Author: "David-Axel Laplaud" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"David-Axel Laplaud"' showing total 120 results

Start Over Author "David-Axel Laplaud"

120 results on '"David-Axel Laplaud"'

1. Investigating the metabolite signature of an altered oral microbiota as a discriminant factor for multiple sclerosis: a pilot study

Author: Léo Boussamet, Emmanuel Montassier, Camille Mathé, Alexandra Garcia, Jérémy Morille, Sita Shah, Emilie Dugast, Sandrine Wiertlewski, Mathilde Gourdel, Corinna Bang, Klarissa H. Stürner, Damien Masson, Arnaud B. Nicot, Nicolas Vince, David-Axel Laplaud, Douglas L. Feinstein, and Laureline Berthelot
Subjects: Multiple sclerosis, Saliva, Gut, Microbiota, Metabolites, Medicine, Science
Abstract: Abstract In multiple sclerosis (MS), alterations of the gut microbiota lead to inflammation. However, the role of other microbiomes in the body in MS has not been fully elucidated. In a pilot case-controlled study, we carried out simultaneous characterization of faecal and oral microbiota and conducted an in-depth analysis of bacterial alterations associated with MS. Using 16S rRNA sequencing and metabolic inference tools, we compared the oral/faecal microbiota and bacterial metabolism pathways in French MS patients (n = 14) and healthy volunteers (HV, n = 21). A classification model based on metabolite flux balance was established and validated in an independent German cohort (MS n = 12, HV n = 38). Our analysis revealed decreases in diversity indices and oral/faecal compartmentalization, the depletion of commensal bacteria (Aggregatibacter and Streptococcus in saliva and Coprobacter and Roseburia in faeces) and enrichment of inflammation-associated bacteria in MS patients (Leptotrichia and Fusobacterium in saliva and Enterobacteriaceae and Actinomyces in faeces). Several microbial pathways were also altered (the polyamine pathway and remodelling of bacterial surface antigens and energetic metabolism) while flux balance analysis revealed associated alterations in metabolite production in MS (nitrogen and nucleoside). Based on this analysis, we identified a specific oral metabolite signature in MS patients, that could discriminate MS patients from HV and rheumatoid arthritis patients. This signature allowed us to create and validate a discrimination model on an independent cohort, which reached a specificity of 92%. Overall, the oral and faecal microbiomes were altered in MS patients. This pilot study highlights the need to study the oral microbiota and oral health implications in patients with autoimmune diseases on a larger scale and suggests that knowledge of the salivary microbiome could help guide the identification of new pathogenic mechanisms associated with the microbiota in MS patients.
Published: 2024
Full Text: View/download PDF

2. 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
Full Text: View/download PDF

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
Full Text: View/download PDF

4. CD8+ T cell-mediated endotheliopathy is a targetable mechanism of neuro-inflammation in Susac syndrome

Author: Catharina C. Gross, Céline Meyer, Urvashi Bhatia, Lidia Yshii, Ilka Kleffner, Jan Bauer, Anna R. Tröscher, Andreas Schulte-Mecklenbeck, Sebastian Herich, Tilman Schneider-Hohendorf, Henrike Plate, Tanja Kuhlmann, Markus Schwaninger, Wolfgang Brück, Marc Pawlitzki, David-Axel Laplaud, Delphine Loussouarn, John Parratt, Michael Barnett, Michael E. Buckland, Todd A. Hardy, Stephen W. Reddel, Marius Ringelstein, Jan Dörr, Brigitte Wildemann, Markus Kraemer, Hans Lassmann, Romana Höftberger, Eduardo Beltrán, Klaus Dornmair, Nicholas Schwab, Luisa Klotz, Sven G. Meuth, Guillaume Martin-Blondel, Heinz Wiendl, and Roland Liblau
Subjects: Science
Abstract: Susac syndrome is an inflammatory pathology of the brain endothelium. Here the authors show that the pathology is driven by CD8 T cells attacking the endothelium, and that blocking T cell-endothelial adhesion ameliorates the disease in a mouse model, and associates with improved clinical score in 4 patients.
Published: 2019
Full Text: View/download PDF

5. Human Induced Pluripotent Stem Cell-Derived Astrocytes Are Differentially Activated by Multiple Sclerosis-Associated Cytokines

Author: Sylvain Perriot, Amandine Mathias, Guillaume Perriard, Mathieu Canales, Nils Jonkmans, Nicolas Merienne, Cécile Meunier, Lina El Kassar, Anselme L. Perrier, David-Axel Laplaud, Myriam Schluep, Nicole Déglon, and Renaud Du Pasquier
Subjects: Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract: Summary: Recent studies highlighted the importance of astrocytes in neuroinflammatory diseases, interacting closely with other CNS cells but also with the immune system. However, due to the difficulty in obtaining human astrocytes, their role in these pathologies is still poorly characterized. Here, we develop a serum-free protocol to differentiate human induced pluripotent stem cells (hiPSCs) into astrocytes. Gene expression and functional assays show that our protocol consistently yields a highly enriched population of resting mature astrocytes across the 13 hiPSC lines differentiated. Using this model, we first highlight the importance of serum-free media for astrocyte culture to generate resting astrocytes. Second, we assess the astrocytic response to IL-1β, TNF-α, and IL-6, all cytokines important in neuroinflammation, such as multiple sclerosis. Our study reveals very specific profiles of reactive astrocytes depending on the triggering stimulus. This model provides ideal conditions for in-depth and unbiased characterization of astrocyte reactivity in neuroinflammatory conditions. : Perriot et al. describe a new protocol to differentiate both resting and reactive astrocytes from human induced pluripotent stem cells in serum-free conditions. They show that astrocytes exhibit highly contrasted responses to serum and to cytokines involved in multiple sclerosis, establishing that this model is suitable to study neuroinflammation. Keywords: induced pluripotent stem cells, differentiation, astrocytes, multiple sclerosis, neuroinflammation
Published: 2018
Full Text: View/download PDF

6. IL-15 Harnesses Pro-inflammatory Function of TEMRA CD8 in Kidney-Transplant Recipients

Author: Gaëlle Tilly, Tra-My Doan-Ngoc, Michelle Yap, Aurélie Caristan, Lola Jacquemont, Richard Danger, Marion Cadoux, Sarah Bruneau, Magali Giral, Pierrick Guerif, Bryan Nicol, Alexandra Garcia, David-Axel Laplaud, Sophie Brouard, Claire Pecqueur Hellman, and Nicolas Degauque
Subjects: TEMRA CD8, kidney transplantation, immunometabolism, IL-15, inflammatory cytokines, glycolysis and oxidative phosphorylation, Immunologic diseases. Allergy, RC581-607
Abstract: The involvement of TEMRA CD8 is evident in a large array of immunological conditions ranging from auto- to allo-immunity. Nevertheless, the factors leading to their accumulation and activation remain ill-defined and, efficient therapeutics to control their inflammatory response is lacking. Here, we show that IL-15-stimulated TEMRA from kidney-transplant (KT) recipients promote inflammation by inducing the expression of CX3CL1 by endothelial cells in an IFN-γ- and TNF-α-dependent manner. The responsiveness of TEMRA to IL-15 is not restricted to chronic stimulation, as TEMRA from healthy volunteers respond earlier and faster when compared to effector memory (EM). IL-15 induces antiapoptotic signals and promotes proliferation dependent of PI3K/Akt, MAPK, and ERK pathways. Without ex vivo stimulation, TEMRA cells are metabolically more active than naive and EM, as shown by their high ATP reservoir and a high expression of genes involved in glycolysis, glutaminolysis, and the Pentose Phosphate Pathway. Upon stimulation, TEMRA adapt their metabolism by sustaining an increased mitochondrial respiration and glycolysis. Finally, we show that the inhibition of glycolysis is highly effective in preventing endothelial inflammation induced by TEMRA from KT recipients. Together, our findings highlight the metabolic fitness that tightly regulates the immune function of TEMRA in physiological and pathogenic situations.
Published: 2017
Full Text: View/download PDF

7. Decreased Frequency of Circulating Myelin Oligodendrocyte Glycoprotein B Lymphocytes in Patients with Relapsing-Remitting Multiple Sclerosis

Author: Annie Elong Ngono, Maud Lepetit, Markus Reindl, Alexandra Garcia, Flora Guillot, Athénaïs Genty, Mélanie Chesneau, Marion Salou, Laure Michel, Fabienne Lefrere, Kathrin Schanda, Berthe-Marie Imbert-Marcille, Nicolas Degauque, Arnaud Nicot, Sophie Brouard, David-Axel Laplaud, and Jean-Paul Soulillou
Subjects: Immunologic diseases. Allergy, RC581-607
Abstract: Although there is no evidence for a role of anti-MOG antibodies in adult MS, no information on B lymphocytes with MOG-committed BCR is available. We report here on the frequency of anti-MOG B cells forming rosettes with polystyrene beads (BBR) covalently bound to the extracellular domain of rhMOG in 38 relapsing-remitting patients (RRMS) and 50 healthy individuals (HI). We show a substantial proportion of circulating anti-MOG-BBR in both RRMS and HI. Strikingly, MOG-specific B cells frequencies were lower in MS than in HI. Anti-MOG antibodies measured by a cell-based assay were not different between MS patients and controls, suggesting a specific alteration of anti-MOG B cells in MS. Although anti-MOG-BBR were higher in CNS fluid than in blood, no difference was observed between MS and controls. Lower frequency of MOG-BBR in MS was not explained by an increased apoptosis, but a trend for lower proliferative capacity was noted. Despite an efficient B cell transmigration across brain derived endothelial cells, total and anti-MOG B cells transmigration was similar between MS and HI. The striking alteration in MOG-specific B cells, independent of anti-MOG antibody titers, challenges our view on the role of MOG-specific B cells in MS.
Published: 2015
Full Text: View/download PDF

8. SVM-Based Tool to Detect Patients with Multiple Sclerosis Using a Commercial EMG Sensor.

Author: Konstantin Akhmadeev, Aya Houssein, Saïd Moussaoui, Einar A. Høgestøl, Ingerid Tutturen, Hanne F. Harbo, Steffan D. Bos-Haugen, Jennifer Graves, David-Axel Laplaud, and Pierre-Antoine Gourraud
Published: 2018
Full Text: View/download PDF

9. Improving the decision to switch from first- to second-line therapy in multiple sclerosis: A dynamic scoring system

Author: Camille Sabathé, Romain Casey, Sandra Vukusic, Emmanuelle Leray, Guillaume Mathey, Jérôme De Sèze, Jonathan Ciron, Sandrine Wiertlewski, Aurélie Ruet, Jean Pelletier, Hélène Zéphir, Laure Michel, Christine Lebrun-Frenay, Xavier Moisset, Eric Thouvenot, Jean-Philippe Camdessanché, Serge Bakchine, Bruno Stankoff, Abdullatif Al Khedr, Philippe Cabre, Elisabeth Maillart, Eric Berger, Olivier Heinzlef, Karolina Hankiewicz, Thibault Moreau, Olivier Gout, Bertrand Bourre, Abir Wahab, Pierre Labauge, Alexis Montcuquet, Gilles Defer, Aude Maurousset, Nicolas Maubeuge, Dalia Dimitri Boulos, Haïfa Ben Nasr, Chantal Nifle, Olivier Casez, David-Axel Laplaud, Yohann Foucher, Université de Nantes, Université de Tours, Inserm, UMR1246 Sphere, Nantes, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Méthodes quantitatives en santé publique (METIS), École des Hautes Études en Santé Publique [EHESP] (EHESP), 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), Pôle de Neurosciences Cliniques, Service de Neurologie, APHM, Hôpital de la Timone, Aix-Marseille University, Marseille, France, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), and Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)
Subjects: Multiple sclerosis, Neurology, Epidemiology, Second-line treatment, Neurology (clinical), Treatment response, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: In relapsing-remitting multiple sclerosis (RRMS), early identification of suboptimal responders can prevent disability progression. Objective: We aimed to develop and validate a dynamic score to guide the early decision to switch from first- to second-line therapy. Methods: Using time-dependent propensity scores (PS) from a French cohort of 12,823 patients with RRMS, we constructed one training and two validation PS-matched cohorts to compare the switched patients to second-line treatment and the maintained patients. We used a frailty Cox model for predicting individual hazard ratios (iHRs). Results: From the validation PS-matched cohort of 348 independent patients with iHR ⩽ 0.69, we reported the 5-year relapse-free survival at 0.14 (95% confidence interval (CI) 0.09–0.22) for the waiting group and 0.40 (95% CI 0.32–0.51) for the switched group. From the validation PS-matched cohort of 518 independent patients with iHR > 0.69, these values were 0.37 (95% CI 0.30–0.46) and 0.44 (95% CI 0.37–0.52), respectively. Conclusions: By using the proposed dynamic score, we estimated that at least one-third of patients could benefit from an earlier switch to prevent relapse.
Published: 2023
Full Text: View/download PDF

10. Aglycosylated extracellular loop of inwardly rectifying potassium channel 4.1 (KCNJ10) provides a target for autoimmune neuroinflammation

Author: Arnaud B Nicot, Jean Harb, Alexandra Garcia, Flora Guillot, Hoa-Le Mai, Camille V Mathé, Jérémy Morille, Amélie Vallino, Emilie Dugast, Sita P Shah, Fabienne Lefrère, Mélinda Moyon, Sandrine Wiertlewski, Ludmilla Le Berre, Karine Renaudin, Jean-Paul Soulillou, Vincent van Pesch, Sophie Brouard, Laureline Berthelot, David-Axel Laplaud, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
Subjects: Cellular and Molecular Neuroscience, Psychiatry and Mental health, Neurology, Kir4.1, glycosylation, EAE, glia, antibody, autoimmunity, Biological Psychiatry
Abstract: Multiple sclerosis is an autoimmune disease of the central nervous system. Yet, the autoimmune targets are still undefined. The extracellular e1 sequence of KCNJ10, the inwardly rectifying potassium channel 4.1, has been subject to fierce debate for its role as a candidate autoantigen in multiple sclerosis. Inwardly rectifying potassium channel 4.1 is expressed in the central nervous system but also in peripheral tissues, raising concerns about the central nervous system-specificity of such autoreactivity. Immunization of C57Bl6/J female mice with the e1 peptide (amino acids 83–120 of Kir4.1) induced anti-e1 immunoglobulin G- and T-cell responses and promoted demyelinating encephalomyelitis with B cell central nervous system enrichment in leptomeninges and T cells/macrophages in central nervous system parenchyma from forebrain to spinal cord, mostly in the white matter. Within our cohort of multiple sclerosis patients (n = 252), 6% exhibited high anti-e1 immunoglobulin G levels in serum as compared to 0.7% in the control cohort (n = 127; P = 0.015). Immunolabelling of inwardly rectifying potassium channel 4.1-expressing white matter glia with the anti-e1 serum from immunized mice increased during murine autoimmune neuroinflammation and in multiple sclerosis white matter as compared with controls. Strikingly, the mouse and human anti-e1 sera labelled astrocytoma cells when N-glycosylation was blocked with tunicamycin. Western blot confirmed that neuroinflammation induces Kir4.1 expression, including its shorter aglycosylated form in murine experimental autoencephalomyelitis and multiple sclerosis. In addition, recognition of inwardly rectifying potassium channel 4.1 using mouse anti-e1 serum in Western blot experiments under unreduced conditions or in cells transfected with the N-glycosylation defective N104Q mutant as compared to the wild type further suggests that autoantibodies target an e1 conformational epitope in its aglycosylated form. These data highlight the e1 sequence of inwardly rectifying potassium channel 4.1 as a valid central nervous system autoantigen with a disease/tissue-specific post-translational antigen modification as potential contributor to autoimmunity in some multiple sclerosis patients.
Published: 2023

11. 84. One-month Humoral Response Following Two Doses of Covid-19 Vaccines in Specific populations – ANRS0001S COV POPART Cohort Study

Author: Paul LOUBET, L I nda Wittkop, Mathieu Chalouni, David-Axel Laplaud, Martine Laville, Bruno Laviolle, Jean-Daniel Lelièvre, Jean-Yves Blay, Benoit Barrou, Benjamin Terrier, Laure Esterle, Stephanie Nguyen, Axel Levier, Eric Tartour, Xavier de Lamballerie, and Odile Launay
Subjects: Infectious Diseases, Oncology
Abstract: Background We evaluated the immune response to COVID-19 vaccines in several specific populations at high risk of severe COVID-19. Methods Participants from the French national multi-center prospective cohort study ANRS0001S COV-POPART were included (11 specific subpopulations: and 2 control groups (18–64 years and over 65 years)). In this preliminary analysis patients and controls who had received at least two vaccine doses have been included. Percentages (95% confidence intervals (CI)) of participants with anti-Spike SARS-CoV-2 IgG antibodies (ELISA) and specific neutralizing antibodies (in vitro neutralization assay) were evaluated at one month after the second dose of COVID-19 vaccine. Results 3703 were included: 2650 participants from specific subpopulations (171 solid cancers, 160 SOT, 100 HCT, 91 chronic renal failures, 141 systemic autoimmune diseases, 157 autoimmune inflammatory rheumatic diseases, 361 multiple sclerosis (MS) or neuromyelitis optica spectrum disorders, 61 hypogammaglobulinemia, 401 diabetic, 739 obeses non-diabetic and 476 HIV) and 1053 controls (893: 18–64 years and 160 over 65 years). Median age was 51.7 years [InterQuartile range: 40.8 – 60.9] and 50.7% were male. Most of the participants received BNT162b2 vaccine (86.4%). In the control group, 100% (95%CI: 99.6;100.0) of those aged 18–64 and 99.4% (96.6; 100.0) of those over 65 years developed anti-Spike IgG antibodies. PLWHIV, cancer and diabetic patients had high rate of responders after two doses with 98.3% (97.2;99.1), 93.0% (88.1;96.3) and 92.0% (88.9;94.5), respectively. The lowest percentage of responders was found in patients with SOT (13.8% (8.8;20.1), HSCT (34.0% (24.8;44.2) and hypogammaglobulinemia (52.5% 39.3;65.4). In both control groups, the frequency of neutralizing antibodies was similar to the anti-Spike IgG antibody response. In the immunodeficient populations, neutralizing antibodies responders tended to be less frequent than anti-Spike antibodies responders. Similar trends than for IgG antibody were identified (Figure 1). Anti-Spike and Neutralizing antibody (Ab) responses (95% CI) one month after the second dose of COVID-19 vaccine in specific and control populations. Conclusion Lower COVID-19 vaccine humoral response was observed in specific populations than in controls, especially in patients with hypogammaglobulinemia, HSCT and SOT. Disclosures Paul LOUBET, MD, PhD, pfizer: Board Member Odile Launay, MD, PhD, AstraZeneca: Financial|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Johnson & Johnson: Advisor/Consultant|Johnson & Johnson: Grant/Research Support|MD: Advisor/Consultant|Moderna: Advisor/Consultant|MSD: Data safety monitoring board|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Data safety monitoring board.
Published: 2022
Full Text: View/download PDF

12. Semi-supervised clustering of quaternion time series: Application to gait analysis in multiple sclerosis using motion sensor data

