Author: "Aleksandra Nadaj-Pakleza" / Topic: business - Searchworks@Jio Institute Digital Library Search Results

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1. A rise in cases of nitrous oxide abuse: neurological complications and biological findings

Author: Cécile Reschwein, Laurent Kremer, Pauline Kalaaji, Stanislas Demuth, Ivana Schroder, Lucas Gauer, Thomas Bogdan, Jérôme De Seze, Paul Voulleminot, Maximilian Einsiedler, Aleksandra Nadaj-Pakleza, and Kévin Bigaut
Subjects: Vitamin, Pediatrics, medicine.medical_specialty, Neurology, Homocysteine, Vitamin B-12, Methylmalonic acid, Toxicology, chemistry.chemical_compound, medicine, Humans, Pandemics, Original Communication, Nitrous oxide, business.industry, SARS-CoV-2, Incidence (epidemiology), COVID-19, Vitamin B 12 Deficiency, medicine.disease, Substance abuse, Vitamin B 12, chemistry, Communicable Disease Control, Subacute Combined Degeneration, Neurology (clinical), business, Substance-related disorders
Abstract: Background The recent lockdown due to the COVID-19 pandemic has been linked to a higher incidence of psychiatric manifestations and substance abuse. The recreative use of nitrous oxide is more and more widespread and neurological complications are frequent. Methods We report clinical characteristics and biological findings of five consecutive patients presenting to our tertiary care center between April 2020 and February 2021 with various neurological symptoms occurring after recent nitrous oxide abuse. Results Our patients presented with subacute combined degeneration of the spinal cord (4/5 patients) or with acute inflammatory demyelinating polyneuropathy (1/5 patients). No patient had reduced vitamin B-12 titer, but all had elevated blood levels of homocysteine and methylmalonic acid. This reflects the functional deficit in vitamin B-12 that can be linked to nitrous oxide consumption. After vitamin B-12 supplementation, clinical signs regressed at least partially in all 5 patients. Conclusion We report an elevated incidence of neurological complications of nitrous oxide abuse occurring during the recent COVID-19 lockdown. Nitrous oxide abuse should be tracked down in patients presenting with compatible neurological symptoms and elevated homocysteinemia. Vitamin B-12 should be supplemented as soon as the diagnosis is made.
Published: 2021

2. Impact of Coronavirus Disease 2019 in a French Cohort of Myasthenia Gravis

Author: Diane Friedman, Djillali Annane, Guillemette Beaudonnet, Emmanuelle Salort-Campana, Bernard Clair, Jean-Baptiste Chanson, Frédérique Audic, Tiphaine Saulnier, Marco Spinazzi, Louis Carla, Gwendal Le Masson, Stéphane Mathis, Alexandra Foubert-Samier, Aleksandra Nadaj-Pakleza, Antoine Soulages, Shahram Attarian, Fanny Duval, Laurent Kremer, Tanya Stojkovic, Françoise Bouhour, Jean-Christophe Antoine, Pascal Cintas, Céline Tard, Sandrine Segovia-Kueny, Marie-Hélène Violleau, Guilhem Solé, Léa Kern, and Armelle Magot
Subjects: Adult, Male, medicine.medical_specialty, Referral, History, 21st Century, law.invention, Serology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, law, Internal medicine, Myasthenia Gravis, medicine, Humans, 030212 general & internal medicine, Aged, Retrospective Studies, Aged, 80 and over, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, Odds ratio, Middle Aged, medicine.disease, Intensive care unit, Myasthenia gravis, 3. Good health, Cohort, France, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study
Abstract: ObjectiveTo describe the clinical characteristics and outcomes of coronavirus disease 2019 (COVID-19) among patients with myasthenia gravis (MG) and identify factors associated with COVID-19 severity in patients with MG.MethodsThe CO-MY-COVID registry was a multicenter, retrospective, observational cohort study conducted in neuromuscular referral centers and general hospitals of the FILNEMUS (Filière Neuromusculaire) network (between March 1, 2020, and June 8, 2020), including patients with MG with a confirmed or highly suspected diagnosis of COVID-19. COVID-19 was diagnosed based on a PCR test from a nasopharyngeal swab or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology, thoracic CT scan, or typical symptoms. The main outcome was COVID-19 severity based on location of treatment/management (home, hospitalized in a medical unit, or in an intensive care unit). We collected information on demographic variables, general history, and risk factors for severe COVID-19. Multivariate ordinal regression models were used to identify factors associated with severe COVID-19 outcomes.ResultsAmong 3,558 patients with MG registered in the French database for rare disorders, 34 (0.96%) had COVID-19. The mean age at COVID-19 onset was 55.0 ± 19.9 years (mean MG duration: 8.5 ± 8.5 years). By the end of the study period, 28 patients recovered from COVID-19, 1 remained affected, and 5 died. Only high Myasthenia Gravis Foundation of America (MGFA) class (≥IV) before COVID-19 was associated with severe COVID-19 (p = 0.004); factors that were not associated included sex, MG duration, and medium MGFA classes (≤IIIb). The type of MG treatment had no independent effect on COVID-19 severity.ConclusionsThis registry-based cohort study shows that COVID-19 had a limited effect on most patients, and immunosuppressive medications and corticosteroids used for MG management are not risk factors for poorer outcomes. However, the risk of severe COVID-19 is elevated in patients with high MGFA classes (odds ratio, 102.6 [4.4–2,371.9]). These results are important for establishing evidence-based guidelines for the management of patients with MG during the COVID-19 pandemic.
Published: 2021

3. A multicenter cross-sectional French study of the impact of COVID-19 on neuromuscular diseases

Author: Vincent Laugel, Karim Wahbi, Lucie Isoline Pisella, Rabab Debs, Sarah Souvannanorath, Martial Mallaret, Thierry Kuntzer, Sylvain Nollet, Jean-Christophe Antoine, Maud Michaud, Rocío-Nur Villar-Quiles, Aude-Marie Grapperon, Sandrine Segovia-Kueny, Pascal Laforêt, Céline Tard, EL-Hadi Hammouda, Géraldine Merret, Kévin Bigaut, Juliette Svahn, Laurent Kremer, Armelle Magot, Jean-Baptiste Noury, Guillemette Beaudonnet, Louise Debergé, Aleksandra Nadaj-Pakleza, Diane Friedman, Yann Péréon, Emmanuelle Salort-Campana, Pascal Cintas, Sara Fernandes, David H. Adams, Annamaria Molon, Fanny Duval, Anthony Behin, Shahram Attarian, Frédérique Audic, Jean-Philippe Camdessanché, Isabelle Desguerre, Tanya Stojkovic, Françoise Bouhour, Marion Masingue, Guilhem Solé, Caroline Espil-Taris, Savine Vicart, Jean-Baptiste Chanson, Assistance Publique - Hôpitaux de Marseille (APHM), Groupe hospitalier Pellegrin, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Lille, Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Strasbourg, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Hôpital Bicêtre, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Raymond Poincaré [AP-HP], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Henri Mondor [Créteil], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-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), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], Lausanne University Hospital, Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Necker - Enfants Malades [AP-HP], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Association française contre les myopathies (AFM-Téléthon), Admin, Oskar, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Thérapie des maladies du muscle strié, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), 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), Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]
Subjects: medicine.medical_specialty, Cross-sectional study, Population, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Health care, medicine, Humans, Pharmacology (medical), Risk factor, education, Myopathy, Pandemics, Genetics (clinical), 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, SARS-CoV-2, Research, COVID-19, General Medicine, medicine.disease, Prognosis, Myasthenia gravis, 3. Good health, Neuromuscular diseases, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Background Due to their health condition, patients with neuromuscular diseases (NMD) are at greater risk of developing serious complications with COVID-19. The objective of this study was to analyze the prevalence of COVID-19 among NMD patients and the risk factors for its impact and severity during the first wave of the pandemic. Clinical data were collected from NMD-COVID-19 patients, between March 25, 2020 and May 11, 2020 in an anonymous survey carried out by expert physicians from the French Health Care Network Filnemus. Results Physicians reported 84 patients, including: 34 with myasthenia gravis, 27 with myopathy and 23 with neuropathy. COVID-19 had no effect on NMD for 48 (58%) patients and 48 (58%) patients developed low COVID-19 severity. COVID-19 caused the death of 9 (11%) NMD patients. Diabetic patients were at greater risk of dying. Patients with diabetes, hypertension or severe forms of NMD had a higher risk of developing a moderate or severe form of COVID-19. In our cohort, corticosteroids and other immunosuppressants were not significantly associated with higher COVID-19 severity for acquired NMD. Conclusion During this period, a small percentage of French NMD patients was affected by COVID-19 compared to the general French population and COVID-19 had a limited short-term effect on them. Diabetes, hypertension and a severe degree of NMD were identified as risk factors of unfavorable outcome following COVID-19. Conversely, in our cohort of patients with acquired NMD, corticosteroids or other immunosuppressants did not appear to be risk factors for more severe COVID-19.
Published: 2021

4. Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies

Author: Mélanie Fradin, Nicolas Sadoul, Xavier Waintraub, Didier Klug, Albert Hagège, Pascal Sabouraud, Arnaud Isapof, Julien Durigneux, Olivier Lascols, Pascal Laforêt, Armelle Magot, Ivana Dabaj, Eloi Marijon, Camille Vatier, Pascal Cintas, Emmanuelle Salort, Bénédicte Gaborit, Antoine Muchir, Xavier Ferrer, Pascale Richard, Corinne Metay, Stéphane Boulé, Sarah Leonard-Louis, Philippe Mabo, V. Tiffreau, Caroline Stalens, Jitendra K. Vohra, Stéphane Schaeffer, Khadija Chikhaoui, Eric Bieth, Sandra Mercier, Pierre Ambrosi, Aleksandra Nadaj-Pakleza, Michèle Mayer, Katja Zeppenfeld, Gisèle Bonne, Véronique Manel, Jean-Marc Davy, Guilhem Sole, Ghassan Moubarak, Nicolas Lamblin, Klaus Dieterich, Christophe Meune, Abdallah Fayssoil, Arnaud Lazarus, Philippe Maury, Karim Wahbi, Philippe Petiot, Isabelle Jéru, Annick Toutain, Corinne Vigouroux, Ana Ferreiro, Maud Michaud, H.M. Bécane, Bruno Eymard, Thomas D. Gossios, Marie-Christine Vantyghem, Saurabh Kumar, Estelle Gandjbakhch, Yann Péréon, T. Thompson, Marie-Christine Minot-Myhié, Anthony Behin, Frédéric Sacher, Philippe Charron, Nicolas Combes, Julien Praline, Dominique Babuty, Emmanuelle Lagrue, Usha B. Tedrow, Jean-Marc Sellal, Florence Petit, Perry M. Elliott, Frédéric Anselme, Philippe Chevalier, Frederic Taithe, Christine Barnerias, Vincent Laugel, Andoni Echaniz-Laguna, Raphaël P. Martins, Alexander F.A. Androulakis, Rabah Ben Yaou, Franck Boccara, Ulrike Walther-Louvier, Tanya Stojkovic, Françoise Bouhour, Annachiara De Sandre-Giovannoli, Susana Quijano-Roy, Françoise Chapon, Jean-Noël Trochu, Céline Tard, Anne Rollin, Jean-Marie Cuisset, Denis Duboc, Raphaël Porcher, Catherine Sarret, Jonathan M. Kalman, Florence Demurger, Damien Bonnet, Christine Francannet, Neal K. Lakdawala, Romain Eschalier, Fabien Labombarda, Kostantinos Savvatis, Raul Juntas Morales, Isabelle Desguerre, Nicolas Lévy, Anne-Claire Brehin, Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU), St Bartholomew's Hospital (London), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-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), Association française contre les myopathies (AFM-Téléthon), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Service de Cardiologie B, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Université de Nantes (UN)-Université de Nantes (UN), Hôpital Ambroise Paré [AP-HP], William Harvey Research Institute, Barts and the London Medical School, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Filière Neuromusculaire (FILNEMUS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Caen Normandie (UNICAEN), Laboratoire d'Informatique Scientifique et Industrielle (LISI), Université de Poitiers-Ecole Nationale Supérieure de Mécanique et d'Aérotechnique [Poitiers] (ISAE-ENSMA), Hôpital Raymond Poincaré [AP-HP], CHU Lille, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), 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 National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Aix Marseille Université (AMU), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de cardiologie [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), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Pasteur [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The Royal Melbourne Hospital, Leiden University Medical Center (LUMC), Universiteit Leiden, Service de neurologie pédiatrique [CHU Necker], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Hôpital Privé Le Bois Ramsay Santé [Lille], Service de génétique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Clermont-Ferrand, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Bordeaux], Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Trousseau [APHP], 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), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), CHU Strasbourg, Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Hôpital Cochin [AP-HP], Hospices Civils de Lyon (HCL), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Lorraine (UL), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Laboratoire d'étude de la motricité humaine - EA 3608 (LEMH), Université de Lille, Droit et Santé, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montréal (UdeM), Laboratoire Génie des procédés papetiers (LGP2 ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), The Heart Hospital [London], University College of London [London] (UCL), This study was funded by grants from the AFM-Téléthon (French Alliance against Myopathies), which was not involved in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. Some of this work was undertaken at University College London (United Kingdom) and St. Bartholomew’s Hospital (London, United Kingdom), which received a portion of funding from the United Kingdom Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], 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), Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-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) (APHP)-CHU Necker - Enfants Malades [AP-HP], Unit of Neuromuscular Morphology [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP]-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest, CHU Bordeaux [Bordeaux], Laboratoire d'Informatique Scientifique et Industrielle (LISI / ENSMA), LISI-ENSMA, Service de Biochimie-Génétique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Endocrinologie et Métabolisme, Unité de Cardiologie et Soins Intensifs, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service de Génétique [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Référence M3C Malformations Cardiaques Congénitales Complexes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Hôpital neurologique, Centre Hospitalier Universitaire de Lille (CHU de Lille), Service Neurologie Pédiatrique, Service de Neuropédiatrie, INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Département de Neurologie, Hôpital Civil de Strasbourg, Groupe Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale, CHU - HÔTEL-DIEU Clermont-Ferrand, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Clinique Ambroise Paré, CHU Cochin [AP-HP], Epilepsie, sommeil et explorations fonctionnelles neuropédiatriques, Hospices Civils de Lyon (HCL)-Hopital Neurologique-Hôpital Femme Mère Enfant, Department of Medicine, Columbia University [New York]-College of Physicians and Surgeons, Service de neurologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Hôpital de Rangueil, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), laboratoire d'étude de la motricité humaine (LEMH EA3608), Université de Montréal - UdeM (CANADA), Laboratoire Génie des procédés papetiers (LGP2), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Myologie, 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], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Hôpital Purpan [Toulouse], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut de Myologie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Tachycardia, medicine.medical_specialty, implantable, Accurate estimation, Ventricular Tachyarrhythmias, Validation Studies as Topic, 030204 cardiovascular system & hematology, tachycardia, Sudden death, LMNA, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, death, Physiology (medical), Internal medicine, defibrillators, medicine, Humans, In patient, 030212 general & internal medicine, sudden, [SDV.GEN]Life Sciences [q-bio]/Genetics, Prediction score, business.industry, Defibrillators, Implantable, ventricular, Tachycardia, Ventricular, Cardiology, Female, medicine.symptom, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business
Abstract: Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator–treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642–0.959), and the calibration slope was 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03058185.
Published: 2019

5. Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort

Author: Aleksandra Nadaj-Pakleza, Lucas Corti, Hélène Puccio, Mathieu Anheim, Jamel Chelly, Cecilia Marelli, Julien Tarabeux, Nicolas Dondaine, Nadège Diedhiou, Odile Gebus, Marilyne Almeras, Pauline Fahrer, Cécile Cauquil, Jean-Baptiste Chanson, Béatrice Lannes, Laura Robelin, Marie Claire Vincent, Mehdi Benkirane, Guillaume Taieb, Christine Tranchant, Gabrielle Rudolf, Matthieu Canuet, Andoni Echaniz-Laguna, Lise Larrieu, Solveig Montaut, and Benoit Lhermitte
Subjects: Vestibular areflexia, Pathology, medicine.medical_specialty, Cerebellum, Ataxia, Cerebellar ataxia, business.industry, Genetic heterogeneity, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Atrophy, medicine.anatomical_structure, Peripheral neuropathy, Neurology, medicine, 030212 general & internal medicine, Neurology (clinical), medicine.symptom, business, Trinucleotide repeat expansion, 030217 neurology & neurosurgery
Abstract: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recessively inherited multisystem ataxia compromising cerebellar, vestibular, and sensory nerves, which has been associated to a pathogenic AAGGG(n) biallelic expansion repeat in the RFC1 gene. Our objective was to assess its prevalence in a French cohort of patients with idiopathic sporadic late-onset ataxia (ILOA), idiopathic early-onset ataxia (IEOA), or Multiple System Atrophy of Cerebellar type (MSA-C). 163 patients were recruited in 3 French tertiary centers: 100 ILOA, 21 IEOA, and 42 patients with possible or probable MSA-C. A pathogenic biallelic RFC1 AAGGG(n) repeat expansion was found in 15 patients: 15/100 in the ILOA group, but none in the IEOA and MSA-C subgroups. 14/15 patients had a CANVAS phenotype. Only 1/15 had isolated cerebellar ataxia, but also shorter biallelic expansions. Two RFC1 AAGGG(n) alleles were found in 78% of patients with a CANVAS phenotype. In one post-mortem case, the pathophysiological involvement of cerebellum and medullar posterior columns was found. Our study confirms the genetic heterogeneity of the CANVAS and that RFC1 repeat expansions should be searched for preferentially in case of unexplained ILOA associated with a sensory neuronopathy, but not particularly in patients classified as MSA-C.
Published: 2021

6. Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis: A Randomized Clinical Trial

Author: Diane Friedman, Tarek Sharshar, Bruno Eymard, Aleksandra Nadaj-Pakleza, Marco Spinazzi, Bernard Clair, Simone Birnbaum, Christine Tranchant, Raphaël Porcher, Antoine Gueguen, Lamiae Grimaldi, S. Demeret, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Neuropathologie expérimentale / Experimental neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Hôpital Hôtel-Dieu [Paris], UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Strasbourg, CHU Rothschild [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Novartis Roche Teva Pharmaceutical Industries Ministère des Affaires Sociales et de la Santé, reported receiving nonfinancial support from Allergan and nonfinancial support from Merz outside the submitted work. Dr Gueguen reported receiving grants from French Ministry of Social Affairs and Health during the conduct of the study, has received honoraria and consulting fees from Novartis, Roche, Merck-Serono, Sanofi-Genzyme, Teva, and Mylan, and has received travel funding from Roche, Novartis, Sanofi-Genzyme. A close relative is an Ipsen employee. No other disclosures were reported., Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Rothschild [AP-HP], HAL UVSQ, Équipe, Institut Pasteur [Paris]-Université de Paris (UP), Université de Paris (UP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Pediatrics, medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], Population, Azathioprine, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Prednisone, Interquartile range, law, medicine, 030212 general & internal medicine, 10. No inequality, education, Original Investigation, education.field_of_study, business.industry, 3. Good health, [SDV] Life Sciences [q-bio], Regimen, Relative risk, Corticosteroid, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; Importance: The tapering of prednisone therapy in generalized myasthenia gravis (MG) presents a therapeutic dilemma; however, the recommended regimen has not yet been validated. Objective: To compare the efficacy of the standard slow-tapering regimen of prednisone therapy with a rapid-tapering regimen. Design: From June 1, 2009, to July 31, 2013, a multicenter, parallel, single-blind randomized trial was conducted to compare 2 regimens of prednisone tapering. Data analysis was conducted from February 18, 2019, to January 23, 2020. A total of 2291 adults with a confirmed diagnosis of moderate to severe generalized MG at 7 specialized centers in France were assessed for eligibility. Interventions: The slow-tapering arm included a gradual increase of the prednisone dose to 1.5 mg/kg every other day and a slow decrease once minimal manifestation status of MG was attained. The rapid-tapering arm consisted of immediate high-dose daily administration of prednisone, 0.75 mg/kg, followed by an earlier and rapid decrease once improved MG status was attained. Azathioprine, up to a maximum dose of 3 mg/kg/d, was prescribed for all participants. Main Outcomes and Measures: The primary outcome was attainment of minimal manifestation status of MG without prednisone at 12 months and without clinical relapse at 15 months. Intention-to-treat analysis was conducted. Results: Of the 2291 patients assessed, 2086 did not fulfill the inclusion criteria, 87 declined to participate, and 1 patient registered after trial closure. A total of 117 patients (58 in the slow-tapering arm and 59 in the rapid-tapering arm) were selected for inclusion by MG specialists and were randomized. The population included 62 men (53%); median age was 65 years (interquartile range, 35-69 years). The proportion of patients having met the primary outcome was higher in the rapid- vs slow-tapering arm (23 [39%] vs 5 [9%]), with a risk ratio of 3.61 (95% CI, 1.64-7.97; P
Published: 2021

7. Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial

Author: Stella Mazurová, John W. Day, Mazen M. Dimachkie, Sónia Tizon, Anna Kostera-Pruszczyk, Tahseen Mozaffar, Joel Charrow, Chafic Karam, Ricardo Maré, Jean-Baptiste Noury, Dewi Guellec, Jorge Alonso-Pérez, Acary Souza Bulle Oliveira, Loren D M Pena, Tianyue Zhou, Sergey Illarioshkin, Nathan Thibault, Marcelo Rugiero, Can Ebru Bekircan-Kurt, Lauren Chase, Monica Sciacco, Mamatha Pasnoor, Jenny Billy, Mark Tarnopolsky, Fabien Zagnoli, Marie Wencel, Sevim Erdem-Ozdamar, Erin Hatcher, Madoka Mori, Céline Tard, Nicolas Mavroudakis, Emmanuelle Salort-Campana, Antonio Toscano, Shafeeq Ladha, Angela Genge, Ans T. van der Ploeg, Michela Guglieri, Judith Johnson, Fanny Duval, Loïc Danjoux, Christopher Hug, Robert D. Henderson, Robert Neel, Luca Solera, Aleksandra Nadaj-Pakleza, Silvia Boschi, Nizar Chahin, Maurizio Gualtiero Moggio, Peter Young, Priya S. Kishnani, Yin-Hsiu Chien, Alexandra Kautzky-Willer, Claire Questienne, Francoise Bouhour, Gabriela A Niizawa, Ekaterina Fedotova, Tiziana Enrica Mongini, Harmke A. van Kooten, Vera Malinova, Sina Helms, Shahram Attarian, Patrick Deegan, Guilhem Sole, Hamilton Cirne, Ludwig Gutmann, Kenneth I. Berger, Laura Carrera Garcia, N A M E van der Beek, Stephanie Dearmey, Suzara Souto Lopes, Anna Potulska-Chromik, Joao Lindolfo Borges, Yesim Parman, Michaela Riedl, Sergey A. Klyushnikov, Olivier Huynh-Ba, Gauthier Remiche, Paula R. Clemens, Andrea Swenson, Stephan Wenninger, Miriam Hufgard-Leitner, Eugen Mengel, Kristina An Haack, Eve Gandolfo, David Reyes-Leiva, Jean-Baptiste Davion, Chester Whitley, Young Chul Choi, Patricia Altemus, Maria Judit Molnar, Perry B. Shieh, Matthias Vorgerd, Julia B Hennermann, Cheryl Smith, Volker Straub, Lauren Noll, Pascal Laforet, Andres Nascimento Osorio, Clarisa Maxit, Anne-Catherine Aubé-Nathier, Ozlem Goker-Alpan, Olimpia Musumeci, Louisa Müller-Miny, Tarekegn Hiwot, Jacqui Langton, Christopher Nance, Daniel Natera-de Benito, Jeffrey Statland, Nicola Longo, Vivien Pautot, Zoltan Grosz, Thomas Stulnig, Matthias Boentert, Anne-Katrin Guettsches, Chong Yew Tan, Erik Ortega, Derralynn Hughes, Hacer Durmus Tekce, Mark Roberts, Lenka Linková, Amel Karaa, Hani Kushlaf, Anthony Behin, Margarida Ramos Lopes, Jordi Diaz-Manera, Alessia Pugliese, Paulo Victor Sgobbi Souza, Carrie Bailey, Jennifer B Avelar, Hirofumi Komaki, Frederic Taithe, Benedikt Schoser, Sabine Specht, Kathryn E Brown, Gerson Carvalho, and Pediatrics
Subjects: medicine.medical_specialty, Population, Walking, FEV1/FVC ratio, stomatognathic system, SDG 3 - Good Health and Well-being, Double-Blind Method, Internal medicine, Statistical significance, Child, Preschool, Enzyme Replacement Therapy, Humans, Treatment Outcome, Glycogen Storage Disease Type II, alpha-Glucosidases, medicine, Respiratory function, Adverse effect, education, Child, Preschool, Alglucosidase alfa, education.field_of_study, business.industry, Standard treatment, virus diseases, Enzyme replacement therapy, Neurology (clinical), business, medicine.drug
Abstract: Summary Background Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease. Methods We did a randomised, double-blind, phase 3 trial at 55 sites in 20 countries. We enrolled individuals (aged ≥3 years) with enzymatically confirmed late-onset Pompe disease who had never received treatment. We used a centralised treatment allocation system to randomly allocate participants to either avalglucosidase alfa or alglucosidase alfa. Participants and investigators were unaware of their treatment allocation. The primary outcome measure was change from baseline to week 49 in upright forced vital capacity percent (FVC%) predicted. We used a hierarchical fixed sequential testing strategy, whereby non-inferiority of avalglucosidase alfa compared with alglucosidase alfa was assessed first, with a non-inferiority margin of 1·1. If non-inferiority was seen, then superiority was tested with a 5% significance level. The key secondary objective was effect on functional endurance, measured by the 6-minute walk test (6MWT). Safety was assessed, including treatment-emergent adverse events and infusion-associated reactions. The modified intent-to-treat population was the primary analysis population for all efficacy analyses. The safety population was the analysis population for safety analyses. This trial is registered with ClinicalTrials.gov , NCT02782741 . We report results of the 49-week primary analysis period. Findings Between Nov 2, 2016, and March 29, 2019, 100 participants were randomly allocated avalglucosidase alfa (n=51) or alglucosidase alfa (n=49). Treatment with avalglucosidase alfa resulted in a least-squares mean improvement in upright FVC% predicted of 2·89% (SE 0·88) compared with 0·46% (0·93) with alglucosidase alfa at week 49 (difference 2·43% [95% CI −0·13 to 4·99]). Non-inferiority was shown because the lower bound of the 95% CI for the difference far exceeded the predefined non-inferiority margin but did not exclude 0 (p=0·0074). Superiority was not reached (p=0·063), so formal testing was stopped, as per the testing hierarchy. Improvements were also seen in the 6MWT with avalglucosidase alfa compared with alglucosidase alfa, with greater increases in distance covered (difference 30·01 m [95% CI 1·33 to 58·69]) and percent predicted (4·71% [0·25 to 9·17]). Treatment-emergent adverse events potentially related to treatment were reported in 23 (45%) of 51 participants in the avalglucosidase alfa group and in 24 (49%) of 49 in the alglucosidase alfa group, and infusion-associated reactions were reported in 13 (26%) participants in the avalglucosidase alfa group and 16 (33%) in the alglucosidase alfa group. Of the five trial withdrawals, all in the alglucosidase alfa group, four were due to adverse events, including two infusion-associated reactions. Serious treatment-emergent adverse events were reported in eight (16%) participants who received avalglucosidase alfa and in 12 (25%) who received alglucosidase alfa. One participant treated with alglucosidase alfa died because of acute myocardial infarction determined to be unrelated to treatment. Antidrug antibody responses were similar in both groups. High and persistent titres (≥12 800) and neutralising antibodies were more common with alglucosidase alfa (in 16 [33%] participants) than with avalglucosidase alfa (ten [20%]). Interpretation We consider that this study provides evidence of clinically meaningful improvement with avalglucosidase alfa therapy over alglucosidase alfa in respiratory function, ambulation, and functional endurance, with no new safety signals reported. An open-label extended-treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa, with the aim for this therapy to become the new standard treatment in late-onset Pompe disease. Funding Sanofi Genzyme.
Published: 2021

