2013

49. Urinary complications and risk factors in symptomatic multiple sclerosis patients. Study of a cohort of 328 patients

Author: Evelyne, Castel-Lacanal, Xavier, Gamé, Michel, Clanet, David, Gasq, Xavier, De Boissezon, Julien, Guillotreau, Véronique, Bourg, Frédérique, Viala, Pascal, Rischmann, and Philippe, Marque
Subjects: Adult, Cohort Studies, Male, Multiple Sclerosis, Lower Urinary Tract Symptoms, Risk Factors, Age Factors, Disease Progression, Quality of Life, Humans, Female, Middle Aged, Retrospective Studies
Abstract: Lower urinary tract dysfunctions (LUTD) are very common in Multiple Sclerosis (MS), have a significant social impact, while the organic impact is discussed. We studied urinary complications and their risk factors in our cohort of MS patients, in order to improve the management of LUTD in MS.Between 2004 and 2009, all patients affected by MS and managed for LUTD were included in a retrospective study. We studied the epidemiological data (age, gender), the clinical data (duration of MS, EDSS score, progression of MS) and the paraclinical data (urinary creatinine clearance, urine culture, urinary tract ultrasonography and in some cases urodynamic assessment and cystography). We then identified the urinary complications and their risk factors.Three hundred twenty eight patients, mean age 49.9 ± 12.3 years, with a MS for 14.3 ± 10 years on average and with a median EDSS score equal to 6 (1-9), were managed for LUTD. One hundred seventy eight (54%) patients developed one or more urinary complications. We identified duration of MS greater than 8.5 years and an EDSS above 7 as risk factors.Urinary complications are common in symptomatic MS, these results imply screening and specialized care to limit the impact on the quality of life but also to prevent urinary complications.
Published: 2013

50. Progressive multifocal leukoencephalopathy in an HIV patient with normal CD4 T-cell count and magnetic resonance imaging

Author: Marie Bernadette Delisle, David Brassat, Michel Clanet, Francesco Scaravilli, and Pierre Delobel
Subjects: Pathology, medicine.medical_specialty, Slow virus, medicine.diagnostic_test, Cd4 t cell, business.industry, Progressive multifocal leukoencephalopathy, Immunology, Human immunodeficiency virus (HIV), Magnetic resonance imaging, medicine.disease_cause, medicine.disease, Central nervous system disease, Infectious Diseases, Immunopathology, medicine, Immunology and Allergy, business
Published: 2004
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