Author: Pierre Drouin, Aymeric Stamm, Laurent Chevreuil, Vincent Graillot, Laetitia Barbin, Pierre‐Antoine Gourraud, David‐Axel Laplaud, and Lise Bellanger
Subjects: Statistics and Probability, Epidemiology
Abstract: Recent approaches in gait analysis involve the use of wearable motion sensors to extract spatio-temporal parameters that characterize multiple aspects of an individual's gait. In particular, the medical community could largely benefit from this type of devices as they could provide the clinicians with a valuable tool for assessing gait impairment. Motion sensor data are however complex and there is an urgent unmet need to develop sound statistical methods for analyzing such data and extracting clinically relevant information. In this article, we measure gait by following the hip rotation over time and the resulting statistical unit is a time series of unit quaternions. We explore the possibility to form groups of patients with similar walking impairment by taking into account their walking data and their global decease severity with semi-supervised clustering. We generalize a compromise-based method named hclustcompro to unit quaternion time series by combining it with the proper dissimilarity quaternion dynamic time warping. We apply this method on patients diagnosed with multiple sclerosis to form groups of patients with similar walking deficiencies while accounting for the clinical assessment of their overall disability. We also compare the compromise-based clustering approach with the method mergeTrees that falls into a sub-class of ensemble clustering named collaborative clustering. The results provide a first proof of both the interest of using wearable motion sensors for assessing gait impairment and the use of prior knowledge to guide the clustering process. It also demonstrates that compromise-based clustering is a more appropriate approach in this context.
Published: 2022

13. 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
Full Text: View/download PDF

14. MRI characteristics of MOG-Ab associated disease in adults: An update

Author: F. Durand-Dubief, Mikael Cohen, François Cotton, Elisabeth Maillart, Natalia Shor, Romain Marignier, Bertrand Bourre, Xavier Ayrignac, A Cobo Calvo, David-Axel Laplaud, C. Papeix, Kumaran Deiva, Jonathan Ciron, Nicolas Collongues, Bertrand Audoin, Hélène Zéphir, Romain Deschamps, Sandra Vukusic, Aurélie Ruet, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), i-SEP (i-SEP), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Harvard Medical School [Boston] (HMS), Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers), Centre hospitalier universitaire de Nantes (CHU Nantes), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, CHU Rouen, Normandie Université (NU), Assistance Publique - Hôpitaux de Marseille (APHM), CHU Strasbourg, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, the NOMADMUS study group, and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM)
Subjects: Adult, Pathology, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Myelitis, Optic neuritis, Disease, Imaging, Myelin oligodendrocyte glycoprotein, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Myelin Oligodendrocyte Glycoprotein, 030212 general & internal medicine, Autoantibodies, Aquaporin 4, Neuromyelitis optica, medicine.diagnostic_test, biology, business.industry, Multiple sclerosis, Neuromyelitis Optica, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, Neurology, biology.protein, Myelin-Oligodendrocyte Glycoprotein, Neurology (clinical), Differential diagnosis, business, Aquaporin-4, 030217 neurology & neurosurgery
Abstract: International audience; Our knowledge of the radiological spectrum of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is growing rapidly. An update on the radiological features of the disease, and its evolution is thus necessary. Magnetic resonance imaging (MRI) has an increasingly important role in the differential diagnosis of MOGAD particularly from aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and multiple sclerosis (MS). Differentiating these conditions is of prime importance because the management is different between the three inflammatory diseases, and thus could prevent further attack-related disability. Therefore, identifying the MRI features suggestive of MOGAD has diagnostic and prognostic implications. We herein review optic nerve, spinal cord and the brain MRI findings from MOGAD adult patients, and compare them to AQP4-NMOSD and MS.
Published: 2021
Full Text: View/download PDF

15. [Clinical forms and pathophysiology of multiple sclerosis]

Author: Sita, Shah and David-Axel, Laplaud
Subjects: Multiple Sclerosis, Brain, Humans, Axons
Abstract: "Clinical forms and pathophysiology of multiple sclerosis Multiple sclerosis is a chronic inflammatory disease of the central nervous system. Its triggering mechanisms are still uncertain, but it has been associated with many genetic and environmental factors. Four clinical forms are classically described. In the brain and spinal cord of patients, inflammatory processes cause myelin degradation, axonal de-generation and neuronal loss. Numerous cellular mechanisms related to autoimmunity are involved in the pathophysiology; their activity is associated with the progression to progressive forms of the disease.""Formes cliniques et physiopathologie de la sclérose en plaques La sclérose en plaques est une maladie inflammatoire chronique du système nerveux central. Ses mécanismes déclencheurs sont encore incertains, mais elle a été associée à de nombreux facteurs génétiques et environnementaux. Quatre formes cliniques sont classiquement décrites. Au sein du cerveau et de la moelle épinière des patients, des processus inflammatoires provoquent la dégradation de la myéline, la dégénérescence axonale et la perte neuronale. De nombreux mécanismes cellulaires liés à l’auto-immunité sont en cause dans la physiopathologie ; leur activité est associée à l’évolution vers des formes progressives de la maladie."
Published: 2022

16. Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study

Author: Michael Levraut, Sabine Laurent-Chabalier, Xavier Ayrignac, Kévin Bigaut, Manon Rival, Sanae Squalli, Hélène Zéphir, Tifanie Alberto, Jean-David Pekar, Jonathan Ciron, Damien Biotti, Bénédicte Puissant-Lubrano, Jean-Philippe Camdessanché, Yannick Tholance, Olivier Casez, Bertrand Toussaint, Jeanne Marion, Thibault Moreau, Daniela Lakomy, Audrey Thomasset, Elisabeth Maillart, Delphine Sterlin, Aude Maurousset, Auriane Rocher, David Axel Laplaud, Edith Bigot-Corbel, Pierre-Olivier Bertho, Jean Pelletier, Joseph Boucraut, Pierre Labauge, Thierry Vincent, Jérôme De Sèze, Isabelle Jahn, Barbara Seitz-Polski, Eric Thouvenot, Christine Lebrun-Frenay, Université Côte d'Azur - Faculté de Médecine (UCA Faculté Médecine), Université Côte d'Azur (UCA), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Les Hôpitaux Universitaires de Strasbourg (HUS), Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), Laboratoire de Biochimie [CHRU Nîmes], Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pôle Neurosciences [CHU Toulouse], Institut Fédératif de Biologie (IFB), Service de Neurologie [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Universitaire [Grenoble] (CHU), Translational microbial Evolution and Engineering (TIMC-TrEE), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), 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 Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-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 Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), 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, Service de Biochimie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Team 5 : Neuroinflammation, mechanisms, therapeutic options (NEMO) (U1064 Inserm - CR2TI), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Laboratoire de Biochimie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Département de Biochimie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Nord Laennec [CHU Nantes], Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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], CHU Strasbourg, Laboratoire Immunologie [Nice], Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Hôpital de l'Archet-Université Côte d'Azur (UCA), 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), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Société Francophone de la Sclérose En Plaques (SFSEP)., and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: MESH: Humans, MESH: Multiple Sclerosis, Multiple Sclerosis, MESH: Demyelinating Diseases* / diagnosis, [SDV]Life Sciences [q-bio], Oligoclonal Bands, MESH: Immunoglobulin kappa-Chains, MESH: Central Nervous System Diseases, MESH: Oligoclonal Bands, Cohort Studies, Immunoglobulin kappa-Chains, Neurology, Central Nervous System Diseases, MESH: Biomarkers, Humans, Female, Neurology (clinical), MESH: Cohort Studies, MESH: Female, Biomarkers, Demyelinating Diseases
Abstract: Background and ObjectivesKappa free light chains (KFLC) seem to efficiently diagnose MS. However, extensive cohort studies are lacking to establish consensus cut-offs, notably to rule out non-MS autoimmune CNS disorders. Our objectives were to (1) determine diagnostic performances of CSF KFLC, KFLC index, and KFLC intrathecal fraction (IF) threshold values that allow us to separate MS from different CNS disorder control populations and compare them with oligoclonal bands' (OCB) performances and (2) to identify independent factors associated with KFLC quantification in MS.MethodsWe conducted a retrospective multicenter study involving 13 French MS centers. Patients were included if they had a noninfectious and nontumoral CNS disorder, eligible data concerning CSF and serum KFLC, albumin, and OCB. Patients were classified into 4 groups according to their diagnosis: MS, clinically isolated syndrome (CIS), other inflammatory CNS disorders (OIND), and noninflammatory CNS disorder controls (NINDC).ResultsOne thousand six hundred twenty-one patients were analyzed (675 MS, 90 CIS, 297 OIND, and 559 NINDC). KFLC index and KFLC IF had similar performances in diagnosing MS from nonselected controls and OIND (p= 0.123 andp= 0.991 for area under the curve [AUC] comparisons) and performed better than CSF KFLC (p< 0.001 for all AUC comparisons). A KFLC index of 8.92 best separated MS/CIS from the entire nonselected control population, with better performances than OCB (p< 0.001 for AUC comparison). A KFLC index of 11.56 best separated MS from OIND, with similar performances than OCB (p= 0.065). In the multivariate analysis model, female gender (p= 0.003), young age (p= 0.013), and evidence of disease activity (p< 0.001) were independent factors associated with high KFLC index values in patients with MS, whereas MS phenotype, immune-modifying treatment use at sampling, and the FLC analyzer type did not influence KFLC index.DiscussionKFLC biomarkers are efficient tools to separate patients with MS from controls, even when compared with other patients with CNS autoimmune disorder. Given these results, we suggest using KFLC index or KFLC IF as a criterion to diagnose MS.Classification of EvidenceThis study provides Class III evidence that KFLC index or IF can be used to differentiate patients with MS from nonselected controls and from patients with other autoimmune CNS disorders.
Published: 2022
Full Text: View/download PDF

17. 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
Full Text: View/download PDF

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

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

19. Comparative Effectiveness of Natalizumab Versus Anti-CD20 in Highly Active Relapsing-Remitting Multiple Sclerosis After Fingolimod Withdrawal

Author: Fabien Rollot, Justine Couturier, Romain Casey, Sandrine Wiertlewski, Marc Debouverie, Jean Pelletier, Jérôme De Sèze, Pierre Labauge, Aurélie Ruet, Eric Thouvenot, Jonathan Ciron, Eric Berger, Olivier Gout, Pierre Clavelou, Bruno Stankoff, Olivier Casez, Bertrand Bourre, Hélène Zephir, Thibault Moreau, Christine Lebrun-Frenay, Elisabeth Maillart, Gilles Edan, Jean-Philippe Neau, Alexis Montcuquet, Philippe Cabre, Jean-Philippe Camdessanché, Gilles Defer, Haifa Ben Nasr, Aude Maurousset, Karolina Hankiewicz, Corinne Pottier, Emmanuelle Leray, Sandra Vukusic, David-Axel Laplaud, 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), Hospices Civils de Lyon (HCL), Fondation Eugène Devic EDMUS, Centre hospitalier universitaire de Nantes (CHU Nantes), CIC Plurithématique de Nantes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ministère des Affaires sociales et de la Santé-Direction générale de l'offre de soins (DGOS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance Publique - Hôpitaux de Marseille (APHM), 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), CHU Strasbourg, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, 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), 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), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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), Service de Neurologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Saint-Antoine [AP-HP], Centre Hospitalier Universitaire [Grenoble] (CHU), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut de recherche sur le cancer, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Pitié-Salpêtrière [AP-HP], 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 [CHU Rennes], CHU Pontchaillou [Rennes], Service de neurologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre référent Sclérose Latérale Amyotrophique et autres maladies du motoneurone [CHU Limoges] (SLA CHU Limoges), CHU Limoges, Service de Neurologie [CHU Limoges], Service de neurologie [Fort-de-France, Martinique], CHU de la Martinique [Fort de France], Service de Neurologie [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), 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), Hôpital Sud Francilien Corbeil-Essonnes, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de neurologie [CH Saint Denis], Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), 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), This study was supported by the Association ANTARES and OFSEP, which is supported by a grant provided by the French State and handled by the 'Agence Nationale de la Recherche,' within the framework of the 'Investments for the Future' program, under the reference ANR-10-COHO-002., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), 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 d'Exploration Métabolique par Résonance Magnétique [Marseille] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)
Subjects: Pharmacology, Flexible model, Fingolimod Hydrochloride, Natalizumab, [SDV]Life Sciences [q-bio], Effectiveness, Fingolimod, Therapeutics, Antigens, CD20, Anti-CD20, Multiple sclerosis, Multiple Sclerosis, Relapsing-Remitting, Recurrence, Humans, Immunologic Factors, Pharmacology (medical), Original Article, Neurology (clinical), Immunosuppressive Agents
Abstract: In France, two therapeutic strategies can be offered after fingolimod (FNG) withdrawal to highly active relapsing–remitting multiple sclerosis (RRMS) patients: natalizumab (NTZ) or anti-CD20. We compared the effectiveness of these two strategies as a switch for FNG within the OFSEP database. The primary endpoint was the time to first relapse. Other outcomes were the relapse rates over 3-month periods, time to worsening the EDSS score, proportion of patients with worsened 24-month MRI, time to treatment discontinuation, and incidence rates of serious adverse events. The dynamics of event rates over time were modeled using multidimensional penalized splines, allowing the possibility to model the effects of covariates in a flexible way, considering non-linearity and interactions. A total of 740 patients were included (337 under anti-CD20 and 403 under NTZ). There was no difference between the two treatments regarding the dynamic of the first occurrence of relapse, with a monthly probability of 5.0% at initiation and 1.0% after 6 months. The rate of EDSS worsening increased in both groups until 6 months and then decreased. No difference in the proportion of patients with new T2 lesions at 24 months was observed. After 18 months of follow-up, a greater risk of NTZ discontinuation was found compared to anti-CD20. This study showed no difference between NTZ and anti-CD20 after the FNG switch regarding the clinical and radiological activity. The effect of these treatments was optimal after 6 months and there was more frequent discontinuation of NTZ after 18 months, probably mainly related to JC virus seroconversions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01202-1.
Published: 2022
Full Text: View/download PDF

20. Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): a randomised, controlled, open-label, phase 3b trial

Author: John F Foley, Gilles Defer, Lana Zhovtis Ryerson, Jeffrey A Cohen, Douglas L Arnold, Helmut Butzkueven, Gary Cutter, Gavin Giovannoni, Joep Killestein, Heinz Wiendl, Karen Smirnakis, Shan Xiao, George Kong, Robert Kuhelj, Nolan Campbell, Anneke van der Walt, Christopher Dwyer, Katherine Buzzard, Judith Spies, John Parratt, Vincent van Pesch, Barbara Willekens, Gaetano Perrotta, Emmanuel Bartholomé, Francois Grand'Maison, Francois Jacques, Paul Giacomini, Reza Vosoughi, Jean-Marc Girard, Jerome de Seze, Christine Lebrun Frenay, Aurelie Ruet, David-Axel Laplaud, Gerd Reifschneider, Bert Wagner, Sebastian Rauer, Refik Pul, Maria Seipelt, Achim Berthele, Luisa Klotz, Boris-Alexander Kallmann, Friedemann Paul, Anat Achiron, Giacomo Lus, Diego Centonze, Francesco Patti, Luigi Grimaldi, Raymond Hupperts, Stephan Frequin, Jiske Fermont, Sara Eichau Madueno, Ana Maria Alonso Torres, Lucienne Costa-Frossard França, Jose Eustasio Meca-Lallana, Luis Brieva Ruiz, Owen Pearson, David Rog, Nikolaos Evangelou, Azza Ismail, Ellen Lathi, Edward Fox, Thomas Leist, Jacob Sloane, Gregory Wu, Bhupendra Khatri, Brian Steingo, Ben Thrower, Mark Gudesblatt, Jonathan Calkwood, Daniel Bandari, John Scagnelli, Christopher Laganke, Derrick Robertson, Lucas Kipp, Martin Belkin, Stanley Cohan, Lawrence Goldstick, Ardith Courtney, Wendy Vargas, Andrew Sylvester, Jayshri Srinivasan, Meena Kannan, Maryann Picone, Jeffrey English, Salvatore Napoli, Roumen Balabanov, Islam Zaydan, Jacqueline Nicholas, Jeffrey Kaplan, Fred Lublin, Emily Riser, Tamara Miller, Enrique Alvarez, Sibyl Wray, Jeffrey Gross, Siddharama Pawate, Carrie Hersh, Lucas McCarthy, Heidi Crayton, Jennifer Graves, NOVA study investigators, Neurology, and Amsterdam Neuroscience - Neuroinfection & -inflammation
Subjects: Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Treatment Outcome, Double-Blind Method, Natalizumab, Leukoencephalopathy, Progressive Multifocal, Humans, Neurology (clinical), Human medicine, Settore MED/26, Magnetic Resonance Imaging
Abstract: Background: Treatment with natalizumab once every 4 weeks is approved for patients with relapsing-remitting multiple sclerosis, but is associated with a risk of progressive multifocal leukoencephalopathy. Switching to extended-interval dosing is associated with lower progressive multifocal leukoencephalopathy risk, but the efficacy of this approach is unclear. We aimed to assess the safety and efficacy of natalizumab once every 6 weeks compared with once every 4 weeks in patients with relapsing-remitting multiple sclerosis. Methods: We did a randomised, controlled, open-label, phase 3b trial (NOVA) at 89 multiple sclerosis centres across 11 countries in the Americas, Europe, and Western Pacific. Included participants were aged 18–60 years with relapsing-remitting multiple sclerosis and had been treated with intravenous natalizumab 300 mg once every 4 weeks with no relapses for at least 12 months before randomisation, with no missed doses in the previous 3 months. Participants were randomly assigned (1:1), using a randomisation sequence generated by the study funder and contract personnel with interactive response technology, to switch to natalizumab once every 6 weeks or continue with once every 4 weeks. The centralised MRI reader, independent neurology evaluation committee, site examining neurologists, site backup examining neurologists, and site examining technicians were masked to study group assignments. The primary endpoint was the number of new or newly enlarging T2 hyperintense lesions at week 72, assessed in all participants who received at least one dose of assigned treatment and had at least one postbaseline MRI, relapse, or neurological examination or efficacy assessment. Missing primary endpoint data were handled under prespecified primary and secondary estimands: the primary estimand included all data, regardless of whether participants remained on the assigned treatment; the secondary estimand classed all data obtained after treatment discontinuation or study withdrawal as missing. Safety was assessed in all participants who received at least one dose of study treatment. Study enrolment is closed and an open-label extension study is ongoing. This study is registered with EudraCT, 2018-002145-11, and ClinicalTrials.gov, NCT03689972. Findings: Between Dec 26, 2018, and Aug 30, 2019, 605 patients were assessed for eligibility and 499 were enrolled and assigned to receive natalizumab once every 6 weeks (n=251) or once every 4 weeks (n=248). After prespecified adjustments for missing data, mean numbers of new or newly enlarging T2 hyperintense lesions at week 72 were 0·20 (95% CI 0·07–0·63) in the once every 6 weeks group and 0·05 (0·01–0·22) in the once every 4 weeks group (mean lesion ratio 4·24 [95% CI 0·86–20·85]; p=0·076) under the primary estimand, and 0·31 (95% CI 0·12–0·82) and 0·06 (0·01–0·31; mean lesion ratio 4·93 [95% CI 1·05–23·20]; p=0·044) under the secondary estimand. Two participants in the once every 6 weeks group with extreme new or newly enlarging T2 hyperintense lesion numbers (≥25) contributed most of the excess lesions. Adverse events occurred in 194 (78%) of 250 participants in the once every 6 weeks group and 190 (77%) of 247 in the once every 4 weeks group, and serious adverse events occurred in 17 (7%) and 17 (7%), respectively. No deaths were reported. There was one case of asymptomatic progressive multifocal leukoencephalopathy (without clinical signs) in the once every 6 weeks group, and no cases in the once every 4 weeks group; 6 months after diagnosis, the participant was without increased disability and remained classified as asymptomatic. Interpretation: We found a numerical difference in the mean number of new or newly enlarging T2 hyperintense lesions at week 72 between the once every 6 weeks and once every 4 weeks groups, which reached significance under the secondary estimand, but interpretation of statistical differences (or absence thereof) is limited because disease activity in the once every 4 weeks group was lower than expected. The safety profiles of natalizumab once every 6 weeks and once every 4 weeks were similar. Although this trial was not powered to assess differences in risk of progressive multifocal leukoencephalopathy, the occurrence of the (asymptomatic) case underscores the importance of monitoring and risk factor consideration in all patients receiving natalizumab. Funding: Biogen.
Published: 2022
Full Text: View/download PDF