8. Respiratory decline in adult patients with Becker muscular dystrophy: A longitudinal study

Author: Bertien Buyse, Sofie Willaert, Dries Testelmans, Anne-Catherine Aubé-Nathier, Bram De Wel, Aleksandra Nadaj-Pakleza, and Kristl G. Claeys
Subjects: 0301 basic medicine, Spirometry, Adult, Male, medicine.medical_specialty, Vital capacity, Neuromuscular disease, Duchenne muscular dystrophy, spirometry, Vital Capacity, Natural history, Walking, Pulmonary function testing, Body Mass Index, BMI, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, BMD, Internal medicine, medicine, Humans, Respiratory function, Longitudinal Studies, Muscular dystrophy, Lung, Genetics (clinical), Aged, medicine.diagnostic_test, DMD-gene, business.industry, Respiration, Middle Aged, medicine.disease, FVC, Muscular Dystrophy, Duchenne, 030104 developmental biology, Neurology, Pediatrics, Perinatology and Child Health, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Becker muscular dystrophy (BMD) is a rare hereditary neuromuscular disease, caused by a genetic defect in the Duchenne Muscular Dystrophy (DMD) gene. We studied the natural history of respiratory function and its affecting factors in 23 adult BMD patients. These important data are needed for (future) clinical trials in BMD but are largely lacking. Patients had a median age of 51 years (28-78y) and median follow-up duration of 14 years (2-25y). We analysed 190 pulmonary function measurements with a median interval of one year (1-17y) and measured a 1.00% decline of Forced Vital Capacity percent predicted (FVC%pred) per year (p = 0.004). Loss of ambulation significantly increased the annual rate of FVC decline and was dependent of patient's body mass index (BMI; p = 0.015), with increases in BMI correlating with an even more rapid deterioration of FVC. A decline in Medical Research Council (MRC) sum score was significantly correlated with a decline in FVC (p = 0.003). We conclude that adult BMD patients experience a significant but mild respiratory decline. However, this decline is significantly more rapid and clinically relevant after loss of ambulation, which warrants a more vigilant follow-up of respiratory function in this subgroup. ispartof: NEUROMUSCULAR DISORDERS vol:31 issue:3 ispartof: location:England status: published
Published: 2020

9. Homozygous C-terminal loss-of-function NaV1.4 variant in a patient with congenital myasthenic syndrome

Author: Aleksandra Nadaj-Pakleza, Michael G. Hanna, Roope Männikkö, Emma Matthews, Emmanuel Fournier, Andoni Echaniz-Laguna, Valérie Biancalana, Hôpital Bicêtre, Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute of Neurology [London], University College of London [London] (UCL), and univOAK, Archive ouverte
Subjects: [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Bioinformatics, channels, Neuromuscular junction, Article, Ophthalmoparesis, 03 medical and health sciences, 0302 clinical medicine, Ptosis, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business.industry, Sodium channel, Muscle weakness, Skeletal muscle, Congenital myasthenic syndrome, medicine.disease, Congenital myopathy, myasthenia, Psychiatry and Mental health, medicine.anatomical_structure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Surgery, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), neuromuscular, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Congenital myasthenic syndromes (CMS) are a group of rare inherited disorders of neuromuscular transmission.1 Clinical presentations range from predominant ptosis, ophthalmoparesis, facial and bulbar weakness, and generalised muscle weakness to predominant limb girdle weakness with sparing of the eye and face muscles. Symptoms may appear during the neonatal period, late childhood, adolescence or even adulthood. Clinical presentation and response to treatment may be influenced by the underlying molecular mechanism. Mutations in more than 30 genes have been identified as causing CMS.1 The primary pathogenic mechanism is defective neuromuscular junction (NMJ) transmission but may include central nervous system and skeletal muscle involvement. Biallelic loss-of-function (LOF) genetic mutations in SCN4A encoding skeletal muscle sodium channel NaV1.4 are a rare cause of CMS.2–6 Heterozygous carriers are asymptomatic, demonstrating recessive inheritance. NaV1.4 conducts the depolarising current of the skeletal muscle action potential that when reduced results in attenuated action potentials and muscle force. Biallelic SCN4A LOF mutations can also be found in patients diagnosed with congenital myopathy6–8 and occasionally hypokalaemic periodic paralysis (hypoPP).9 10 A common pathogenic mechanism can account for the notion that patients diagnosed with SCN4A -associated CMS may present with additional features of myopathy5 or hypoPP.4 The mutant NaV1.4 channels within SCN4A LOF clinical spectra show distinct functional defects. Mutations associated with congenital myopathy show a range of alterations on NaV1.4 channel function but one allele is often null.6–8 Hitherto reported CMS-associated mutations enhance channel inactivation2–5 and typically affect fourth voltage sensing domain (VSD) of NaV1.4, the key VSD implicated in control of …
Published: 2020

10. Abundant electrical myotonia and left ventricular noncompaction: Unusual features of Danon disease due to a novel mutation in LAMP2 gene

Author: Franck Letournel, Aude Tassin, Paul Richard, Aleksandra Nadaj-Pakleza, Vivien Pautot, Philippe Codron, Damien Sternberg, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Pathology, medicine.medical_specialty, LAMP2, business.industry, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, medicine.disease, Myotonia, Phenotype, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Neurology, Mutation (genetic algorithm), medicine, Left ventricular noncompaction, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Danon disease, Neurology (clinical), business, Novel mutation, Gene, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery
Abstract: International audience
Published: 2019

11. Long term longitudinal study of muscle function in patients with glycogen storage disease type IIIa

Author: Abdallah Fayssoil, Bruno Eymard, Gwenn Ollivier, François Petit, Aurélie Canal, Aleksandra Nadaj-Pakleza, Karim Wahbi, Jean-Yves Hogrel, Anthony Behin, Pascal Laforêt, Valérie Decostre, Kahina Kachetel, Marie De Antonio, and Philippe Labrune
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Longitudinal study, Time Factors, Adolescent, Endocrinology, Diabetes and Metabolism, Metabolic myopathy, Glycogen storage disease type III, Biochemistry, Glycogen debranching enzyme, Glycogen Storage Disease Type III, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Muscular Diseases, Internal medicine, Genetics, medicine, Humans, Purdue Pegboard Test, Glycogen storage disease, Longitudinal Studies, Molecular Biology, Retrospective Studies, Hand Strength, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Clinical trial, Cross-Sectional Studies, Outcome and Process Assessment, Health Care, 030104 developmental biology, Physical therapy, Female, business, 030217 neurology & neurosurgery
Abstract: Glycogen storage disease type III (GSDIII) is an autosomal recessive disorder caused by mutations in the AGL gene coding for the glycogen debranching enzyme. Current therapy is based on dietary adaptations but new preclinical therapies are emerging. The identification of outcome measures which are sensitive to disease progression becomes critical to assess the efficacy of new treatments in upcoming clinical trials. In order to prepare future longitudinal studies or therapeutic trials with large cohorts, information about disease progression is required. In this study we present preliminary longitudinal data of Motor Function Measure (MFM), timed tests, Purdue pegboard test, and handgrip strength collected over 5 to 9years of follow-up in 13 patients with GSDIII aged between 13 and 56years old. Follow-up for nine of the 13 patients was up to 9years. Similarly to our previous cross-sectional retrospective study, handgrip strength significantly decreased with age in patients older than 37years. MFM scores started to decline after the age of 35. The Purdue pegboard score also significantly reduced with increasing age (from 13years of age) but with large inter-visit variations. The time to stand up from a chair or to climb 4 stairs increased dramatically in some but not all patients older than 30years old. In conclusion, this preliminary longitudinal study suggests that MFM and handgrip strength are the most sensitive muscle function outcome measures in GSDIII patients from the end of their third decade. Sensitive muscle outcome measures remain to be identified in younger GSDIII patients but is challenging as muscle symptoms remain discrete and often present as accumulated fatigue.
Published: 2017

