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

Author: Chadia Ed‐driouch, Florent Chéneau, Françoise Simon, Guillaume Pasquier, Benoit Combès, Anne Kerbrat, Emmanuelle Le Page, Sophie Limou, Nicolas Vince, David‐Axel Laplaud, Franck Mars, Cédric Dumas, Gilles Edan, and Pierre‐Antoine Gourraud
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Objective Multiple sclerosis (MS) is a multifactorial disease with increasingly complicated management. Our objective is to use on‐demand computational power to address the challenges of dynamically managing MS. Methods A phase 3 clinical trial data (NCT00906399) were used to contextualize the medication efficacy of peg‐interferon beta‐1a vs placebo on patients with relapsing–remitting MS (RRMS). Using a set of reference patients (PORs), selected based on adequate features similar to those of an individual patient, we visualize disease activity by measuring the percentage of relapses, accumulation of new T2 lesions on MRI, and worsening EDSS during the clinical trial. Results We developed MS Vista, a functional prototype of clinical decision support system (CDSS), with a user‐centered design and distributed infrastructure. MS Vista shows the medication efficacy of peginterferon beta‐1a versus placebo for each individual patient with RRMS. In addition, MS Vista initiated the integration of a longitudinal magnetic resonance imaging (MRI) viewer and interactive dual physician‐patient data display to facilitate communication. Interpretation The pioneer use of PORs for each individual patient enables personalized analytics sustaining the dialog between neurologists, patients and caregivers with quantified evidence.
Published: 2022
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2. Pregnancy-related healthcare utilization among women with multiple sclerosis

Author: Marie Mainguy, Emmanuelle Le Page, Laure Michel, and Emmanuelle Leray
Subjects: multiple sclerosis, pregnancy, healthcare utilization, prenatal care, recommendations, administrative data, Neurology. Diseases of the nervous system, RC346-429
Abstract: IntroductionMany studies have investigated pregnancy in women with multiple sclerosis (MS). However, no study has measured prenatal healthcare utilization in women with MS or adherence to follow-up recommendations to improve antenatal care quality. A better knowledge of the quality of antenatal care in women with MS would help identify and better support women with insufficient follow-up. Our objective was to measure the level of compliance to prenatal care recommendations in women with MS using data from the French National Health Insurance Database.MethodsThis retrospective cohort study included all pregnant women with MS who gave live birth in France between 2010 and 2015. Using the French National Health Insurance Database, follow-up visits with gynecologists, midwives, and general practitioners (GPs) were identified, as well as ultrasound exams and laboratory tests. Based on the Adequacy of Prenatal Care Use and Content and Timing of care in Pregnancy indices, a new tool adapted to the French recommendations was developed to measure and classify the antenatal care trajectory (adequate or inadequate). Explicative factors were identified using multivariate logistic regression models. A random effect was included because women may have had more than one pregnancy during the study period.ResultsIn total, 4,804 women with MS (N = 5,448 pregnancies ending in live births) were included. When considering only visits with gynecologists/midwives, 2,277 pregnancies (41.8%) were considered adequate. When adding visits with GP, their number increased to 3,646 (66.9%). Multivariate models showed that multiple pregnancy and higher medical density were associated with better adherence to follow-up recommendations. Conversely, adherence was lower in 25–29-year-old and >40-year-old women, in women with very low income, and agricultural and self-employed workers. No visits, ultrasound exams, and laboratory tests were recorded in 87 pregnancies (1.6%). In 50% of pregnancies, women had at least one visit with a neurologist during the pregnancy, and women restarted disease-modifying therapy (DMT) within 6 months after delivery in 45.9% of pregnancies.DiscussionMany women consulted their GP during pregnancy. This could be linked to a low density of gynecologists but may also reflect the preferences of women. Our findings can help adapt recommendations and healthcare providers' practices according to the women's profiles.
Published: 2023
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3. Effects of socioeconomic status on excess mortality in patients with multiple sclerosis in France: A retrospective observational cohort studyResearch in context

Author: Sarah Wilson, Floriane Calocer, Fabien Rollot, Mathieu Fauvernier, Laurent Remontet, Laure Tron, Sandra Vukusic, Emmanuelle Le Page, Marc Debouverie, Jonathan Ciron, Aurélie Ruet, Jérôme De Sèze, Hélène Zephir, Thibault Moreau, Christine Lebrun-Frénay, David-Axel Laplaud, Pierre Clavelou, Pierre Labauge, Eric Berger, Jean Pelletier, Olivier Heinzlef, Eric Thouvenot, Jean Philippe Camdessanché, Emmanuelle Leray, Olivier Dejardin, and Gilles Defer
Subjects: Multiple sclerosis, Excess mortality, Net survival, Socio-economic status, Flexible model, Observational cohort study, Public aspects of medicine, RA1-1270
Abstract: Summary: Background: The effects of socio-economic status on mortality in patients with multiple sclerosis is not well known. The objective was to examine mortality due to multiple sclerosis according to socio-economic status. Methods: A retrospective observational cohort design was used with recruitment from 18 French multiple sclerosis expert centers participating in the Observatoire Français de la Sclérose en Plaques. All patients lived in metropolitan France and had a definite or probable diagnosis of multiple sclerosis according to either Poser or McDonald criteria with an onset of disease between 1960 and 2015. Initial phenotype was either relapsing-onset or primary progressive onset. Vital status was updated on January 1st 2016. Socio-economic status was measured by an ecological index, the European Deprivation Index and was attributed to each patient according to their home address. Excess death rates were studied according to socio-economic status using additive excess hazard models with multidimensional penalised splines. The initial hypothesis was a potential socio-economic gradient in excess mortality. Findings: A total of 34,169 multiple sclerosis patients were included (88% relapsing onset (n = 30,083), 12% progressive onset (n = 4086)), female/male sex ratio 2.7 for relapsing-onset and 1.3 for progressive-onset). Mean age at disease onset was 31.6 (SD = 9.8) for relapsing-onset and 42.7 (SD = 10.8) for progressive-onset. At the end of follow-up, 1849 patients had died (4.4% for relapsing-onset (n = 1311) and 13.2% for progressive-onset (n = 538)). A socio-economic gradient was found for relapsing-onset patients; more deprived patients had a greater excess death rate. At thirty years of disease duration and a year of onset of symptoms of 1980, survival probability difference (or deprivation gap) between less deprived relapsing-onset patients (EDI = −6) and more deprived relapsing-onset patients (EDI = 12) was 16.6% (95% confidence interval (CI) [10.3%–22.9%]) for men and 12.3% (95%CI [7.6%–17.0%]) for women. No clear socio-economic mortality gradient was found in progressive-onset patients. Interpretation: Socio-economic status was associated with mortality due to multiple sclerosis in relapsing-onset patients. Improvements in overall care of more socio-economically deprived patients with multiple sclerosis could help reduce these socio-economic inequalities in multiple sclerosis-related mortality. Funding: This study was funded by the ARSEP foundation “Fondation pour l'aide à la recherche sur la Sclérose en Plaques” (Grant Reference Number 1122). Data collection has been 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, Observatoire Français de la Sclérose en Plaques (OFSEP).
Published: 2023
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4. Discontinuation of second- versus first-line disease-modifying treatment in middle-aged patients with multiple sclerosis

Author: Maëlle Chappuis, Chloé Rousseau, Emma Bajeux, Sandrine Wiertlewski, David Laplaud, Emmanuelle Le Page, Laure Michel, Gilles Edan, Anne Kerbrat, CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigation Clinique [Rennes] (CIC), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Multiple Sclerosis, Fingolimod Hydrochloride, Treatment discontinuation, [SDV]Life Sciences [q-bio], Natalizumab, Middle Aged, Age, Multiple Sclerosis, Relapsing-Remitting, Neurology, Recurrence, Humans, Neurology (clinical), Immunosuppressive Agents, Retrospective Studies
Abstract: International audience; Background and purpose: There has been scant research on the consequences of discontinuing second-line disease-modifying treatment (DMT) in middle-aged patients with multiple sclerosis (MS). The objective was therefore to examine the occurrence of focal inflammatory activity after the discontinuation of second versus first-line DMT in patients over 45 years.Methods: Patients who had been treated for at least 6 months with second (natalizumab, fingolimod, anti CD20) or first-line DMT and who stopped their DMT were retrospectively included. Kaplan-Meier survival curves were used to study the occurrence of relapse and MRI activity according to the type of DMT stopped. Proportional hazard Cox models were calculated to identify factors associated with focal inflammatory activity. The annualized relapse rate was calculated under treatment and for every 3 months after DMT discontinuation.Results: We included 232 patients (median age: 52.8 years), 49 of whom stopped second-line DMT. The probability of having a relapse within the year following discontinuation was 6% for first-line DMT, 9% for fingolimod and 43% for natalizumab. In multivariate analysis, the probability of relapse after DMT discontinuation was significantly increased with natalizumab compared to first-line DMT (HR = 3.24; 95% CI [1.52; 6.90]). A peak of relapse was observed at 0-3 months after stopping natalizumab or fingolimod.Conclusion: Our study suggests that the risk of inflammatory activity is greater after discontinuation of natalizumab compared to other DMT even in middle-aged patients. As for younger patients, natalizumab discontinuation should only be considered if there is an adequate substitution of a different therapy. .
Published: 2022
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5. Multiple Sclerosis CSF Is Enriched With Follicular T Cells Displaying a Th1/Eomes Signature