21. Ofatumumab versus Teriflunomide in Multiple Sclerosis

Author: Hauser S. L., Bar-Or A., Cohen J. A., Comi G., Correale J., Coyle P. K., Cross A. H., de Seze J., Leppert D., Montalban X., Selmaj K., Wiendl H., Kerloeguen C., Willi R., Li B., Kakarieka A., Tomic D., Goodyear A., Pingili R., Haring D. A., Ramanathan K., Merschhemke M., Kappos L., Stephen L Hauser, Ludwig Kappos, Amit Bar-Or, Jeffrey A Cohen, Giancarlo Comi, Jorge Correale, Patricia K Coyle, Anne Cross, Jerome de Seze, Xavier Montalban, Krzysztof Selmaj, Heinz Wiendl, Stephen C Reingold, Garry R Cutter, Thomas Doerner, Hans-Peter Hartung, Per Soelberg Sørensen, Israel Steiner, Jerry S Wolinsky, Carlos Ballario, Christian Calvo Vildoso, Jorge Gustavo Jose, Norma Haydee Deri, Susana Liwacki, Jeannette Lechner-Scott, John Parratt, Suzanne Hodgkinson, Eva-Maria Maida, Fritz Leutmezer, Barbara Willekens, Bart Van Wijmeersch, Guy Laureys, Jo Caekebeke, Karine Geens, Ludo Vanopdenbosch, Olivier Deryck, Valerie Delvaux, Vincent Van Pesch, Ivan Milanov, Ivaylo Tarnev, Lyubomir Haralanov, Maria Manova Slavova, Penko Shotekov, Francois Emond, Francois Grandmaison, Francois Jacques, Liesly Lee, Marie Sarah Gagne Brosseau, Mark Freedman, Martin Cloutier, Robert Carruthers, Sarah Morrow, Yves Lapierre, Anton Vladic, Hana Bokun, Igor Antoncic, Marija Bosnjak Pasic, Mario Habek, Silva Butkovic Soldo, Vladimira Vuletic, Alena Martinkova, Eva Meluzinova, Ivana Stetkarova, Jan Mares, Jolana Markova, Marta Vachova, Martin Valis, Michaela Tyblova, Michal Dufek, Ondrej Skoda, Pavel Hradilek, Ana Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina Svendsen, Mads Ravnborg, Peter Vestergaard Rasmussen, Katrin Gross-Paju, Sulev Haldre, Juha Pekka Eralinna, Marja-Liisa Sumelahti, Bruno Brochet, Celine Louapre, Christine Lebrun-Frenay, David Axel Laplaud, Gilles Edan, Giovanni Castelnovo, Marc Debouverie, Patrick Vermersch, Pierre Clavelou, Pierre Labauge, Achim Berthele, Aiden Haghikia, Anselm Kornhuber, Arnfin Bergmann, Benedikt Frank, Birte Elias-Hamp, Bjoern Tackenberg, Brigitte Wildemann, Erik Strauss, Eugen Schlegel, Florian Then Bergh, Gereon Nelles, Hayrettin Tumani, Karl-Otto Sigel, Martin Stangel, Matthias Boehringer, Olaf Martin Hoffmann, Patrick Oschmann, Reinhard Hohlfeld, Silke Walter, Sylvia Menck, Till Sprenger, Tjalf Ziemssen, Veit Ulrich Becker, Vera Straeten, Konstantinos Kilidireas, Konstantinos Voumvourakis, Nikolaos Fakas, Nikolaos Grigoriadis, Agnes Koves, Csilla Rozsa, Krisztina Kovacs, Laszlo Vecsei, Satori Maria, Zita Biro, Anshu Rohatgi, Dheeraj Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha Pandit, Meena Angamuthu Kanikannan, Pahari Ghosh, Rahul Chakor, Rahul Kulkarni, Roopkumar Gursahani, Sangeeta Ravat, Srinivasa Rangasetty, Suresh Kumar, Alla Shifrin, Arnon Karni, Radi Shahien, Ron Milo, Antonio Uccelli, Carlo Pozzilli, Francesco Sacca, Giacomo Lus, Girolama Alessandra Marfia, Laura Brambilla, Marco Salvetti, Massimo Filippi, Mauro Zaffaroni, Paolo Gallo, Silvia Rossi, Simona Bonavita, Valeria Studer, Andrejs Millers, Guntis Karelis, Jolanta Kalnina, Dalia Mickeviciene, Rasa Kizlaitiene, Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Beatrijs Wokke, Bob W Van Oosten, Peter Van Domburg, Raymond Hupperts, Rogier Q Hintzen, Astrid Edland, Cesar Castaneda, Julio Perez, Martin Gavidia, Andrzej Wiak, Bartosz Karaszewski, Elzbieta Jasinska, Halina Bartosik Psujek, Iwona Jastrzebska, Jaroslaw Slawek, Maciej Maciejowski, Miroslaw Dziki, Monika Adamczyk Sowa, Robert Bonek, Waldemar Fryze, Ana Martins Da Silva, Angela Timoteo, Antonio Vasco Salgado, Carlos Capela, Carlos Veira, Filipe Correia, Joao Cerqueira, Joao De Sa, Livia De Sousa, Raquel Gouveia, Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, Dmitry Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Egon Kurca, Georgi Krastev, Miroslav Brozman, Peter Koleda, Peter Turcani, Peter Valkovic, Viera Hancinova, Vladimir Donath, Chris Retief, Michael Isaacs, Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virgina Meca Lallana, Xaviere Montalban Gairin, Fredrik Piehl, Jan Lycke, Chiara Zecca, Tobias Derfuss, Thy-Sheng Lin, Somsak Tiamkao, Ayse Nur Yuceyar, Aysun Soysal, Belgin Petek Balci, Cavit Boz, Husnu Efendi, Murat Terzi, Serhan Sevim, Serkan Ozakbas, Andrew Gale, Ben Turner, David Barnes, David Paling, Eli Silber, James Overell, Matthew Craner, Aaron Carlson, Adam Wolff, Adaeze Onuoha, Adnan Subei, Ahmad Ata, Aimee Borazanci, Akram Dastagir, Alberto Vasquez, Alison Brooke Allen, Andrew P Keegan, Angel Carrasco, Angel R Chinea Martinez, Ann Bass, Annette Okai, April Erwin, Ariel Antezana-Antezana, Barbara Green, Bharathy E Sundaram, Bhupendra Khatri, Bhupesh Dihenia, Bogdan Gheorghiu, Brian Costell, Brian Steingo, Bruce L Hughes, Carrie M Hersh, Christopher Laganke, Christopher Luzzio, Corey Ford, Craig Edward Herrman, Craig Senzon, Cynthia Huffman, Daniel R Wynn, David D O Bear, David Lesch, David H Mattson, David Weisman, Deborah A Burke, Dennis W Dietrich, Deren Huang, Derrick Robertson, Djamchid Lotfi, Don Joseph Alfonso, Dusan Stefoski, Edward J Fox, Emily Pharr, Enrique Alvarez, Evanthia Bernitsas, Faria Amjad, Gabriel Pardo, Geoffrey Eubank, Gerald Mcintosh, Giles F Crowell, Hemanth Rao, J Michael Hemphill, Jack H Florin, Jacqueline Nicholas, James Napier, James Scott, Jason M Silversteen, Javier Vasallo, Jean-Raphael Schneider, Jeanette Wendt, Jeffrey Cohen, Jeffrey Gross, Jeffrey Groves, Jeffrey Kaplan, Jessica Stulc, Joanna A Cooper, John Foley, John Scagnelli, Jonathan C Calkwood, Jose Pizarro Otero, Jose Rafecas, Joshua Katz, Juliette S Saad, Katherine Standley, Keith Edwards, Kenneth Sharlin, Khurram Bashir, Kimberly Wagner, Kore Liow, Larry Lee Blankenship Jr, Laszlo Mate, Liliana Montoya, Lon D Lynn, Mark Agius, Mark Cascione, Mark Allan Goldstein, Mark Janicki, Martin R Bialow, Mary Denise Hughes, Matthew J Baker, Michelle Apperson, Michelle B Kuczma, M Mateo Paz Soldan, Mirela Cerghet, Nathaniel Robb Whaley, Paul K Winner, Pavle Repovic, Praful Kelkar, Romero Rekha Pillai, Ricardo Ayala, Richard Sater, Randall Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert Naismith, Ronald S Murray, Samuel Hunter, Sara Qureshi, Sharon Lynch, Sibyl Wray, Silvia R Delgado, Stacy Donlon, Stanley Cohan, Stanya Smith, Stuart James Shafer, Susan Azalone, Susan Hibbs, Tamara A Miller, Thomas Giancarlo, Troy Desai, Varun K Saxena, Virginia Simnad, William David Honeycutt, William Logan, William E McElveen, William Wagner, University of California [San Francisco] (UCSF), University of California, Perelman School of Medicine, University of Pennsylvania [Philadelphia], Cleveland Clinic, IRCCS Ospedale San Raffaele [Milan, Italy], Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia [Buenos Aires] (FLENI), FLENI, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, University Hospital Basel [Basel], Vall d'Hebron University Hospital [Barcelona], University of Warmia and Mazury [Olsztyn], University of Münster, Novartis Pharma S.A.S., Novartis Pharmaceuticals, University of Basel (Unibas), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Willekens, Barbara, ASCLEPIOS I and ASCLEPIOS II Trial Groups, Hauser, S. L., Bar-Or, A., Cohen, J. A., Comi, G., Correale, J., Coyle, P. K., Cross, A. H., de Seze, J., Leppert, D., Montalban, X., Selmaj, K., Wiendl, H., Kerloeguen, C., Willi, R., Li, B., Kakarieka, A., Tomic, D., Goodyear, A., Pingili, R., Haring, D. A., Ramanathan, K., Merschhemke, M., Kappos, L., Asclepios, I and ASCLEPIOS II Trial Group, Filippi, M, L Hauser, Stephen, Kappos, Ludwig, Bar-Or, Amit, A Cohen, Jeffrey, Comi, Giancarlo, Correale, Jorge, K Coyle, Patricia, Cross, Anne, de Seze, Jerome, Montalban, Xavier, Selmaj, Krzysztof, Wiendl, Heinz, C Reingold, Stephen, R Cutter, Garry, Doerner, Thoma, Hartung, Hans-Peter, Soelberg Sørensen, Per, Steiner, Israel, S Wolinsky, Jerry, Ballario, Carlo, Calvo Vildoso, Christian, Gustavo Jose, Jorge, Haydee Deri, Norma, Liwacki, Susana, Lechner-Scott, Jeannette, Parratt, John, Hodgkinson, Suzanne, Maida, Eva-Maria, Leutmezer, Fritz, Van Wijmeersch, Bart, Laureys, Guy, Caekebeke, Jo, Geens, Karine, Vanopdenbosch, Ludo, Deryck, Olivier, Delvaux, Valerie, Van Pesch, Vincent, Milanov, Ivan, Tarnev, Ivaylo, Haralanov, Lyubomir, Manova Slavova, Maria, Shotekov, Penko, Emond, Francoi, Grandmaison, Francoi, Jacques, Francoi, Lee, Liesly, Sarah Gagne Brosseau, Marie, Freedman, Mark, Cloutier, Martin, Carruthers, Robert, Morrow, Sarah, Lapierre, Yve, Vladic, Anton, Bokun, Hana, Antoncic, Igor, Bosnjak Pasic, Marija, Habek, Mario, Butkovic Soldo, Silva, Vuletic, Vladimira, Martinkova, Alena, Meluzinova, Eva, Stetkarova, Ivana, Mares, Jan, Markova, Jolana, Vachova, Marta, Valis, Martin, Tyblova, Michaela, Dufek, Michal, Skoda, Ondrej, Hradilek, Pavel, Voldsgaard Jensen, Ana, Hvilsted Nielsen, Helle, Svendsen, Kristina, Ravnborg, Mad, Vestergaard Rasmussen, Peter, Gross-Paju, Katrin, Haldre, Sulev, Pekka Eralinna, Juha, Sumelahti, Marja-Liisa, Brochet, Bruno, Louapre, Celine, Lebrun-Frenay, Christine, Axel Laplaud, David, Edan, Gille, Castelnovo, Giovanni, Debouverie, Marc, Vermersch, Patrick, Clavelou, Pierre, Labauge, Pierre, Berthele, Achim, Haghikia, Aiden, Kornhuber, Anselm, Bergmann, Arnfin, Frank, Benedikt, Elias-Hamp, Birte, Tackenberg, Bjoern, Wildemann, Brigitte, Strauss, Erik, Schlegel, Eugen, Then Bergh, Florian, Nelles, Gereon, Tumani, Hayrettin, Sigel, Karl-Otto, Stangel, Martin, Boehringer, Matthia, Martin Hoffmann, Olaf, Oschmann, Patrick, Hohlfeld, Reinhard, Walter, Silke, Menck, Sylvia, Sprenger, Till, Ziemssen, Tjalf, Ulrich Becker, Veit, Straeten, Vera, Kilidireas, Konstantino, Voumvourakis, Konstantino, Fakas, Nikolao, Grigoriadis, Nikolao, Koves, Agne, Rozsa, Csilla, Kovacs, Krisztina, Vecsei, Laszlo, Maria, Satori, Biro, Zita, Rohatgi, Anshu, Khurana, Dheeraj, Durai Pandian, Jeyaraj, Dev Mukherji, Joy, Pandit, Lekha, Angamuthu Kanikannan, Meena, Ghosh, Pahari, Chakor, Rahul, Kulkarni, Rahul, Gursahani, Roopkumar, Ravat, Sangeeta, Rangasetty, Srinivasa, Kumar, Suresh, Shifrin, Alla, Karni, Arnon, Shahien, Radi, Milo, Ron, Uccelli, Antonio, Pozzilli, Carlo, Sacca, Francesco, Lus, Giacomo, Alessandra Marfia, Girolama, Brambilla, Laura, Salvetti, Marco, Filippi, Massimo, Zaffaroni, Mauro, Gallo, Paolo, Rossi, Silvia, Bonavita, Simona, Studer, Valeria, Millers, Andrej, Karelis, Gunti, Kalnina, Jolanta, Mickeviciene, Dalia, Kizlaitiene, Rasa, Carbajal Ramirez, Angelica, Jose Lopez Prieto, Juan, Wokke, Beatrij, W Van Oosten, Bob, Van Domburg, Peter, Hupperts, Raymond, Q Hintzen, Rogier, Edland, Astrid, Castaneda, Cesar, Perez, Julio, Gavidia, Martin, Wiak, Andrzej, Karaszewski, Bartosz, Jasinska, Elzbieta, Bartosik Psujek, Halina, Jastrzebska, Iwona, Slawek, Jaroslaw, Maciejowski, Maciej, Dziki, Miroslaw, Adamczyk Sowa, Monika, Bonek, Robert, Fryze, Waldemar, Martins Da Silva, Ana, Timoteo, Angela, Vasco Salgado, Antonio, Capela, Carlo, Veira, Carlo, Correia, Filipe, Cerqueira, Joao, De Sa, Joao, De Sousa, Livia, Gouveia, Raquel, Sergeevna Agafina, Alina, Naumovna Belova, Anna, Viktorovich Sazonov, Deni, Pokhabov, Dmitry, Igorevna Kairbekova, Ekaterina, Gennadievna Arefieva, Elena, Axatovich Khabirov, Farit, Vyacheslavovich Litvinenko, Igor, Stolyarov, Igor, Aleksandrovna Sokolova, Irina, Ivanovna Volkova, Larisa, Vafaevna Davydovskaya, Maria, Nikolaevna Zaharova, Maria, Alekseevna Malkova, Nadezhda, Agafonovna Totolyan, Natalia, Vasilievich Dorogov, Nikolay, Anatolievna Sivertseva, Stella, Kurca, Egon, Krastev, Georgi, Brozman, Miroslav, Koleda, Peter, Turcani, Peter, Valkovic, Peter, Hancinova, Viera, Donath, Vladimir, Retief, Chri, Isaacs, Michael, Saiz Hinarejos, Albert, Rodriguez Antigüedad, Alfredo, Casanova Estruch, Bonaventura, Oreja-Guevara, Celia, Reig Rosello, Gemma, Carlos Alvarez Cermeño, Jose, Martinez Rodriguez, Jose, Meca Lallana, Jose, Antonio Garcia Merino, Juan, Forero Diaz, Lucia, Costa Frossard Franca, Lucienne, Querol Gutierrez, Lui, Ramio Torrenta, Llui, Serrano Castro, Pedro, Arroyo Gonzalez, Rafael, Eichau Madueño, Sara, Martinez Yelamos, Sergio, Castillo Trivino, Tamara, Meca Lallana, Virgina, Montalban Gairin, Xaviere, Piehl, Fredrik, Lycke, Jan, Zecca, Chiara, Derfuss, Tobia, Lin, Thy-Sheng, Tiamkao, Somsak, Nur Yuceyar, Ayse, Soysal, Aysun, Petek Balci, Belgin, Boz, Cavit, Efendi, Husnu, Terzi, Murat, Sevim, Serhan, Ozakbas, Serkan, Gale, Andrew, Turner, Ben, Barnes, David, Paling, David, Silber, Eli, Overell, Jame, Craner, Matthew, Carlson, Aaron, Wolff, Adam, Onuoha, Adaeze, Subei, Adnan, Ata, Ahmad, Borazanci, Aimee, Dastagir, Akram, Vasquez, Alberto, Brooke Allen, Alison, P Keegan, Andrew, Carrasco, Angel, R Chinea Martinez, Angel, Bass, Ann, Okai, Annette, Erwin, April, Antezana-Antezana, Ariel, Green, Barbara, E Sundaram, Bharathy, Khatri, Bhupendra, Dihenia, Bhupesh, Gheorghiu, Bogdan, Costell, Brian, Steingo, Brian, L Hughes, Bruce, M Hersh, Carrie, Laganke, Christopher, Luzzio, Christopher, Ford, Corey, Edward Herrman, Craig, Senzon, Craig, Huffman, Cynthia, R Wynn, Daniel, O Bear, David D, Lesch, David, H Mattson, David, Weisman, David, A Burke, Deborah, W Dietrich, Denni, Huang, Deren, Robertson, Derrick, Lotfi, Djamchid, Joseph Alfonso, Don, Stefoski, Dusan, J Fox, Edward, Pharr, Emily, Alvarez, Enrique, Bernitsas, Evanthia, Amjad, Faria, Pardo, Gabriel, Eubank, Geoffrey, Mcintosh, Gerald, F Crowell, Gile, Rao, Hemanth, Michael Hemphill, J, H Florin, Jack, Nicholas, Jacqueline, Napier, Jame, Scott, Jame, M Silversteen, Jason, Vasallo, Javier, Schneider, Jean-Raphael, Wendt, Jeanette, Cohen, Jeffrey, Gross, Jeffrey, Groves, Jeffrey, Kaplan, Jeffrey, Stulc, Jessica, A Cooper, Joanna, Foley, John, Scagnelli, John, C Calkwood, Jonathan, Pizarro Otero, Jose, Rafecas, Jose, Katz, Joshua, S Saad, Juliette, Standley, Katherine, Edwards, Keith, Sharlin, Kenneth, Bashir, Khurram, Wagner, Kimberly, Liow, Kore, Lee Blankenship Jr, Larry, Mate, Laszlo, Montoya, Liliana, D Lynn, Lon, Agius, Mark, Cascione, Mark, Allan Goldstein, Mark, Janicki, Mark, R Bialow, Martin, Denise Hughes, Mary, J Baker, Matthew, Apperson, Michelle, B Kuczma, Michelle, Mateo Paz Soldan, M, Cerghet, Mirela, Robb Whaley, Nathaniel, K Winner, Paul, Repovic, Pavle, Kelkar, Praful, Rekha Pillai, Romero, Ayala, Ricardo, Sater, Richard, Trudell, Randall, Fairborn Armstrong, Robert, Thomas Nahouraii, Robert, Naismith, Robert, S Murray, Ronald, Hunter, Samuel, Qureshi, Sara, Lynch, Sharon, Wray, Sibyl, R Delgado, Silvia, Donlon, Stacy, Cohan, Stanley, Smith, Stanya, James Shafer, Stuart, Azalone, Susan, Hibbs, Susan, A Miller, Tamara, Giancarlo, Thoma, Desai, Troy, K Saxena, Varun, Simnad, Virginia, David Honeycutt, William, Logan, William, E McElveen, William, Wagner, William, Stephen, L Hauser, Ludwig, Kappo, Amit, Bar-Or, Jeffrey, A Cohen, Giancarlo, Comi, Jorge, Correale, Patricia, K Coyle, Anne, Cro, Jerome de Seze, Xavier, Montalban, Krzysztof, Selmaj, Heinz, Wiendl, Stephen, C Reingold, Garry, R Cutter, Thomas, Doerner, Hans-Peter, Hartung, Per Soelberg Sørensen, Israel, Steiner, Jerry, S Wolinsky, Carlos, Ballario, Christian Calvo Vildoso, Jorge Gustavo Jose, Norma Haydee Deri, Susana, Liwacki, Jeannette, Lechner-Scott, John, Parratt, Suzanne, Hodgkinson, Eva-Maria, Maida, Fritz, Leutmezer, Barbara, Willeken, Bart Van Wijmeersch, Guy, Laurey, Karine, Geen, Ludo, Vanopdenbosch, Olivier, Deryck, Valerie, Delvaux, Vincent Van Pesch, Ivan, Milanov, Ivaylo, Tarnev, Lyubomir, Haralanov, Maria Manova Slavova, Penko, Shotekov, Francois, Emond, Francois, Grandmaison, Francois, Jacque, Liesly, Lee, Marie Sarah Gagne Brosseau, Mark, Freedman, Martin, Cloutier, Robert, Carruther, Sarah, Morrow, Yves, Lapierre, Anton, Vladic, Hana, Bokun, Igor, Antoncic, Marija Bosnjak Pasic, Mario, Habek, Silva Butkovic Soldo, Vladimira, Vuletic, Alena, Martinkova, Eva, Meluzinova, Ivana, Stetkarova, Jan, Mare, Jolana, Markova, Marta, Vachova, Martin, Vali, Michaela, Tyblova, Michal, Dufek, Ondrej, Skoda, Pavel, Hradilek, Ana Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina, Svendsen, Mads, Ravnborg, Peter Vestergaard Rasmussen, Katrin, Gross-Paju, Sulev, Haldre, Juha Pekka Eralinna, Marja-Liisa, Sumelahti, Bruno, Brochet, Celine, Louapre, Christine, Lebrun-Frenay, David Axel Laplaud, Gilles, Edan, Giovanni, Castelnovo, Marc, Debouverie, Patrick, Vermersch, Pierre, Clavelou, Pierre, Labauge, Achim, Berthele, Aiden, Haghikia, Anselm, Kornhuber, Arnfin, Bergmann, Benedikt, Frank, Birte, Elias-Hamp, Bjoern, Tackenberg, Brigitte, Wildemann, Erik, Strau, Eugen, Schlegel, Florian Then Bergh, Gereon, Nelle, Hayrettin, Tumani, Karl-Otto, Sigel, Martin, Stangel, Matthias, Boehringer, Olaf Martin Hoffmann, Patrick, Oschmann, Reinhard, Hohlfeld, Silke, Walter, Sylvia, Menck, Till, Sprenger, Tjalf, Ziemssen, Veit Ulrich Becker, Vera, Straeten, Konstantinos, Kilidirea, Konstantinos, Voumvouraki, Nikolaos, Faka, Nikolaos, Grigoriadi, Agnes, Kove, Csilla, Rozsa, Krisztina, Kovac, Laszlo, Vecsei, Satori, Maria, Zita, Biro, Anshu, Rohatgi, Dheeraj, Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha, Pandit, Meena Angamuthu Kanikannan, Pahari, Ghosh, Rahul, Chakor, Rahul, Kulkarni, Roopkumar, Gursahani, Sangeeta, Ravat, Srinivasa, Rangasetty, Suresh, Kumar, Alla, Shifrin, Arnon, Karni, Radi, Shahien, Ron, Milo, Antonio, Uccelli, Carlo, Pozzilli, Sacca', Francesco, Giacomo, Lu, Girolama Alessandra Marfia, Laura, Brambilla, Marco, Salvetti, Massimo, Filippi, Mauro, Zaffaroni, Paolo, Gallo, Silvia, Rossi, Simona, Bonavita, Valeria, Studer, Andrejs, Miller, Guntis, Kareli, Jolanta, Kalnina, Dalia, Mickeviciene, Rasa, Kizlaitiene, Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Beatrijs, Wokke, Bob, W Van Oosten, Peter Van Domburg, Raymond, Huppert, Rogier, Q Hintzen, Astrid, Edland, Cesar, Castaneda, Julio, Perez, Martin, Gavidia, Andrzej, Wiak, Bartosz, Karaszewski, Elzbieta, Jasinska, Halina Bartosik Psujek, Iwona, Jastrzebska, Jaroslaw, Slawek, Maciej, Maciejowski, Miroslaw, Dziki, Monika Adamczyk Sowa, Robert, Bonek, Waldemar, Fryze, Ana Martins Da Silva, Angela, Timoteo, Antonio Vasco Salgado, Carlos, Capela, Carlos, Veira, Filipe, Correia, Joao, Cerqueira, Joao De Sa, Livia De Sousa, Raquel, Gouveia, Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, Dmitry, Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor, Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Egon, Kurca, Georgi, Krastev, Miroslav, Brozman, Peter, Koleda, Peter, Turcani, Peter, Valkovic, Viera, Hancinova, Vladimir, Donath, Chris, Retief, Michael, Isaac, Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia, Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virgina Meca Lallana, Xaviere Montalban Gairin, Fredrik, Piehl, Jan, Lycke, Chiara, Zecca, Tobias, Derfu, Thy-Sheng, Lin, Somsak, Tiamkao, Ayse Nur Yuceyar, Aysun, Soysal, Belgin Petek Balci, Cavit, Boz, Husnu, Efendi, Murat, Terzi, Serhan, Sevim, Serkan, Ozakba, Andrew, Gale, Ben, Turner, David, Barne, David, Paling, Eli, Silber, James, Overell, Matthew, Craner, Aaron, Carlson, Adam, Wolff, Adaeze, Onuoha, Adnan, Subei, Ahmad, Ata, Aimee, Borazanci, Akram, Dastagir, Alberto, Vasquez, Alison Brooke Allen, Andrew, P Keegan, Angel, Carrasco, Angel, R Chinea Martinez, Ann, Ba, Annette, Okai, April, Erwin, Ariel, Antezana-Antezana, Barbara, Green, Bharathy, E Sundaram, Bhupendra, Khatri, Bhupesh, Dihenia, Bogdan, Gheorghiu, Brian, Costell, Brian, Steingo, Bruce, L Hughe, Carrie, M Hersh, Christopher, Laganke, Christopher, Luzzio, Corey, Ford, Craig Edward Herrman, Craig, Senzon, Cynthia, Huffman, Daniel, R Wynn, David D, O Bear, David, Lesch, David, H Mattson, David, Weisman, Deborah, A Burke, Dennis, W Dietrich, Deren, Huang, Derrick, Robertson, Djamchid, Lotfi, Don Joseph Alfonso, Dusan, Stefoski, Edward, J Fox, Emily, Pharr, Enrique, Alvarez, Evanthia, Bernitsa, Faria, Amjad, Gabriel, Pardo, Geoffrey, Eubank, Gerald, Mcintosh, Giles, F Crowell, Hemanth, Rao, J Michael Hemphill, Jack, H Florin, Jacqueline, Nichola, James, Napier, James, Scott, Jason, M Silversteen, Javier, Vasallo, Jean-Raphael, Schneider, Jeanette, Wendt, Jeffrey, Cohen, Jeffrey, Gro, Jeffrey, Grove, Jeffrey, Kaplan, Jessica, Stulc, Joanna, A Cooper, John, Foley, John, Scagnelli, Jonathan, C Calkwood, Jose Pizarro Otero, Jose, Rafeca, Joshua, Katz, Juliette, S Saad, Katherine, Standley, Keith, Edward, Kenneth, Sharlin, Khurram, Bashir, Kimberly, Wagner, Kore, Liow, Larry Lee Blankenship Jr, Laszlo, Mate, Liliana, Montoya, Lon, D Lynn, Mark, Agiu, Mark, Cascione, Mark Allan Goldstein, Mark, Janicki, Martin, R Bialow, Mary Denise Hughes, Matthew, J Baker, Michelle, Apperson, Michelle, B Kuczma, M Mateo Paz Soldan, Mirela, Cerghet, Nathaniel Robb Whaley, Paul, K Winner, Pavle, Repovic, Praful, Kelkar, Romero Rekha Pillai, Ricardo, Ayala, Richard, Sater, Randall, Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert, Naismith, Ronald, S Murray, Samuel, Hunter, Sara, Qureshi, Sharon, Lynch, Sibyl, Wray, Silvia, R Delgado, Stacy, Donlon, Stanley, Cohan, Stanya, Smith, Stuart James Shafer, Susan, Azalone, Susan, Hibb, Tamara, A Miller, Thomas, Giancarlo, Troy, Desai, Varun, K Saxena, Virginia, Simnad, William David Honeycutt, William, Logan, William, E McElveen, William, Wagner, University of California [San Francisco] (UC San Francisco), University of California (UC), University of Pennsylvania, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Herrada, Anthony, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
Subjects: Male, MESH: Multiple Sclerosis, Relapsing-Remitting, T-Lymphocytes, Hydroxybutyrates, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Pharmacology, Relapsing-Remitting, MESH: Magnetic Resonance Imaging, chemistry.chemical_compound, 0302 clinical medicine, Teriflunomide, Monoclonal, MESH: Double-Blind Method, 030212 general & internal medicine, Humanized, MESH: Toluidines, B-Lymphocytes, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Subcutaneous, B-Lymphocyte, Brain, General Medicine, Magnetic Resonance Imaging, MESH: Crotonates, Crotonates, Pyrimidine metabolism, Disease Progression, Female, MESH: Disease Progression, Antibody, Human, Adult, Multiple Sclerosis, Toluidines, medicine.drug_class, Injections, Subcutaneous, Injections, Subcutaneou, Monoclonal antibody, Ofatumumab, Settore MED/26, Antibodies, Monoclonal, Humanized, Crotonate, Antibodies, Injections, 03 medical and health sciences, MESH: Brain, Multiple Sclerosis, Relapsing-Remitting, Double-Blind Method, MESH: B-Lymphocytes, Nitriles, medicine, Humans, MESH: Kaplan-Meier Estimate, MESH: Humans, business.industry, Multiple sclerosis, MESH: Injections, Subcutaneous, MESH: Adult, medicine.disease, MESH: Male, MESH: T-Lymphocytes, T-Lymphocyte, Multicenter study, chemistry, MESH: Antibodies, Monoclonal, Humanized, biology.protein, Human medicine, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P
Published: 2020
Full Text: View/download PDF