12. Myasthénie auto-immune séronégative

Author: Oana Catar, Aleksandra Nadaj-Pakleza, and Anne-Catherine Aubé-Nathier
Subjects: 0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, business.industry, Medicine, General Medicine, Auto immune, business, Molecular biology, 030217 neurology & neurosurgery, General Biochemistry, Genetics and Molecular Biology
Abstract: La myasthenie est une maladie auto-immune avec, dans 80 % des cas, des anticorps diriges contre le recepteur de l’acetylcholine (anti-RACh) positifs et deux formes cliniques distinctes, oculaire et generalisee. Les formes seronegatives sont relativement rares et cliniquement heterogenes. Le diagnostic de la myasthenie seronegative reste souvent difficile, notamment pour les formes oculaires et est essentiellement base sur une symptomatologie fluctuante caracteristique. La decouverte des anticorps anti-RACh a faible affinite et des nouveaux anticorps comme les anti-MuSK (diriges contre le recepteur specifique de la tyrosine kinase), les anti-LRP4 (diriges contre la proteine 4 reliee au recepteur des lipoproteines de faible densite), les anti-agrine ou les anti-cortactine constitue un avancement considerable dans la comprehension de la physiopathologie de la myasthenie. Selon le profil serologique, il est possible de prevoir la gravite potentielle de la maladie, la reponse aux traitements et le risque de pathologie thymique associee.
Published: 2017

13. Cognitive profile of patients with glycogen storage disease type III: a clinical description of seven cases

Author: François Petit, Valérie Hahn-Barma, Marcela Gargiulo, Ariane Herson, Philippe Labrune, Bruno Eymard, Aleksandra Nadaj-Pakleza, Pascal Laforêt, and Claire-Cécile Michon
Subjects: Adult, Male, medicine.medical_specialty, Pilot Projects, Neuropsychological Tests, Glycogen storage disease type III, Executive Function, Glycogen Storage Disease Type III, Young Adult, Cognition, Memory, Social cognition, Genetics, Humans, Medicine, Apathy, Episodic memory, Genetics (clinical), Language, business.industry, Neuropsychology, Middle Aged, Executive functions, medicine.disease, Physical therapy, Female, medicine.symptom, Cognition Disorders, business, Psychopathology, Clinical psychology
Abstract: Glycogen storage disease type III (GSDIII) is a rare autosomal recessive disorder due to glycogen debranching enzyme (GDE) deficiency. It results in a multisystemic disease with predominant hepatic and myopathic symptoms. While frequent social maladjustment has been observed in our clinical practice, cognitive and psychological disturbances have never been assessed. The aim of this pilot study was to examine and characterize the cognitive profile of patients with GSDIII. Seven patients (six women and one man, mean age: 38.7 ± 11.6 years) with GSDIII underwent a neuropsychological set of tests assessing global cognitive efficiency, executive functions, social cognition, apathy, and episodic memory. All patients presented previous psychopathological history. We observed attention fluctuations for each patient, and impaired global cognitive efficiency with deficiencies in executive functions in 5/7 patients. Emotional skills (social cognition) were impaired in five patients. Memory was mostly preserved. The impairment in social cognition (recognition of emotions and ability to attribute mental states to others) and executive functions observed could be a consequence of orbito-frontal dysfunction due to the abnormal glycogen metabolism characteristic of the underlying disease. These results are consistent with the hypothesis of a central nervous system involvement in patients with GSDIII, but need to be confirmed in future research. This could explain the social and economic difficulties, and the lack of compliance to the medical follow-up presented by these patients. It suggests that these disturbances need to be taken into account when planning the medical management of patients with GSDIII.
Published: 2014

14. Myoadenylate deaminase deficiency: a frequent cause of muscle pain A case detected by exercise testing

Author: Pascal Reynier, Lydie Lim, Aleksandra Nadaj-Pakleza, Gilles Simard, Antoine Bruneau, Cédric Le Maréchal, Franck Letournel, Chadi Homedan, Maeva Palayer, Laboratoire de Neurobiologie et Transgénèse (LNBT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Génétique moléculaire et génétique épidémiologique, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mitochondrie : Régulations et Pathologie, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre de reference des maladies neuromusculaires Nantes-Angers, CHU d'Angers et Nantes, Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)
Subjects: Exercise stress testing, Adult, Male, medicine.medical_specialty, Purine-Pyrimidine Metabolism, Inborn Errors, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, AMP Deaminase, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, Gynecology, Exercise Tolerance, business.industry, [SDV.BA]Life Sciences [q-bio]/Animal biology, Homozygote, AMP deaminase, General Medicine, Myalgia, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, Mutation, Exercise Test, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery
Abstract: Le deficit en myoadenylate desaminase (MAD, MIM#615511) est la cause la plus frequente de myopathies metaboliques avec une prevalence estimee entre 1 et 2 % de la population generale. Nous rapportons le cas d’un homme de 39 ans souffrant depuis 4 ans de douleurs musculaires squelettiques invalidantes d’apparition progressive avec, comme seul signe biologique, une augmentation moderee de creatine kinase (CK). Ce cas clinique nous donne l’opportunite de faire le point sur cette pathologie frequente et meconnue, ainsi que sur l’interet des explorations metaboliques dynamiques realisees lors d’epreuves d’effort sur cyclo-ergometre. Cet examen clinicobiologique non invasif, a l’interface entre la physiologie et la biologie, nous a en effet permis d’identifier chez ce patient une absence totale d’elevation physiologique de l’ammoniemie lors de l’effort, evocatrice d’un deficit en MAD. Ce deficit enzymatique en MAD a par la suite ete confirme par histochimie et l’etude moleculaire qui a revele la presence du variant pathogene homozygote retrouve de maniere recurrente chez la majorite des patients dans le gene de l’adenosine monophosphate desaminase 1 (AMPD1).
Published: 2017

15. Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases

Author: Antje Bornemann, Lukas J. Schnitzler, Christian Hartmann, Peter De Jonghe, Jens Reimann, Peter Van den Bergh, Andreas Meisel, Jörg B. Schulz, Jens A. Petersen, Aleksandra Nadaj-Pakleza, Joachim Weis, Philip Van Damme, Kristl G. Claeys, Andreas Ferbert, Elisabeth J. Rushing, Tobias Schreckenbach, Thomas Tousseyn, Jean-Jacques Martin, Werner Stenzel, Dietmar Rudolf Thal, Susanne Petri, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, University of Zurich, and Claeys, Kristl G
Subjects: HIV-NM, 2716 Genetics (clinical), Weakness, Paraproteinemia, Pathology, medicine.medical_specialty, HIV-associated nemaline myopathy, lcsh:Medicine, 610 Medicine & health, Late onset, Review, Muscle disorder, Myopathies, Nemaline, SLONM, 03 medical and health sciences, 0302 clinical medicine, Nemaline myopathy, Atrophy, medicine, 2736 Pharmacology (medical), Animals, Humans, Pharmacology (medical), ddc:610, Age of Onset, Myopathy, Genetics (clinical), Immunosuppression Therapy, Muscle biopsy, medicine.diagnostic_test, business.industry, Muscles, lcsh:R, Monoclonal gammopathy, High-Throughput Nucleotide Sequencing, General Medicine, medicine.disease, 10040 Clinic for Neurology, 030220 oncology & carcinogenesis, NGS, Immunology, MGUS, Human medicine, medicine.symptom, business, 030217 neurology & neurosurgery, Stem Cell Transplantation
Abstract: Orphanet journal of rare diseases : OJRD 12(1), 86 (2017). doi:10.1186/s13023-017-0640-2, Published by BioMed Central, London
Published: 2017