Author: Jérémy, Morille, Marion, Mandon, Stéphane, Rodriguez, David, Roulois, Simon, Leonard, Alexandra, Garcia, Sandrine, Wiertlewski, Emmanuelle, Le Page, Laureline, Berthelot, Arnaud, Nicot, Camille, Mathé, Flora, Lejeune, Karin, Tarte, Céline, Delaloy, Patricia, Amé, David, Laplaud, Laure, Michel, Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang Bretagne, EFS, GMSI (Grant for Multiple Sclerosis Innovation), Merck KGaA, LabEx IGO program - 'Investment into the Future' French Government program [ANR-11-LABX-0016], ARSEP foundation (Aide a la Recherche sur la Sclerose En Plaques), Association ANTARES, INCR (Institut des Neurosciences Cliniques de Rennes), and ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011)
Subjects: B-Lymphocytes, Multiple Sclerosis, [SDV]Life Sciences [q-bio], Humans, Lymphocyte Count, T-Lymphocytes, Helper-Inducer, Th1 Cells, Lymphocyte Activation, T-Box Domain Proteins
Abstract: International audience; Background and Objectives Tertiary lymphoid structures and aggregates are reported in the meninges of patients with multiple sclerosis (MS), especially at the progressive stage, and are strongly associated with cortical lesions and disability. Besides B cells, these structures comprise follicular helper T (Tfh) cells that are crucial to support B-cell differentiation. Tfh cells play a pivotal role in amplifying autoreactive B cells and promoting autoantibody production in several autoimmune diseases, but very few are known in MS. In this study, we examined the phenotype, frequency, and transcriptome of circulating cTfh cells in the blood and CSF of patients with relapsing-remitting MS (RRMS). Methods The phenotype and frequency of cTfh cells were analyzed in the blood of 39 healthy controls and 41 untreated patients with RRMS and in the CSF and paired blood of 10 patients with drug-naive RRMS at diagnosis by flow cytometry. Using an in vitro model of blood-brain barrier, we assessed the transendothelial migratory abilities of the different cTfh-cell subsets. Finally, we performed an RNA sequencing analysis of paired CSF cTfh cells and blood cTfh cells in 8 patients sampled at their first demyelinating event. Results The blood phenotype and frequency of cTfh cells were not significantly modified in patients with RRMS. In the CSF, we found an important infiltration of Tfh1 cells, with a high proportion of activated PD1(+) cells. We demonstrated that the specific subset of Tfh1 cells presents increased migration abilities to cross an in vitro model of blood-brain barrier. Of interest, even at the first demyelinating event, cTfh cells in the CSF display specific characteristics with upregulation of EOMES gene and proinflammatory/cytotoxic transcriptomic signature able to efficiently distinguish cTfh cells from the CSF and blood. Finally, interactome analysis revealed potential strong cross talk between pathogenic B cells and CSF cTfh cells, pointing out the CSF as opportune supportive compartment and highlighting the very early implication of B-cell helper T cells in MS pathogenesis. Discussion Overall, CSF enrichment in activated Tfh1 as soon as disease diagnosis, associated with high expression of EOMES, and a predicted high propensity to interact with CSF B cells suggest that these cells probably contribute to disease onset and/or activity.
Published: 2022
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6. Disease modifying therapies and disease activity during pregnancy and postpartum in a contemporary cohort of relapsing Multiple Sclerosis patients

Author: Lucile Lescot, Mathilde Lefort, Soizic Leguy, Emmanuelle Le Page, Sandra Vukusic, Gilles Edan, Anne Kerbrat, Christine Lebrun-Frenay, Jérome De Sèze, David Axel Laplaud, Sandrine Wiertlewski, Emmanuelle Leray, Laure Michel, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), EHESP-ARENES (EHESP-ARENES), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work has been done with data from the OFSEP (http://www.ofsep.org/fr/), 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 program under the reference ANR-10-COHO-002 OFSEP and by the Eugene Devic Foundation Against Multiple Sclerosis., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Jonchère, Laurent, and Cohortes - Observatoire Français de la Sclérose en Plaques - - OFSEP2010 - ANR-10-COHO-0002 - COHO - VALID
Subjects: Multiple sclerosis, [SDV] Life Sciences [q-bio], [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Neurology, [SDV]Life Sciences [q-bio], Neurology (clinical), General Medicine, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Disease modifying yherapies, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Post-partum, Relapses
Abstract: International audience; BACKGROUND: In Multiple Sclerosis (MS) women, therapeutic management for pregnancy planning and during pregnancy still represents a challenge regarding timing of disease-modifying therapies (DMT) stop, risk of disease reactivation and potential fetal toxicity. The objective of this study was to describe disease activity during pregnancy and postpartum depending on treatment status before conception in women with MS. METHODS: 339 MS patients who have achieved a pregnancy between 2007 and 2017 were included. Women were classified according to their exposure to DMT in the 18 months period prior to pregnancy (untreated / first- / second/third-line treatment). RESULTS: 122 women were not exposed to DMT prior to conception, whereas 147 were exposed to first-line DMT and 70 to second/third line DMT (73% to natalizumab and 23% to fingolimod) before conception. In the first-line group, the ARR decreased from 0.39 during the year before conception to 0.21 during pregnancy, whereas it increased in the second/third-line group from 0.59 to 0.78. 47.1% of the second/third-line group faced at least one relapse during pregnancy and the time from conception to first relapse was significantly shorter in this group (p < 10(-4)). The risk of relapse during pregnancy and postpartum was associated with occurrence of pre-conception relapses and second/third line DMT exposure before pregnancy. CONCLUSION: Careful consideration should be given to natalizumab and fingolimod exposed patients before conception as they are at higher risk of reactivation of MS during pregnancy.
Published: 2022
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7. Assessing the Risk of Relapse Requiring Corticosteroids After In Vitro Fertilization in Women With Multiple Sclerosis

Author: Marie Mainguy, Hélène Tillaut, Adeline Degremont, Emmanuelle Le Page, Christelle Mainguy, Solène Duros, Elisabeth Polard, Emmanuelle Leray, Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), Recherche sur les services et le management en santé (RSMS), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Milieux Environnementaux, Transferts et Interactions dans les hydrosystèmes et les Sols (METIS), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Collectif de recherche handicap, autonomie et société inclusive (CoRHASI), This work was funded by Fondation pour l’aide à la recherche sur la sclérose en plaques (ARSEP)., EHESP, SCD, and École Pratique des Hautes Études (EPHE)
Subjects: Multiple sclerosis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Neurology (clinical), [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology
Abstract: Background and Objectives:Several studies have shown an increased risk of relapse after In Vitro Fertilization (IVF) in women with Multiple Sclerosis (MS), especially when a GnRH agonists stimulation protocol was used. Our objective was to investigate the risk of relapse after IVF in women with multiple sclerosis, overall and according to stimulation protocol (GnRH agonists vs antagonists), using data from the French national health insurance database.Methods:This retrospective cohort study included all women with MS who have benefited from IVF between January 1, 2010 and December 31, 2015 in France. Three-month exposed periods after IVF were compared to unexposed periods before IVF, each woman being her own control. Four outcomes were considered: annualized relapse rate (ARR), proportion of IVF with relapse, difference in the number of relapse “after – before” and the delay from IVF to the first relapse. Relapses were identified by an algorithm based on MS-related hospital admissions and use of corticosteroid therapy. Stimulation protocols and disease-modifying therapies (DMT) were identified using drugs claims. Zero-inflated Poisson regression models adjusted for age at IVF and presence of DMT were used. A random effect on the woman was included because women may have multiple IVF procedures. Subgroup analyses by stimulation protocol and IVF outcome (pregnancy or failure) were conducted.Results:A total of 225 women accounting for 338 IVF were included (mean age at first IVF 34.6 ± 4.5 years; 36% of women had at least two IVF during the period). No increase in the risk of relapse after IVF was found overall (before vs. after IVF: respectively 0.20 vs. 0.18 relapse per patient-year; resp. 7.7% vs. 7.1% of IVF with women having at least one relapse) and in subgroups. A lower ARR before and after IVF was observed among women who remained treated until IVF.Discussion:The maintenance of DMT until IVF appeared to be a determining factor in reducing the risk of relapse. Women with MS should be reassured as we did not show an increased risk of relapse requiring use of corticosteroids therapy after IVF neither with GnRH agonists nor with GnRH antagonists.
Published: 2022
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8. Switching from natalizumab administration at the day hospital to administration at home. A 1 year prospective study of patient experience and quality of life in 30 consecutive patients with multiple sclerosis (TYSAD-35)

Author: Simon Lamy, David Veillard, Hélène Doyen, Anne Kerbrat, Laure Michel, Emilie Chretien, Ahmad Ousmen, Gilles Edan, and Emmanuelle Le Page
Subjects: Neurology, Neurology (clinical), General Medicine
Published: 2023
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9. Trends in disease-modifying therapy use in patients with multiple sclerosis using a 10-year population-based cohort study in France

Author: Soline Leblanc, Mathilde Lefort, Emmanuelle Le Page, Laure Michel, Emmanuelle Leray, Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Collectif de recherche handicap, autonomie et société inclusive (CoRHASI), This work was supported by 'Institut des Neurosciences Cliniques de Rennes', France., and EHESP, SCD
Subjects: Cohort Studies, Multiple sclerosis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, untreated, General Neuroscience, Humans, Pharmacology (medical), Disease-modifying therapies, Health administrative database, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), France, Time-series
Abstract: International audience; Background: The availability of new disease-modifying therapies (DMTs) for patients with multiple sclerosis (MS) provides an opportunity for improving outcomes but makes disease management more complex. Our study aimed to describe changes in therapeutic practices over the period 2009-2018 and measure the impact of the arrival of oral DMTs on the use of injectable DMTs.Methods: Data were extracted from a representative 1/97 sample of the French population covered by the healthcare insurance system. Study period was set from 1 January 2009 to 31 December 2018. Four periods of MS identification were defined (before 2009, 2009-2011, 2012-2015 and 2016-2018).Results: Overall, 1,508 patients with MS were included, of whom 876 (58.1%) were treated at least once over the study period. Untreated patients were older and had more comorbidities than treated ones. First-line DMTs were the most frequent initial DMT (78.5%) and a shift has operated from injectable to oral drugs over time. The proportion of patients receiving several DMTs increased with the number of available drugs. End 2018, beta interferon, glatiramer acetate, teriflunomide, dimethylfumarate, fingolimod and natalizumab shared nearly equal parts.Conclusions: This study provides valuable insights into the real-world use of DMTs and changes that have operated over time.
Published: 2022
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10. COPP-MS: COrticosteroids during the Post-Partum in relapsing Multiple Sclerosis patients

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

Author: Alexandra Garcia, Emilie Dugast, Sita Shah, Jérémy Morille, Christine Lebrun-Frenay, Eric Thouvenot, Jérôme De Sèze, Emmanuelle Le Page, Sandra Vukusic, Aude Maurousset, Eric Berger, Olivier Casez, Pierre Labauge, Aurélie Ruet, Catarina Raposo, Fabien Bakdache, Régine Buffels, Fabienne Le Frère, Arnaud Nicot, Sandrine Wiertlewski, Pierre-Antoine Gourraud, Laureline Berthelot, David Laplaud, Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Centre d’Investigation Clinique de Nantes (CIC Nantes), and Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: MESH: Leukocytes, Mononuclear, MESH: Humans, MESH: Multiple Sclerosis, Relapsing-Remitting, Neurology, MESH: Antibodies, Monoclonal, Humanized, [SDV]Life Sciences [q-bio], MESH: Multiple Sclerosis, Neurology (clinical)
Abstract: Background and ObjectivesOcrelizumab (OCR), a humanized anti-CD20 monoclonal antibody, is highly efficient in patients with relapsing-remitting multiple sclerosis (RR-MS). We assessed early cellular immune profiles and their association with disease activity at treatment start and under therapy, which may provide new clues on the mechanisms of action of OCR and on the disease pathophysiology.MethodsA first group of 42 patients with an early RR-MS, never exposed to disease-modifying therapy, was included in 11 centers participating to an ancillary study of the ENSEMBLE trial (NCT03085810) to evaluate the effectiveness and safety of OCR. The phenotypic immune profile was comprehensively assessed by multiparametric spectral flow cytometry at baseline and after 24 and 48 weeks of OCR treatment on cryopreserved peripheral blood mononuclear cells and analyzed in relation to disease clinical activity. A second group of 13 untreated patients with RR-MS was included for comparative analysis of peripheral blood and CSF. The transcriptomic profile was assessed by single-cell qPCRs of 96 genes of immunologic interest.ResultsUsing an unbiased analysis, we found that OCR as an effect on 4 clusters of CD4+T cells: one corresponding to naive CD4+T cells was increased, the other clusters corresponded to effector memory (EM) CD4+CCR6−T cells expressing homing and migration markers, 2 of them also expressing CCR5 and were decreased by the treatment. Of interest, one CD8+T-cell cluster was decreased by OCR corresponding to EM CCR5-expressing T cells with high expression of the brain homing markers CD49d and CD11a and correlated with the time elapsed since the last relapse. These EM CD8+CCR5+T cells were enriched in the CSF of patients with RR-MS and corresponded to activated and cytotoxic cells.DiscussionOur study provides novel insights into the mode of action of anti-CD20, pointing toward the role of EM T cells, particularly a subset of CD8 T cells expressing CCR5.
Published: 2023
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12. Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study

Author: Martine El-Etr, Jérôme De Seze, Patrick Hautecoeur, Françoise Durand-Dubief, Jean Pelletier, Etienne-Emile Baulieu, Francesco Patti, David-Axel Laplaud, L. Gignoux, Maria Trojano, Emmanuelle Le Page, Sandra Vukusic, Pierre Clavelou, Luca Durelli, Iuliana Ionescu, David Brassat, Eric Berger, Catherine Cornu, Laurent Remontet, Nadine Bossard, Giovanni Castelnovo, Marc Debouverie, François Cotton, Olivier Heinzlef, Romain Marignier, Thibault Moreau, Christine Lebrun-Frenay, 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), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service Hospitalo-Universitaire de Pharmacologie et Toxicologie - Lyon (SHUPT Lyon), Service de Biostatistiques [Lyon], 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), Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Università degli studi di Torino = University of Turin (UNITO), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Strasbourg, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance Publique - Hôpitaux de Marseille (APHM), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Neurologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHI Poissy-Saint-Germain, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), University of Catania [Italy], Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Association Européenne contre les Leucodystrophies, Myelin Project, Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques, Programme Hospitalier de Recherche Clinique 2005, Ministère des Affaires Sociales et de la Santé, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Università degli studi di Torino (UNITO), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle neurosciences [Hôpital de Purpan - Toulouse], CHU Toulouse [Toulouse], Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), 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), Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Università degli studi di Bari Aldo Moro (UNIBA), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Nomegestrol acetate, medicine.medical_specialty, relapses, Norpregnadienes, [SDV]Life Sciences [q-bio], Relapse rate, progesterone, Gastroenterology, sex hormones, Multiple sclerosis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, Recurrence, Internal medicine, estradiol, Medicine, Humans, Post partum, Transdermal, business.industry, Postpartum Period, post-partum, Megestrol, medicine.disease, 17 beta estradiol, 3. Good health, Neurology, chemistry, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, 030215 immunology
Abstract: Background: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy. Objective: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo. Methods: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo. Results: Recruitment was stopped prematurely due to slow inclusions ( n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58–1.39), placebo = 0.97 (0.63–1.50) ( p = 0.79)). Conclusion: POPARTMUS failed showing efficacy of a NOMAc–E2 combination in preventing post-partum relapses.
Published: 2021
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13. Disease reactivation after fingolimod cessation in Multiple Sclerosis patients with pregnancy desire: A retrospective study

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

Author: Olivier Casez, Mikael Cohen, Eric Thouvenot, Adil Maarouf, C. Bensa, Céline Callier, Jonathan Ciron, Pierre Labauge, David Laplaud, Naila Makhani, Bertrand Bourre, Abdulatif Al Khedr, Guillaume Mathey, Thibault Moreau, Sfsep Risc, Sandra Vukusic, Pierre Clavelou, Fabien Rollot, Céline Louapre, Jérôme De Seze, Eric Berger, Daniel Pelletier, A.-M. Guennoc, Aksel Siva, Christina J. Azevedo, Ayman Tourbah, Darin T. Okuda, Alain Créange, F. Durand-Dubief, Philippe Cabre, Jean-Philippe Camdessanché, Hélène Zéphir, Emmanuelle Le Page, Nathalie Derache, Orhun H. Kantarci, Jean-Philippe Neau, Patrick Vermersch, Aurélie Ruet, Lydiane Mondot, Ofsep Investigators, Christine Lebrun-Frénay, Université Côte d'Azur (UCA), Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), 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, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), CHU Pontchaillou [Rennes], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN), CHU Strasbourg, CHU Toulouse [Toulouse], Neurologie générale et maladies inflammatoires 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 Rouen, Normandie Université (NU), CHU de la Martinique [Fort de France], Centre Hospitalier Universitaire [Grenoble] (CHU), Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Amiens-Picardie, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Henri Mondor, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Raymond Poincaré [AP-HP], Maladies et hormones du système nerveux (DHNS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital de la Timone [CHU - APHM] (TIMONE), Mayo Clinic [Jacksonville], Cerrahpasa Faculty of Medicine, Istanbul University, University of Southern California (USC), Yale University School of Medicine, University of Texas Southwestern Medical Center [Dallas], This study was funded through the Observatoire Français de la Sclérose En Plaques, which is supported by grant ANR-10-COHO-002 provided by the French State and handled by the Agence Nationale de la Recherche within the framework of the Investments for the Future program by the Eugène Devic European Database for Multiple Sclerosis Foundation against multiple sclerosis and by the Aide pour la Recherche sur la Sclérose En Plaques Foundation., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), 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), Lille Neurosciences & Cognition - U 1172 (LilNCog), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Yale School of Medicine [New Haven, Connecticut] (YSM), Jonchère, Laurent, and Cohortes - Observatoire Français de la Sclérose en Plaques - - OFSEP2010 - ANR-10-COHO-0002 - COHO - VALID
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Multivariate analysis, Multiple Sclerosis, Adolescent, [SDV]Life Sciences [q-bio], 01 natural sciences, 010104 statistics & probability, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine, Humans, 0101 mathematics, Original Investigation, Clinically isolated syndrome, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, Radiotherapy, business.industry, Multiple sclerosis, Research, Hazard ratio, Magnetic resonance imaging, Conversion, General Medicine, Middle Aged, medicine.disease, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], Online Only, Cross-Sectional Studies, Neurology, Sample size determination, Female, France, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study
Abstract: This cohort study investigates risk factors associated with time to a multiple sclerosis clinical event among patients with radiologically isolated syndrome., Key Points Question Are there clinical or demographic factors associated with time to clinical symptoms of multiple sclerosis among patients with radiologically isolated syndrome? Findings In this cohort study of 372 individuals with radiologically isolated syndrome, young age, the presence of spinal cord lesions, and gadolinium-enhancing lesions on the index magnetic resonance imaging scan were associated with increased risk of onset of clinical symptoms of multiple sclerosis. Meaning These findings identify 3 risk factors associated with multiple sclerosis at the preclinical stage of central nervous system demyelinating disease defined by radiologically isolated syndrome., Importance Younger age, oligoclonal bands, and infratentorial and spinal cord lesions are factors associated with an increased 10-year risk of clinical conversion from radiologically isolated syndrome (RIS) to multiple sclerosis (MS). Whether disease-modifying therapy is beneficial for individuals with RIS is currently unknown. Objectives To evaluate the 2-year risk of a clinical event (onset of clinical symptoms of MS) prospectively, identify factors associated with developing an early clinical event, and simulate the sample size needed for a phase III clinical trial of individuals with RIS meeting 2009 RIS criteria. Design, Setting, and Participants This cohort study used data on prospectively followed-up individuals with RIS identified at 1 of 26 tertiary centers for MS care in France that collect data for the Observatoire Français de la Sclérose en Plaques database. Participants were aged 10 to 80 years with 2 or more magnetic resonance imaging (MRI) scans after study entry and an index scan after 2000. All diagnoses were validated by an expert group, whose review included a double centralized MRI reading. Data were analyzed from July 2020 to January 2021. Exposure Diagnosis of RIS. Main Outcomes and Measures Risk of clinical event and associated covariates at index scan were analyzed among all individuals with RIS. Time to the first clinical event was compared by covariates, and sample size estimates were modeled based on identified risk factors. Results Among 372 individuals with RIS (mean [SD] age at index MRI scan, 38.6 [12.1] years), 354 individuals were included in the analysis (264 [74.6%] women). A clinical event was identified among 49 patients (13.8%) within 2 years, which was associated with an estimated risk of conversion of 19.2% (95% CI, 14.1%-24.0%). In multivariate analysis, age younger than 37 years (hazard ratio [HR], 4.04 [95% CI, 2.00-8.15]; P
Published: 2021
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15. High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice

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

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

Author: Caroline Lavie, Fabien Rollot, Françoise Durand-Dubief, Romain Marignier, Iuliana Ionescu, Romain Casey, Thibault Moreau, Patricia Tourniaire, Michael Hutchinson, Marie Béatrice D’Hooghe, David-Axel Laplaud, Pierre Clavelou, Jérôme De Sèze, Marc Debouverie, David Brassat, Jean Pelletier, Christine Lebrun-Frenay, Emmanuelle Le Page, Giovanni Castelnovo, Eric Berger, Patrick Hautecoeur, Olivier Heinzlef, Luca Durelli, Marinella Clerico, Maria Trojano, Francesco Patti, Sandra Vukusic, A. Alpérovitch, H. Carton, M.B. d’Hooghe, O. Hommes, M. Hutchinson, P. Adeleine, A. Biron, P. Cortinovis-Tourniaire, J. Grimaud, M. Hours, T. Moreau, S. Vukusic, C. Confavreux, G. Chauplannaz, D. Latombe, M. Clanet, G. Lau, L. Rumbach, J.Y. Goas, F. Rouhart, A. Mazingue, E. Roullet, M. Madigand, P. Hautecoeur, P. Brunet, G. Edan, C. Allaire, G. Riffault, J. Leche, T. Benoit, C. Simonin, F. Ziegler, J.C. Baron, Y. Rivrain, R. Dumas, D. Loche, J.C. Bourrin, B. Huttin, B. Delisse, I. Gibert, C. Boulay, M. Verceletto, G. Durand, G. Bonneviot, R. Gil, M.A. Hedreville, C. Belair, R.J. Poitevin, J.L. Devoize, P. Wyremblewski, F. Delestre, A. Setiey, G. Comi, M. Filippi, A. Ghezzi, V. Martinelli, P. Rossi, M. Zaffaroni, M.R. Tola, M.P. Amato, C. Fioretti, G. Meucci, M. Inglese, G.L. Mancardi, D. Gambi, A. Thomas, M. Cavazzuti, A. Citterio, A. Heltberg, H.J. Hansen, O. Fernandez, F. Romero, T. Arbizu, J.J. Hernandez, C. De Andres de Frutos, D. Geffner Sclarky, Y. Aladro Benito, P. Reyes Yanes, M Aguilar, J.A. Burguera, R. Yaya, W. Bonakim Dib, D. Arzua-Mouronte, C.J.M. Sindic, R. Medaer, H. Roose, K.M.J. Geens, D. Guillaume, M. Van Zandycke, J. Janssens, M. Cornette, L. Mol, F. Weilbach, P. Flachenecker, H.P. Hartung, J. Haas, I. Tendolkar, E. Sindrn, H.W. Kölmel, D. Reichel, M. Rauch, S. Preuss, S. Poser, E. Mauch, S. Strausser-Fuchs, H. Kolleger, S. Hawkins, S.J.L. Howell, J.E. Rees, A. Thompson, M. Johnson, M. Boggild, R.P. Gregory, D. Bates, I. Bone, C. Polman, S. Frequin, P. Jongen, J. Correia de Sa, M.E. Rio, S. Huber, J. Lechner-Scott, L. Kappos, I. Ionescu, C. Cornu, M. El-Etr, E.E. Baulieu, M Schumacher, D.H. Miller, M. Pugeat, C. d’Archangues, J. Conard, J. Ménard, R. Sitruk-Ware, C. Pelissier, S. Dat, J. Belaïsch-Allard, N. Athéa, D. Büschsenschutz, O. Lyon-Caen, R. Gonsette, J.P. Boissel, P. Ffrench, F. Durand-Dubief, F. Cotton, C. Pachai, L. Bracoud, G. Androdias, R. Marignier, D.A. Laplaud, S. Wiertlewski, C. Lanctin-Garcia, G. Couvreur, G. Madinier, P. Clavelou, F. Taithe, D. Aufauvre, N. Guy, A. Ferrier, J. De Sèze, N. Collongues, M. Debouverie, F. Viala, D. Brassat, A. Gerdelat-Mas, P. Henry, J. Pelletier, A. Rico-Lamy, C. Lebrun-Frenay, E. Lepage, V. Deburghraeve, G. Castelnovo, E. Berger, M. Blondiau, O. Heinzlef, M. Coustans, C. Clerc, L. Rieu, M. Lauxerois, G. Hinzelin, J.C. Ouallet, D. Minier, P. Vion, N. Gromaire-Fayolle, N. Derache, E. Thouvenot, M. Sallansonnet-Froment, P. Tourniaire, L. Toureille, F. Borgel, B. Stankoff, C. Moroianu, A.M. Guennoc, C.L. Tournier-Gervason, S. Peysson, M. Trojano, F. Patti, E. D’Amico, L. Motti, L. Durelli, A. Tavella, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Service de neurologie fonctionnelle et d'épileptologie [Hôpital Pierre Wertheimer-HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Henri Duffaut (Avignon), National MS Center Melsbroek, Vrije Universiteit Brussel [Bruxelles] (VUB), Vrije Universiteit Brussel (VUB), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Laboratoire de Neuroimagerie in Vivo (LNV), CHU Strasbourg-Centre National de la Recherche Scientifique (CNRS), Les Hôpitaux Universitaires de Strasbourg (HUS), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Neurologie vasculaire, pathologie neuro-dégénérative et explorations fonctionnelles du système nerveux [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Neurologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL), centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Università degli studi di Torino = University of Turin (UNITO), University of Catania [Italy], Hospices Civils de Lyon, Departement de Neurologie (HCL), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Protéines membranaires transductrices d'énergie (PMTE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut des Géosciences de l’Environnement (IGE), Institut de Recherche pour le Développement (IRD)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Environnement Ville Société (EVS), École normale supérieure - Lyon (ENS Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Solvay (France), Laboratoire des Mécanismes et Transfert en Géologie (LMTG), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Institute of Evolutionary Biology, University of Edinburgh, Université de Lille, Sciences et Technologies, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Différenciation, interaction, activation et migration des sous-populations lymphocitaires humaines, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Motricité, interactions, performance EA 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), Laboratoire Ecologie Fonctionnelle et Environnement (ECOLAB), Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Chimie Physique D'Orsay (LCPO), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), RMN et optique : De la mesure au biomarqueur, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Department of Neurology, CHU Lyon, Institut de Recherche de Chimie Paris (IRCP), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Hôpital de Hautepierre [Strasbourg], Laboratoire de Réactivité des Surfaces et des Interfaces (LRSI), Département de Physico-Chimie (DPC), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Empenn, Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques, European Leukodystrophies Association, PHRC National, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pierre Wertheimer, Département de Neurologie, Laboratoire de Mathématiques (LAMA), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Nottingham Scientific Limited, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Turin, Università degli studi di Torino (UNITO), University of Bari Aldo Moro (UNIBA), Department of Neurosciences, Università degli studi di Catania [Catania], Centre de recherche en neurosciences de Lyon (CRNL), Neuroépidémiologie, Institut de Physique du Globe de Paris (IPGP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut de Recherche pour le Développement (IRD)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École nationale supérieure d'architecture de Lyon (ENSAL)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Nationale des Travaux Publics de l'État (ENTPE)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ministère de la Culture (MC), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lavie, Caroline, Rollot, Fabien, Durand-Dubief, Françoise, Marignier, Romain, Ionescu, Iuliana, Casey, Romain, Moreau, Thibault, Tourniaire, Patricia, Hutchinson, Michael, D’Hooghe, Marie Béatrice, Laplaud, David-Axel, Clavelou, Pierre, De Sèze, Jérôme, Debouverie, Marc, Brassat, David, Pelletier, Jean, Lebrun-Frenay, Christine, Le Page, Emmanuelle, Castelnovo, Giovanni, Berger, Eric, Hautecoeur, Patrick, Heinzlef, Olivier, Durelli, Luca, Clerico, Marinella, Trojano, Maria, Patti, Francesco, Vukusic, Sandra, on behalf of PRIMS and POPARTMUS, Investigator, Filippi, Massimo, Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Neuroimagerie: méthodes et applications (Empenn), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire de glaciologie et géophysique de l'environnement (LGGE), Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire Motricité, Interactions, Performance, Université de Nantes (UN), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), CEA-Direction de l'Energie Nucléaire (CEA-DEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-CEA-Direction de l'Energie Nucléaire (CEA-DEN), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Service de neurologie [Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service de Neurologie [CHU Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Service de Neurologie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Clinical sciences, Neuroprotection & Neuromodulation, and Neurology
Subjects: relapses, Neurology, [SDV]Life Sciences [q-bio], MESH: Pregnancy Complications / physiopathology, 0302 clinical medicine, MESH: Pregnancy, Anesthesia, Conduction, Recurrence, MESH: Anesthesia, Conduction / adverse effects, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, reproductive and urinary physiology, relapse, Postpartum Period, post-partum, MESH: Follow-Up Studies, MESH: Multiple Sclerosis / physiopathology, Obstetrical Analgesia, MESH: Multiple Sclerosis / chemically induced, Anesthesia, Female, pregnancy, Adult, medicine.medical_specialty, Clinical Neurology, Multiple sclerosis, MESH: Postpartum Period, 03 medical and health sciences, medicine, Humans, Multiple sclerosi, Post partum, Retrospective Studies, Pregnancy, MESH: Humans, MESH: Pregnancy Complications / chemically induced, business.industry, Neurotoxicity, MESH: Adult, MESH: Retrospective Studies, neuraxial analgesia, medicine.disease, MESH: Recurrence, Multiple sclerosis, neuraxial analgesia, post-partum, pregnancy, Pregnancy Complications, Increased risk, Neurology (clinical), [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: Background: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses. Objective: To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy. Methods: We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992–1995 and 2005–2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis. Results: A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78). Conclusion: Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.
Published: 2019
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18. Focal and diffuse cervical spinal cord damage in patients with early relapsing–remitting MS: A multicentre magnetisation transfer ratio study

Author: Clarisse Carra Dallière, Anne Kerbrat, Gilles Edan, Virginie Callot, Nicolas Collongues, Jean Pelletier, Jérôme De Seze, Emmanuelle Le Page, Josefina Maranzano, David Brassat, Jean-Christophe Ferré, Pierre Labauge, Benoît Combès, C. Barillot, Adil Maarouf, Nicolas Menjot de Champfleur, Elise Bannier, Xavier Ayrignac, Atef Badji, Françoise Durand-Dubief, 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)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Service de Neurologie [CHU Rennes], CHU Pontchaillou [Rennes], Département de Radiologie [CHU de Rennes], Université de Rennes (UR), Centre d'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), 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), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Unité de Neuroimagerie Fonctionnelle [Montréal] (UNF-CRIUGM), Université de Montréal (UdeM)-Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), École Polytechnique de Montréal (EPM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Université de Toulouse (UT), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), PHRC/12-07, Programme Hospitalier de Recherche Clinique, Edan, Gilles, Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Université Fédérale Toulouse Midi-Pyrénées, Empenn, Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire de Neuroimagerie in Vivo (LNV), CHU Strasbourg-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), 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], 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), and Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, MESH: Cervical Cord / diagnostic imaging, MESH: Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging, Neuroimaging, Inversion recovery, quantitative MRI, Lesion, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, medicine, Humans, In patient, 030212 general & internal medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Neuroimaging, Spinal cord, MESH: Humans, Magnetisation transfer, business.industry, Multiple sclerosis, magnetisation transfer imaging, MESH: Magnetic Resonance Imaging / methods, Cervical Cord, relapsing–remitting multiple sclerosis, MESH: Adult, medicine.disease, Magnetic Resonance Imaging, Sagittal plane, MESH: Male, medicine.anatomical_structure, Neurology, Relapsing remitting, Female, MESH: Cervical Cord / pathology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), medicine.symptom, Nuclear medicine, business, MESH: Female, MESH: Multiple Sclerosis, Relapsing-Remitting / pathology, 030217 neurology & neurosurgery
Abstract: Background: Studies including patients with well-established multiple sclerosis (MS) have shown a significant and disability-related reduction in the cervical spinal cord (SC) magnetisation transfer ratio (MTR). Objectives: The objectives are to (1) assess whether MTR reduction is already measurable in the SC of patients with early relapsing–remitting multiple sclerosis (RRMS) and (2) describe its spatial distribution. Methods: We included 60 patients with RRMS Results: Mean whole SC MTR was significantly lower in patients than controls (33.7 vs 34.9 pu, p = 0.00005), even after excluding lesions (33.9 pu, p = 0.0003). We observed a greater mean reduction in MTR for vertebral levels displaying the highest lesion loads (C2–C4). In the axial plane, we observed a greater mean MTR reduction at the SC periphery and barycentre. Conclusion: Cervical SC tissue damage measured using MTR is not restricted to macroscopic lesions in patients with early RRMS and is not homogeneously distributed.
Published: 2019
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19. Co-occurrence of MS and ALS: a clue in favor of common pathophysiological findings?

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

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

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

Author: Gilles Edan, Emmanuelle Le Page, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (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), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1)
Subjects: medicine.medical_specialty, business.industry, Multiple sclerosis, [SDV]Life Sciences [q-bio], MEDLINE, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Neurology, Medicine, 030212 general & internal medicine, Neurology (clinical), business, Intensive care medicine, 030217 neurology & neurosurgery
Abstract: International audience; The therapeutic arsenal for preventing multiple sclerosis (MS) relapses strongly improved over the last 20 years with more than 10 disease-modifying drugs now available. However, relapses can still occur, requiring treatment with corticosteroids to accelerate recovery...
Published: 2017
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22. Induction Therapy for Patients with Multiple Sclerosis: Why? When? How?

Author: Gilles Edan, Emmanuelle Le Page, Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, medicine.medical_specialty, Multiple Sclerosis, Neurology, Clinical Neurology, Drug Administration Schedule, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Pharmacotherapy, Maintenance therapy, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Glatiramer acetate, Randomized Controlled Trials as Topic, Mitoxantrone, business.industry, Multiple sclerosis, Glatiramer Acetate, Induction Chemotherapy, Interferon-beta, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, 3. Good health, Observational Studies as Topic, Psychiatry and Mental health, Treatment Outcome, Current Opinion, Immunology, Alemtuzumab, Neurology (clinical), Peptides, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; The concept of induction treatment followed by long-term maintenance treatment in multiple sclerosis (MS) has attracted considerable attention. The combination of mitoxantrone as the induction therapy followed by an immunomodulatory drug (e.g., interferon beta or glatiramer acetate) as the maintenance therapy is of particular interest. This approach is suitable for patients with particularly aggressive disease, characterised by frequent relapses with incomplete recovery and the accumulation of focal lesions visible on magnetic resonance imaging. A long-term study has shown that a short (6 month) course of mitoxantrone followed by maintenance therapy with an immunomodulatory drug brings about a rapid reduction in disease activity and subsequent sustained disease control for at least 5 years. Furthermore, randomised studies have demonstrated that induction with mitoxantrone followed by maintenance treatment affords better disease control than monotherapy with an interferon beta. Natalizumab is also effective in patients with very active MS, but has a propensity to result in rebound inflammatory disease activity on withdrawal. More recently, a mere 5-day course of 12-mg intravenous perfusions of alemtuzumab was found to bring long-term clinical benefits in early relapsing MS patients at risk of developing severe systemic autoimmune disease within the space of a few years.
Published: 2013
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23. Cognition and quality of life in clinically isolated syndrome patients starting a disease modifying therapy in the QUALICIS study may not predict treatment response at one year

Author: Charlotte Sakarovitch, Thibault Moreau, Pierre Clavelou, Emmanuelle Le Page, Mikael Cohen, Christine Lebrun, Ayman Tourbah, Patrick Vermersch, Heloise Joly, Bruno Brochet, Centre Hospitalier Universitaire de Nice (CHU Nice), Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), HABITER - EA 2076 (HABITER), Université de Reims Champagne-Ardenne (URCA)-Maison des Sciences Humaines de Champagne-Ardenne (MSH-URCA), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Reference 000448/1, Bayer Schering, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Health-related quality of life, [SDV]Life Sciences [q-bio], Contrast Media, Gadolinium, Disease, Treatment response, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Cognition, Adjuvants, Immunologic, Subcutaneous Absorption, Quality of life, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, CIS, Clinically isolated syndrome, Drug Substitution, business.industry, Multiple sclerosis, Interferon beta-1b, Brain, Prognosis, medicine.disease, 3. Good health, Neurology, Cohort, Quality of Life, Physical therapy, Female, Neurology (clinical), business, Beta interferon, 030217 neurology & neurosurgery, Demyelinating Diseases, Follow-Up Studies, MRI
Abstract: International audience; Cognition and health-related quality of life (HRQoL) are early involved in multiple sclerosis (MS). The aim of QUALICIS study was to monitor cognition and HRQoL prospectively in a cohort of clinically isolated syndrome (CIS) patients starting a treatment with subcutaneous beta-1b interferon as a first disease modifying treatment (DMT), and to assess their correlation with the clinical outcome 6 years later. Relapse history, EDSS and yearly standardized brain MRI data were also collected. 37 patients were included. Cognition and HRQoL remained stable over treatment period. At baseline, we found that SDMT was moderately correlated to T2 lesion load (r = − 0.47, p = 0.04). Baseline SDMT was predictive of HRQoL at year 2 (r = 0.53, p = 0.02). Regarding 6-year outcome, the most specific predictive factor of favorable outcome was achieving “No Evidence of Disease Activity” (NEDA) status at year 1. In this group, all the patients had a stable EDSS score and none switched to a second line therapy. In the “non-NEDA” group, 44% of patients experienced EDSS worsening and 38.9% switched to a second line therapy. The number of gadolinium enhancing lesions on baseline scan was the only predictive factor of poor outcome in this subgroup of patients (2 vs. 0.13, p = 0.03). Our results suggest that NEDA at 1 year could be used to predict long term outcome after initiation of DMT in CIS. For non-NEDA patients, monitoring SDMT and brain atrophy could be potentially relevant, but this should be confirmed on a larger sample. © 2017 Elsevier B.V.
Published: 2017
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24. Poussées tardives et évolution du handicap chez les patients atteints de sclérose en plaques secondairement progressive

Author: Chloé Rousseau, Gilles Edan, Kevin Ahrweiller, Anne Kerbrat, Emmanuelle Leray, Emma Bajeux, and Emmanuelle Le Page
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction L’evolution de l’activite inflammatoire focale avec l’âge chez les patients atteints de SEP secondairement progressive (SEP-SP) a ete peu exploree, et la question du traitement de fond chez ces patients reste debattue. Objectifs (1) Decrire l’evolution a long terme des poussees dans une cohorte de patients SEP-SP ; (2) Identifier les facteurs associes a la persistance des poussees ; (3) Evaluer l’impact des poussees sur l’aggravation du handicap. Methodes Il s’agit d’une etude retrospective a partir de la base EDMUS de Rennes. Les patients suivis regulierement pour une SEP-SP ont ete inclus. Les taux annualises de poussee (TAP) ont ete evalues, ainsi que les facteurs associes aux poussees (âge, sexe, duree d’evolution, handicap). L’influence des poussees sur le temps pour atteindre un score EDSS 6 depuis le debut de la phase progressive, et sur l’aggravation irreversible du handicap au decours de differentes periodes ont ete analysees. Resultats Nous avons inclus 506 patients avec duree moyenne de suivi de 14,3 ± 7,3 annees en phase progressive. Le TAP diminue avec l’âge des patients (43 % pour 10 ans) et la duree de la maladie (46 % pour 5 ans). Les poussees n’influencent pas le temps pour atteindre l’EDSS 6, mais sont associees a une augmentation du risque d’aggravation irreversible du handicap a court terme durant les premieres annees de phase progressive (HR = 3,32 ; IC95 % [1,54 ; 6,31] de 0 a 3 ans et HR = 2,14 ; IC95 % [1,16 ; 3,58] de 3 a 5 ans). Discussion Les poussees persistent en phase SP pour une minorite de patients et leur frequence diminue avec l’âge et la duree d’evolution de la phase progressive. Elles semblent avoir un impact sur l’aggravation du handicap a court terme durant les premieres annees de phase progressive. Cet impact reste limite a un stade plus evolue. Conclusion Les poussees concernent essentiellement les patients les plus jeunes en debut de phase secondairement progressive, suggerant un interet particulier des traitements de fond a visee immunologique a ce stade.
Published: 2018
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25. Pertinence des soins : le modèle Choosing wisely® (CW) est-il applicable à la prise en charge de la sclérose en plaques (SEP) en France ? Une étude pilote du GRESEP

Author: Jérôme De Seze, Hélène Zéphir, Emmanuelle Le Page, Bruno Trumbic, David Laplaud, Jean-Christophe Ouallet, and C. Bensa
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction La campagne CW vise a ameliorer la pertinence des soins par la limitation des explorations et traitements superflus selon les societes savantes. Les preconisations sont discutees entre medecins et patients pour une decision partagee. Objectifs Evaluer la faisabilite et l’interet du modele CW dans la prise en charge de la sclerose en plaques (SEP) en pratique quotidienne en France. Methodes Preconisations elaborees par deux groupes de travail independants selon une methode derivee du consensus formalise de la Haute Autorite de sante. Resultats Sept preconisations ont ete retenues, relatives a la place des potentiels evoques multimodaux dans le diagnostic, au traitement des poussees par corticoides (dose, voie, contexte d’administration), a la prise en charge anti-infectieuse des patients sous autosondage intermittent, au traitement de la fatigue. Par exemple : dans le traitement des poussees de SEP, il n’est pas indispensable d’administrer systematiquement une corticotherapie a forte dose par voie IV, si la voie orale peut etre utilisee. Discussion L’acceptabilite de ces preconisations par des praticiens non specialises, ainsi que leur impact sur les pratiques reelles restent a evaluer. Conclusion Le modele CW est contributif a l’analyse de la pertinence des soins de SEP en pratique quotidienne. Informations complementaires BIOGEN France a apporte un soutien financier a l’organisation de la reunion entre le groupe de redaction et le groupe de cotation, sans prendre part a la conception de l’etude, a la selection des recommandations et a leur contenu.
Published: 2018
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26. Caractéristique de la cohorte française des syndromes radiologiques isolés (RIS)