22. Mechanism of action of s1p receptor modulators in multiple sclerosis: The double requirement

Author: William Camu, Régis Bordet, Eric Thouvenot, David-Axel Laplaud, Jérôme De Seze, Jean-Christophe Ouallet, Département de Pharmacologie Médicale [Lille] (Pôle Recherche), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, 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), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (BMNST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), 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 [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, 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), Service de Neurologie [Nîmes], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Le Bihan, Sylvie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Faculté de Médecine Henri Warembourg - Université de Lille, Institut des Neurosciences de Montpellier (INM), 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 Strasbourg (UNISTRA)-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 Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Multiple Sclerosis, Sphingosine-1-phosphate, [SDV]Life Sciences [q-bio], Sphingosine-1-phosphate receptor, Neuroprotection, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Neuroinflammation, Sphingosine, Animals, Humans, Medicine, 030212 general & internal medicine, Neurodegeneration, Receptor, Sphingosine-1-Phosphate Receptors, Fingolimod Hydrochloride, business.industry, Multiple sclerosis, Brain, Fingolimod, medicine.disease, [SDV] Life Sciences [q-bio], Neurology, chemistry, Immune System, Neurology (clinical), Lysophospholipids, business, Neuroscience, Immunosuppressive Agents, 030217 neurology & neurosurgery, Signal Transduction, medicine.drug
Abstract: International audience; The ideal treatment for multiple sclerosis (MS) would target both the neuroinflammatory component of the disease (peripheral and central) and its neurodegenerative component, via modulation of a ubiquitous and pleiotropic common target. Sphingosine-1-phosphate (S1P), a product of sphingosine metabolism, regulates many biological functions (including cell proliferation and survival, cell migration, the immune response and cardiovascular function) via five subtypes of receptor. These receptors are expressed in all types of brain cells where they modulate a number of processes involved in neuronal plasticity, including myelination, neurogenesis and neuroprotection. This profile has aroused interest in modulation of S1P function as a therapeutic target in many brain diseases, particularly those in which the immune system plays a role in the development of brain lesions. Fingolimod, a S1P receptor modulator, exerts its beneficial effects in MS through its anti-inflammatory and anti-neurodegenerative effects. This review discusses recent evidence indicating that fingolimod may target both the inflammatory and neurodegenerative components of the disease process in MS.
Published: 2020
Full Text: View/download PDF

23. Single-Cell Analysis to Better Understand the Mechanisms Involved in MS

Author: Emilie Dugast, Sita Shah, David-Axel Laplaud, KERANDEL-DION, Céline, Team 5 : Neuroinflammation, mechanisms, therapeutic options (NEMO) (U1064 Inserm - CR2TI), 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 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 (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Neurologie [CHU Nantes], and Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Nord Laënnec
Subjects: Central Nervous System, CD4-Positive T-Lymphocytes, lymphocytes, [SDV]Life Sciences [q-bio], Organic Chemistry, astrocytes, microglia, oligodendrocytes, General Medicine, CD8-Positive T-Lymphocytes, multiple sclerosis, Catalysis, single cell, Computer Science Applications, [SDV] Life Sciences [q-bio], Inorganic Chemistry, Humans, Single-Cell Analysis, Physical and Theoretical Chemistry, monocytes, Molecular Biology, Spectroscopy
Abstract: International audience; Multiple sclerosis is a chronic and inflammatory disease of the central nervous system. Although this disease is widely studied, many of the precise mechanisms involved are still not well known. Numerous studies currently focusing on multiple sclerosis highlight the involvement of many major immune cell subsets, such as CD4+ T cells, CD8+ T cells and more recently B cells. However, our vision of its pathology has remained too broad to allow the proper use of targeted therapeutics. This past decade, new technologies have emerged, enabling deeper research into the different cell subsets at the single-cell level both in the periphery and in the central nervous system. These technologies could allow us to identify new cell populations involved in the disease process and new therapeutic targets. In this review, we briefly introduce the major single-cell technologies currently used in studies before diving into the major findings from the multiple sclerosis research from the past 5 years. We focus on results that were obtained using single-cell technologies to study immune cells and cells from the central nervous system.
Published: 2022
Full Text: View/download PDF

24. 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
Full Text: View/download PDF

25. A French cohort for assessing COVID-19 vaccine responses in specific populations

Author: Benoit Barrou, David-Axel Laplaud, Odile Launay, Stéphanie Nguyen, Jean-Daniel Lelièvre, Jean-Yves Blay, Benjamin Terrier, Martine Laville, Anne Thiebaut, Jacques Morel, Xavier de Lamballerie, Béatrice Parfait, Bruno Laviolle, Jean-François Viallard, Linda Wittkop, François Vrtovsnik, Jean-Philippe Spano, Paul Loubet, Maryvonne Hourmant, Marie Lachâtre, Eric Tartour, Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Léon Bérard [Lyon], 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), Association Francaise d'Etudes et de Recherches sur l'Obesite, Partenaires INRAE, Hospices Civils de Lyon (HCL), 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 d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire [Grenoble] (CHU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS00001S, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Service d'Urologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL-SU, Gestionnaire, 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 d'Immunologie et de Maladies Infectieuses (CIMI), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], Université de Bordeaux (UB), Université de Paris (UP), Institut de Recherche pour le Développement (IRD), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Virulence Bactérienne et Infections Chroniques (VBIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Grenoble, Université Paris Diderot - Paris 7 (UPD7), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, medicine.medical_specialty, 2019-20 coronavirus outbreak, COVID-19 Vaccines, Adolescent, Coronavirus disease 2019 (COVID-19), Epidemiology, [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, Immunocompromised Host, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Young adult, ComputingMilieux_MISCELLANEOUS, Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, business.industry, COVID-19, General Medicine, Middle Aged, Antibodies, Neutralizing, Virology, 3. Good health, Viral infection, 030220 oncology & carcinogenesis, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study
Abstract: International audience; No abstract available
Published: 2021
Full Text: View/download PDF

26. Cumulative effects of therapies on disability in relapsing multiple sclerosis

Author: Romain Casey, Fabien Rollot, Gilles Edan, David-Axel Laplaud, Emmanuelle Leray, Sandra Vukusic, Sandrine Wiertlewski, Marc Debouverie, 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), 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), 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), École des Hautes Études en Santé Publique [EHESP] (EHESP), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), CHU Pontchaillou [Rennes], Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence Nationale de la Recherche, Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques, Eugène Devic EDMUS Foundation, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de 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), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, Adult, medicine.medical_specialty, Treatment response, [SDV]Life Sciences [q-bio], cumulative effect, Multiple sclerosis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Humans, Disabled Persons, 030212 general & internal medicine, Cumulative effect, business.industry, Cumulative effects, treatment response, medicine.disease, 3. Good health, long-term observational study, Neurology, Female, Neurology (clinical), Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery
Abstract: Background: Long-term effectiveness of treatment remains a key question in multiple sclerosis (MS) and the cumulative effects of past treatment have not been investigated so far. Objective: Explore the relationship between treatment exposure and disability risk in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: A total of 2285 adult patients from the French nationwide cohort were included. Outcomes were irreversible EDSS4, and conversion to secondary progression of multiple sclerosis (SPMS). Associations between treatments and risk of disability were assessed using a novel weighted cumulative exposure model, assuming a 3-year lag to account for reverse causality. This flexible approach accounts for past exposure in a multivariate Cox proportional hazards model by computing a weight function. Results: At baseline, mean ± standard deviation age of patients was 33.4 ± 8.9 years and 75.0% were women. A 15-year continuous treatment starting 20 years ago was associated with a decrease in risk of 26% for irreversible EDSS4, and 34% for SPMS compared to a 5-year treatment starting 10 years ago. The risk of disability decreased with increasing duration of exposure to disease-modifying treatment (DMT). Conclusion: Long-term use of treatments in RRMS has a stronger beneficial cumulative impact than only early uses and delays the occurrence of moderate disability and conversion to SPMS.
Published: 2021
Full Text: View/download PDF