16. Cross-sectional retrospective study of muscle function in patients with glycogen storage disease type III

Author: Kahina Kachetel, Pascal Laforêt, Valérie Decostre, Philippe Labrune, Gwenn Ollivier, Aurélie Canal, Anthony Behin, Karim Wahbi, Bruno Eymard, Marie De Antonio, François Petit, Aleksandra Nadaj-Pakleza, Sylvain Leveugle, and Jean-Yves Hogrel
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Aging, Adolescent, Metabolic myopathy, Muscle Strength Dynamometer, Glycogen storage disease type III, Manual Muscle Testing, 03 medical and health sciences, Glycogen Storage Disease Type III, Young Adult, 0302 clinical medicine, medicine, Purdue Pegboard Test, Humans, In patient, Muscle, Skeletal, Genetics (clinical), Retrospective Studies, Muscle Weakness, Hand Strength, business.industry, Metabolic disorder, Retrospective cohort study, Middle Aged, medicine.disease, Clinical trial, 030104 developmental biology, Cross-Sectional Studies, Neurology, Pediatrics, Perinatology and Child Health, Physical therapy, Arm, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Glycogen storage disease type III is an inherited metabolic disorder characterized by liver and muscle impairment. This study aimed to identify promising muscle function measures for future studies on natural disease progression and therapeutic trials. The age-effect on the manual muscle testing (MMT), the hand-held dynamometry (HHD), the motor function measure (MFM) and the Purdue pegboard test was evaluated by regression analysis in a cross-sectional retrospective single site study. In patients aged between 13 and 56 years old, the Purdue pegboard test and dynamometry of key pinch and knee extension strength were age-sensitive with annual losses of 1.49, 1.10 and 0.70% of the predicted values (%pred), respectively. The MFM score and handgrip strength were also age-sensitive but only in patients older than 29 and 37 years old with annual losses of 1.42 and 1.84%pred, respectively. Muscle strength assessed by MMT and elbow extension measured by HHD demonstrated an annual loss of less than 0.50%pred and are thus unlikely to be promising outcome measures for future clinical trials. In conclusion, our results identified age-sensitive outcomes from retrospective data and may serve for future longitudinal studies in which an estimation of the minimal number of subjects is provided.
Published: 2016

17. Expanded phenotypic spectrum of the m.8344AG 'MERRF' mutation: data from the German mitoNET registry

Author: Aleksandra Nadaj-Pakleza, Kristl G. Claeys, Holger Prokisch, Jörg B. Schulz, Ronald R. Lautenschläger, Joachim Weis, Klaus A. Kuhn, Thomas Klopstock, Jochen Schäfer, Marcus Deschauer, Cornelia Kornblum, Judith Altmann, Robert Kopajtich, Sandra Jackson, Diana Lehmann, Ludger Schöls, Boriana Büchner, and Kathrin N. Karle
Subjects: 0301 basic medicine, Male, Pathology, RNA, Mitochondrial, Cohort Studies, Epilepsy, 0302 clinical medicine, epidemiology [MERRF Syndrome], Mitochondrial myopathy, Germany, Medicine, genetics [RNA], Registries, Age of Onset, genetics [MERRF Syndrome], Brain, Middle Aged, Heteroplasmy, Pedigree, Phenotype, Neurology, RNA, Transfer, Lys, Female, medicine.symptom, Adult, medicine.medical_specialty, Ataxia, Adolescent, Mitochondrial disease, genetics [RNA, Transfer, Lys], epidemiology [Germany], 03 medical and health sciences, Humans, ddc:610, diagnostic imaging [Brain], Aged, Cerebellar ataxia, business.industry, medicine.disease, MERRF Syndrome, 030104 developmental biology, drug therapy [MERRF Syndrome], physiopathology [MERRF Syndrome], Mutation, Myoclonic epilepsy, RNA, Neurology (clinical), business, Myoclonus, 030217 neurology & neurosurgery
Abstract: The m.8344A>G mutation in the MTTK gene, which encodes the mitochondrial transfer RNA for lysine, is traditionally associated with myoclonic epilepsy and ragged-red fibres (MERRF), a multisystemic mitochondrial disease that is characterised by myoclonus, seizures, cerebellar ataxia, and mitochondrial myopathy with ragged-red fibres. We studied the clinical and paraclinical phenotype of 34 patients with the m.8344A>G mutation, mainly derived from the nationwide mitoREGISTER, the multicentric registry of the German network for mitochondrial disorders (mitoNET). Mean age at symptom onset was 24.5 years ±10.9 (6-48 years) with adult onset in 75 % of the patients. In our cohort, the canonical features seizures, myoclonus, cerebellar ataxia and ragged-red fibres that are traditionally associated with MERRF, occurred in only 61, 59, 70, and 63 % of the patients, respectively. In contrast, other features such as hearing impairment were even more frequently present (72 %). Other common features in our cohort were migraine (52 %), psychiatric disorders (54 %), respiratory dysfunction (45 %), gastrointestinal symptoms (38 %), dysarthria (36 %), and dysphagia (35 %). Brain MRI revealed cerebral and/or cerebellar atrophy in 43 % of our patients. There was no correlation between the heteroplasmy level in blood and age at onset or clinical phenotype. Our findings further broaden the clinical spectrum of the m.8344A>G mutation, document the large clinical variability between carriers of the same mutation, even within families and indicate an overlap of the phenotype with other mitochondrial DNA-associated syndromes.
Published: 2015

18. Rola biopsji mięśnia szkieletowego w diagnostyce chorób nerwowo-mięśniowych

Author: Biruta Kierdaszuk, Aleksandra Nadaj-Pakleza, and Anna Kamińska
Subjects: Muscle tissue, Pathology, medicine.medical_specialty, Muscle biopsy, medicine.diagnostic_test, business.industry, medicine.disease, Oculopharyngeal muscular dystrophy, medicine.anatomical_structure, Mitochondrial myopathy, Biopsy, medicine, Surgery, Neurology (clinical), medicine.symptom, Inclusion body myositis, Muscular dystrophy, Myopathy, business
Abstract: Muscle biopsy is required to provide a definitive diagnosis in many neuromuscular disorders. Biopsy findings may indicate whether the pathological process is of neurogenic or myopathic origin. The muscle biopsy may give important information on the course of the disease (acute or chronic) and on the disease stage and progression. The interpretation of muscle biopsy, including histochemical and ultrastructural analysis, is a key factor in the diagnosis of muscular dystrophies, glycogenoses, inflammatory myopathies and congenital myopathies. An assessment of muscle biopsy on electron microscopy enables a definite diagnosis of oculopharyngeal muscular dystrophy, mitochondrial myopathy or inclusion body myositis. This paper presents an overview of general indications for muscle biopsy, biopsy procedures, as well as transportation and preparation of muscle tissue for final microscopic analysis. The interpretation of specific microscopic findings and a brief discussion on the clinical usefulness of muscle biopsy in the era of molecular diagnosis are also presented.
Published: 2010

19. Limb-girdle muscular dystrophy related to LAMA2 mutations: an unusual familial coincidence responsible for the phenotypic variability and diagnostic difficulties

Author: V. Guillet-Pichon, C. Beroud, Aleksandra Nadaj-Pakleza, F. Leturcq, and K. Claeys
Subjects: Neurology, business.industry, Pediatrics, Perinatology and Child Health, medicine, Neurology (clinical), Anatomy, medicine.disease, business, Phenotype, Genetics (clinical), Limb-girdle muscular dystrophy
Published: 2017

20. Permanent muscle weakness in M<scp>C</scp> Ardle disease

Author: Carlo M. Vincitorio, Marc Jeanpierre, Tanya Stojkovic, Pascal Laforêt, Carmen Navarro, Susana Teijeira, Aleksandra Nadaj-Pakleza, Elisabeth Dion, Irene Vietez, and Bruno Eymard
Subjects: medicine.medical_specialty, Weakness, Proximal muscle weakness, Muscle biopsy, medicine.diagnostic_test, Physiology, business.industry, Muscle weakness, Dystrophy, Surgery, Cellular and Molecular Neuroscience, Physiology (medical), Internal medicine, Myology, Biopsy, medicine, Neurology (clinical), medicine.symptom, business, Wasting
Abstract: McArdle disease is an autosomal recessive muscle glycogenosis. In the typical clinical presentation, only exercise-related symptoms are noted. Nevertheless, permanent weakness may occur, usually late in life. In this study we report on the clinical and genetic features of fixed muscle weakness in McArdle disease. Among the 80 McArdle patients being followed at the Institute of Myology of the Salpetriere Hospital, 9 patients have permanent weakness. The diagnosis of McArdle disease was confirmed by muscle biopsy and genetic investigations. Two patterns of muscle weakness and wasting were noted: (1) proximal and symmetric in 5 patients; and (2) asymmetric, mimicking facioscapulohumeral dystrophy (FSHD) in 4 patients. Computerized tomography scan showed fatty infiltration in the shoulder and pelvic girdle muscles. There was no clear correlation between genotype and the severity of muscle weakness. Proximal muscle weakness appeared after the age of 40 years and affected 11% of subjects in our series of 80 McArdle patients. Among patients over 40 years of age, 37.5% had muscle weakness.
Published: 2009