Author: Patrick Vermersch, Céline Callier, Françoise Durand-Dubief, Pierre Labauge, Emmanuelle Le Page, Christine Lebrun-Frenay, Caroline Papeix, and Ofsep, Sfsep, Risc
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction Le RIS est caracterise par une decouverte fortuite sur l’IRM cerebrale ou de la moelle, d’images qui suggere une maladie demyelinisante sans symptomes. Objectifs En prospectif, les dossiers sont centralises et analyses selon une procedure standardisee. L’objectif est de confirmer le diagnostic, recueillir des donnees cliniques, biologiques et d’imagerie pour promouvoir les recherches. Methodes Il s’agit d’une cohorte prospective nationale, comprenant 35 centres specialise en SEP, regroupant tous les cas de suspicion de RIS depuis 2004. Les dossiers de RIS sont identifies dans chaque centre par le specialiste local de la SEP. Le coordonnateur national recueille tous les cas de RIS, les antecedents medicaux du patient et une lecture IRM en double insu permet de statuer sur le statut RIS du patient. Resultats En decembre 2016, nous avions : 72,5 % de femmes, 27,5 % d’hommes, âge moyen 36,4 ans. Les motifs d’IRM sont variables. Pour un suivi moyen de 34 mois, 30 % des patients ont converti cliniquement ; 34 % dissemine sur l’IRM cerebrale avant la conversion clinique. A ce jour, 26,5 % patients ont une dissemination sur l’IRM cerebrale sans conversion clinique. Le statut RIS est valide sur l’imagerie et les antecedents medicaux. Discussion La cohorte a une centralisation standardisee avec un suivi clinique, radiologique et biologique annuel. Les donnees prospectives recueillies ne semblent pas differer de celles publiees en 2009 sur un echantillon retrospectif plus petit. Il est important d’ameliorer la detection des patients et de mieux caracteriser certains symptomes neurologiques atypiques qui pourraient etre consideres comme des formes atypiques de SEP. Conclusion Ces donnees doivent etre incluses et confirmees dans une cohorte mondiale. Une etude europeenne de phase III (TERIS) commence en 2017, evalue l’efficacite du teriflunomide versus placebo dans le report du premier evenement. Informations complementaires Nous tenons a remercier les medecins participant a l’OFSEP pour leur contribution : C. Carra Dalliere, C. Louapre, S. Wiertlewski, D. Brassat, B. Brochet, E. Thouvenot, A. Tourbah, E. Berger, G. Mathey, T. Moreau, J. De Seze, J. Ciron, B. Bourre, J.P. Camdessanche, P. Cabre, P. Clavelou, G. Defer, A. Creange, K. Deiva, A. Al Khedr, O. Casez, L. Magy, J. Pelletier, O. Heinzlef, C. Bensa, B. Stankoff, T. De Broucker, A. Guennoc, S. Vukusic, L. Mondot, M. Cohen.
Published: 2018
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27. Evidence for a two-stage disability progression in multiple sclerosis

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

Author: Emmanuelle Le Page and Gilles Edan
Subjects: Adult, Central Nervous System, Oncology, medicine.medical_specialty, Multiple Sclerosis, Methylprednisolone, Pharmacotherapy, Clinical Protocols, Maintenance therapy, Internal medicine, medicine, Humans, Glatiramer acetate, Mitoxantrone, Cumulative dose, business.industry, Multiple sclerosis, Interferon beta-1a, Interferon-beta, medicine.disease, Surgery, Clinical trial, Early Diagnosis, Treatment Outcome, Neurology, Drug Therapy, Combination, Female, Neurology (clinical), business, Immunosuppressive Agents, medicine.drug
Abstract: The concept of induction treatment followed by a long-term maintenance treatment has attracted much attention for the treatment of multiple sclerosis. In particular, the combination of induction therapy with mitoxantrone followed by maintenance therapy with an immunomodulatory treatment such as an interferon-beta or glatiramer acetate is of particular interest. This approach is suitable for patients with particularly aggressive disease, characterised by frequent early relapses with incomplete recovery and multiple gadolinium-enhancing T1 lesions on magnetic resonance imaging. Long-term studies show that a short (six-month) course of mitoxantrone provides a rapid reduction in disease activity and sustained disease control up to at least five years of maintenance therapy with an immunomodulatory treatment. Clinical benefit seems to be greatest when patients with aggressive disease are treated early. Randomised studies have demonstrated that induction with mitoxantrone followed by maintenance treatment provides superior disease control to monotherapy with an interferon-beta. With the treatment protocol recommended for use in France (six monthly administrations of mitoxantrone iv at a cumulative dose of 72 mg/m(2)), mitoxantrone is generally well-tolerated. These findings encourage the use of such induction regimens in patients who present early signs of aggressive disease.
Published: 2009
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29. Alemtuzumab as rescue therapy in a cohort of 16 aggressive multiple sclerosis patients previously treated by Mitoxantrone: an observational study

Author: Isabelle Cardiet, Emmanuelle Leray, Véronique Deburghgraeve, Marie-Antoinette Lester, Emmanuelle Le Page, Gilles Edan, CHU Pontchaillou [Rennes], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), 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), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), 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), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Neurology, Multiple Sclerosis, [SDV]Life Sciences [q-bio], Antineoplastic Agents, Antibodies, Monoclonal, Humanized, Cohort Studies, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Pharmacotherapy, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Humans, 030212 general & internal medicine, Alemtuzumab, Mitoxantrone, medicine.diagnostic_test, business.industry, Multiple sclerosis, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Surgery, Treatment Outcome, Cohort, Disease Progression, Drug Therapy, Combination, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug, Cohort study
Abstract: International audience; Our study aimed to describe safety and neurological impact of alemtuzumab as last-line rescue therapy in aggressive multiple sclerosis (MS) patients, previously treated by Mitoxantrone (MITOX). Between June 2004 and October 2013, 13 patients received alemtuzumab at 20 mg/day and 3 at 12 mg/day for 5 days. EDSS, relapses, secondary progression were prospectively assessed 12 and 6 months before treatment, at baseline and every 3 months. Mean follow-up was 6.2 years [1–10]. Mean age at alemtuzumab start was 40 years [26–49] for 8 Secondary Progressive (SP) and 30 years [26–35] for 8 Relapsing-Remitting (RR) patients. MS duration was 13.7 (±3) and 8.3 (±4) years, respectively. During the 12 months before alemtuzumab, annual relapse rate was 0.75 and 3.14, respectively and the 16 patients accumulated 2–30 new gadolinium enhancing lesions. 4 patients (suboptimal responders) received alemtuzumab during MITOX and 12 patients 1–7.8 years after MITOX. Out of 8 SPMS, 2 were disease free up to last visit (4.7 and 8 years), 5 improved or stabilized but only transiently and 1 worsened. Out of 8 RRMS, 1 remained stable up to last visit (8.7 years) despite 1 relapse and active MRI at 18 months and 7 improved (1–4 point EDSS): 4 remained disease free up to last visit (12, 24, 38 months and 7 years), 2 were successfully retreated at 25 and 33 months and 1 worsened progressively 24 months after alemtuzumab. 2 patients developed Grave’s disease and 1 hypothyroidism. Alemtuzumab controls aggressive RRMS despite previous use of MITOX.
Published: 2015
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30. 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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31. Quand adresser un patient atteint de sclérose en plaques en évaluationmultidisciplinaire ?

Author: Emmanuelle Le Page
Abstract: La sclerose en plaques (SEP) est l’affection neurologique potentiellement invalidante la plus frequente de l’adulte jeune. Les risques sont l’installation de handicaps physiques et cognitifs a plus ou moins long terme, retentissant sur l’environnement personnel, social, familial et professionnel des patients. Les situations peuvent donc etre complexes, depassant les competences du neurologue seul et necessitant alors l’intervention d’un ensemble de professionnels de sante pour assurer une prise en charge globale : des medecins (medecine physique et readaptation, ophtalmologistes, psychiatres, urologues, etc.), des paramedicaux (kinesitherapeutes, infirmieres, ergotherapeutes, orthophonistes, dieteticiennes, psychologues, neuropsychologues, etc.) et des assistantes sociales. Les consultations multidisciplinaires SEP offrent la possibilite a un meme patient de rencontrer le meme jour en un meme lieu plusieurs de ces intervenants : ils feront des propositions a mettre en place par les professionnels de proximite qui doivent rester les acteurs privilegies de la prise en charge des patients (le neurologue referent du patient, le medecin de medecine physique et readaptation du centre le plus proche de son domicile, l’infirmiere, le kinesitherapeute de proximite, etc.). Dans certaines regions, la mise en place de ces consultations multidisciplinaires s’articule avec les reseaux SEP ou des reseaux pour personnes handicapees qui permettent d’identifier un maillage de correspondants medicaux et paramedicaux ayant acces a des formations specifiques sur la SEP, ce qui contribue a attenuer les disparites d’acces a des soins adaptes et de qualite suivant le lieu de residence des patients.
Published: 2009
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32. Alemtuzumab en France : données des autorisations d’importation à 1 an

Author: Xavier Ayrignac, Elisabeth Maillart, Pierre Labauge, Jérôme De Seze, Sandra Vukusic, Nicolas Collongues, and Emmanuelle Le Page
Subjects: Gynecology, medicine.medical_specialty, Neurology, business.industry, medicine, Neurology (clinical), business
Abstract: Introduction L’alemtuzumab, qui a demontre une efficacite superieure a l’interferon beta-1-a dans le traitement des formes actives de sclerose en plaques remittente-recurrente, souleve cependant des questions concernant son innocuite. Objectifs Caracteriser le profil des patients traites par alemtuzumab en France en 2015 dans le cadre de l’autorisation exceptionnelle d’importation et preciser le profil de securite et d’efficacite a 1 an. Patients et methodes Trente-cinq demandes d’autorisation d’importation d’alemtuzumab ont ete analysees de maniere retrospective. Nous avons analyse les caracteristiques demographiques des patients, la severite de la maladie au moment du traitement (poussees, EDSS, evolution recente de l’EDSS et donnees IRM) et les traitements prealables. Nous avons egalement etudie les effets secondaires rapportes : reactions immediates a la perfusion et effets retardes notamment reactions dysimmunitaires et infections. Resultats Caracteristiques des patients : âge au debut du traitement : 37 ans (16–60) ; duree d’evolution de la SEP : 10,8 ans (1,5–26) ; EDSS moyen : 6 (2,5–9,5) avec progression ≥ 1 point de l’EDSS et ≥ 2 poussees dans l’annee precedente chez 11 et 22 malades respectivement. En termes de tolerance : reaction immediate (essentiellement cutanee) : n = 14 patients, reactions tardives : n = 4 (suivi moyen : 5 mois). A 6 mois, l’EDSS etait inchange. Discussion L’alemtuzumab est actuellement prescrit en France chez des patients ayant une maladie tres severe, avec un handicap deja important. On remarque une stabilisation du handicap et une diminution de la frequence des poussees a 6 mois. Les reactions immediates sont frequentes mais entrainent rarement un arret du traitement ; les reactions tardives sont rares dans les 6 premiers mois. Conclusion L’alemtuzumab est actuellement place tardivement dans les schemas therapeutiques proposes aux patients. L’analyse de son efficacite est par consequent difficile. Le profil de tolerance semble proche des donnees existantes.
Published: 2016
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33. Suivi cognitif et thymique longitudinal de patients atteints d’un syndrome cliniquement isolé

Author: Christine Lebrun, Patrick Vermersch, Bruno Brochet, Emmanuelle Le Page, Heloise Joly, Cohen Mikael, and Pierre Clavelou
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction La mise en place d’un traitement immunomodulateur chez les patients atteints d’un syndrome cliniquement isole (SCI) a haut risque de developper une sclerose en plaques permet de retarder cette evolution. Objectifs Cette etude visait a evaluer les repercussions au long court de l’introduction de ce traitement sur les plans cognitif et thymique des patients atteints d’un SCI. Patients et methodes QUALICIS etait une etude multicentrique longitudinale sur 4 ans, comprenant chaque annee une evaluation cognitive (capacites attentionnelles, mnesiques, et executives), et thymique (anxiete, depression). Ont ete inclus 35 patients presentant un SCI (23 femmes et 12 hommes), et commencant un traitement sous-cutane par l’interferon beta-1b, d’un âge moyen de 34 ans (18–52), d’un niveau d’etude moyen de 12 ans (9–20), et ayant un score d’EDSS median de 0,9 (0–3). Resultats A l’inclusion, des scores faibles (−0,5 ET) etaient observes aux epreuves evaluant la vitesse de traitement (SDMT), la memoire episodique verbale (Grober et Buschke), et la flexibilite mentale (WCST). Dans le temps, les scores se sont ameliores a toutes les epreuves proposees hormis a celles evaluant la flexibilite mentale (erreurs perseveratives) et les capacites visuo-spatiales. Un plus grand nombre de patients presentait un etat d’anxiete et de depression a l’inclusion qu’a la fin de l’etude. Discussion Les defauts cognitifs observes a l’inclusion concordent avec les donnees de la litterature avec au premier plan un ralentissement de la vitesse de traitement et des faiblesses aux niveaux mnesique et executif. Ce profil est evocateur de dysfonctionnements sous-cortico-frontaux. La degradation des capacites visuo-spatiales pourrait decouler de l’apparition de troubles ophtalmiques ce qui sera evalue grâce a l’etude ancillaire. Conclusion Des recherches ulterieures viseront a investiguer les liens de causalite entre la cognition, le moral, et la qualite de vie, puis a les confronter aux donnees ophtalmologiques et d’imagerie cerebrale.
Published: 2016
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34. Mitoxantrone to treat multiple sclerosis

Author: Gilles Edan and Emmanuelle Le Page
Subjects: medicine.medical_specialty, Blinding, business.industry, Cross-sectional study, Multiple sclerosis, Clinical study design, Confounding, Case-control study, Retrospective cohort study, medicine.disease, Immunology, medicine, Observational study, Intensive care medicine, business
Abstract: This chapter focuses on the various study designs used to estimate long-term treatment effects of disease-modifying therapies (DMTs) in multiple sclerosis (MS). It also discusses their strengths and weaknesses and the methodological challenges. Results suggest that sustained early treatment in MS patients can delay progression to significant disability and the studies support the concept that early treatment with DMTs has long-lasting effects. Long-term follow-up of patients have significant limitations, including loss of randomization and blinding, incomplete ascertainment, and the absence of an appropriate comparator. Long-term non-randomized observational trials (NROTs) include a wide range of study designs, such as prospective and retrospective cohort studies, case-control studies, and cross-sectional studies, with the common feature that any intervention studied is determined by clinical practice and not by the protocol. Several epidemiological and statistical methods are available to deal with confounding, in both design and analytical phases of NROTs.
Published: 2011
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35. Acute fulminant demyelinating disease: a descriptive study of 60 patients

Author: Gilles Edan, Pierre Labauge, Frédéric Blanc, Marc Debouverie, Olivier Gout, Jérôme De Seze, Christine Lebrun, David Laplaud, Hélène Zéphir, Emmanuelle Le Page, Sophie Pittion, Romain Deschamps, Valérie Jaillon, Patrick Vermersch, Pierre Clavelou, Jean Pelletier, Véronique Bourg, Gilles Defer, Philippe Cabre, Sandrine Wiertlewski, Irina Malikova, and Clotilde Boulay
Subjects: Adult, Male, medicine.medical_specialty, Pediatrics, Multiple Sclerosis, Databases, Factual, Fulminant, Cohort Studies, Arts and Humanities (miscellaneous), medicine, Demyelinating disease, Humans, Prospective cohort study, Retrospective Studies, First episode, medicine.diagnostic_test, business.industry, Multiple sclerosis, Brain, Magnetic resonance imaging, Retrospective cohort study, Middle Aged, medicine.disease, Prognosis, Magnetic Resonance Imaging, Surgery, Spinal Cord, Disease Progression, Female, Neurology (clinical), business, Cohort study, Demyelinating Diseases
Abstract: Acute demyelinating encephalomyelitis (ADEM) is characterized by a severe inflammatory attack, frequently secondary to infectious events or vaccinations. To date, no clear criteria exist for ADEM, and the risk of subsequent evolution to multiple sclerosis (MS) remains unknown.To evaluate the risk of evolution to MS after a first episode of ADEM.Observational, retrospective case study.Thirteen French MS centers. Patients We retrospectively studied 60 patients with ADEM who were older than 15 years with no history suggestive of an inflammatory event who presented to MS centers from January 1, 1995, through December 31, 2005. We excluded 6 patients with multiphasic ADEM because this is a rare condition and somewhat difficult to classify. After a mean follow-up of 3.1 years (range, 1-10 years), the remaining 54 patients were then classified into 2 groups: monophasic ADEM (ADEM group) (n = 35) and clinically definite MS (MS group) (n = 19).Clinical, laboratory, magnetic resonance imaging, and follow-up data were evaluated for each group.Patients in the ADEM group more frequently had atypical symptoms of MS (26 of 35 [74%]) than patients with MS (8 of 19 [42%]) (P = .02). Oligoclonal bands were more frequently observed in the MS group (16 of 19 [84%]) than in the ADEM group (7 of 35 [20%]) (P.001). Patients in the ADEM group more frequently had gray matter involvement (21 of 35 [60%]) than those in the MS group (2 of 19 [11%]) (P.001). On the basis of these results, we consider that the presence of any 2 of the following 3 criteria could be used to differentiate patients with ADEM from those with MS in our cohort: atypical clinical symptoms for MS, absence of oligoclonal bands, and gray matter involvement. On this basis, 29 of the 35 patients in the ADEM group (83%) and 18 of the 19 patients in the MS group (95%) were classified in the appropriate category.Our study found some differences concerning the risk of evolution to clinically definite MS after a first demyelinating episode suggestive of ADEM. These findings led us to propose criteria that should now be tested in a larger, prospective cohort study.
Published: 2007

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

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

37. Prise en charge de l’échappement thérapeutique au fingolimod (FTY) en France : un état des lieux à partir de 93 patients atteints de SEP rémittente récurrente

Author: Caroline Papeix, Christine Lebrun, Jérôme De Seze, Emmanuelle Le Page, Pierre Labauge, Mikael Cohen, and Clarisse Carra-Dalliere
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction Sous FTY, indique dans la SEP remittente recurrente active (RRA), certains patients presentent des poussees, voire des rebonds d’activite de la maladie. Il n’existe pas de recommandation pour cet echappement therapeutique. Objectifs Colliger les caracteristiques des patients francais consideres en ET au FTY, decrire l’attitude therapeutique des neurologues et l’evolution a un an des patients, en fonction de cette attitude. Methodes Etude observationnelle retrospective multicentrique francaise rassemblant des patients atteints de SEP-RRA provenant de 20 centres tertiaires referents pour les maladies inflammatoires. L’ET etait defini comme la survenue d’une poussee associee a une activite radiologique sur l’IRM cerebrale (lesion[s] rehaussee[s] par le gadolinium et/ou nouvelle[s] lesion[s] en hypersignalT2). Les donnees cliniques, radiologiques et la decision therapeutique etaient collectees de maniere anonymisee par formulaire Google doc. Resultats Quatre-vingt-treize patients ont ete inclus (23H/70F ; âge moyen : 36 ans). Le traitement dans l’annee precedente etait : natalizumab (35/93 = 38 %), immunomodulateur (31/93 = 33 %) ou aucun (21/93 = 23 %). Au moment de l’ET, la duree moyenne de traitement etait : 7,4 mois ; le FTY a ete majoritairement poursuivi (60/93 = 65 %). Soixante-deux patients (67 %) ont ete reevalues a un an. Dans le groupe « poursuite FTY » : 56 % des patients ont presente au moins une nouvelle poussee, contre 37 % dans le groupe « switch ». Vingt-sept patients (44 %) sont encore sous FTY. Discussion Initialement, le FTY est majoritairement poursuivi : a un an, la plupart de ces patients ont presente une poussee. Dans le groupe ayant change de traitement, ce taux est inferieur. Dans le sous-groupe de patients auparavant sous natalizumab et toujours sous FTY a un an, 14/19 (74 %) ont presente au moins 1 nouvelle poussee, donnee contre l’hypothese d’un rebond tardif a l’arret du natalizumab. Conclusion Lorsque le FTY est poursuivi, malgre une situation d’ET, la plupart des patients presentent une nouvelle poussee a un an. En cas d’ET, il ne parait donc pas licite de poursuivre le meme traitement. Informations complementaires L’evolution a un an sera connue pour la quasi-totalite des patients en avril.
Published: 2015
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38. [Drug therapy in multiple sclerosis]

Author: Emmanuelle, Le Page and Gilles, Edan
Subjects: Multiple Sclerosis, Adjuvants, Immunologic, Humans, Immunosuppressive Agents
Abstract: For the last 10 years, three disease-modifying-therapy drugs have been approved by the French health authorities for the treatment of relapsing-remitting MS: two of them are immunomodulatory agents (interferon beta 1a or 1b and glatiramer acetate), administered by subcutaneous or intramuscular injections at different time points, reducing by about 30% the risk of relapses. The third drug approved is an immunosuppressive agent, mitoxantrone, administered intravenously at a dose of 12 mg/m2 per month up to a maximum cumulative dose of 72 mg/m2, used as a second line therapy in rapidly worsening relapsing MS non responder to immunomodulatory agents. The impact of such medications in MS patients with gradual progression of disability has not yet been established either in secondary or primary progressive MS.
Published: 2006

39. Neutralizing antibodies to interferon beta in multiple sclerosis: analytical evaluation for validation of a cytopathic effect assay

Author: Catherine Massart, Emmanuelle Le Page, Joel Oger, Gilles Edan, and Jacqueline Gibassier
Subjects: Adult, Male, Multiple Sclerosis, medicine.drug_class, viruses, Clinical Biochemistry, Indicator Dilution Techniques, Enzyme-Linked Immunosorbent Assay, Monoclonal antibody, Biochemistry, Virus, Antibodies, Neutralization Tests, Cell Line, Tumor, Medicine, Bioassay, Humans, Cytopathic effect, biology, business.industry, Multiple sclerosis, Biochemistry (medical), Titrimetry, Reproducibility of Results, General Medicine, Interferon-beta, Middle Aged, medicine.disease, biology.organism_classification, Virology, Cell culture, Vesicular stomatitis virus, biology.protein, Female, Antibody, business
Abstract: Background Recent guidelines have recommended the use of validated assays for the measurement of neutralizing antibodies (NABs) to interferon beta (IFNβ) in patients with multiple sclerosis (MS). In an attempt of validation, we studied the analytical performance of a bioassay based on antiviral cytopathic effect (CPE) using WISH cells and the vesicular stomatitis virus (WISH/VSV CPE). Methods NAB titres measured with the WISH/VSV CPE assay in 63 sera from IFNβ-treated MS patients were compared to those obtained with the reference CPE method using A549 cells and the encephalomyocarditis virus. Binding antibodies (BABs) were measured using a capture ELISA as a screening test for NABs. Results No false-negative BAB was obtained in our patients. The between-run coefficients of variation (CVs) determined with log10 titres of the NIH anti-IFNβ (G038-501-572) yielded good results (≤ 10.4%) and within-run variability was excellent (CV ≤ 2%). The log10 titres obtained with both CPE assays were highly correlated (r = 0.969 and r = 0.884 for anti-IFNβ-1a and anti-IFNβ-1b, respectively). The same patients were found NAB-positive with both CPE assays. Conclusion Because of its good precision, sensitivity and excellent correlation with the reference CPE method, the WISH/VSV CPE bioassay can be used in the follow-up of IFNβ-treated MS patients.
Published: 2006

40. Rationale for the use of mitoxantrone in multiple sclerosis

Author: Sean Patrick Morrissey, Emmanuelle Le Page, and Gilles Edan
Subjects: Oncology, medicine.medical_specialty, Multiple Sclerosis, Combination therapy, Drug Administration Schedule, Internal medicine, medicine, Humans, Lymphocytes, Glatiramer acetate, Adverse effect, Inflammation, Mitoxantrone, Cardiotoxicity, business.industry, Multiple sclerosis, medicine.disease, Surgery, Regimen, Treatment Outcome, Neurology, Methylprednisolone, Cytokines, Drug Therapy, Combination, Neurology (clinical), Immunotherapy, business, Immunosuppressive Agents, medicine.drug
Abstract: Mitoxantrone is a member of the anthracendione family developed to treat malignancies and increasingly used to treat multiple sclerosis (MS). It has been studied as a treatment for MS since the late 1980s, and is licensed in a number of countries for progressive and worsening MS. Review of the published earlier open-label, and more recently of controlled trials suggests that mitoxantrone is efficacious in cases of worsening MS that have an inflammatory component as evidenced by progression with or without superimposed relapses and/or gadolinium (Gd) enhancing magnetic resonance (MR) lesions. Today there is no robust evidence of efficacy in primary progressive MS or in later stages of secondary progressive MS beyond an EDSS score of 6. Relevant immunomodulatory mechanisms act both on T- and B-cell function, and mitoxantrone has selective immune effects in MS by decreasing levels of TNF-alpha, IL-2, IL-2R-beta1, IL-10 and IFN-gamma. Adverse events include nausea, alopecia, infections, menstrual disorders, risk of cardiotoxicity and malignancy. Different regimens are used according to different regulatory demands in different countries. The two most commonly used regimens are every 3 months intravenous (i.v.) 12 mg/m2 for 2 years or 20 mg mitoxantrone (i.v.) combined with 1 g methylprednisolone (i.v.) every 4 weeks for 6 months. The cumulative life dose in MS patients is 140 mg/m2. Mitoxantrone is currently used as a second line drug in MS patients whose disease is not controlled by beta-interferon or glatiramer acetate. In this review, we will discuss the clinical disease patterns of MS patients who are most likely to benefit from mitoxantrone, its magnitude of clinical effect, and limitations of using mitoxantrone in MS. Mitoxantrone as a second line therapy in non-responders of beta-interferon and glatiramer acetate will be assessed. Recent strategies of combination therapy, and the optimal dose regimen will also be discussed.
Published: 2004

41. Correlation between Brain MRI and Health Related Quality of Life in Early Treated MS Patients and Clinically Isolated Syndrome (P03.051)

Author: Bruno Brochet, Mikael Cohen, Patrick Vermersch, Christine Lebrun Frenay, Emmanuelle Le Page, Ayman Tourbah, Pierre Clavelou, and Thibault Moreau
Subjects: Health related quality of life, medicine.medical_specialty, Clinically isolated syndrome, business.industry, McDonald criteria, Mean age, Disease course, Lesion load, Internal medicine, Brain mri, Physical therapy, Medicine, Neurology (clinical), business, Prospective cohort study
Abstract: Objective: To compare brain MRI and health related quality of life (HRQOL) at the initiation of disease modifying therapy (DMD) in patients with clinically isolated syndrome (CIS) and clinically definite multiple sclerosis (CDMS). Background Few studies assessed correlation between MRI and HRQOL. In a previous study, we reported negative correlations between HRQOL, lesion load (LL) and brain parenchymal fraction (BPF) in early treated CDMS patients. Design/Methods: Our prospective study included patients with either CIS fulfilling 2005 McDonald criteria or CDMS. Patients started their first DMD at the inclusion. Annual assessment included clinical data, EDSS score, French version of MSQol-54 questionnaire, and 1.5T conventional brain MRI (T1 with and without gadolinium injection, T2 spin echo, proton density and FLAIR sequences). Images were analysed using the SepINRIA software to obtain T2-LL and BPF. Results: 60 patients were included. Mean age was 32 years (16-49) and F/M sex ratio was 2.2. Mean baseline EDSS was 1 (0-5). CIS patients differed from CDMS group by a lower EDSS score (mean 0.8 vs. 1.7, p=0.003), a lower T2-LL (2.8 vs. 6.5 cc3, p=0.002). BPF was not significantly different between the two groups (91.7% vs 90.5%, p=0.2). At the beginning of DMD, HRQOL was significantly better in CIS group considering total, physical and mental components. In CDMS group, T2-LL was significantly correlated to "role limitations-physical" (Pearson9s r coefficient: -0.45, p=0.04) and "role limitations-emotional" (r=-0.44, p=0.05) scores, whereas in CIS group, it was only correlated to "role limitations-emotional" (r=-0.427, p=0.05), independently of EDSS. Conclusions: Results suggest that alteration of physical dimensions of HRQOL is associated with accumulation of T2 lesions during disease course. Therefore, earlier DMD initiation could prevent degradation of HRQOL during follow-up. Longitudinal study is on going to assess impact of early treatment on HRQOL and potential correlations with brain MRI parameters. Supported by: Grants from Merck Serono and Bayer Schering Pharma. Disclosure: Dr. Cohen has received personal compensation for activities with Schering-Plough Corporation, Biogen Idec, Serono, Inc., Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals, and Novartis. Dr. Brochet has received personal compensation for activities with Bayer HealthCare, Novartis, Merck Serono, and Biogen Idec. Dr. Brochet has received personal compensation in an editorial capacity for LEN. Dr. Brochet has received research support from Merck Serono, Biogen Idec, and Bayer HealthCare. Dr. Clavelou has received personal compensation for activities with Schering-Plough Corporation, Biogen Idec, Serono, Inc., and Sanofi-Aventis Pharmaceuticals, Inc. as a speaker. Dr. Le Page has nothing to disclose. Dr. Vermersch has received personal compensation for activites with Merck Serono, Bayer Schering, Teva-Aventis, Biogen Idec, Allmirall, and Novartis as a consultant and/or speaker. Dr. Tourbah has received personal compensation for activities with Schering AG, Biogen Idec, Serono, Inc. and Sanofi-Aventis Pharmaceuticals, Inc. as a speaker. Dr. Moreau has received research support from Biogen Idec, Sanofi Aventis and Teva Pharma, Bayer Schering, Merck Serono and Novartis. Dr. Lebrun has received personal compensation for activities with Schering, Biogen Idec, Serono and Sanofi as a speaker.Dr. Lebrun has received personal compensation in an editorial capacity for Elsevier.
Published: 2012
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42. Corrigendum to 'Neutralizing antibodies to interferon beta in multiple sclerosis: Analytical evaluation for validation of a cytopathic effect assay' [Clinica Chimica Acta 337 (2007) 185–191]

Author: Emmanuelle Le Page, Joel Oger, Gilles Edan, Jacqueline Gibassier, and Catherine Massart
Subjects: biology, Interferon beta, business.industry, Multiple sclerosis, Biochemistry (medical), Clinical Biochemistry, General Medicine, medicine.disease, Biochemistry, Virology, Immunology, biology.protein, medicine, Antibody, business, Cytopathic effect
Published: 2007
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