27. sj-pdf-1-msj-10.1177_1352458520980366.pdf – Supplemental material for Cumulative effects of therapies on disability in relapsing multiple sclerosis

Author: Rollot, Fabien, Casey, Romain, Leray, Emmanuelle, Debouverie, Marc, Edan, Gilles, Wiertlewski, Sandrine, Vukusic, Sandra, and David-Axel Laplaud
Subjects: FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 110904 Neurology and Neuromuscular Diseases
Abstract: Supplemental material, sj-pdf-1-msj-10.1177_1352458520980366.pdf for Cumulative effects of therapies on disability in relapsing multiple sclerosis by Fabien Rollot, Romain Casey, Emmanuelle Leray, Marc Debouverie, Gilles Edan, Sandrine Wiertlewski, Sandra Vukusic and David-Axel Laplaud in Multiple Sclerosis Journal
Published: 2021
Full Text: View/download PDF

28. BEST-MS: A prospective head-to-head comparative study of natalizumab and fingolimod in active relapsing MS

Author: Eric Berger, Clarisse Carra, Christine Lebrun-Frenay, Patrick Vermersch, Chrystelle Cappé, Gilles Defer, Béatrice Pignolet, David Brassat, Marc Debouverie, Bruno Brochet, Lydiane Mondot, Aurélie Ruet, Hélène Zéphir, Nathalie Derache, Guillaume Mathey, Kévin Bigaut, Sandrine Wiertlewski, Jérôme De Seze, David-Axel Laplaud, Mikael Cohen, Pierre Labauge, Florence Bucciarelli, Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Hôpital Pasteur [Nice] (CHU), Pôle neurosciences [Hôpital de Purpan - Toulouse], CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), 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 Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre 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), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Ressources et de Compétences Sclérose en Plaques (CRCSEP), 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), 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), Projet Fédératif Hospitalo-Universitaire IMmune-Mediated INflammatory diseases aNd Targeted Therapies [Lille] (FHU IMMINeNT), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg
Subjects: Oncology, medicine.medical_specialty, Head to head, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, natalizumab, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, therapeutics, Humans, magnetic resonance imaging, Prospective Studies, 030212 general & internal medicine, fingolimod, medicine.diagnostic_test, Fingolimod Hydrochloride, business.industry, Magnetic resonance imaging, medicine.disease, Fingolimod, 3. Good health, Neurology, Neurology (clinical), Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS) Objective: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing–remitting MS Method: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity. Results: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group ( p = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p = 0.029). Conclusion: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing–remitting MS. Our results suggest a superiority of NTZ over FTY.
Published: 2020
Full Text: View/download PDF

29. Help the decision of switch for multiple sclerosis patients with Dynamic Propensity Scores

Author: Camille Sabathé, David-Axel Laplaud, Sandra Vukusic, Romain Casey, Yohann Foucher, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], 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), Service de Neurologie [Hospices civils de Lyon - Hôpital Pierre Wertheimer], Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Fondation Eugène Devic EDMUS, Centre hospitalier universitaire de Nantes (CHU Nantes), and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques
Subjects: [STAT.AP]Statistics [stat]/Applications [stat.AP], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

30. BEST MS : étude nationale prospective comparant l’efficacité du natalizumab et du fingolimod dans les formes actives de sclérose en plaques

Author: Gilles Defer, Mikael Cohen, Patrick Vermersch, Bruno Brochet, Jérôme De Seze, Christine Lebrun, Eric Berger, Pierre Labauge, Marc Debouverie, Lydiane Mondot, Florence Bucciarelli, Béatrice Pignolet, David Brassat, David-Axel Laplaud, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Toulouse [Toulouse], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], 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 Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département de neurologie [Montpellier], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université de Montpellier (UM), and Les Hôpitaux Universitaires de Strasbourg (HUS)
Subjects: 03 medical and health sciences, 0302 clinical medicine, Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030212 general & internal medicine, Neurology (clinical), 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction L’arsenal therapeutique s’est enrichi dans le traitement des formes actives de sclerose en plaques (SEP), mais tres peu d’etudes comparent les molecules de maniere prospective. Objectifs L’etude BEST-MS a demarre en 2013 pour comparer de maniere prospective l’efficacite de deux principales molecules disponibles a cette date pour les formes actives de SEP : le natalizumab (NTZ) et le fingolimod (FTY). Patients et methodes BEST-MS est une etude prospective multicentrique. Les patients presentaient une SEP active (1 poussee en 12 mois sous traitement de premiere ligne avec au moins 9 hypersignaux T2 a l’IRM, ou 2 poussees en 12 mois avec signes d’agressivite IRM chez les patients naifs). Le choix du traitement (NTZ ou FTY) etait a la discretion du neurologue. Un suivi clinique (poussees, EDSS) et IRM etait realise a l’inclusion et a 1 an. Resultats Deux cents trente patients ont ete inclus (âge moyen : 38,2 ans ; F/H : 3,1 ; FTY : 117 ; NTZ : 113). Les caracteristiques a l’inclusion etaient comparables entre les deux groupes. A 1 an, le NTZ montre une superiorite sur le nombre de nouvelles lesions T2 (0,7 vs 1,4, p = 0,01), le nombre de lesions rehaussees (0,03 vs 0,5, p Discussion BEST-MS est la 1ere etude prospective comparant l’efficacite du NTZ et du FTY. Le NTZ montre une superiorite par rapport au FTY sur les criteres IRM. Le TAP est aussi plus faible, mais la majorite des poussees sont survenues pendant les 4 premiers mois de traitement dans les 2 groupes. Le taux d’arret de traitement est plus eleve sous FTY, essentiellement pour intolerance Conclusion Le NTZ montre une meilleure efficacite que le FTY dans les formes actives de SEP sur les parametres cliniques et IRM.
Published: 2020
Full Text: View/download PDF

31. Integrative molecular profiling of autoreactive CD4 T cells in autoimmune hepatitis

Author: Sophie Conchon, Alexandra Garcia, Béatrice Clémenceau, Fabienne Vavasseur, Sarah Habes, Hélène Aublé, Sophie Brouard, Laurine Gil, Florence Tanné, Anaïs Cardon, David-Axel Laplaud, Caroline Chevalier, Jean-Paul Judor, Jean-François Mosnier, Pierre Milpied, Chuang Dong, Jérôme Gournay, Inaki Cervera-Marzal, Erwan Kervagoret, Amédée Renand, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre d'Investigation Clinique gastro-nutrition [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hépato-gastroentérologie [CHU Nantes], Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Institut des Maladies de l’Appareil Digestif [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), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), ANR-19-CE17-0024,DISTAL,Signature lymphocytaire T auto-antigène-spécifique au cours des maladies auto-immunes du foie(2019), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, Adult, CD4-Positive T-Lymphocytes, Male, Receptors, CXCR5, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, Receptors, Antigen, T-Cell, Epitopes, T-Lymphocyte, Autoimmune hepatitis, Biology, Autoantigens, Epitope, Flow cytometry, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Antigen, medicine, Humans, Single-cell RNA-seq, ComputingMilieux_MISCELLANEOUS, Autoantibodies, B-Lymphocytes, Autoreactive CD4 T cells, Hepatology, medicine.diagnostic_test, Sequence Analysis, RNA, T-cell receptor, Autoantibody, Autoreactive TCR clonotypes, Middle Aged, medicine.disease, Phenotype, 3. Good health, Tumor Necrosis Factor Receptor Superfamily, Member 7, [SDV] Life Sciences [q-bio], Hepatitis, Autoimmune, 030104 developmental biology, Immunology, 030211 gastroenterology & hepatology, Female, Soluble liver antigen, Immunologic Memory
Abstract: International audience; Background & aims: In most autoimmune disorders, crosstalk of B cells and CD4 T cells results in the accumulation of autoantibodies. In autoimmune hepatitis (AIH), the presence of anti-soluble liver antigen (SLA) autoantibodies is associated with reduced overall survival, but the associated autoreactive CD4 T cells have not yet been characterised. Herein, we isolated and deeply characterised SLA-specific CD4 T cells in patients with AIH.Methods: We used brief ex vivo restimulation with overlapping SLA peptides to isolate and phenotype circulating SLA-specific CD4 T cells, and integrative single-cell RNA-seq (scRNA-seq) to characterise their transcriptome and T-cell receptor (TCR) repertoire. Autoreactive TCRs were cloned and used to identify dominant SLA-derived epitopes. SLA-specific CD4 T cells were tracked in peripheral blood through TCR sequencing to identify their phenotypic niche. We further characterised disease-associated peripheral blood T cells by high-content flow cytometry in 42 patients with AIH and 17 controls with non-alcoholic steatohepatitis.Results: Autoreactive SLA-specific CD4 T cells were only detected in patients with anti-SLA autoantibodies and had a memory PD-1+CXCR5-CCR6-CD27+ phenotype. ScRNA-seq revealed their pro-inflammatory/B-helper profile. SLA81-100 and SLA177-204 contain dominant T-cell epitopes. Autoreactive TCR clonotypes were predominantly found in the memory PD-1+CXCR5-CD4 T cells, which were significantly increased in the blood of patients with AIH and supported B-cell differentiation through IL-21. Finally, we identified specific T-cell phenotypes linked to disease activity and IgG level during AIH.Conclusions: We provide a deep characterisation of rare circulating autoreactive CD4 T cells and identify their peripheral reservoir in AIH. We also propose a specific phenotype of autoreactive T cells related to AIH disease activity, which will be essential to track, delineate, and potentially target these pathogenic cells.Lay summary: One principal characteristic of autoimmune hepatitis (AIH), like for many other autoimmune diseases, is the accumulation of autoantibodies produced by B lymphocytes following their interaction with autoreactive CD4 T lymphocytes. In this study, we identified and characterised with high resolution these CD4 T cells. This will be essential to track, delineate, and potentially target them during AIH.
Published: 2020
Full Text: View/download PDF

32. Corrigendum to 'Oligoclonal myelin-reactive T-cell infiltrates derived from neuromyelitis optica spectrum disorder (NMOSD) lesions are enriched in Th17 cells' [Clinical Immunology 130 (2009) 133–144]

Author: Monica Montes, Xin Zhang, Laureline Berthelot, David-Axel Laplaud, Sophie Brouard, Jianping Jin, Sarah Rogan, Diane Armao, Valerie Jewells, Jean-Paul Soulillou, and Silva Markovic-Plese
Subjects: Immunology, Immunology and Allergy
Published: 2022
Full Text: View/download PDF

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

Author: Romain Casey, David-Axel Laplaud, Fabien Rollot, François Cotton, Bertrand Fontaine, Thibault Moreau, Jérôme De Seze, Bruno Stankoff, Francis Guillemin, Michel Clanet, Bruno Brochet, Sandra Vukusic, Jean Pelletier, Marc Debouverie, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut François Magendie, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Neurologie vasculaire, pathologie neuro-dégénérative et explorations fonctionnelles du système nerveux [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CIC 1433 Epidémiologie clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherche en Myologie, and Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Databases, Factual, registry, Multiple sclerosis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Humans, Registries, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, database, business.industry, Middle Aged, medicine.disease, University hospital, 3. Good health, Neurology, quality, Female, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Neurology (clinical), Medical emergency, business, 030217 neurology & neurosurgery
Abstract: The care of multiple sclerosis (MS) in France is based on two complementary interlinked networks: MS expert centers in university hospitals and regional networks of neurologists. The routine use of European database for multiple sclerosis (EDMUS) in all those centers has paved the way for the constitution of a national registry, designated as Observatoire Français de la Sclérose En Plaques (OFSEP). It promotes a prospective, standardized, high-quality, and multimodal collection of data. On June 2018, there were 68.097 files, with 71.1% females, representing 761,185 person-years. This huge database is open to the scientific community and might contribute exploring unresolved issues and unmet needs in MS.
Published: 2018
Full Text: View/download PDF

34. Recommendations for the use of Rituximab in neuromyelitis optica spectrum disorders

Author: Nicolas Collongues, Jonathan Ciron, Françoise Durand-Dubief, Sandra Vukusic, C. Papeix, David Brassat, David-Axel Laplaud, Elisabeth Maillart, Bertrand Audoin, Romain Marignier, Bertrand Bourre, Hélène Zéphir, Département Neurologie [CHU Toulouse], Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), AP-HM, CHU Timone, Pole de Neurosciences Cliniques, Department of Neurology, Marseille, France., Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (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), Department of neurology, university hospital of Rouen, 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), Department of neurology, Sclérose en Plaques, pathologies de la myéline et neuro-inflammation, hôpital neurologique Pierre-Wertheimer, hospices civils de Lyon, Inserm U1028 CNRS UMR 5292, FLUID Team, faculté de médecine Laennec, centre de recherche en neurosciences de Lyon, Department of neurology, Sclérose en Plaques, pathologies de la myéline et neuro-inflammation, hôpital neurologique Pierre-Wertheimer, hospices civils de Lyon, Lyon, Department of neurology, university hospital of Nantes, Department of Neurology, University Hospital Strasbourg, Clinical Investigation Center, Inserm U1434, university hospital of Strasbourg, Biopathology of Myelin, neuroprotection and therapeutic Strategies, Inserm U1119, university hospital of Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Département de neurologie [Lille], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: medicine.medical_specialty, 03 medical and health sciences, 0302 clinical medicine, Rescue therapy, medicine, Humans, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, CD20, Neuromyelitis optica, biology, business.industry, Neuromyelitis Optica, Antibodies, Monoclonal, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Vaccination, Preventive therapy, Neurology, Neuromyelitis Optica Spectrum Disorders, Practice Guidelines as Topic, biology.protein, Rituximab, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: There is growing evidence of a preventive effect of Rituximab (RTX) in neuromyelitis optica spectrum disorders (NMO-SD). This monoclonal antibody against CD20 is becoming the most widely used preventive therapy in NMO-SD, as a first-line therapy or as a rescue therapy. Nevertheless, considerable heterogeneity still exists concerning the pre-treatment work-up, the vaccinations required before and under treatment, the number and dosage of infusions, prevention of the risk of infusion-related reactions, prevention of infections under treatment, and frequency of therapeutic cycles. Thanks to a collaborative work among NMO-SD experts belonging to the NOMADMUS project, we provide here recommendations for all these topics concerning RTX use in NMO-SD.
Published: 2018
Full Text: View/download PDF

35. An intermediate level of CD161 expression defines a novel activated, inflammatory, and pathogenic subset of CD8 + T cells involved in multiple sclerosis

Author: J. Morille, Isabel Vogel, Laureline Berthelot, Sandrine Wiertlewski, Steven Nedellec, Stéphanie Kilens, Nicolas Degauque, Arnaud Bourreille, Emilie Dugast, Alexandra Garcia, Arnaud Nicot, Marion Salou, Laurent David, Fabienne Le Frère, Marylène Jacq-Foucher, David-Axel Laplaud, Eric Charpentier, Sophie Brouard, Audrey Donnart, Bryan Nicol, Pierre-Antoine Gourraud, Laure Michel, 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), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Structure fédérative de recherche François Bonamy (SFR François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Service de Neurologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Nord Laënnec, 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), CIC Plurithématique de Nantes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ministère des Affaires sociales et de la Santé-Direction générale de l'offre de soins (DGOS)-Centre hospitalier universitaire de Nantes (CHU Nantes), LabEx IGO 'Immunotherapy, Graft, Oncology' [Nantes], This work has been supported by a grant from the ARSEPFoundation and by the ANTARES Association., Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), and CHATEL, Stephanie
Subjects: 0301 basic medicine, CD8(+) T cells, [SDV]Life Sciences [q-bio], Immunology, Biology, Natural killer T cell, [SDV] Life Sciences [q-bio], Multiple sclerosis, 03 medical and health sciences, Interleukin 21, CD8 þ T cells, 030104 developmental biology, 0302 clinical medicine, Neuroinflammation, Central nervous system, Interleukin 12, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, 030217 neurology & neurosurgery, CD8, CD161, Interleukin 3
Abstract: International audience; Several lines of evidence support a key role for CD8+ T cells in central nervous system tissue damage of patients with multiple sclerosis. However, the precise phenotype of the circulating CD8+ T cells that may be recruited from the peripheral blood to invade the CNS remains largely undefined to date. It has been suggested that IL-17 secreting CD8 (Tc17) T cells may be involved, and in humans these cells are characterized by the expression of CD161. We focused our study on a unique and recently described subset of CD8 T cells characterized by an intermediate expression of CD161 as its role in neuroinflammation has not been investigated to date. The frequency, phenotype, and function of CD8+ T cells with an intermediate CD161 expression level were characterized ex-vivo, in vitro, and in situ using RNAseq, RT-PCR, flow cytometry, TCR sequencing, and immunohistofluorescence of cells derived from healthy volunteers (n = 61), MS subjects (n = 90), as well as inflammatory (n = 15) and non-inflammatory controls (n = 6). We report here that CD8+CD161int T cells present characteristics of effector cells, up-regulate cell-adhesion molecules and have an increased ability to cross the blood-brain barrier and to secrete IL-17, IFNγ, GM-CSF, and IL-22. We further demonstrate that these cells are recruited and enriched in the CNS of MS subjects where they produce IL-17. In the peripheral blood, RNAseq, RT-PCR, high-throughput TCR repertoire analyses, and flow cytometry confirmed an increased effector and transmigration pattern of these cells in MS patients, with the presence of supernumerary clones compared to healthy controls. Our data demonstrate that intermediate levels of CD161 expression identifies activated and effector CD8+ T cells with pathogenic properties that are recruited to MS lesions. This suggests that CD161 may represent a biomarker and a valid target for the treatment of neuroinflammation.
Published: 2018
Full Text: View/download PDF

36. L’interféron bêta-1a sous-cutané 22/44 μg démontre une efficacité comparable à celle du tériflunomide chez les patients atteints de sclérose en plaques nouvellement traités – Étude menée avec l’Observatoire français de la sclérose en plaques (OFSEP)