21. Muscle imaging in patients with tubular aggregate myopathy caused by mutations in STIM1

Author: Fabiana Fattori, Giorgio Tasca, Adele D'Amico, Enrico Bertini, Marc Vialle, Mauro Monforte, Aleksandra Nadaj-Pakleza, Enzo Ricci, and John Vissing
Subjects: Male, Pathology, MRI pattern, Thigh, medicine.disease_cause, Biceps, Congenital, Medicine, Child, Tomography, Genetics (clinical), Mutation, medicine.diagnostic_test, Subscapularis muscle, Skeletal, Anatomy, Middle Aged, musculoskeletal system, TAM, tubular aggregate myopathy, Magnetic Resonance Imaging, Muscle imaging, X-Ray Computed, Neoplasm Proteins, CT, computed tomography, Settore MED/26 - NEUROLOGIA, medicine.anatomical_structure, Neurology, Muscle, Myopathies, Female, medicine.symptom, Myopathies, Structural, Congenital, inorganic chemicals, Adult, medicine.medical_specialty, Adolescent, STIM1, Muscle MRI, Article, Structural, Humans, Stromal Interaction Molecule 1, Myopathy, Muscle, Skeletal, Aged, Muscle biopsy, business.industry, Genetic heterogeneity, Membrane Proteins, Magnetic resonance imaging, Tubular aggregate myopathy, Pediatrics, Perinatology and Child Health, Neurology (clinical), business, Tomography, X-Ray Computed
Abstract: Highlights • We characterized muscle imaging pattern in STIM1-related myopathy. • The subscapularis muscle was preferentially affected in the upper girdle. • Flexor hallucis longus was consistently affected in the lower limbs. • Muscle involvement is homogeneous and different from non-STIM1 patients., Tubular aggregate myopathy is a genetically heterogeneous disease characterized by tubular aggregates as the hallmark on muscle biopsy. Mutations in STIM1 have recently been identified as one genetic cause in a number of tubular aggregate myopathy cases. To characterize the pattern of muscle involvement in this disease, upper and lower girdles and lower limbs were imaged in five patients with mutations in STIM1, and the scans were compared with two patients with tubular aggregate myopathy not caused by mutations in STIM1. A common pattern of involvement was found in STIM1-mutated patients, although with variable extent and severity of lesions. In the upper girdle, the subscapularis muscle was invariably affected. In the lower limbs, all the patients showed a consistent involvement of the flexor hallucis longus, which is very rarely affected in other muscle diseases, and a diffuse involvement of thigh and posterior leg with sparing of gracilis, tibialis anterior and, to a lesser extent, short head of biceps femoris. Mutations in STIM1 are associated with a homogeneous involvement on imaging despite variable clinical features. Muscle imaging can be useful in identifying STIM1-mutated patients especially among other forms of tubular aggregate myopathy.
Published: 2015

22. Muscle imaging in STIM1-mutated tubular aggregate myopathy patients

Author: Enzo Ricci, E. Bertini, Adele D'Amico, Mauro Monforte, M. Vialle, John Vissing, Fabiana Fattori, Aleksandra Nadaj-Pakleza, and Giorgio Tasca
Subjects: Pathology, medicine.medical_specialty, Aggregate (composite), Neurology, business.industry, Pediatrics, Perinatology and Child Health, Medicine, STIM1, Neurology (clinical), medicine.symptom, business, Myopathy, Genetics (clinical)
Published: 2015

23. OPALE: A patient registry for laminopathies and emerinopathies in France

Author: R. Ben Yaou, Pascal Cintas, Marie-Christine Vantyghem, R. Juntas-Morales, Gisèle Bonne, Pascale Richard, Susana Quijano-Roy, Aleksandra Nadaj-Pakleza, A. De Sandre-Giovannol, Corinne Vigouroux, Guilhem Solé, Denis Duboc, F. Leturcq, Yann Péréon, E. Campanna-Salort, Karim Wahbi, Bruno Eymard, Fabien Labombarda, and Jean-Marie Cuisset
Subjects: 0301 basic medicine, medicine.medical_specialty, Patient registry, business.industry, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Neurology, Pediatrics, Perinatology and Child Health, Emergency medicine, medicine, Neurology (clinical), business, 030217 neurology & neurosurgery, Genetics (clinical)
Published: 2016

24. Muscle pathology in 31 patients with calpain 3 gene mutations

Author: Małgorzata Dorobek, Anna Kamińska, Barbara Ryniewicz, Aleksandra Nadaj-Pakleza, Klaudia Nestorowicz, and Elzbieta Szmidt-Salkowska
Subjects: Male, Pathology, medicine.medical_specialty, Adolescent, Biopsy, Blotting, Western, Muscle Proteins, Gene mutation, medicine.disease_cause, medicine, Humans, Muscular dystrophy, Child, Mutation, Muscle biopsy, medicine.diagnostic_test, biology, business.industry, Calpain, Brain, medicine.disease, Immunohistochemistry, Muscular Dystrophies, Limb-Girdle, Child, Preschool, biology.protein, Surgery, Female, Neurology (clinical), Differential diagnosis, business, Limb-girdle muscular dystrophy
Abstract: Background and purpose At present, more than 20 different forms of limb-girdle muscular dystrophies (LGMDs) are known (at least 7 autosomal dominant and 14 autosomal recessive). Although these different forms show some typical phenotypic characteristics, the existing clinical overlap makes their differential diagnosis difficult. Limb-girdle muscular dystrophy type 2 (LGMD2A) is the most prevalent LGMD in many European as well as Brazilian communities and is caused by mutations in the gene CAPN3. Laboratory testing, such as calpain immunohistochemistry and Western-blot analysis, is not totally reliable, since up to 20% of molecularly confirmed LGMD2A show normal content of calpain 3 and a third of LGMD2A biopsies have normal calpain 3 proteolytic activity in the muscle. Thus, genetic testing is considered as the only reliable diagnostic criterion in LGMD2A. Material and methods In an attempt to find a correlation between genotype and muscle pathology in limb-girdle muscular dystrophy 2A we performed histopathological investigation of a group of 31 patients subdivided according to the type of pathologic CAPN3 gene mutation. Results In all biopsies typical features of muscular dystrophy such as fiber necrosis and regeneration, variation in fiber size and fibrosis were noted. Lobulated fibers were often encountered in the muscle biopsies of LGMD2A patients. Such fibers were more frequent in patients with 550delA mutation. Conclusions These findings may be helpful in establishing diagnostic strategies in LGMD.
Published: 2013

25. Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional Observational Study

Author: Hugo Varet, Guilhem Solé, Dominique Menard, Celia Boutte, Khadija Amarof, Valerie Drouin-Garraud, Jack Puymirat, Gerard Riviere, Felix Rougier, Françoise Chapon, Marguerite Preudhomme, Anne-Laure Bedat-Millet, Xavier Ferrer, Dalil Hamroun, Tanya Stojkovich, Vincent Tiffreau, Pascal Cintas, Romain K. Gherardi, Laurent Magy, Céline Dogan, Karima Ghorab, Françoise Bouhour, Marianne Fabbro, Sybille Pellieux, Gilbert Caranhac, Romain Deschamps, Rémi Bellance, Helene Gervais-Bernard, Pascal Laforêt, Marie-Christine Minot, Sabrina Sacconi, Emmanuelle Campana-Salort, Marie-Christine Arne Bes, Claude Desnuelle, Aleksandra Nadaj-Pakleza, Andoni Urtizberea, Christophe Vial, François Boyer, Anthony Behin, Armelle Magot, Fabien Zagnoli, Bruno Eymard, Yann Péréon, Jean Pouget, Guillaume Bassez, Marie De Antonio, Sandrine Katsahian, Alain Geille, Claude Bourlier, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU de Fort de France, Centre de Reference des Maladies Neuromusculaires - Atlantique Occitanie Caraïbe (CRMN - AOC), CHU Rouen, Normandie Université (NU), Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU de la Martinique [Fort de France], Groupement Hospitalier Est, Centre Hospitalier Universitaire [Grenoble] (CHU), Santé publique, vieillissement, qualité de vie et réadaptation des sujets fragiles - EA 3797 (SPVQVRSF), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Service de Médecine Physique Neurologique-Traumatologique [Reims], Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Sébastopol, Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des maladies neuromusculaires et de la SLA, Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Attention, Orientation et Chronobiologie (COMETE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Bordeaux [Bordeaux], Service de Neurologie [CHU Limoges], CHU Limoges, Centre de référence national neuropathies périphériques rares [CHU Limoges], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Explorations Fonctionnelles, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Référence des Maladies Neuromusculaires Rares de l'Enfant et de l'Adulte Nantes-Angers, Maintenance Myélinique et Neuropathies Périphériques (MMNP), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôtel-Dieu de Nantes, Université de Nantes (UN), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Neuro-Oncologie [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Biologie Valrose (IBV), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Hôpital Marin, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital d'Instruction des Armées Clermont Tonnerre, Service de Santé des Armées, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Jonchère, Laurent, Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest, CHU Toulouse [Toulouse], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Univ. Littoral Côte d’Opale, Univ. Artois, Université de Lille, Université Paris-Est Créteil Val-de-Marne - Paris 12 [UPEC UP12], CHU Montpellier, Hôpital Pierre Zobda-Quitman [CHU de la Martinique], Neurologie et Explorations Fonctionnelles du Système Nerveux [Toulouse], Centre Hospitalier Universitaire [Grenoble] [CHU], Centre Hospitalier Universitaire de Reims [CHU Reims], Hôpital de la Timone [CHU - APHM] [TIMONE], Centre Hospitalier Universitaire de Nice [CHU Nice], Centre hospitalier universitaire de Nantes [CHU Nantes], Centre Hospitalier Universitaire d'Angers [CHU Angers], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 [URePSSS], Association française contre les myopathies [AFM-Téléthon], and Université Pierre et Marie Curie - Paris 6 [UPMC]
Subjects: Male, 0301 basic medicine, Databases, Factual, Physiology, Cross-sectional study, Myotonic dystrophy, lcsh:Medicine, Disease, computer.software_genre, Laryngology, 0302 clinical medicine, Medicine and Health Sciences, Ethnicities, Medicine, French People, lcsh:Science, education.field_of_study, Multidisciplinary, Death rates, Database, Cognitive Neurology, Mortality rate, Dysphagia, 3. Good health, Phenotype, Cognitive impairment, Neurology, Physiological Parameters, Female, Research Article, Adult, Maternal inheritance, Cognitive Neuroscience, Population, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, 03 medical and health sciences, Population Metrics, Adults, Humans, Obesity, Sex Distribution, education, Demography, Population Biology, Cataracts, business.industry, lcsh:R, Body Weight, Biology and Life Sciences, medicine.disease, Myotonia, Thyroid disorder, Health Care, Ophthalmology, Cross-Sectional Studies, 030104 developmental biology, Otorhinolaryngology, Socioeconomic Factors, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Age Groups, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Lens Disorders, People and Places, Cognitive Science, lcsh:Q, Population Groupings, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Health Statistics, Morbidity, Age of onset, business, computer, 030217 neurology & neurosurgery, Neuroscience
Abstract: International audience; BACKGROUND: Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity, challenging both medical management and clinical trials. The CTG expansion size is the main factor determining the age of onset although no factor can finely predict phenotype and prognosis. Differences between males and females have not been specifically reported. Our aim is to study gender impact on DM1 phenotype and severity.METHODS: We first performed cross-sectional analysis of main multiorgan clinical parameters in 1409 adult DM1 patients (\textgreater18y) from the DM-Scope nationwide registry and observed different patterns in males and females. Then, we assessed gender impact on social and economic domains using the AFM-Téléthon DM1 survey (n = 970), and morbidity and mortality using the French National Health Service Database (n = 3301). RESULTS: Men more frequently had (1) severe muscular disability with marked myotonia, muscle weakness, cardiac, and respiratory involvement; (2) developmental abnormalities with facial dysmorphism and cognitive impairment inferred from low educational levels and work in specialized environments; and (3) lonely life. Alternatively, women more frequently had cataracts, dysphagia, digestive tract dysfunction, incontinence, thyroid disorder and obesity. Most differences were out of proportion to those observed in the general population. Compared to women, males were more affected in their social and economic life. In addition, they were more frequently hospitalized for cardiac problems, and had a higher mortality rate.CONCLUSION: Gender is a previously unrecognized factor influencing DM1 clinical profile and severity of the disease, with worse socio-economic consequences of the disease and higher morbidity and mortality in males. Gender should be considered in the design of both stratified medical management and clinical trials
Published: 2016

26. T.P.41

Author: Gwenn Ollivier, Aleksandra Nadaj-Pakleza, Aurélie Canal, Valérie Decostre, J.Y. Hogrel, and P. Laforêt
Subjects: medicine.medical_specialty, Glycogen, business.industry, Outcome measures, Physiology, Glycogen storage disease type III, medicine.disease, Motor function, Surgery, Glycogen debranching enzyme, Clinical trial, chemistry.chemical_compound, Neurology, chemistry, Pediatrics, Perinatology and Child Health, medicine, Neurology (clinical), Negative correlation, Dietary modifications, business, Genetics (clinical)
Abstract: Glycogen storage disease type 3 (GSD3) is an autosomal recessive disorder caused by mutations in the AGL gene coding for the glycogen debranching enzyme, which releases glucose from glycogen. Current therapy is primarily based on dietary modifications but pharmacological approaches are emerging. The pattern of muscle clinical involvement is poorly described in the literature. However, the need for outcome measures is becoming crucial to assess the efficacy of new treatments in future clinical trials. Here we present a cross-sectional study of 17 GSD3 patients aged between 12 and 56 years old. We found that above 20 years of age the Motor Function Measure (MFM) scale total score decreased with increasing age. A negative correlation was found between age and MFM total score (rho = −0.841, p
Published: 2014

27. M.P.4.02 Permanent muscle weakness in McArdle disease

Author: Bruno Eymard, Aleksandra Nadaj-Pakleza, P. Laforêt, Carmen Navarro, Susana Teijeira, M. Jeanpierre, C. Vincitorio, and T. Stojkovic
Subjects: medicine.medical_specialty, MCARDLE DISEASE, Neurology, business.industry, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, Cardiology, Muscle weakness, Neurology (clinical), medicine.symptom, business, Genetics (clinical)
Published: 2007

28. G.P.11.04 Pattern and evolution of skeletal muscle involvement in glycogenosis type III (debrancher deficiency): Muscle imaging findings from childhood to adult age

Author: P. Laforêt, Aleksandra Nadaj-Pakleza, Philippe Labrune, A. Mollet, Pierre G. Carlier, J. Renoux, Bruno Eymard, and Anthony Behin
Subjects: medicine.medical_specialty, business.industry, DEBRANCHER DEFICIENCY, Skeletal muscle, Adult age, Endocrinology, medicine.anatomical_structure, Neurology, Internal medicine, Pediatrics, Perinatology and Child Health, Medicine, Neurology (clinical), business, Genetics (clinical)
Published: 2009

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28 results on '"Aleksandra Nadaj-Pakleza"'

1. A rise in cases of nitrous oxide abuse: neurological complications and biological findings

2. Impact of Coronavirus Disease 2019 in a French Cohort of Myasthenia Gravis

3. A multicenter cross-sectional French study of the impact of COVID-19 on neuromuscular diseases

4. Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies

5. Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort

6. Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis: A Randomized Clinical Trial

7. Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial

8. Respiratory decline in adult patients with Becker muscular dystrophy: A longitudinal study

9. Homozygous C-terminal loss-of-function NaV1.4 variant in a patient with congenital myasthenic syndrome

10. Abundant electrical myotonia and left ventricular noncompaction: Unusual features of Danon disease due to a novel mutation in LAMP2 gene

11. Long term longitudinal study of muscle function in patients with glycogen storage disease type IIIa

12. Myasthénie auto-immune séronégative

13. Cognitive profile of patients with glycogen storage disease type III: a clinical description of seven cases

14. Myoadenylate deaminase deficiency: a frequent cause of muscle pain A case detected by exercise testing

15. Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases

16. Cross-sectional retrospective study of muscle function in patients with glycogen storage disease type III

17. Expanded phenotypic spectrum of the m.8344AG 'MERRF' mutation: data from the German mitoNET registry

18. Rola biopsji mięśnia szkieletowego w diagnostyce chorób nerwowo-mięśniowych

19. Limb-girdle muscular dystrophy related to LAMA2 mutations: an unusual familial coincidence responsible for the phenotypic variability and diagnostic difficulties

20. Permanent muscle weakness in M<scp>C</scp> Ardle disease

21. Muscle imaging in patients with tubular aggregate myopathy caused by mutations in STIM1

22. Muscle imaging in STIM1-mutated tubular aggregate myopathy patients

23. OPALE: A patient registry for laminopathies and emerinopathies in France

24. Muscle pathology in 31 patients with calpain 3 gene mutations

25. Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional Observational Study

26. T.P.41

27. M.P.4.02 Permanent muscle weakness in McArdle disease

28. G.P.11.04 Pattern and evolution of skeletal muscle involvement in glycogenosis type III (debrancher deficiency): Muscle imaging findings from childhood to adult age

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28 results on '"Aleksandra Nadaj-Pakleza"'

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