Author: David-Axel Laplaud, Emmanuelle Boutmy, Caroline Foch, Fabien Rollot, Kurt Marhardt, and Meritxell Sabidó
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction Une comparaison des donnees de vraie vie de l’interferon beta-1a sous-cutane 22/44 μg (IFNβ-1a) et du teriflunomide (TFN) peut permettre de mieux comprendre les avantages de ces deux traitements. Objectifs Comparer l’efficacite de l’IFNβ-1a vs TFN via l’incidence des poussees, la progression du handicap confirmee a 6 mois (Annee-2) et l’absence de preuve d’activite de la maladie (NEDA-3 ; Annee-1). Patients et methodes L’analyse porte sur les patients SEP-RR ( Resultats Les cohortes IFNβ-1a (n = 244) et TFN (n = 688) ont montre respectivement en annee 2 : 39,4 % (IC 95 %, 34,7–51,4) versus 49,2 % (42,7–54,7) avaient ≥ 1 poussees (HR, 0,79 [0,59–1,06]) ; 8,5 % (IC 95 %, 2,2–22,3) versus 11,4 % (6,4–22) ont presente une progression du handicap (OR, 0,72 [0,24–2,13]). En Annee 1 : 73,1 % (IC a 95 %, 40,0 a 79,6) versus 55,1 % (43,7 a 68,5) ont obtenu le NEDA-3 (OR : 2,22 [0,90–5,56]). Discussion Aucune difference d’incidence des poussees, de progression du handicap ou d’atteinte du NEDA-3 n’a ete observee entre les patients traites par IFNβ-1a vs TFN. La methode IPTW n’a pas equilibre tous les facteurs confondants a baseline entre les groupes, notamment pour l’analyse de la progression du handicap et du NEDA-3. La petite taille de l’echantillon limite la puissance des analyses. Conclusion Cette etude de donnees de vraie vie suggere que l’IFNβ-1a et le TFN ont une efficacite comparable chez les patients atteints de SEP-RR. Informations complementaires Cette etude a ete sponsorisee par Merck KGaA, Darmstadt, Allemagne et utilisee les donnees de l’OFSEP (Observatoire francais de la Sclerose En Plaques) qui est finance par l’Agence Nationale de la Recherche ANR-10-COHO-002, Eugene Devic EDMUS Fondation contre la sclerose en plaques, Fondation ARSEP.
Published: 2020
Full Text: View/download PDF

37. sj-pdf-1-msj-10.1177_1352458520978218 – Supplemental material for Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study

Author: Vukusic, Sandra, Ionescu, Iuliana, Cornu, Catherine, Bossard, Nadine, Durand-Dubief, Françoise, Cotton, François, Durelli, Luca, Marignier, Romain, Gignoux, Laurence, David-Axel Laplaud, Moreau, Thibault, Clavelou, Pierre, Seze, Jérôme De, Debouverie, Marc, Brassat, David, Pelletier, Jean, Lebrun-Frenay, Christine, Page, Emmanuelle Le, Castelnovo, Giovanni, Berger, Eric, Hautecoeur, Patrick, Heinzlef, Olivier, Trojano, Maria, Patti, Francesco, Etienne-Emile Baulieu, Remontet, Laurent, and El-Etr, Martine
Subjects: FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 110904 Neurology and Neuromuscular Diseases
Abstract: Supplemental material, sj-pdf-1-msj-10.1177_1352458520978218 for Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study by Sandra Vukusic, Iuliana Ionescu, Catherine Cornu, Nadine Bossard, Françoise Durand-Dubief, François Cotton, Luca Durelli, Romain Marignier, Laurence Gignoux, David-Axel Laplaud, Thibault Moreau, Pierre Clavelou, Jérôme De Seze, Marc Debouverie, David Brassat, Jean Pelletier, Christine Lebrun-Frenay, Emmanuelle Le Page, Giovanni Castelnovo, Eric Berger, Patrick Hautecoeur, Olivier Heinzlef, Maria Trojano, Francesco Patti, Etienne-Emile Baulieu, Laurent Remontet and Martine El-Etr in Multiple Sclerosis Journal
Published: 2020
Full Text: View/download PDF

38. sj-pdf-2-msj-10.1177_1352458520978218 – Supplemental material for Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study

Author: Vukusic, Sandra, Ionescu, Iuliana, Cornu, Catherine, Bossard, Nadine, Durand-Dubief, Françoise, Cotton, François, Durelli, Luca, Marignier, Romain, Gignoux, Laurence, David-Axel Laplaud, Moreau, Thibault, Clavelou, Pierre, Seze, Jérôme De, Debouverie, Marc, Brassat, David, Pelletier, Jean, Lebrun-Frenay, Christine, Page, Emmanuelle Le, Castelnovo, Giovanni, Berger, Eric, Hautecoeur, Patrick, Heinzlef, Olivier, Trojano, Maria, Patti, Francesco, Etienne-Emile Baulieu, Remontet, Laurent, and El-Etr, Martine
Subjects: FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 110904 Neurology and Neuromuscular Diseases
Abstract: Supplemental material, sj-pdf-2-msj-10.1177_1352458520978218 for Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study by Sandra Vukusic, Iuliana Ionescu, Catherine Cornu, Nadine Bossard, Françoise Durand-Dubief, François Cotton, Luca Durelli, Romain Marignier, Laurence Gignoux, David-Axel Laplaud, Thibault Moreau, Pierre Clavelou, Jérôme De Seze, Marc Debouverie, David Brassat, Jean Pelletier, Christine Lebrun-Frenay, Emmanuelle Le Page, Giovanni Castelnovo, Eric Berger, Patrick Hautecoeur, Olivier Heinzlef, Maria Trojano, Francesco Patti, Etienne-Emile Baulieu, Laurent Remontet and Martine El-Etr in Multiple Sclerosis Journal
Published: 2020
Full Text: View/download PDF

39. Progressive Multifocal Leukoencephalopathy Incidence and Risk Stratification Among Natalizumab Users in France

Author: Xavier Moisset, Elisabeth Maillart, Julie Pique, Ofsep Investigators, Pierre Labauge, Bruno Stankoff, Eric Thouvenot, Bertrand Bourre, Fabien Rollot, Hélène Zéphir, Nathalie Derache, Gilles Edan, Sandra Vukusic, Audrey Rico-Lamy, Christine Lebrun-Frenay, David-Axel Laplaud, Eric Berger, Nicolas Maubeuge, Ayman Tourbah, Sandrine Wiertlewski, A.-M. Guennoc, Céline Labeyrie, Patrick Vermersch, Olivier Heinzlef, Mathieu Vaillant, Karolina Hankiewicz, C. Bensa, Philippe Cabre, Jérôme De Seze, Aurélie Ruet, Thibault Moreau, Romain Casey, Ivania Patry, Romain Marignier, Abdullatif Al-Khedr, Abir Wahab, Alexis Montcuquet, Chantal Nifle, Jean-Philippe Camdessanché, Guillaume Mathey, David Brassat, Service de Neurologie [Lyon], CHU Lyon, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, 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), Hospices Civils de Lyon (HCL), Fondation Eugène Devic EDMUS, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-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), 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], Neuroinflammation: imagerie et thérapie de la sclérose en plaques, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Neurology, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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 [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Neuro-Dol (Neuro-Dol), Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), 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), CHI Poissy-Saint-Germain, CHU Amiens-Picardie, Service de Neurologie, Fondation Ophtalmologique Rothschild, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), CHU de la Martinique [Fort de France], Service de Neurologie [CHU Limoges], CHU Limoges, Service de neurologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Saint-Etienne, Service de neurologie [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Neurologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de neurologie [CH Saint Denis], Centre Hospitalier de Saint-Denis [Ile-de-France], Hôpital Sud Francilien Corbeil Essonne, Centre Hospitalier de Versailles André Mignot (CHV), Service de neurologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de neurologie [Le Kremlin Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, OFSEP (Observatoire Français de la Sclérose en Plaques) is supported by grant ANR-10-COHO-002 from 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 EDMUS Foundation Against Multiple Sclerosis, and by the ARSEP 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), Université de Rennes (UR), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), 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), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Pierre Wertheimer, Département de Neurologie, Lille Inflammation Research International Center (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie [Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, ANR-10-COHO-002-01/10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Vialaron, Sylvie, and Cohortes - Observatoire Français de la Sclérose en Plaques - - OFSEP2010 - ANR-10-COHO-0002 - COHO - VALID
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Population, JC virus, Rate ratio, medicine.disease_cause, 03 medical and health sciences, symbols.namesake, Immunocompromised Host, Young Adult, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Risk Factors, medicine, Humans, Immunologic Factors, 030212 general & internal medicine, Poisson regression, Registries, education, Original Investigation, education.field_of_study, business.industry, Progressive multifocal leukoencephalopathy, Incidence (epidemiology), Incidence, Leukoencephalopathy, Progressive Multifocal, medicine.disease, JC Virus, 3. Good health, Discontinuation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, symbols, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), France, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; Importance:Risk of developing progressive multifocal leukoencephalopathy (PML) is the major barrier to using natalizumab for patients with multiple sclerosis (MS). To date, the association of risk stratification with PML incidence has not been evaluated.Objective:To describe the temporal evolution of PML incidence in France before and after introduction of risk minimization recommendations in 2013.Design, Setting, and Participants:This observational study used data in the MS registry OFSEP (Observatoire Français de la Sclérose en Plaques) collected between April 15, 2007, and December 31, 2016, by participating MS expert centers and MS-dedicated networks of neurologists in France. Patients with an MS diagnosis according to current criteria, regardless of age, were eligible, and those exposed to at least 1 natalizumab infusion (n = 6318) were included in the at-risk population. A questionnaire was sent to all centers, asking for a description of their practice regarding PML risk stratification. Data were analyzed in July 2018.Exposures:Time from the first natalizumab infusion to the occurrence of PML, natalizumab discontinuation plus 6 months, or the last clinical evaluation.Main Outcomes and Measures:Incidence was the number of PML cases reported relative to the person-years exposed to natalizumab. A Poisson regression model for the 2007 to 2016 period estimated the annual variation in incidence and incidence rate ratio (IRR), adjusted for sex and age at treatment initiation and stratified by period (2007-2013 and 2013-2016).Results:In total, 6318 patients were exposed to natalizumab during the study period, of whom 4682 (74.1%) were female, with a mean (SD [range]) age at MS onset of 28.5 (9.1 [1.1-72.4]) years; 45 confirmed incident cases of PML were diagnosed in 22 414 person-years of exposure. The crude incidence rate for the whole 2007 to 2016 period was 2.00 (95% CI, 1.46-2.69) per 1000 patient-years. Incidence significantly increased by 45.3% (IRR, 1.45; 95% CI, 1.15-1.83; P = .001) each year before 2013 and decreased by 23.0% (IRR, 0.77; 95% CI, 0.61-0.97; P = .03) each year from 2013 to 2016.Conclusions and Relevance:The results of this study suggest, for the first time, a decrease in natalizumab-associated PML incidence since 2013 in France that may be associated with a generalized use of John Cunningham virus serologic test results; this finding appears to support the continuation and reinforcement of educational activities and risk-minimization strategies in the management of disease-modifying therapies for multiple sclerosis.
Published: 2020
Full Text: View/download PDF

40. J Clin Apher

Author: Marc Debouverie, Hélène Zéphir, Linda Wittkop, Bruno Brochet, Mathilde Deloire, Pierre Clavelou, Sophie Pittion, Christine Germain, Paul Perez, Patrick Vermersch, Aurélie Ruet, Cécile Dulau, Jean-Christophe Ouallet, David-Axel Laplaud, Jérôme De Seze, Florian Thevenot, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Moderate to severe, Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Optic Neuritis, Adolescent, Aucun, 030204 cardiovascular system & hematology, law.invention, Double blind, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Adrenal Cortex Hormones, Recurrence, Internal medicine, Clinical endpoint, Medicine, Humans, MORPH3Eus, Optic neuritis, Aged, Plasma Exchange, business.industry, Multiple sclerosis, Hematology, General Medicine, Middle Aged, medicine.disease, 3. Good health, Plasma Exchanges, Clinical trial, Phenotype, Treatment Outcome, Sample Size, Disease Progression, Female, Steroids, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030215 immunology
Abstract: INTRODUCTION: No randomized controlled clinical trial of therapeutic plasma exchanges (TPE) has yet been performed for moderate-to-severe relapses of multiple sclerosis (MS). OBJECTIVE: To compare TPE to sham-TPE in patients with a recent steroid-resistant moderate-to-severe MS relapse. METHODS: Patients presenting with an MS relapse of less than 2 months without improvement and 15 days after a course of steroids were randomized. Specific criteria were used for each relapse type to define moderate-to-severe disability. The primary endpoint was the proportion of patients with at least a moderate improvement based on objective and functional evaluation after 1 month. RESULTS: Thirty-eight patients were randomized. The intention-to-treat analysis included 14 patients in the TPE group and 17 in the Sham-TPE group. The proportion of patients with at least moderate improvement at 1 month did not differ between the groups (P = .72), although 57.1% of the TPE group had full recovery compared with 17.6% of the sham group. Considering optic neuritis (ON), a significant difference in the proportion of different levels of improvement was observed in favor of the TPE group (P = .04). The combined Kurtzke's functional systems scores were significantly more improved in the TPE group than in the sham-TPE group at months 1 (P
Published: 2020
Full Text: View/download PDF

41. 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
Full Text: View/download PDF

42. CD8+ T cell-mediated endotheliopathy is a targetable mechanism of neuro-inflammation in Susac syndrome

Author: Marius Ringelstein, L. M. Yshii, Ilka Kleffner, Stephen W. Reddel, Brigitte Wildemann, Todd A. Hardy, Markus Schwaninger, Guillaume Martin-Blondel, Nicholas Schwab, Delphine Loussouarn, John Parratt, Marc Pawlitzki, Henrike Plate, Eduardo Beltrán, Catharina C. Gross, Anna R. Tröscher, Tanja Kuhlmann, Tilman Schneider-Hohendorf, Klaus Dornmair, Jan Dörr, Roland S. Liblau, Urvashi Bhatia, Hans Lassmann, Sven G. Meuth, Luisa Klotz, Sebastian Herich, Markus Kraemer, Jan Bauer, Céline Meyer, David-Axel Laplaud, Wolfgang Brück, Romana Höftberger, Michael Barnett, Michael E. Buckland, Andreas Schulte-Mecklenbeck, Heinz Wiendl, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), 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), Medizinische Universität Wien = Medical University of Vienna, Institute for Experimental and Clinical Pharmacology and Toxicology [Lübeck, Germany], University of Lübeck [Germany], Institute of Neuropathology [Göttingen, Germany], University Medical Center Göttingen (UMG), 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 d’Anatomopathologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Royal North Shore Hospital [Sydney, Australia], Microsoft Research [Redmond], Microsoft Corporation [Redmond, Wash.], The University of Sydney, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Heidelberg, Medical Faculty, University of Vienna [Vienna], Institute of Clinical Neuroimmunology [Munich, Germany], Ludwig-Maximilians University [Munich] (LMU), Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Le Bihan, Sylvie, MECANISMES INTEGRES DE L'INFLAMMATION - Infiltration tissulaire des macrophages et inflammation : identification d'inhibiteurs de la migration cellulaire en trois dimensions. - - MigreFlame2010 - ANR-10-MIDI-0013 - MI2 - VALID, Blanc 2013 - Migration des lymp^hocytes T CD8 T dans le système nerveux central - - T cell Mig2013 - ANR-13-BSV3-0003 - Blanc 2013 - VALID, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Ruhr University Bochum (RUB), Universitätsklinikum Knappschaftskrankenhaus = University Hospital Knappschaftskrankenhaus [Bochum], Universität zu Lübeck = University of Lübeck [Lübeck], Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Royal North Shore Hospital (RNSH), Royal Prince Alfred Hospital [Sydney, Australia], Ludwig-Maximilians-Universität München (LMU), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), ANR-10-MIDI-0013,MigreFlame,Infiltration tissulaire des macrophages et inflammation : identification d'inhibiteurs de la migration cellulaire en trois dimensions.(2010), ANR-13-BSV3-0003,T cell Mig,Migration des lymp^hocytes T CD8 T dans le système nerveux central(2013), Centre de Physiopathologie Toulouse Purpan (CPTP - U1043 INSERM - UMR5282 CNRS - UT3), University Medical Center Göttingen [Germany], Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, and Service des maladies infectieuses et tropicales[Toulouse]
Subjects: 0301 basic medicine, MESH: Integrin alpha4 / metabolism, [SDV]Life Sciences [q-bio], Neuroimmunology, General Physics and Astronomy, Autoimmunity, 0302 clinical medicine, Natalizumab, Cytotoxic T cell, MESH: Animals, lcsh:Science, MESH: Endothelium, Vascular / drug effects, Multidisciplinary, MESH: Central Nervous System / immunology, MESH: Endothelium, Vascular / pathology, MESH: Microvessels / pathology, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, MESH: Cell Adhesion / drug effects, [SDV.IMM]Life Sciences [q-bio]/Immunology, Function and Dysfunction of the Nervous System, MESH: Central Nervous System / pathology, medicine.drug, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Mice, Transgenic, Science, Central nervous system, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Immune system, MESH: Microvessels / immunology, medicine, MESH: Cell Adhesion / immunology, Neuroinflammation, Susac Syndrome, MESH: Central Nervous System / blood suppl, MESH: Humans, business.industry, MESH: Adult, General Chemistry, MESH: Integrin alpha4 / antagonists & inhibitors, MESH: Male, Granzyme B, Susac syndrome, neuro-inflammation, endotheliopathy, 030104 developmental biology, Immunology, lcsh:Q, MESH: Endothelium, Vascular / immunology, MESH: Microvessels / drug effects, MESH: Disease Models, Animal, business, MESH: Female, 030217 neurology & neurosurgery, CD8
Abstract: International audience; Neuroinflammation is often associated with blood-brain-barrier dysfunction, which contributes to neurological tissue damage. Here, we reveal the pathophysiology of Susac syndrome (SuS), an enigmatic neuroinflammatory disease with central nervous system (CNS) endotheliopathy. By investigating immune cells from the blood, cerebrospinal fluid, and CNS of SuS patients, we demonstrate oligoclonal expansion of terminally differentiated activated cytotoxic CD8+ T cells (CTLs). Neuropathological data derived from both SuS patients and a newly-developed transgenic mouse model recapitulating the disease indicate that CTLs adhere to CNS microvessels in distinct areas and polarize granzyme B, which most likely results in the observed endothelial cell injury and microhemorrhages. Blocking T-cell adhesion by anti-α4 integrin-intervention ameliorates the disease in the preclinical model. Similarly, disease severity decreases in four SuS patients treated with natalizumab along with other therapy. Our study identifies CD8+ T-cell-mediated endotheliopathy as a key disease mechanism in SuS and highlights therapeutic opportunities.disease severity decreases in four SuS patients treated with natalizumab along with other therapy. Our study identifies CD8+ T-cell-mediated endotheliopathy as a key disease mechanism in SuS and highlights therapeutic opportunities.
Published: 2019
Full Text: View/download PDF

43. CD8

Author: Catharina C, Gross, Céline, Meyer, Urvashi, Bhatia, Lidia, Yshii, Ilka, Kleffner, Jan, Bauer, Anna R, Tröscher, Andreas, Schulte-Mecklenbeck, Sebastian, Herich, Tilman, Schneider-Hohendorf, Henrike, Plate, Tanja, Kuhlmann, Markus, Schwaninger, Wolfgang, Brück, Marc, Pawlitzki, David-Axel, Laplaud, Delphine, Loussouarn, John, Parratt, Michael, Barnett, Michael E, Buckland, Todd A, Hardy, Stephen W, Reddel, Marius, Ringelstein, Jan, Dörr, Brigitte, Wildemann, Markus, Kraemer, Hans, Lassmann, Romana, Höftberger, Eduardo, Beltrán, Klaus, Dornmair, Nicholas, Schwab, Luisa, Klotz, Sven G, Meuth, Guillaume, Martin-Blondel, Heinz, Wiendl, and Roland, Liblau
Subjects: Adult, Central Nervous System, Male, Susac Syndrome, Integrin alpha4, Natalizumab, Neuroimmunology, Mice, Transgenic, Autoimmunity, Middle Aged, Article, Disease Models, Animal, Young Adult, Microvessels, Cell Adhesion, Animals, Humans, Female, Endothelium, Vascular, T-Lymphocytes, Cytotoxic
Abstract: Neuroinflammation is often associated with blood-brain-barrier dysfunction, which contributes to neurological tissue damage. Here, we reveal the pathophysiology of Susac syndrome (SuS), an enigmatic neuroinflammatory disease with central nervous system (CNS) endotheliopathy. By investigating immune cells from the blood, cerebrospinal fluid, and CNS of SuS patients, we demonstrate oligoclonal expansion of terminally differentiated activated cytotoxic CD8+ T cells (CTLs). Neuropathological data derived from both SuS patients and a newly-developed transgenic mouse model recapitulating the disease indicate that CTLs adhere to CNS microvessels in distinct areas and polarize granzyme B, which most likely results in the observed endothelial cell injury and microhemorrhages. Blocking T-cell adhesion by anti-α4 integrin-intervention ameliorates the disease in the preclinical model. Similarly, disease severity decreases in four SuS patients treated with natalizumab along with other therapy. Our study identifies CD8+ T-cell-mediated endotheliopathy as a key disease mechanism in SuS and highlights therapeutic opportunities., Susac syndrome is an inflammatory pathology of the brain endothelium. Here the authors show that the pathology is driven by CD8 T cells attacking the endothelium, and that blocking T cell-endothelial adhesion ameliorates the disease in a mouse model, and associates with improved clinical score in 4 patients.
Published: 2019

44. Comparative effectiveness of teriflunomide vs dimethyl fumarate in multiple sclerosis

Author: Patrick Vermersch, Ivania Patry, Nicolas Maubeuge, Catherine Lubetzki, Ofsep Study Groups, David-Axel Laplaud, Bruno Stankoff, Bruno Brochet, Eric Thouvenot, Céline Labeyrie, Jean-Philippe Camdessanché, Olivier Gout, Laure Michel, Chantal Nifle, Abdullatif Al Khedr, Emmanuelle Leray, Gilles Edan, Marc Debouverie, Laetitia Barbin, David Brassat, Yohann Foucher, Thibault Moreau, Romain Casey, Jean Pelletier, Christine Lebrun-Frenay, Sandra Vukusic, Laurent Magy, Olivier Heinzlef, Philippe Cabre, Caroline Papeix, Ayman Tourbah, Gilles Defer, Abir Wahab, Pierre Clavelou, Eric Berger, Jérôme De Seze, A.-M. Guennoc, Fabien Rollot, Olivier Casez, Sandrine Wiertlewski, Thomas Debroucker, Pierre Labauge, Bertrand Bourre, 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), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Service de Neurologie [Lyon], CHU Lyon, 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), Service de Neurologie, Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, 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), Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de neurologie [Rennes], Université de Rennes (UR), Department of Neurology, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de neurologie [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU de la Martinique [Fort de France], CHU Pitié-Salpêtrière [AP-HP], Public Health Agency of Canada, CHI Poissy-Saint-Germain, Service de Neurologie [CHU de Poissy], CHU De Poissy, Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Recherches Critiques sur le Droit (CERCRID), Université Lumière - Lyon 2 (UL2)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service de Neurologie [CHU Limoges], CHU Limoges, 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), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, 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), École des Hautes Études en Santé Publique [EHESP] (EHESP), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Supported by Fondation ARSEP, CHU Nantes (Appel d’Offre Interne), and Association ANTARES. The French Observatoire of Multiple Sclerosis 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. The study was supported by West Neurosciences Network and Société Francophone de Scl´erose en Plaques, Fondation ARSEP, and by Appel d’Offre Interne du CHU de Nantes., SFSEP and OFSEP groups : Fontaine B, Marignier R, Durand-Dubief F, Mathey G, Le Page E, Peaureaux-Averseng D, Ouallet JC, Ruet A, Collongues N, Hautecoeur P, Zephir H, Maillard E, Cohen M, Derache N, Branger P, Ayrignac X, Carra-Dalliere C, Fromont A, Chamard-Witkowski L, Taithe F, Moisset X, Audoin B, Rico-Lamy A, Castelnovo G, Giannesini C, Fagniez O, Bensa C, Gueguen A, Kasonde IT, De Vilmarest A, Montcuquet A, Vaillants M, Beltran S, Creange A, Ayache S, Abdellaoui M, Pottier C, Slesari I, Deburghraeve V, Neau JP, Servan J, Pico F, Henry C, Hankiewicz K., 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), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de neurologie, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), CHU Saint-Etienne, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-IFR70-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2), Fondation Ophtalmologique Rothschild, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université de Montpellier (UM)-Université Montpellier 1 (UM1), Le Bihan, Sylvie, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], 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 des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Adult, Male, medicine.medical_specialty, Toluidines, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hydroxybutyrates, Effectiveness, Dimethyl fumarate, Multiple sclerosis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, Internal medicine, Teriflunomide, Nitriles, medicine, Humans, 030212 general & internal medicine, 10. No inequality, Adverse effect, ComputingMilieux_MISCELLANEOUS, Intention-to-treat analysis, Expanded Disability Status Scale, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Fingolimod Hydrochloride, Odds ratio, Middle Aged, Discontinuation, Treatment Outcome, chemistry, Crotonates, Propensity score matching, Disease Progression, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectiveIn this study, we compared the effectiveness of teriflunomide (TRF) and dimethyl fumarate (DMF) on both clinical and MRI outcomes in patients followed prospectively in the Observatoire Français de la Sclérose en Plaques.MethodsA total of 1,770 patients with relapsing-remitting multiple sclerosis (RRMS) (713 on TRF and 1,057 on DMF) with an available baseline brain MRI were included in intention to treat. The 1- and 2-year postinitiation outcomes were relapses, increase of T2 lesions, increase in Expanded Disability Status Scale score, and reason for treatment discontinuation. Propensity scores (inverse probability weighting) and logistic regressions were estimated.ResultsThe confounder-adjusted proportions of patients were similar in TRF- compared to DMF-treated patients for relapses and disability progression after 1 and 2 years. However, the adjusted proportion of patients with at least one new T2 lesion after 2 years was lower in DMF compared to TRF (60.8% vs 72.2%, odds ratio [OR] 0.60, p < 0.001). Analyses of reasons for treatment withdrawal showed that lack of effectiveness was reported for 8.5% of DMF-treated patients vs 14.5% of TRF-treated patients (OR 0.54, p < 0.001), while adverse events accounted for 16% of TRF-treated patients and 21% of DMF-treated patients after 2 years (OR 1.39, p < 0.001).ConclusionsAfter 2 years of treatment, we found similar effectiveness of DMF and TRF in terms of clinical outcomes, but with better MRI-based outcomes for DMF-treated patients, resulting in a lower rate of treatment discontinuation due to lack of effectiveness.Classification of evidenceThis study provides Class III evidence that for patients with RRMS, TRF and DMF have similar clinical effectiveness after 2 years of treatment.
Published: 2019
Full Text: View/download PDF

45. 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
Full Text: View/download PDF

46. Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data

Author: Bruce C V Campbell, Charles B L M Majoie, Gregory W Albers, Bijoy K Menon, Nawaf Yassi, Gagan Sharma, Wim H van Zwam, Robert J van Oostenbrugge, Andrew M Demchuk, Francis Guillemin, Philip White, Antoni Dávalos, Aad van der Lugt, Kenneth S Butcher, Aboubaker Cherifi, Henk A Marquering, Geoffrey Cloud, Juan M Macho Fernández, Jeremy Madigan, Catherine Oppenheim, Geoffrey A Donnan, Yvo B W E M Roos, Jai Shankar, Hester Lingsma, Alain Bonafé, Hélène Raoult, María Hernández-Pérez, Aditya Bharatha, Reza Jahan, Olav Jansen, Sébastien Richard, Elad I Levy, Olvert A Berkhemer, Marc Soudant, Lucia Aja, Stephen M Davis, Timo Krings, Marie Tisserand, Luis San Román, Alejandro Tomasello, Debbie Beumer, Scott Brown, David S Liebeskind, Serge Bracard, Keith W Muir, Diederik W J Dippel, Mayank Goyal, Jeffrey L Saver, Tudor G Jovin, Michael D Hill, Peter J Mitchell, Puck SS Fransen, Lucie A van den Berg, Hester F Lingsma, Albert J Yoo, Wouter J Schonewille, Jan Albert Vos, Paul J Nederkoorn, Marieke JH Wermer, Marianne AA van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama à Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Jaap Kappelle, Rob H Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Willem Jan J. van Rooij, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Joseph C.J. Bot, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Ewout W. Steyerberg, Zwenneke Flach, Henk A. Marquering, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Ludo F.M. Beenen, René van den Berg, Peter J. Koudstaal, Wim H. van Zwam, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Diederik W.J. Dippel, Martin M. Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich Mattle, Nils Wahlgren, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Corina Puppels, Wilma Pellikaan, Annet Geerling, Annemieke Lindl-Velema, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Joke de Meris, Kirsten Janssen, Willy Struijk, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie-Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets, Merel Boers, Emilie Santos, Jordi Borst, Ivo Jansen, Manon Kappelhof, Marit Lucas, Ralph Geuskens, Renan Sales Barros, Roeland Dobbe, Marloes Csizmadia, MD Hill, M Goyal, AM Demchuk, BK Menon, M Eesa, KJ Ryckborst, MR Wright, NR Kamal, L Andersen, PA Randhawa, T Stewart, S Patil, P Minhas, M Almekhlafi, S Mishra, F Clement, T Sajobi, A Shuaib, WJ Montanera, D Roy, FL Silver, TG Jovin, DF Frei, B Sapkota, JL Rempel, J Thornton, D Williams, D Tampieri, AY Poppe, D Dowlatshahi, JH Wong, AP Mitha, S Subramaniam, G Hull, MW Lowerison, M Salluzzi, M Maxwell, S Lacusta, E Drupals, K Armitage, PA Barber, EE Smith, WF Morrish, SB Coutts, C Derdeyn, B Demaerschalk, D Yavagal, R Martin, R Brant, Y Yu, RA Willinsky, A Weill, C Kenney, H Aram, PK Stys, TW Watson, G Klein, D Pearson, P Couillard, A Trivedi, D Singh, E Klourfeld, O Imoukhuede, D Nikneshan, S Blayney, R Reddy, P Choi, M Horton, T Musuka, V Dubuc, TS Field, J Desai, S Adatia, A Alseraya, V Nambiar, R van Dijk, NJ Newcommon, B Schwindt, KS Butcher, T Jeerakathil, B Buck, K Khan, SS Naik, DJ Emery, RJ Owen, TB Kotylak, RA Ashforth, TA Yeo, D McNally, M Siddiqui, M Saqqur, D Hussain, H Kalashyan, A Manosalva, M Kate, L Gioia, S Hasan, A Mohammad, M Muratoglu, A Cullen, P Brennan, A O'Hare, S Looby, D Hyland, S Duff, M McCusker, B Hallinan, S Lee, J McCormack, A Moore, M O'Connor, C Donegan, L Brewer, A Martin, S Murphy, K O'Rourke, S Smyth, P Kelly, T Lynch, T Daly, P O'Brien, A O'Driscoll, M Martin, R Collins, T Coughlan, D McCabe, D O'Neill, M Mulroy, O Lynch, T Walsh, M O'Donnell, T Galvin, J Harbison, P McElwaine, K Mulpeter, C McLoughlin, M Reardon, E Harkin, E Dolan, M Watts, N Cunningham, C Fallon, S Gallagher, P Cotter, M Crowe, R Doyle, I Noone, M Lapierre, VA Coté, S Lanthier, C Odier, A Durocher, J Raymond, N Daneault, Y Deschaintre, B Jankowitz, L Baxendell, L Massaro, C Jackson-Graves, S Decesare, P Porter, K Armbruster, A Adams, J Billigan, J Oakley, A Ducruet, A Jadhav, D-V Giurgiutiu, A Aghaebrahim, V Reddy, M Hammer, M Starr, V Totoraitis, L Wechsler, S Streib, S Rangaraju, D Campbell, M Rocha, D Gulati, T Krings, L Kalman, A Cayley, J Williams, R Wiegner, LK Casaubon, C Jaigobin, JM del Campo, E Elamin, JD Schaafsma, R Agid, R Farb, K ter Brugge, BL Sapkoda, BW Baxter, K Barton, A Knox, A Porter, A Sirelkhatim, T Devlin, C Dellinger, N Pitiyanuvath, J Patterson, J Nichols, S Quarfordt, J Calvert, H Hawk, C Fanale, A Bitner, A Novak, D Huddle, R Bellon, D Loy, J Wagner, I Chang, E Lampe, B Spencer, R Pratt, R Bartt, S Shine, G Dooley, T Nguyen, M Whaley, K McCarthy, J Teitelbaum, W Poon, N Campbell, M Cortes, C Lum, R Shamloul, S Robert, G Stotts, M Shamy, N Steffenhagen, D Blacquiere, M Hogan, M AlHazzaa, G Basir, H Lesiuk, D Iancu, M Santos, H Choe, DC Weisman, K Jonczak, A Blue-Schaller, Q Shah, L MacKenzie, B Klein, K Kulandaivel, O Kozak, DJ Gzesh, LJ Harris, JS Khoury, J Mandzia, D Pelz, S Crann, L Fleming, K Hesser, B Beauchamp, B Amato-Marzialli, M Boulton, P Lopez- Ojeda, M Sharma, S Lownie, R Chan, R Swartz, P Howard, D Golob, D Gladstone, K Boyle, M Boulos, J Hopyan, V Yang, L Da Costa, CA Holmstedt, AS Turk, R Navarro, E Jauch, S Ozark, R Turner, S Phillips, J Shankar, J Jarrett, G Gubitz, W Maloney, R Vandorpe, M Schmidt, J Heidenreich, G Hunter, M Kelly, R Whelan, L Peeling, PA Burns, A Hunter, I Wiggam, E Kerr, M Watt, A Fulton, P Gordon, I Rennie, P Flynn, G Smyth, S O'Leary, N Gentile, G Linares, P McNelis, K Erkmen, P Katz, A Azizi, M Weaver, C Jungreis, S Faro, P Shah, H Reimer, V Kalugdan, G Saposnik, A Bharatha, Y Li, P Kostyrko, T Marotta, W Montanera, D Sarma, D Selchen, J Spears, JH Heo, K Jeong, DJ Kim, BM Kim, YD Kim, D Song, K-J Lee, J Yoo, OY Bang, S Rho, J Lee, P Jeon, KH Kim, J Cha, SJ Kim, S Ryoo, MJ Lee, S-I Sohn, C-H Kim, H-G Ryu, J-H Hong, H-W Chang, C-Y Lee, J Rha, Bruce CV Campbell, Leonid Churilov, Bernard Yan, Richard Dowling, Thomas J Oxley, Teddy Y Wu, Gabriel Silver, Amy McDonald, Rachael McCoy, Timothy J Kleinig, Rebecca Scroop, Helen M Dewey, Marion Simpson, Mark Brooks, Bronwyn Coulton, Martin Krause, Timothy J Harrington, Brendan Steinfort, Kenneth Faulder, Miriam Priglinger, Susan Day, Thanh Phan, Winston Chong, Michael Holt, Ronil V Chandra, Henry Ma, Dennis Young, Kitty Wong, Tissa Wijeratne, Hans Tu, Elizabeth Mackay, Sherisse Celestino, Christopher F Bladin, Poh Sien Loh, Amanda Gilligan, Zofia Ross, Skye Coote, Tanya Frost, Mark W Parsons, Ferdinand Miteff, Christopher R Levi, Timothy Ang, Neil Spratt, Lara Kaauwai, Monica Badve, Henry Rice, Laetitia de Villiers, P. Alan Barber, Ben McGuinness, Ayton Hope, Maurice Moriarty, Patricia Bennett, Andrew Wong, Alan Coulthard, Andrew Lee, Jim Jannes, Deborah Field, Simon Salinas, Elise Cowley, Barry Snow, John Kolbe, Richard Stark, John King, Richard Macdonnell, John Attia, Cate D'Este, Hans-Christoph Diener, Elad I. Levy, Vitor Mendes Pereira, Gregory W. Albers, Christophe Cognard, David J. Cohen, Werner Hacke, Tudor G. Jovin, Heinrich P. Mattle, Raul G. Nogueira, Adnan H. Siddiqui, Dileep R. Yavagal, Rüdiger von Kummer, Wade Smith, Francis Turjman, Scott Hamilton, Richard Chiacchierini, Arun Amar, Nerses Sanossian, Yince Loh, B Baxter, VK Reddy, A Horev, M Star, A Siddiqui, LN Hopkins, K Snyder, R Sawyer, S Hall, V Costalat, C Riquelme, P Machi, E Omer, C Arquizan, I Mourand, M Charif, X Ayrignac, N Menjot de Champfleur, N Leboucq, G Gascou, M Moynier, R du Mesnil de Rochemont, O Singer, J Berkefeld, C Foerch, M Lorenz, W Pfeilschifer, E Hattingen, M Wagner, SJ You, S Lescher, H Braun, S Dehkharghani, SR Belagaje, A Anderson, A Lima, M Obideen, D Haussen, R Dharia, M Frankel, V Patel, K Owada, A Saad, L Amerson, C Horn, S Doppelheuer, K Schindler, DK Lopes, M Chen, R Moftakhar, C Anton, M Smreczak, JS Carpenter, S Boo, A Rai, T Roberts, A Tarabishy, L Gutmann, C Brooks, J Brick, J Domico, G Reimann, K Hinrichs, M Becker, E Heiss, C Selle, A Witteler, S Al-Boutros, M-J Danch, A Ranft, S Rohde, K Burg, C Weimar, V Zegarac, C Hartmann, M Schlamann, S Göricke, A Ringlestein, I Wanke, C Mönninghoff, M Dietzold, R Budzik, T Davis, G Eubank, WJ Hicks, P Pema, N Vora, J Mejilla, M Taylor, W Clark, A Rontal, J Fields, B Peterson, G Nesbit, H Lutsep, H Bozorgchami, R Priest, O Ologuntoye, S Barnwell, A Dogan, K Herrick, C Takahasi, N Beadell, B Brown, S Jamieson, MS Hussain, A Russman, F Hui, D Wisco, K Uchino, Z Khawaja, I Katzan, G Toth, E Cheng-Ching, M Bain, S Man, A Farrag, P George, S John, L Shankar, A Drofa, R Dahlgren, A Bauer, A Itreat, A Taqui, R Cerejo, A Richmond, P Ringleb, M Bendszus, M Möhlenbruch, T Reiff, H Amiri, J Purrucker, C Herweh, M Pham, O Menn, I Ludwig, I Acosta, C Villar, W Morgan, C Sombutmai, F Hellinger, E Allen, M Bellew, R Gandhi, E Bonwit, J Aly, RD Ecker, D Seder, J Morris, M Skaletsky, J Belden, C Baker, LS Connolly, P Papanagiotou, C Roth, A Kastrup, M Politi, F Brunner, M Alexandrou, H Merdivan, C Ramsey, C Given II, S Renfrow, V Deshmukh, K Sasadeusz, F Vincent, JT Thiesing, J Putnam, A Bhatt, A Kansara, D Caceves, T Lowenkopf, L Yanase, J Zurasky, S Dancer, B Freeman, T Scheibe-Mirek, J Robison, J Roll, D Clark, M Rodriguez, B-FM Fitzsimmons, O Zaidat, JR Lynch, M Lazzaro, T Larson, L Padmore, E Das, A Farrow-Schmidt, A Hassan, W Tekle, C Cate, O Jansen, C Cnyrim, F Wodarg, C Wiese, A Binder, C Riedel, A Rohr, N Lang, H Laufs, S Krieter, L Remonda, M Diepers, J Añon, K Nedeltchev, T Kahles, S Biethahn, M Lindner, V Chang, C Gächter, C Esperon, M Guglielmetti, JF Arenillas Lara, M Martínez Galdámez, AI Calleja Sanz, E Cortijo Garcia, P Garcia Bermejo, S Perez, P Mulero Carrillo, E Crespo Vallejo, M Ruiz Piñero, L Lopez Mesonero, FJ Reyes Muñoz, C Brekenfeld, J-H Buhk, A Krützelmann, G Thomalla, B Cheng, C Beck, J Hoppe, E Goebell, B Holst, U Grzyska, G Wortmann, S Starkman, G Duckwiler, R Jahan, N Rao, S Sheth, K Ng, A Noorian, V Szeder, M Nour, M McManus, J Huang, J Tarpley, S Tateshima, N Gonzalez, L Ali, D Liebeskind, J Hinman, M Calderon-Arnulphi, C Liang, J Guzy, S Koch, K DeSousa, G Gordon-Perue, M Elhammady, E Peterson, V Pandey, S Dharmadhikari, P Khandelwal, A Malik, R Pafford, P Gonzalez, K Ramdas, G Andersen, D Damgaard, P Von Weitzel-Mudersbach, C Simonsen, N Ruiz de Morales Ayudarte, M Poulsen, L Sørensen, S Karabegovich, M Hjørringgaard, N Hjort, T Harbo, K Sørensen, E Deshaies, D Padalino, A Swarnkar, JG Latorre, E Elnour, Z El-Zammar, M Villwock, H Farid, A Balgude, L Cross, K Hansen, M Holtmannspötter, D Kondziella, J Hoejgaard, S Taudorf, H Soendergaard, A Wagner, M Cronquist, T Stavngaard, M Cortsen, LH Krarup, T Hyldal, H-P Haring, S Guggenberger, M Hamberger, J Trenkler, M Sonnberger, K Nussbaumer, C Dominger, E Bach, BD Jagadeesan, R Taylor, J Kim, K Shea, R Tummala, H Zacharatos, D Sandhu, M Ezzeddine, A Grande, D Hildebrandt, K Miller, J Scherber, A Hendrickson, M Jumaa, S Zaidi, T Hendrickson, V Snyder, M Killer-Oberpfalzer, J Mutzenbach, F Weymayr, E Broussalis, K Stadler, A Jedlitschka, A Malek, N Mueller-Kronast, P Beck, C Martin, D Summers, J Day, I Bettinger, W Holloway, K Olds, S Arkin, N Akhtar, C Boutwell, S Crandall, M Schwartzman, C Weinstein, B Brion, S Prothmann, J Kleine, K Kreiser, T Boeckh-Behrens, H Poppert, S Wunderlich, ML Koch, V Biberacher, A Huberle, G Gora-Stahlberg, B Knier, T Meindl, D Utpadel-Fischler, M Zech, M Kowarik, C Seifert, B Schwaiger, A Puri, S Hou, A Wakhloo, M Moonis, N Henninger, R Goddeau, F Massari, A Minaeian, JD Lozano, M Ramzan, C Stout, A Patel, A Tunguturi, S Onteddu, R Carandang, M Howk, M Ribó, E Sanjuan, M Rubiera, J Pagola, A Flores, M Muchada, P Meler, E Huerga, S Gelabert, P Coscojuela, A Tomasello, D Rodriguez, E Santamarina, O Maisterra, S Boned, L Seró, A Rovira, CA Molina, M Millán, L Muñoz, N Pérez de la Ossa, M Gomis, L Dorado, E López-Cancio, E Palomeras, J Munuera, P García Bermejo, S Remollo, C Castaño, R García-Sort, P Cuadras, P Puyalto, M Hernández-Pérez, M Jiménez, A Martínez-Piñeiro, G Lucente, A Dávalos, A Chamorro, X Urra, V Obach, A Cervera, S Amaro, L Llull, J Codas, M Balasa, J Navarro, H Ariño, A Aceituno, S Rudilosso, A Renu, JM Macho, L San Roman, J Blasco, A López, N Macías, P Cardona, H Quesada, F Rubio, L Cano, B Lara, MA de Miquel, L Aja, J Serena, E Cobo, Kennedy R Lees, J Arenillas, R Roberts, F Al-Ajlan, L Zimmel, S Patel, J Martí-Fàbregas, M Salvat-Plana, S Bracard, Xavier Ducrocq, René Anxionnat, Pierre-Alexandre Baillot, Charlotte Barbier, Anne-Laure Derelle, Jean-Christophe Lacour, Yves Samson, Nader Sourour, Flore Baronnet-Chauvet, Frédéric Clarencon, Sophie Crozier, Sandrine Deltour, Federico Di Maria, Raphael Le Bouc, Anne Leger, Gurkan Mutlu, Charlotte Rosso, Zoltan Szatmary, Marion Yger, Chiara Zavanone, Serge Bakchine, Laurent Pierot, Nathalie Caucheteux, Laurent Estrade, Krzysztof Kadziolka, Alexandre Leautaud, Céline Renkes, Isabelle Serre, Hubert Desal, Benoît Guillon, Claire Boutoleau-Bretonniere, Benjamin Daumas-Duport, Solène De Gaalon, Pascal Derkinderen, Sarah Evain, Fanny Herisson, David-Axel Laplaud, Thibaud Lebouvier, Alina Lintia-Gaultier, Hélène Pouclet-Courtemanche, Tiphaine Rouaud, Violaine Rouaud Jaffrenou, Aurélia Schunck, Mathieu Sevin-Allouet, Frederique Toulgoat, Sandrine Wiertlewski, Jean-Yves Gauvrit, Thomas Ronziere, Vincent Cahagne, Jean-Christophe Ferre, Jean-François Pinel, Jean-Louis Mas, Jean-François Meder, Amen-Adam Al Najjar-Carpentier, Julia Birchenall, Eric Bodiguel, David Calvet, Valérie Domigo, Sylvie Godon-Hardy, Vincent Guiraud, Catherine Lamy, Loubna Majhadi, Ludovic Morin, Olivier Naggara, Denis Trystram, Guillaume Turc, Jérôme Berge, Igor Sibon, Patrice Menegon, Xavier Barreau, François Rouanet, Sabrina Debruxelles, Annabelle Kazadi, Pauline Renou, Olivier Fleury, Anne Pasco-Papon, Frédéric Dubas, Jildaz Caroff, Sophie Godard Ducceschi, Marie-Aurélie Hamon, Alderic Lecluse, Guillaume Marc, Maurice Giroud, Frédéric Ricolfi, Yannick Bejot, Adrien Chavent, Arnaud Gentil, Apolline Kazemi, Guy-Victor Osseby, Charlotte Voguet, Marie-Hélène Mahagne, Jacques Sedat, Yves Chau, Laurent Suissa, Sylvain Lachaud, Emmanuel Houdart, Christian Stapf, Frédérique Buffon Porcher, Hugues Chabriat, Pierre Guedin, Dominique Herve, Eric Jouvent, Jérôme Mawet, Jean-Pierre Saint-Maurice, Hans-Martin Schneble, Norbert Nighoghossian, Nadia-Nawel Berhoune, Françoise Bouhour, Tae-Hee Cho, Laurent Derex, Sandra Felix, Hélène Gervais-Bernard, Benjamin Gory, Luis Manera, Laura Mechtouff, Thomas Ritzenthaler, Roberto Riva, Fabrizio Salaris Silvio, Caroline Tilikete, Raphael Blanc, Michaël Obadia, Mario Bruno Bartolini, Antoine Gueguen, Michel Piotin, Silvia Pistocchi, Hocine Redjem, Jacques Drouineau, Jean-Philippe Neau, Gaelle Godeneche, Matthias Lamy, Emilia Marsac, Stephane Velasco, Pierre Clavelou, Emmanuel Chabert, Nathalie Bourgois, Catherine Cornut-Chauvinc, Anna Ferrier, Jean Gabrillargues, Betty Jean, Anna-Raquel Marques, Nicolas Vitello, Olivier Detante, Marianne Barbieux, Kamel Boubagra, Isabelle Favre Wiki, Katia Garambois, Florence Tahon, Vasdev Ashok, Oguzhan Coskun, Georges Rodesch, Bertrand Lapergue, Frédéric Bourdain, Serge Evrard, Philippe Graveleau, Jean Pierre Decroix, Adrien Wang, François Sellal, Guido Ahle, Gabriela Carelli, Marie-Hélène Dugay, Claude Gaultier, Ariel Pablo Lebedinsky, Lavinia Lita, Raul Mariano Musacchio, Catherine Renglewicz-Destuynder, Alain Tournade, Françis Vuillemet, Francisco Macian Montoro, Charbel Mounayer, Frederic Faugeras, Laetitia Gimenez, Catherine Labach, Géraldine Lautrette, Christian Denier, Guillaume Saliou, Olivier Chassin, Claire Dussaule, Elsa Melki, Augustin Ozanne, Francesco Puccinelli, Marina Sachet, Mariana Sarov, Jean-François Bonneville, Thierry Moulin, Alessandra Biondi, Elisabeth De Bustos Medeiros, Fabrice Vuillier, Patrick Courtheoux, Fausto Viader, Marion Apoil-Brissard, Mathieu Bataille, Anne-Laure Bonnet, Julien Cogez, Emmanuel Touze, Xavier Leclerc, Didier Leys, Mohamed Aggour, Pierre Aguettaz, Marie Bodenant, Charlotte Cordonnier, Dominique Deplanque, Marie Girot, Hilde Henon, Erwah Kalsoum, Christian Lucas, Jean-Pierre Pruvo, Paolo Zuniga, Caroline Arquizan, Vincent Costalat, Paolo Machi, Isabelle Mourand, Carlos Riquelme, Pierre Bounolleau, Charles Arteaga, Anthony Faivre, Marc Bintner, Patrice Tournebize, Cyril Charlin, Françoise Darcel, Pascale Gauthier-Lasalarie, Marcia Jeremenko, Servane Mouton, Jean-Baptiste Zerlauth, Chantal Lamy, Deramond Hervé, Hosseini Hassan, André Gaston, Francis-Guy Barral, Pierre Garnier, Rémy Beaujeux, Valérie Wolff, Denis Herbreteau, Séverine Debiais, Alicia Murray, Gary Ford, Andy Clifton, Janet Freeman, Ian Ford, Hugh Markus, Joanna Wardlaw, Andy Molyneux, Thompson Robinson, Steff Lewis, John Norrie, Fergus Robertson, Richard Perry, Anand Dixit, Andrew Clifton, Christine Roffe, Sanjeev Nayak, Kyriakos Lobotesis, Craig Smith, Amit Herwadkar, Naga Kandasamy, Tony Goddard, John Bamford, Ganesh Subramanian, Rob Lenthall, Edward Littleton, Sal Lamin, Kelley Storey, Rita Ghatala, Azra Banaras, John Aeron-Thomas, Bath Hazel, Holly Maguire, Emelda Veraque, Louise Harrison, Rekha Keshvara, James Cunningham, Clinical Neurophysiology, Weimar, Christian (Beitragende*r), Radiology and nuclear medicine, Rheumatology, ACS - Atherosclerosis & ischemic syndromes, RS: Carim - B05 Cerebral small vessel disease, RS: CARIM - R3.03 - Cerebral small vessel disease, RS: Carim - B06 Imaging, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: CARIM - R3.11 - Imaging, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, MUMC+: MA AIOS Neurologie (9), The Royal Melbourne Hospital, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Stanford University, University of Calgary, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Universitat Autònoma de Barcelona (UAB), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Alberta, Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Monash University [Melbourne], St George’s University Hospitals, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dalhousie University [Halifax], Neuroradiologie [Hôpital Gui de Chauliac], Hôpital Gui de Chauliac [Montpellier], Service de Neuroradiologie [Rennes], CHU Pontchaillou [Rennes], St. Michael's Hospital, University of California [Los Angeles] (UCLA), University of California, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), 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), University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Toronto Western Hospital, Hôpital Foch [Suresnes], Vall d'Hebron University Hospital [Barcelona], Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Glasgow, Queen Elizabeth University Hospital (Glasgow), David Geffen School of Medicine [Los Angeles], University of California-University of California, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Radiology & Nuclear Medicine, Public Health, Neurology, Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Neurovascular Disorders, ACS - Amsterdam Cardiovascular Sciences, Graduate School, ACS - Pulmonary hypertension & thrombosis, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, ARD - Amsterdam Reproduction and Development, Biomedical Engineering and Physics, APH - Personalized Medicine, APH - Quality of Care, and AMS - Restoration & Development
Subjects: SELECTION, COMPUTED TOMOGRAPHIC PERFUSION, Medizin, Perfusion scanning, 030204 cardiovascular system & hematology, Brain Ischemia, 0302 clinical medicine, Modified Rankin Scale, REPERFUSION, Stroke, ComputingMilieux_MISCELLANEOUS, Thrombectomy, Aged, 80 and over, medicine.diagnostic_test, Penumbra, Endovascular Procedures, Brain, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Treatment Outcome, Cerebral blood flow, Tissue Plasminogen Activator, INFARCT, Cardiology, Female, TRIAL, CT, medicine.medical_specialty, Perfusion Imaging, Neuroimaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, Fibrinolytic Agents, ALTEPLASE, Internal medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Aged, business.industry, MECHANICAL THROMBECTOMY, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Magnetic resonance imaging, Odds ratio, medicine.disease, Neurology (clinical), business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Fibrinolytic agent, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.Methods In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1,2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mu m(2)/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.Findings We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0.47 [95% CI 0.30-0.72], p=0.0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0.77 [0.69-0.86] per 10 mL, p(interaction)=0.29; diffusion MRI OR 0.87 [0.81-0.94] per 10 mL, p(interaction)=0.94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.Interpretation Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imagingto-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Copyright (C) 2018 Elsevier Ltd. All rights reserved.
Published: 2019
Full Text: View/download PDF

47. Historique de la sclérose en plaques

Author: G. Fournié, B. Le Mauff, Bryan Nicol, L. Lanotte, Agnès Fromont, David Brassat, Pierre Branger, I. Rebeix, S. Pittion-Vouyovitch, M. Benamar, Fabian Docagne, Alexandra Garcia, Olivier Toutirais, R. Bernard-Valnet, Cécile Donzé, J. Morille, A.-L. Dubessy, Vincent Damotte, Charles Pierrot-Deseilligny, P. Hautecœur, L. Michel, B. Stankoff, Sandra Vukusic, Isabelle Bardou, David-Axel Laplaud, Marc Debouverie, Gilles Defer, Nathalie Derache, Olivier Dejardin, B. Fontaine, Abdelhadi Saoudi, Denis Vivien, Héloïse Lebas, Floriane Calocer, M. Michieletto, D. Merkler, Emmanuelle Leray, A. Dejean, Guillaume Mathey, N. Benallègue, and D. Seilhean
Published: 2019
Full Text: View/download PDF

48. Épidémiologie, environnement et génétique dans la sclérose en plaques

Author: Héloïse Lebas, Olivier Toutirais, D. Seilhean, Emmanuelle Leray, Nathalie Derache, Cécile Donzé, B. Le Mauff, L. Lanotte, G. Fournié, Agnès Fromont, Guillaume Mathey, Olivier Dejardin, Abdelhadi Saoudi, N. Benallègue, Floriane Calocer, D. Merkler, P. Hautecœur, B. Stankoff, Sandra Vukusic, B. Fontaine, Vincent Damotte, L. Michel, Pierre Branger, M. Michieletto, Denis Vivien, David Brassat, A. Dejean, Fabian Docagne, Alexandra Garcia, Gilles Defer, R. Bernard-Valnet, S. Pittion-Vouyovitch, Isabelle Bardou, A.-L. Dubessy, J. Morille, M. Benamar, I. Rebeix, Charles Pierrot-Deseilligny, David-Axel Laplaud, Marc Debouverie, and Bryan Nicol
Subjects: business.industry, Medicine, business
Published: 2019
Full Text: View/download PDF

49. MSJ894713_supplementary_table – Supplemental material for High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice

Author: Couloume, Laura, Barbin, Laetitia, Leray, Emmanuelle, Wiertlewski, Sandrine, Page, Emmanuelle Le, Kerbrat, Anne, Solenn Ory, Port, Damien Le, Edan, Gilles, David-Axel Laplaud, and Michel, Laure
Subjects: FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 110904 Neurology and Neuromuscular Diseases
Abstract: Supplemental material, MSJ894713_supplementary_table for High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice by Laura Couloume, Laetitia Barbin, Emmanuelle Leray, Sandrine Wiertlewski, Emmanuelle Le Page, Anne Kerbrat, Solenn Ory, Damien Le Port, Gilles Edan, David-Axel Laplaud and Laure Michel in Multiple Sclerosis Journal
Published: 2019
Full Text: View/download PDF

50. SMILE: a predictive model for scoring the severity of relapses in multIple sclerosis

Author: F. Le Frere, Anne Kerbrat, Yohann Foucher, Arthur Chatton, L. Michel, David-Axel Laplaud, E. Le Page, David Veillard, F. Lejeune, Sandrine Wiertlewski, Gilles Edan, Natacha Jousset, Stéphanie Hamonic, Jean-Christophe Ouallet, Bruno Brochet, Aurélie Ruet, 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), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, 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), CHU Bordeaux [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours, 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 ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Adult, medicine.medical_specialty, Multiple Sclerosis, Ataxia, Neurology, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Logistic regression, Disability Evaluation, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Lasso (statistics), Recurrence, Internal medicine, Relapse phenotype, Humans, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Therapeutic strategy, Neuroradiology, business.industry, Multiple sclerosis, medicine.disease, 3. Good health, Predictive model, Relapse recovery, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, EDSS, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), relapse severity and residual disability are difficult to predict. Nevertheless, this information is crucial both for guiding relapse treatment strategies and for informing patients. OBJECTIVE: We, therefore, developed and validated a clinical-based model for predicting the risk of residual disability at 6 months post-relapse in MS. METHODS: We used the data of 186 patients with RRMS collected during the COPOUSEP multicentre trial. The outcome was an increase of ≥ 1 EDSS point 6 months post-relapse treatment. We used logistic regression with LASSO penalization to construct the model, and bootstrap cross-validation to internally validate it. The model was externally validated with an independent retrospective French single-centre cohort of 175 patients. RESULTS: The predictive factors contained in the model were age > 40 years, shorter disease duration, EDSS increase ≥ 1.5 points at time of relapse, EDSS = 0 before relapse, proprioceptive ataxia, and absence of subjective sensory disorders. Discriminative accuracy was acceptable in both the internal (AUC 0.82, 95% CI [0.73, 0.91]) and external (AUC 0.71, 95% CI [0.62, 0.80]) validations. CONCLUSION: The predictive model we developed should prove useful for adapting therapeutic strategy of relapse and follow-up to individual patients.
Published: 2019
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

120 results on '"David-Axel Laplaud"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources