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1. Clinical, Cognitive and Neural Effects of Potentiation of ECT by rTMS in Treatment-Resistant Depression (STIMAGNECT2)

Author: University Hospital, Rouen, Centre Hospitalier Sainte Anne, Paris, and Maud Rothärmel, Principal investigator
Published: 2024

2. Effects of a Walking Intervention With Additional Weights on the Unaffected Leg in People After Stroke (ANANTA)

Author: Centre Hospitalier Sainte Anne, Paris and Département d'Epidémiologie Clinique, Hôpital Hôtel-Dieu, Paris
Published: 2021

3. Conséquences psychopathologiques du confinement

Author: Anne Giersch, Laurence Lalanne, Mélissa C. Allé, Florence Thibaut, Pierre A. Geoffroy, C. Schroder, Astrid Chevance, Fabienne Ligier, Paul Brunault, Renaud Jardri, Fabrice Berna, Julie Rolling, Guillaume Vaiva, Amaury C. Mengin, U1114 Neuropsychologie Cognitive et Physiophatologie de la Schizophrénie, Institut National de la Santé et de la Recherche Médicale (INSERM), Département de psychiatrie [CHU Strasbourg] (FMTS), CHU Strasbourg-Fédération de Médecine Translationelle de Strasbourg (FMTS), Aarhus University [Aarhus], Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Service de psychiatrie de l’enfant et de l’adolescent, hôpitaux universitaires de Strasbourg, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Fondation FondaMental [Créteil], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U1172 Inserm), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Pôle de Psychiatrie [Lille], PRES Université Lille Nord de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre National de Ressources et Résilience (CN2R), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service d’Addictologie « Moreau de Tours » [CH Sainte-Anne - APHP], Centre Hospitalier Sainte Anne [Paris]-GHU Paris Psychiatrie & Neurosciences, Imagerie et Cerveau (iBrain - Inserm U1253 - UNIV Tours), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Qualité de vie et Santé psychologique [Tours] (QualiPsy), Université de Tours, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm - Paris Descartes), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Sainte Anne [Paris], Neuropsychologie Cognitive et Physiophatologie de la Schizophrénie (Inserm U1114 - UNISTRA), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Qualité de vie et Santé psychologique [Tours] (QualiPsy - E.E. 1901), Université de Tours (UT), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), International Association of Women's Mental Health (Université de Paris), Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques (CRESS - U1153), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lille Neurosciences & Cognition - U 1172 (LilNCog), Centre National de Ressources et de Résilience [Lille] (CN2R), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Psychotherapist, Hallucinations, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Prison, Anxiety, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, Arts and Humanities (miscellaneous), medicine, Social isolation, media_common, Depression, [SCCO.NEUR]Cognitive science/Neuroscience, Dépression, PTSD, Boredom, 16. Peace & justice, medicine.disease, 030227 psychiatry, Eating disorders, Sleep deprivation, Psychiatry and Mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, TSPT, Domestic violence, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, Psychology, Anxiété, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Psychopathology, Confinement
Abstract: International audience; Les effets psychologiques de l’isolement ont déjà été décrits dans la littérature (expéditions polaires, sous-marins, prison). Néanmoins, l’échelle du confinement mis en œuvre à l’occasion de la pandémie à COVID-19 est inédite. Il nous faut non seulement relire les études publiées, mais aussi anticiper les problèmes psychologiques qui pourraient survenir pendant ou à distance du confinement. Nous avons fait le choix d’aller au-delà de la littérature COVID-19 pour examiner les implications des conséquences connues du confinement : l’ennui, l’isolement social, le stress, le manque de sommeil. L’anxiété, le trouble de stress post-traumatique, la dépression et les conduites suicidaires, les conduites addictives, les violences domestiques sont des effets décrits du confinement, mais les mécanismes d’émergence de ces troubles et leurs interrelations restent à étudier. Par exemple, quels sont les mécanismes d’émergence du trouble de stress post-traumatique dans le cadre du confinement ? Nous rappelons aussi les points de vigilance à garder sur des conséquences telles que les troubles des conduites alimentaires, les hallucinations, curieusement ignorées dans la littérature sur le confinement, alors qu’une vaste littérature fait le lien entre isolement social et hallucinations. Du fait de conséquences psychopathologiques larges, il nous faut partir à la recherche des différents symptômes pour permettre leur prise en charge. Nous résumons rapidement les approches diagnostiques et thérapeutiques déjà mises en place, comme la télémédecine, qui connaît un développement rapide à l’occasion de la crise du COVID-19.
Published: 2020

4. Neurological Involvement in Childhood Evans Syndrome

Author: Hervé Chambost, Frédéric Rieux-Laucat, Olivier Hermine, Nathalie Aladjidi, Albane Gareton, Thomas Pincez, Pascale Varlet, Frédéric Millot, Gérard Michel, Jean-Marc Durand, Guy Leverger, Hubert Ducou Le Pointe, Bénédicte Neven, Hélène Zéphir, Y Perel, Judith Landman-Parker, Alexis Mathian, Marlène Pasquet, Mohamed Hamidou, Thierry Leblanc, Marie Hully, Helder Fernandes, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Montréal (UdeM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Sainte Anne [Paris], CHU Bordeaux [Bordeaux], Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neurologie pédiatrique [CHU Necker], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Université de Montréal [Montréal], Centre Hospitalier Sainte-Anne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Evans syndrome, Adolescent, lymphoproliferation, Primary Immunodeficiency Diseases, Autoimmune cytopenia, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Immunology, Population, Neurological disorder, medicine.disease_cause, primary immunodeficiency, Hypogammaglobulinemia, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Immunology and Allergy, neurological disorder, Child, education, Purpura, Thrombocytopenic, Idiopathic, Cytopenia, education.field_of_study, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Immunoglobulins, Intravenous, Infant, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Immune dysregulation, medicine.disease, Thrombocytopenia, Thrombocytopenic purpura, CTLA deficiency, 3. Good health, 030104 developmental biology, Child, Preschool, Primary immunodeficiency, [SDV.IMM]Life Sciences [q-bio]/Immunology, Steroids, Anemia, Hemolytic, Autoimmune, Nervous System Diseases, business, 030215 immunology
Abstract: International audience; PURPOSE: Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) are associated in the definition of Evans syndrome (ES). The occurrence of neurological involvement in this population is poorly described and suggests an underlying primary immunodeficiency (PID). We aimed to describe the clinical manifestations, evolution, and PID profiles of these patients.METHODS: OBS'CEREVANCE is a French, nationwide prospective cohort that includes children with chronic ITP, AIHA, and ES. Patients with a neurological involvement were described. Centralized radiological and pathological reviews and genetic analyses were performed.RESULTS: On October 2016, eight patients (7/181 ES, 1/371 AIHA, and 0/615 ITP) were identified, all male, with a median age (range) at cytopenia onset of 11.5 years (1.6-15.8). Neurological symptoms appeared with a median delay of 6 years (2.5-18) after cytopenia and were polymorphic: seizures (n = 4), cranial nerve palsy (n = 2), Brown-Sequard syndrome (n = 2), intracranial pressure (n = 2), vertigo (n = 1), and/or sensory neuropathy (n = 1). Magnetic resonance imaging (MRI) showed inflammatory lesions, confirmed by pathology for five patients with macrophagic or lymphoplasmocytic infiltrates. All patients had other relevant immunopathological manifestations: pulmonary nodules (n = 6), lymphoproliferation (n = 4), abnormal immunophenotype (n = 8), and hypogammaglobulinemia (n = 7). Treatment consisted of steroids that improved symptomatology and MRI. Five patients relapsed and three had an asymptomatic radiological progression. A PID was identified in 3/8 patients: 22q11.2 microdeletion (n = 1) and CTLA deficiency (n = 2).CONCLUSION: Neurological involvement is a rare and severe late event in the course of childhood ES, which can reveal an underlying PID. Imaging and pathology examination highlight a causative immune dysregulation that may guide targeted therapeutic strategies.
Published: 2019

5. MRI Atlas of IDH Wild-Type Supratentorial Glioblastoma: Probabilistic Maps of Phenotype, Management, and Outcomes

Author: Pietro Gori, Fabrice Chrétien, Edouard Dezamis, Kanako Sato, Johan Pallud, Ariane Fleury, Emmanuèle Lechapt, Pauline Roca, Jean-François Meder, Alexandre Roux, Catherine Oppenheim, Pascale Varlet, Frédéric Dhermain, Stéphanie Lion, Myriam Edjlali, Marc Zanello, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Laboratoire de Neuroimagerie Assistée par Ordinateur (LNAO), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service d'Imagerie Morphologique et Fonctionnel [Paris], Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Neurochirurgie, Centre hospitalier Sainte-Anne (Paris), Université Sorbonne Paris Cité (USPC), Laboratoire Traitement et Communication de l'Information (LTCI), Institut Mines-Télécom [Paris] (IMT)-Télécom Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Neuro-oncologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Psychiatrie et Neurosciences (U894), Télécom ParisTech-Institut Mines-Télécom [Paris] (IMT), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, computer.software_genre, 030218 nuclear medicine & medical imaging, Lesion, 03 medical and health sciences, 0302 clinical medicine, Text mining, Atlases as Topic, Imaging, Three-Dimensional, Voxel, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Radiology, Nuclear Medicine and imaging, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Brain Mapping, business.industry, Brain Neoplasms, Retrospective cohort study, Middle Aged, Phenotype, Magnetic Resonance Imaging, Isocitrate Dehydrogenase, 3. Good health, Radiation therapy, Isocitrate dehydrogenase, 030220 oncology & carcinogenesis, Spatial normalization, Female, Radiology, medicine.symptom, business, Glioblastoma, computer
Abstract: Background Tumor location is a main prognostic parameter in patients with glioblastoma. Probabilistic MRI-based brain atlases specifying the probability of tumor location associated with important demographic, clinical, histomolecular, and management data are lacking for isocitrate dehydrogenase (IDH) wild-type glioblastomas. Purpose To correlate glioblastoma location with clinical phenotype, surgical management, and outcomes by using a probabilistic analysis in a three-dimensional (3D) MRI-based atlas. Materials and Methods This retrospective study included all adults surgically treated for newly diagnosed IDH wild-type supratentorial glioblastoma in a tertiary adult surgical neuro-oncology center (2006-2016). Semiautomated tumor segmentation and spatial normalization procedures to build a 3D MRI-based atlas were validated. The authors performed probabilistic analyses by using voxel-based lesion symptom mapping technology. The Liebermeister test was used for binary data, and the generalized linear model was used for continuous data. Results A total of 392 patients (mean age, 61 years ± 13; 233 men) were evaluated. The authors identified the preferential location of glioblastomas according to subventricular zone, age, sex, clinical presentation, revised Radiation Therapy Oncology Group-Recursive Partitioning Analysis class, Karnofsky performance status, O6-methylguanine DNA methyltransferase promoter methylation status, surgical management, and survival. The superficial location distant from the eloquent area was more likely associated with a preserved functional status at diagnosis (348 of 392 patients [89%], P < .05), a large surgical resection (173 of 392 patients [44%], P < .05), and prolonged overall survival (163 of 334 patients [49%], P < .05). In contrast, deep location and location within eloquent brain areas were more likely associated with an impaired functional status at diagnosis (44 of 392 patients [11%], P < .05), a neurologic deficit (282 of 392 patients [72%], P < .05), treatment with biopsy only (183 of 392 patients [47%], P < .05), and shortened overall survival (171 of 334 patients [51%], P < .05). Conclusion The authors identified the preferential location of isocitrate dehydrogenase wild-type glioblastomas according to parameters of interest and provided an image-based integration of multimodal information impacting survival results. This suggests the role of glioblastoma location as a surrogate and multimodal parameter integrating several known prognostic factors. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Huang in this issue.
Published: 2019

6. Modifications of the endosomal compartment in fibroblasts from sporadic Alzheimer’s disease patients are associated with cognitive impairment

Author: Laura Xicota, Julien Lagarde, Fanny Eysert, Benjamin Grenier-Boley, Isabelle Rivals, Alexandra Botté, Sylvie Forlani, Sophie Landron, Clément Gautier, Cecilia Gabriel, Michel Bottlaender, Jean-Charles Lambert, Mounia Chami, Marie Sarazin, Marie-Claude Potier, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), GHU Paris Psychiatrie et Neurosciences, Université Paris Cité (UPCité), Université Paris-Saclay, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université de Lille, CHU Lille, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Recherches SERVIER (IRS), Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Xicota, Laura
Subjects: [SDV] Life Sciences [q-bio], Cellular and Molecular Neuroscience, Psychiatry and Mental health, [SDV]Life Sciences [q-bio], Biological Psychiatry
Abstract: Morphological alterations of the endosomal compartment have been widely described in post-mortem brains from Alzheimer’s disease (AD) patients and subjects with Down syndrome (DS) who are at high risk for AD. Immunostaining with antibodies against endosomal markers such as Early Endosome Antigen 1 (EEA1) revealed increased size of EEA1-positive puncta. In DS, peripheral cells such as peripheral blood mononuclear cells (PBMCs) and fibroblasts, share similar phenotype even in the absence of AD. We previously found that PBMCs from AD patients have larger EEA1-positive puncta, correlating with brain amyloid load. Here we analysed the endosomal compartment of fibroblasts from a very well characterised cohort of AD patients (IMABio3) who underwent thorough clinical, imaging and biomarkers assessments. Twenty-one subjects were included (7 AD with mild cognitive impairment (AD-MCI), 7 AD with dementia (AD-D) and 7 controls) who had amyloid-PET at baseline (PiB) and neuropsychological tests at baseline and close to skin biopsy. Fibroblasts isolated from skin biopsies were immunostained with anti-EEA1 antibody and imaged using a spinning disk microscope. Endosomal compartment ultrastructure was also analysed by electron microscopy. All fibroblast lines were genotyped and their AD risk factors identified. Our results show a trend to an increased EEA1-positive puncta volume in fibroblasts from AD-D as compared to controls (p.adj = 0.12) and reveal enhanced endosome area in fibroblasts from AD-MCI and AD-AD versus controls. Larger puncta size correlated with PiB retention in different brain areas and with worse cognitive scores at the time of biopsy as well as faster decline from baseline to the time of biopsy. Finally, we identified three genetic risk factors for AD (ABCA1, COX7C and MYO15A) that were associated with larger EEA1 puncta volume. In conclusion, the endosomal compartment in fibroblasts could be used as cellular peripheral biomarker for both amyloid deposition and cognitive decline in AD patients.
Published: 2023

7. Stratifying sudden death risk in adults with drug‐resistant focal epilepsy: The <scp>SUDEP‐CARE</scp> score

Author: Chris Serrand, Sylvain Rheims, Marie Faucanié, Arielle Crespel, Vera Dinkelacker, William Szurhaj, Arnaud Biraben, Fabrice Bartolomei, Nathalie de Grissac, Elizabeth Landré, Marie Denuelle, Laurent Vercueil, Cécile Marchal, Louis Maillard, Philippe Derambure, Sophie Dupont, Vincent Navarro, Thibault Mura, Audrey Jaussent, Valérie Macioce, Philippe Ryvlin, Marie‐Christine Picot, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Hautepierre [Strasbourg], Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Lille, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Sainte Anne [Paris], Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire [Grenoble] (CHU), Domaine expérimental de Vassal (MONTP DOM VASSAL), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Montpellier (UM), Unité de Neurologie Fonctionnelle et d'Épileptologie, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut de Génomique Fonctionnelle (IGF), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Sudden Death, Epilepsy, SUDEP, Neurology, Risk score, Neurology (clinical), case-control, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background and purpose - A clinical risk score for sudden unexpected death in epilepsy (SUDEP) in patients with drug-resistant focal epilepsy could help improve prevention. Methods - A case-control study was conducted including (i) definite or probable SUDEP cases collected by the French National Sentinel Mortality Epilepsy Network and (ii) control patients from the French national research database of epilepsy monitoring units. Patients with drug-resistant focal epilepsy were eligible. Multiple logistic regressions were performed. After sensitivity analysis and internal validation, a simplified risk score was developed from the selected variables. Results - Sixty-two SUDEP cases and 620 controls were included. Of 21 potential predictors explored, seven were ultimately selected, including generalized seizure frequency (>1/month vs.
Published: 2022

8. Delaying standard combined chemoradiotherapy after surgical resection does not impact survival in newly diagnosed glioblastoma patients

Author: Guillaume, Louvel, Philippe, Metellus, Georges, Noel, Sophie, Peeters, Jacques, Guyotat, Julien, Duntze, Pierre-Jean, Le Reste, Phong, Dam Hieu, Thierry, Faillot, Fabien, Litre, Nicolas, Desse, Antoine, Petit, Evelyne, Emery, Jimmy, Voirin, Johann, Peltier, François, Caire, Jean-Rodolphe, Vignes, Jean-Luc, Barat, Olivier, Langlois, Philippe, Menei, Sarah N, Dumont, Marc, Zanello, Edouard, Dezamis, Frédéric, Dhermain, Johan, Pallud, Anne, Vital, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Radiothérapie moléculaire (UMR 1030), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurochirurgie [CHU Marseille], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Paul Strauss, CRLCC Paul Strauss, Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], CHU Pontchaillou [Rennes], Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de neurochirurgie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, University of Naples Federico II = Università degli studi di Napoli Federico II, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital pasteur [Colmar], Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service de Neurochirurgie [CHU Limoges], CHU Limoges, CHU de Bordeaux Pellegrin [Bordeaux], Hôpital Privé Clairval [Marseille], CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuro-oncologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau d'Etude des Gliomes, REG, Service de neurochirurgie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Università degli studi di Napoli Federico II, Département de Neurochirurgie [CHU Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-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)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Centre Hospitalier Sainte-Anne, Hôpital Beaujon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Standard combined chemoradiotherapy, Prognostic factors, Disease-Free Survival, Time, 03 medical and health sciences, 0302 clinical medicine, Temozolomide, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Progression-free survival, Antineoplastic Agents, Alkylating, Proportional Hazards Models, Retrospective Studies, Radiotherapy, Brain Neoplasms, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Hazard ratio, Chemoradiotherapy, Hematology, Middle Aged, Combined Modality Therapy, Confidence interval, 3. Good health, Surgery, Time interval, Radiation therapy, Oncology, Quartile, 030220 oncology & carcinogenesis, Concomitant, Female, business, Glioblastoma, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; BACKGROUND:To assess the influence of the time interval between surgical resection and standard combined chemoradiotherapy on survival in newly diagnosed and homogeneously treated (surgical resection plus standard combined chemoradiotherapy) glioblastoma patients; while controlling confounding factors (extent of resection, carmustine wafer implantation, functional status, neurological deficit, and postoperative complications).METHODS:From 2005 to 2011, 692 adult patients (434 men; mean of 57.5 ± 10.8 years) with a newly diagnosed glioblastoma were enrolled in this retrospective multicentric study. All patients were treated by surgical resection (65.5% total/subtotal resection, 34.5% partial resection; 36.7% carmustine wafer implantation) followed by standard combined chemoradiotherapy (radiotherapy at a median dose of 60 Gy, with daily concomitant and adjuvant temozolomide). Time interval to standard combined chemoradiotherapy was analyzed as a continuous variable and as a dichotomized variable using median and quartiles thresholds. Multivariate analyses using Cox modeling were conducted.RESULTS:The median progression-free survival was 10.3 months (95% CI, 10.0-11.0). The median overall survival was 19.7 months (95% CI, 18.5-21.0). The median time to initiation of combined chemoradiotherapy was 1.5 months (25% quartile, 1.0; 75% quartile, 2.2; range, 0.1-9.0). On univariate and multivariate analyses, OS and PFS were not significantly influenced by time intervals to adjuvant treatments. On multivariate analysis, female gender, total/subtotal resection and RTOG-RPA classes 3 and 4 were significant independent predictors of improved OS.CONCLUSIONS:Delaying standard combined chemoradiotherapy following surgical resection of newly diagnosed glioblastoma in adult patients does not impact survival.
Published: 2016

9. Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia

Author: Sarah Weckhuysen, Margitta Seeck, Bart Dermaut, Alfred Meurs, Michel Baulac, Stéphanie Baulac, Pierre de la Grange, Francine Chassoux, Elise Marsan, Fabienne Picard, Eric LeGuern, Cécile Marchal, Pierre Thomas, Isabelle An-Gourfinkel, Mélanie Morin-Brureau, Christine Kallay Zetchi, Virginie Lambrecq, Martine Fohlen, HAL-UPMC, Gestionnaire, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des épilepsies rares [CHU Pitié-Salpêtrière], Unité fonctionnelle d'épilepsie [CHU Pitié-Salpêtrière], 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)-IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Service de Neurologie [CHU 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 d'épileptologie [CHU de Bordeaux], CHU Bordeaux [Bordeaux], Service de Neurochirurgie Pediatrique, Fondation Ophtalmologique Rotschild, Department of Neurology [Genève], Hôpitaux Universitaires de Genève (HUG), University of Geneva Medical School, Center for Medical Genetics [Ghent], Ghent University Hospital, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Dpt of Neurology [Gent], Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Sainte Anne, Centre hospitalier Sainte Anne, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Service de Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Neuroprotection & Neuromodulation
Subjects: 0301 basic medicine, Male, DEPDC5, DNA Mutational Analysis, mTORC1, Gene mutation, Cohort Studies, Epilepsy, 0302 clinical medicine, genetics, Child, Medicine(all), Aged, 80 and over, TOR Serine-Threonine Kinases, GTPase-Activating Proteins, Middle Aged, NPRL3, Magnetic Resonance Imaging, 3. Good health, Malformations of Cortical Development, mTOR pathway, Neurology, SUDEP 22 text pages, Child, Preschool, 5 figures, 1 table, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adult, Biology, 03 medical and health sciences, Young Adult, familial focal epilepsies, NPRL2, medicine, Humans, Genetic Predisposition to Disease, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], PI3K/AKT/mTOR pathway, 35 references, Aged, Family Health, Tumor Suppressor Proteins, Infant, Newborn, fical cortical dysplasia, Infant, GATOR2 complex, Cortical dysplasia, 3249 words (including summary), medicine.disease, complex genes, ddc:616.8, Repressor Proteins, 030104 developmental biology, Positron-Emission Tomography, Involvement of Gator, Mutation, Cancer research, Neurology (clinical), Epilepsies, Partial, Human medicine, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; ObjectiveThe discovery of mutations in DEPDC5 in familial focal epilepsies has introduced a novel pathomechanism to a field so far dominated by ion channelopathies. DEPDC5 is part of a complex named GAP activity toward RAGs (GATOR) complex 1 (GATOR1), together with the proteins NPRL2 and NPRL3, and acts to inhibit the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) pathway. GATOR1 is in turn inhibited by the GATOR2 complex. The mTORC1 pathway is a major signaling cascade regulating cell growth, proliferation, and migration. We aimed to study the contribution of GATOR complex genes to the etiology of focal epilepsies and to describe the associated phenotypical spectrum.MethodsWe performed targeted sequencing of the genes encoding the components of the GATOR1 (DEPDC5, NPRL2, and NPRL3) and GATOR2 (MIOS, SEC13, SEH1L, WDR24, and WDR59) complex in 93 European probands with focal epilepsy with or without focal cortical dysplasia. Phospho-S6 immunoreactivity was used as evidence of mTORC1 pathway activation in resected brain tissue of patients carrying pathogenic variants.ResultsWe identified four pathogenic variants in DEPDC5, two in NPRL2, and one in NPRL3. We showed hyperactivation of the mTORC1 pathway in brain tissue from patients with NPRL2 and NPRL3 mutations. Collectively, inactivating mutations in GATOR1 complex genes explained 11% of cases of focal epilepsy, whereas no pathogenic mutations were found in GATOR2 complex genes. GATOR1-related focal epilepsies differ clinically from focal epilepsies due to mutations in ion channel genes by their association with focal cortical dysplasia and seizures emerging from variable foci, and might confer an increased risk of sudden unexplained death in epilepsy (SUDEP).SignificanceGATOR1 complex gene mutations leading to mTORC1 pathway upregulation is an important cause of focal epilepsy with cortical malformations and represents a potential target for novel therapeutic approaches.
Published: 2016

10. Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort

Author: Johan, Pallud, Etienne, Audureau, Georges, Noel, Robert, Corns, Emmanuèle, Lechapt-Zalcman, Julien, Duntze, Vladislav, Pavlov, Jacques, Guyotat, Phong Dam, Hieu, Pierre-Jean, Le Reste, Thierry, Faillot, Claude-Fabien, Litre, Nicolas, Desse, Antoine, Petit, Evelyne, Emery, Jimmy, Voirin, Johann, Peltier, François, Caire, Jean-Rodolphe, Vignes, Jean-Luc, Barat, Olivier, Langlois, Edouard, Dezamis, Eduardo, Parraga, Marc, Zanello, Edmond, Nader, Michel, Lefranc, Luc, Bauchet, Bertrand, Devaux, Philippe, Menei, Philippe, Metellus, Anne, Vital, Centre Hospitalier Sainte-Anne, Université Paris Descartes - Paris 5 ( UPD5 ), Centre Paul Strauss, CRLCC Paul Strauss, Centre Hospitalier Universitaire de Caen, CHU Caen, Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), CHU Pontchaillou [Rennes], Service de neurochirurgie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Neurochirurgie, CHU Caen-Caen University Hospital, CHU Amiens-Picardie-Hôpital Nord - Amiens, Laboratoire de Neurochirurgie, Centre hospitalier Sainte-Anne (Paris), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Micro et nanomédecines biomimétiques ( MINT ), Université d'Angers ( UA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Bretagne Loire ( UBL ), CHU Angers, Centre de Recherches en Oncologie biologique et Oncopharmacologie ( CRO2 ), Aix Marseille Université ( AMU ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Leeds General Infirmary (LGI), Leeds Teaching Hospitals NHS Trust, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurochirurgie [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), Hôpital pasteur [Colmar], CHU Strasbourg, CHU Amiens-Picardie, Service de Neurochirurgie [CHU Limoges], CHU Limoges, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Privé Clairval [Marseille], Service de neurochirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de neurochirurgie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Centre Hospitalier Sainte-Anne, Unité d’Epidémiologie et de Biostatistiques [APHP Cochin-Broca-Hôtel Dieu], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Réseau d'Etude des Gliomes, REG, Service de neurochirurgie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Università degli studi di Napoli Federico II, CHU de Bordeaux Pellegrin [Bordeaux], Centre d'Études Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de Neurochirurgie [CHU Angers], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Neurochirurgie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Micro et Nanomédecines Biomimétiques, and Université Bretagne Loire (UBL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA)
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Survival, [SDV]Life Sciences [q-bio], Clinical Investigations, Kaplan-Meier Estimate, Disease-Free Survival, Cohort Studies, Young Adult, medicine, Humans, Progression-free survival, Young adult, Antineoplastic Agents, Alkylating, Aged, Aged, 80 and over, Carmustine, [ SDV ] Life Sciences [q-bio], Brain Neoplasms, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Hazard ratio, carmustine wafers, Chemoradiotherapy, Middle Aged, 3. Good health, Surgery, Treatment Outcome, Oncology, Chemotherapy, Adjuvant, Cohort, Propensity score matching, Female, Neurology (clinical), business, Glioblastoma, medicine.drug, Cohort study
Abstract: CERVOXY COLL; International audience; BACKGROUND: The standard of care for newly diagnosed glioblastoma is maximal safe surgical resection, followed by chemoradiation therapy. We assessed carmustine wafer implantation efficacy and safety when used in combination with standard care. METHODS: Included were adult patients with (n = 354, implantation group) and without (n = 433, standard group) carmustine wafer implantation during first surgical resection followed by chemoradiation standard protocol. Multivariate and case-matched analyses (controlled propensity-matched cohort, 262 pairs of patients) were conducted. RESULTS: The median progression-free survival was 12.0 months (95% CI: 10.7-12.6) in the implantation group and 10.0 months (9.0-10.0) in the standard group and the median overall survival was 20.4 months (19.0-22.7) and 18.0 months (17.0-19.0), respectively. Carmustine wafer implantation was independently associated with longer progression-free survival in patients with subtotal/total surgical resection in the whole series (adjusted hazard ratio [HR], 0.76 [95% CI: 0.63-0.92], P = .005) and after propensity matching (HR, 0.74 [95% CI: 0.60-0.92], P = .008), whereas no significant difference was found for overall survival (HR, 0.95 [0.80-1.13], P = .574; HR, 1.06 [0.87-1.29], P = .561, respectively). Surgical resection at progression whether alone or combined with carmustine wafer implantation was independently associated with longer overall survival in the whole series (HR, 0.58 [0.44-0.76], P \textless .0001; HR, 0.54 [0.41-0.70], P \textless .0001, respectively) and after propensity matching (HR, 0.56 [95% CI: 0.40-0.78], P \textless .0001; HR, 0.46 [95% CI: 0.33-0.64], P \textless .0001, respectively). The higher postoperative infection rate in the implantation group did not affect survival. CONCLUSIONS: Carmustine wafer implantation during surgical resection followed by the standard chemoradiation protocol for newly diagnosed glioblastoma in adults resulted in a significant progression-free survival benefit
Published: 2015

11. Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial

Author: Sharshar, Tarek, Porcher, Raphaël, Asfar, Pierre, Grimaldi, Lamiae, Jabot, Julien, Argaud, Laurent, Lebert, Christine, Bollaert, Pierre Édouard, Harlay, Marie Line, Chillet, Patrick, Maury, Éric, Santoli, Francesco, Blanc, Pascal, Sonneville, Romain, Vu, Dinh Chuyen, Rohaut, Benjamin, Mazeraud, Aurélien, Alvarez, Jean Claude, Navarro, Vincent, Clair, Bernard, Outin, Hervé D., Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Hôtel-Dieu [Paris], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Lorraine (UL), Hôpital de Hautepierre [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital de Châlons-en-Champagne, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Hôpital Robert Ballanger [Aulnay-sous-Bois], Centre Hospitalier René Dubos [Pontoise], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier d'Etampes, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [Garches], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], and Valse investigators and for the Groupe d’Explorations Neurologiques en Reanimation (GENER): Laurent Argaud, Eric Azabou, François Beloncle, Omar Ben-Hadj, Pascal Blanc, Pierre-Edouard Bollaert, Francis Bolgert, Lila Bouadma, Patrick Chillet, Bernard Clair, Philippe Corne, Raphaël Clere-Jehl, Martin Cour, Arielle Crespel, Véronique Déiler, Jean Dellamonica, Sophie Demeret, Marie-Line Harley, Matthieu Henry-Lagarrigue, Julien Jabot, Nicholas Heming, Romain Hernu, Achille Kouatchet, Christine Lebert, Nicolas Lerolle, Eric Maury, Sophie Letrou, Aurélien Mazeraud, Alain Mercat, Satar Mortaza, Bruno Mourvillier, Hervé Outin, Catherine Paugham-Burtz, Marc Pierrot, Marion Provent, Benjamin Rohaut, Sylvie De La Salle, François Santoli, Maleka Schenk, Shidasp Siami, Vincent Souday, Tarek Sharshar, Romain Sonneville, Jean-François Timsit, Marie Thuong, Nicolas Weiss
Subjects: [SDV]Life Sciences [q-bio], Generalised convulsive status epilepticus, Valproic acid, Intensive care unit, Critical Care and Intensive Care Medicine, Seizure
Abstract: Background Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20–40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE. Methods This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90. Results A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89–1.19); p = 0.58]. There were no between-group differences for secondary outcomes. Conclusions VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15. Trial registration No. NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.
Published: 2023

12. Human Subinsular Asymmetry Studied by Diffusion Tensor Imaging and Fiber Tracking

Author: Y. Cointepas, Catherine Oppenheim, J.-F. Mangin, C. Poupon, J.-F. Meder, Sebastian Rodrigo, Olivier Naggara, Narly Golestani, D. Le Bihan, service de neuroradiologie [Paris], Hôpital Sainte-Anne, Laboratoire d'Imagerie et de Spectroscopie ( LRMN ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Institut d'imagerie neurofonctionnelle ( IIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -ENST-Assistance publique - Hôpitaux de Paris (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -École des hautes études en sciences sociales ( EHESS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Traitement et Communication de l'Information ( LTCI ), Télécom ParisTech-Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Neuroimagerie Assistée par Ordinateur ( LNAO ), Service Hospitalier Frédéric Joliot ( SHFJ ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Center for Neuroscience and Behavioral Medicine, Children's National Medical Center, Human Brain Research Center [Kyoto] ( HBRC ), Kyoto University [Kyoto], Service NEUROSPIN ( NEUROSPIN ), National Institutes of Health [Bethesda] ( NIH ), IFR de Neuroimagerie Fonctionnelle ( IFR 49 ), DIMF, Université Paris Descartes - Paris 5 ( UPD5 ) -Centre Hospitalier Sainte-Anne, Service de neuroradiologie [Paris], Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut d'imagerie neurofonctionnelle (IIN), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École des hautes études en sciences sociales (EHESS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Ecole Nationale Supérieure des Télécommunications (ENST)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Traitement et Communication de l'Information (LTCI), Télécom ParisTech-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neuroimagerie Assistée par Ordinateur (LNAO), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Human Brain Research Center [Kyoto] (HBRC), Kyoto University, Service NEUROSPIN (NEUROSPIN), National Institutes of Health [Bethesda] (NIH), IFR de Neuroimagerie Fonctionnelle (IFR 49), Université Paris Descartes - Paris 5 (UPD5)-Centre Hospitalier Sainte-Anne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure des Télécommunications (ENST)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École des hautes études en sciences sociales (EHESS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, and Institut National de la Santé et de la Recherche Médicale (INSERM)-ENST-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École des hautes études en sciences sociales (EHESS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Functional Laterality, 0302 clinical medicine, Reference Values, Arcuate fasciculus, MESH : Female, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, media_common, Cerebral Cortex, 05 social sciences, MESH: Reference Values, Brain, Anatomy, MESH : Adult, MESH : Diffusion Magnetic Resonance Imaging, medicine.anatomical_structure, MESH : Cerebral Cortex, Female, Psychology, Adult, MESH : Male, media_common.quotation_subject, Uncinate fasciculus, MESH: Diffusion Magnetic Resonance Imaging, MESH : Reference Values, Occipitofrontal fasciculus, Asymmetry, 050105 experimental psychology, Lateralization of brain function, White matter, MESH: Brain, 03 medical and health sciences, Fractional anisotropy, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, MESH: Functional Laterality, MESH : Functional Laterality, MESH: Humans, Functional, MESH : Humans, MESH: Adult, MESH: Cerebral Cortex, MESH: Male, Diffusion Magnetic Resonance Imaging, MESH : Brain, Neurology (clinical), MESH: Female, Neuroscience, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: International audience; BACKGROUND AND PURPOSE: Our aim was to improve our understanding of the subinsular white matter microstructural asymmetries in healthy right-handed subjects. Structural brain asymmetries could be related to functional asymmetries such as hemisphere language dominance or handedness. Besides the known gray matter asymmetries, white matter asymmetries could also play a key role in the understanding of hemispheric specialization, notably that of language. MATERIALS AND METHODS: White matter asymmetries were studied by diffusion tensor imaging at 1.5T (41 diffusion-gradient directions; b-value set to 700 s/mm(2); matrix, 128(2); in-plane resolution, 1.875 x 1.875 mm; section thickness, 2.0 mm) and fiber tracking (BrainVISA software). The main white matter bundles passing through the subinsular area were segmented, and fractional anisotropy (FA) was measured along each of the segmented bundles. RESULTS: In line with published results, we found an asymmetry of the arcuate fasciculus and the subinsular white matter, namely left-greater-than-right FA in right-handed controls. Furthermore, by segmenting major tracts coursing through this region, we showed that the subinsular portions of the uncinate fasciculus (UF) and the inferior occipitofrontal fasciculus (IOF) contribute to this FA asymmetry. Those tracts have been reported to be likely implicated in the language network. CONCLUSION: Because the left hemisphere hosts language functions in most right-handers, the significant leftward asymmetry observed within the arcuate fasciculus, the subinsular part of the UF and IOF may be related to the hemispheric specialization for language.
Published: 2007

13. Comparison between fresh and fixed human biopsies using spectral and lifetime measurements: Fluorescence analysis using one and two photon excitations

Author: Amira Zaylaa, D. Abi Haidar, A. Ibrahim, Pascale Varlet, Fanny Poulon, Marc Zanello, Bertrand Devaux, Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurochirurgie, Centre hospitalier Sainte-Anne (Paris), Department of Electrical and Computer Engineering, American University of Beirut, Laboratoire de Neuropathologie, Centre Hospitalier Sainte Anne, and Zaylaa, Amira
Subjects: Fluorescence-lifetime imaging microscopy, Fluorophore, Materials science, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Analytical chemistry, 02 engineering and technology, Spectroscopic analysis, 01 natural sciences, 010309 optics, chemistry.chemical_compound, Two-photon excitation microscopy, lifetime domain measurements, 0103 physical sciences, fresh tissues, Laser-induced fluorescence, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Excitation wavelength, human biopsies, 021001 nanoscience & nanotechnology, Fluorescence, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Wavelength, fixed tissues, chemistry, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology
Abstract: International audience; The purpose of this study is to make a comparison between the fluorescence emissions of fresh extracted human biopsies and fixed human biopsies, in order to evaluate the impact of fixation on autofluoresence signal. Our group is developing an endo-microscope to image brain tissues in-vivo, however to date, in order to validate our technology the easiest type of samples we can access are fixed samples. However, the fixation is still challenging. For that, we aim through this study to determine whether we should pursue to work on fixed samples or we should shift to work on fresh biopsies. Data were collected on spectroscopic, lifetime measurement and fluorescence imaging setups with visible and two-photon excitations wavelengths. Five fresh and five fixed samples are involved in the experiment. Endogenous fluorescence of fixed biopsies were calculated. Experimental results reveal that at 405 nm and 810 nm, the fresh samples have an intensity of fluorescence two times higher than that of fixed samples. However, for each fluorophore and each excitation wavelength, the lifetime for fresh samples is shorter than that for fixed samples. Still, further studies and investigations involving the comparison between different samples are required to strengthen our findings.
Published: 2015

14. It’s not what you say, it’s how you say it: A retrospective study of the impact of prosody on own-name P300 in comatose patients

Author: Estelle, Pruvost-Robieux, Nathalie, André-Obadia, Angela, Marchi, Tarek, Sharshar, Marco, Liuni, Martine, Gavaret, Jean-Julien, Aucouturier, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de neurologie fonctionnelle et d'épileptologie [Hôpital Pierre Wertheimer-HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Alta Voce SAS, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Male, Disorders of consciousness, Acoustic properties, Electroencephalography, Evoked potentials, Event-Related Potentials, P300, P300 wave, Speech Acoustics, Sensory Systems, Semantics, Own name protocol, Neurology, Physiology (medical), Speech Perception, Humans, Female, ERP (Evoked Related Potential), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Coma
Abstract: International audience; ObjectiveThe acoustic characteristics of stimuli influence the characteristics of the corresponding evoked potentials in healthy subjects. Own-name stimuli are used in clinical practice to assess the level of consciousness in intensive care units. The influence of the acoustic variability of these stimuli has never been evaluated. Here, we explored the influence of this variability on the characteristics of the subject’s own name (SON) P300.MethodsWe retrospectively analyzed 251 disorders of consciousness patients from Lyon and Paris Hospitals who underwent an “own-name protocol”. A reverse correlation analysis was performed to test for an association between acoustic properties of own-names stimuli used and the characteristics of the P300 wave observed.ResultsOwn-names pronounced with increasing pitch prosody showed P300 responses 66 ms earlier than own-names that had a decreasing prosody [IC95% = 6.36; 125.9 ms].ConclusionsSpeech prosody of the stimuli in the “own name protocol” is associated with latencies differences of the P300 response among patients for whom these responses were observed. Further investigations are needed to confirm these results.SignificanceSpeech prosody of the stimuli in the “own name protocol” is a non-negligible parameter, associated with P300 latency differences. Speech prosody should be standardized in SON P300 studies.
Published: 2022

15. Using a multiomics approach to unravel a septic shock specific signature in skeletal muscle

Author: Baptiste Duceau, Michael Blatzer, Jean Bardon, Thibault Chaze, Quentin Giai Gianetto, Florence Castelli, François Fenaille, Lucie Duarte, Thomas Lescot, Christophe Tresallet, Bruno Riou, Mariette Matondo, Olivier Langeron, Pierre Rocheteau, Fabrice Chrétien, Adrien Bouglé, Neuropathologie expérimentale - Experimental neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Descartes - Paris 5 (UPD5), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Henri Mondor, Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaboHUB, CHU Saint-Antoine [AP-HP], Sorbonne Université (SU), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), GHU Paris Psychiatrie et Neurosciences, The study was funded by a grant of the French Ministry of Higher Education, Research and Innovation (Agence Nationale de la Recherche ANR-17-CE14-0035) to F. Chrétien. Drs A. Bouglé and B. Duceau were the recipients of a research fellowship grant from the Institut Pasteur (Paris, France) and Assistance Publique – Hôpitaux de Paris (Paris, France)., and ANR-17-CE14-0035,PUSHUPS,Etude de la dysfonction des cellules souches musculaires au cours du sepsis(2017)
Subjects: Male, Proteomics, Multidisciplinary, Critical Illness, Sepsis, [SDV]Life Sciences [q-bio], Humans, Female, Prospective Studies, Muscle, Skeletal, Shock, Septic
Abstract: Sepsis is defined as a dysregulated host response to infection leading to organs failure. Among them, sepsis induces skeletal muscle (SM) alterations that contribute to acquired-weakness in critically ill patients. Proteomics and metabolomics could unravel biological mechanisms in sepsis-related organ dysfunction. Our objective was to characterize a distinctive signature of septic shock in human SM by using an integrative multi-omics approach. Muscle biopsies were obtained as part of a multicenter non-interventional prospective study. Study population included patients in septic shock (S group, with intra-abdominal source of sepsis) and two critically ill control populations: cardiogenic shock (C group) and brain dead (BD group). The proteins and metabolites were extracted and analyzed by High-Performance Liquid Chromatography-coupled to tandem Mass Spectrometry, respectively. Fifty patients were included, 19 for the S group (53% male, 64 ± 17 years, SAPS II 45 ± 14), 12 for the C group (75% male, 63 ± 4 years, SAPS II 43 ± 15), 19 for the BD group (63% male, 58 ± 10 years, SAPS II 58 ± 9). Biopsies were performed in median 3 days [interquartile range 1–4]) after intensive care unit admission. Respectively 31 patients and 40 patients were included in the proteomics and metabolomics analyses of 2264 proteins and 259 annotated metabolites. Enrichment analysis revealed that mitochondrial pathways were significantly decreased in the S group at protein level: oxidative phosphorylation (adjusted p = 0.008); branched chained amino acids degradation (adjusted p = 0.005); citrate cycle (adjusted p = 0.005); ketone body metabolism (adjusted p = 0.003) or fatty acid degradation (adjusted p = 0.008). Metabolic reprogramming was also suggested (i) by the differential abundance of the peroxisome proliferator-activated receptors signaling pathway (adjusted p = 0.007), and (ii) by the accumulation of fatty acids like octanedioic acid dimethyl or hydroxydecanoic. Increased polyamines and depletion of mitochondrial thioredoxin or mitochondrial peroxiredoxin indicated a high level of oxidative stress in the S group. Coordinated alterations in the proteomic and metabolomic profiles reveal a septic shock signature in SM, highlighting a global impairment of mitochondria-related metabolic pathways, the depletion of antioxidant capacities, and a metabolic shift towards lipid accumulation.ClinicalTrial registration: NCT02789995. Date of first registration 03/06/2016.
Published: 2022

16. Management of Upper Respiratory Tract Infections by Different Medical Practices, Including Homeopathy, and Consumption of Antibiotics in Primary Care: The EPI3 Cohort Study in France 2007–2008

Author: Lamiae Grimaldi-Bensouda, Bernard Bégaud, Michel Rossignol, Bernard Avouac, France Lert, Frederic Rouillon, Jacques Bénichou, Jacques Massol, Gerard Duru, Anne-Marie Magnier, Lucien Abenhaim, Didier Guillemot, HAL UPMC, Gestionnaire, Pharmacoépidémiologie et maladies infectieuses, Institut Pasteur [Paris] (IP), LASER ANALYTICA, Paris (LA-SER), Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), McGill University = Université McGill [Montréal, Canada], LA-SER Montréal, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Sainte Anne, Centre hospitalier Sainte Anne, Unité de biostatistiques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Cyklad group, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), London School of Hygiene and Tropical Medicine (LSHTM), LASER ANALYTICA Europe Limited, London (LA-SER), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), his study was funded by Laboratoires Boiron, France. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Bacterial Diseases, Male, Pediatrics, Medical Doctors, Pulmonology, Epidemiology, Health Care Providers, Anti-Inflammatory Agents, Pathology and Laboratory Medicine, Cohort Studies, 0302 clinical medicine, Medicine and Health Sciences, Public and Occupational Health, 030212 general & internal medicine, Practice Patterns, Physicians', Sinusitis, Child, Respiratory Tract Infections, education.field_of_study, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Evidence-Based Medicine, Respiratory tract infections, Disease Management, Homeopathy, Middle Aged, 3. Good health, 030205 complementary & alternative medicine, Anti-Bacterial Agents, Infectious Diseases, Medical Microbiology, Research Design, Child, Preschool, Medicine, Female, France, medicine.symptom, Family Practice, Cohort study, Research Article, Adult, medicine.medical_specialty, Clinical Pathology, Antipyretics, Infectious Disease Control, Adolescent, Clinical Research Design, Science, Population, Research and Analysis Methods, Microbiology, Infectious Disease Epidemiology, 03 medical and health sciences, Complementary and Alternative Medicine, Adverse Reactions, General Practitioners, Microbial Control, Physicians, medicine, Upper Respiratory Tract Infections, Humans, education, Primary Care, Aged, Pharmacology, Survey Research, business.industry, Pharmacoepidemiology, Infant, Newborn, Biology and Life Sciences, Infant, Odds ratio, medicine.disease, Medical Practice Management, Confidence interval, Health Care, Clinical Microbiology, Otitis, Survey Methods, Health Care Surveys, Respiratory Infections, Bacterial Pneumonia, Clinical Medicine, business, Medical Humanities, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BackgroundPrescribing of antibiotics for upper respiratory tract infections (URTI) varies substantially in primary care.ObjectivesTo describe and compare antibiotic and antipyretic/anti-inflammatory drugs use, URTI symptoms' resolution and occurrence of potentially-associated infections in patients seeking care from general practitioners (GPs) who exclusively prescribe conventional medications (GP-CM), regularly prescribe homeopathy within a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho).MethodThe EPI3 survey was a nationwide population-based study of a representative sample of 825 GPs and their patients in France (2007-2008). GP recruitment was stratified by self-declared homeopathic prescribing preferences. Adults and children with confirmed URTI were asked to participate in a standardized telephone interview at inclusion, one-, three- and twelve-month follow up. Study outcomes included medication consumption, URTI symptoms' resolution and potentially-associated infections (sinusitis or otitis media/externa) as reported by patients. Analyses included calibration to account for non-respondents and groups were compared using multivate analyses adjusting for baseline differences with a propensity score.Results518 adults and children with URTI (79.3% rhinopharyngitis) were included (36.9% response rate comparable between groups). As opposed to GP-CM patients, patients in the GP-Ho group showed significantly lower consumption of antibiotics (Odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.27-0.68) and antipyretic/anti-inflammatory drugs (OR = 0.54, 95% CI: 0.38-0.76) with similar evolution in related symptoms (OR = 1.16, 95% CI: 0.64-2.10). An excess of potentially-associated infections (OR = 1.70, 95% CI: 0.90-3.20) was observed in the GP-Ho group (not statistically significant). No difference was found between GP-CM and GP-Mx patients.ConclusionPatients who chose to consult GPs certified in homeopathy used less antibiotics and antipyretic/anti-inflammatory drugs for URTI than those seen by GPs prescribing conventional medications. No difference was observed in patients consulting GPs within mixed-practice. A non-statistically significant excess was estimated through modelling for associated infections in the GP-Ho group and needs to be further studied.
Published: 2014

17. NMOSD typical brain lesions after COVID-19 mRNA vaccination

Author: Julie Lévi-Strauss, Corentin Provost, Noémie Wane, Thomas Jacquemont, Nicolas Mélé, GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Martinez Rico, Clara
Subjects: Aquaporin 4, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Neurology, Neuromyelitis Optica, Vaccination, Brain, COVID-19, Humans, RNA, Messenger, Neurology (clinical), Nervous System Diseases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Autoantibodies
Abstract: International audience; No abstract available
Published: 2022

18. Influence of prior intravenous thrombolysis on outcome after failed mechanical thrombectomy: ETIS registry analysis

Author: Claire, Rozes, Benjamin, Maier, Benjamin, Gory, Romain, Bourcier, Maeva, Kyheng, Julien, Labreuche, Arturo, Consoli, Mikael, Mazighi, Raphaël, Blanc, Jildaz, Caroff, Francois, Eugene, Olivier, Naggara, Florent, Gariel, Igor, Sibon, Bertrand, Lapergue, Gaultier, Marnat, Ian, Seiler, CHU Bordeaux [Bordeaux], Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neuroradiologie [Suresnes], Hôpital Foch [Suresnes], Fondation Ophtalmologique Adolphe de Rothschild [Paris], Service de Neuroradiologie [CHU de Bicêtre], Service de Neuroradiologie [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Sainte Anne [Paris], Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Neuro-Radiologie [Bordeaux] (DNR - Bordeaux), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Mechanical Thrombolysis, medicine.medical_treatment, Intervention, Arterial Occlusive Diseases, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Brain Ischemia, Hematoma, Fibrinolytic Agents, Modified Rankin Scale, Statistical significance, Clinical endpoint, Humans, Medicine, Thrombolytic Therapy, Registries, Stroke, Ischemic Stroke, Retrospective Studies, Thrombectomy, business.industry, Cerebral infarction, General Medicine, Thrombolysis, medicine.disease, Mechanical thrombectomy, Treatment Outcome, Anesthesia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Surgery, Neurology (clinical), business, Intracranial Hemorrhages
Abstract: BackgroundDespite constant improvements in recent years, sufficient reperfusion after mechanical thrombectomy (MT) is not reached in up to 15% of patients with large vessel occlusion stroke (LVOS). The outcome of patients with unsuccessful reperfusion after MT especially after intravenous thrombolysis (IVT) use is not known. We investigated the influence of initial IVT in this particular group of patients with failed intracranial recanalization.MethodsWe conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry from January 2015 to December 2019. Patients presenting with LVOS of the anterior circulation and final modified Thrombolysis in Cerebral Infarction score (mTICI) of 0, 1 or 2a were included. Posterior circulation, isolated cervical carotid occlusions and successful reperfusions (mTICI 2b, 2c or 3) were excluded. The primary endpoint was favorable outcome (modified Rankin Scale score of 0–2) after 3 months. Secondary endpoints were safety outcomes including mortality, any intracranial hemorrhage (ICH), parenchymal hematoma (PH) and symptomatic intracranial hemorrhage (sICH) rates.ResultsAmong 5076 patients with LVOS treated with MT, 524 patients with insufficient recanalization met inclusion criteria, of which 242 received IVT and 282 did not. Functional outcome was improved in the MT+IVT group compared with the MT alone group, although the difference did not reach statistical significance (23.0% vs 12.9%; adjusted OR=1.82; 95% CI 0.98 to 3.38; p=0.058). However, 3 month mRS shift analysis showed a significant benefit of IVT (adjusted OR=1.68; 95% CI 1.56 to 6.54). ICH and sICH rates were similar in both groups, although PH rate was higher in the MT+IVT group (adjusted OR=3.20; 95% CI 1.56 to 6.54).ConclusionsAmong patients with LVOS in the anterior circulation and unsuccessful MT, IVT was associated with improved functional outcome even after unsuccessful MT. Despite recent trials questioning the place of IVT in the LVOS reperfusion strategy, these findings emphasize a subgroup of patients still benefiting from IVT.
Published: 2021

19. Imaging of non-tumorous and tumorous human brain tissues with full-field optical coherence tomography

Author: Johan Pallud, Fabrice Chrétien, Fabrice Harms, Claude Boccara, Kate Grieve, Pascale Varlet, Bertrand Devaux, Osnath Assayag, Institut Langevin - Ondes et Images (UMR7587) (IL), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service Neurochirurgie, Centre hospitalier Sainte Anne, Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Sainte-Anne, Centre Hospitalier Sainte Anne, Sorbonne Université (SU)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), Institut Langevin ondes et images, Centre National de la Recherche Scientifique (CNRS)-ESPCI ParisTech-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique ( CNRS ) -ESPCI ParisTech-Université Paris Diderot - Paris 7 ( UPD7 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), and Université Paris Descartes - Paris 5 ( UPD5 )
Subjects: Pathology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 01 natural sciences, Optical imaging, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, [ SDV.MHEP.CHI ] Life Sciences [q-bio]/Human health and pathology/Surgery, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, Tissues and Organs (q-bio.TO), [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], [ PHYS.PHYS.PHYS-OPTICS ] Physics [physics]/Physics [physics]/Optics [physics.optics], medicine.diagnostic_test, OCT, optical coherence tomography, Human brain, Glioma, 3. Good health, medicine.anatomical_structure, Neurology, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SPI.OPTI ] Engineering Sciences [physics]/Optics / Photonic, [ INFO.INFO-BT ] Computer Science [cs]/Biotechnology, Physics - Optics, medicine.medical_specialty, [ SDV.MHEP.AHA ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Cognitive Neuroscience, Brain tumor, FOS: Physical sciences, [SDV.CAN]Life Sciences [q-bio]/Cancer, Brain imaging, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Article, 010309 optics, White matter, 03 medical and health sciences, Optical coherence tomography, Neuroimaging, FF-OCT, full field optical coherence tomography, 0103 physical sciences, medicine, Medical imaging, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Digital pathology, Radiology, Nuclear Medicine and imaging, business.industry, [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, Quantitative Biology - Tissues and Organs, medicine.disease, Choroid plexus papilloma, Physics - Medical Physics, FOS: Biological sciences, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, Medical Physics (physics.med-ph), Neurology (clinical), business, 030217 neurology & neurosurgery, Optics (physics.optics)
Abstract: A prospective study was performed on neurosurgical samples from 18 patients to evaluate the use of full-field optical coherence tomography (FF-OCT) in brain tumor diagnosis. FF-OCT captures en face slices of tissue samples at 1 μm resolution in 3D to a penetration depth of around 200 μm. A 1 cm2 specimen is scanned at a single depth and processed in about 5 min. This rapid imaging process is non-invasive and requires neither contrast agent injection nor tissue preparation, which makes it particularly well suited to medical imaging applications. Temporal chronic epileptic parenchyma and brain tumors such as meningiomas, low-grade and high-grade gliomas, and choroid plexus papilloma were imaged. A subpopulation of neurons, myelin fibers and CNS vasculature were clearly identified. Cortex could be discriminated from white matter, but individual glial cells such as astrocytes (normal or reactive) or oligodendrocytes were not observable. This study reports for the first time on the feasibility of using FF-OCT in a real-time manner as a label-free non-invasive imaging technique in an intraoperative neurosurgical clinical setting to assess tumorous glial and epileptic margins., Highlights • Demonstration of full-field optical coherence tomography imaging of human brain samples • Potential as an intraoperative tool for determining tissue architecture and content in minutes • Myelin fibers, neurons, microcalcifications, tumor cells, microcysts, and vessels identified • Good correspondence with histological slides, allowing clinical use for tissue selection
Published: 2013

20. Optimizing statistical parametric mapping analysis of 18F-FDG PET in children

Author: Philippe Chaumet-Riffaud, Lucie Hertz-Pannier, Frédérique Archambaud, Catherine Chiron, Sebastian Rodrigo, Viviane Bouilleret, Francine Chassoux, Olivier Dulac, Institut d'Imagerie BioMédicale (I2BM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut d'imagerie neurofonctionnelle (IIN), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École des hautes études en sciences sociales (EHESS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Ecole Nationale Supérieure des Télécommunications (ENST)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Biophysique et Médecine Nucleaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neuropédiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurochirurgie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre Hospitalier Sainte-Anne, This work was supported by a grant provided by the Fondation pour la Recherche sur le Cerveau (FRC)., Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure des Télécommunications (ENST)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École des hautes études en sciences sociales (EHESS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut d'Imagerie BioMédicale ( I2BM ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Institut d'imagerie neurofonctionnelle ( IIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -ENST-Assistance publique - Hôpitaux de Paris (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -École des hautes études en sciences sociales ( EHESS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Centre Hospitalier Sainte-Anne, and BMC, Ed.
Subjects: SPM, FDG, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Statistical parametric mapping, 030218 nuclear medicine & medical imaging, 18f fdg pet, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, [ SDV.IB.MN ] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, 0302 clinical medicine, Control data, Medicine, Radiology, Nuclear Medicine and imaging, Set (psychology), Children, Cardiac imaging, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Original Research, Complement (set theory), Epilepsy, business.industry, Pattern recognition, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, PET, Artificial intelligence, business, Nuclear medicine, 030217 neurology & neurosurgery
Abstract: Background Statistical parametric mapping (SPM) procedure is an objective tool to analyze 18F-fluoro-2-deoxy-d-glucose-positron-emission tomography (FDG-PET) images and a useful complement to visual analysis. However, SPM requires a comparison to control data set that cannot be obtained in healthy children for ethical reasons. Using adults as controls showed some limitations. The purpose of the present study was to generate and validate a group of pseudo-normal children as a control group for FDG-PET studies in pediatrics. Methods FDG-PET images of 47 children (mean ± SD age 10.2 ± 3.1 years) with refractory symptomatic (MRI-positive, n = 20) and cryptogenic (MRI-negative, n = 27) focal epilepsy planned for surgery were analyzed using visual and SPM analysis. Performances of SPM analysis were compared using two different control groups: (1) an adult control group consisting of healthy young adults (n = 25, 30.5 ± 5.8 years, adult PET template) and (2) a pediatric pseudo-control group consisting of patients (n = 24, 10.6 ± 3.1 years, children PET template) with refractory focal epilepsy but with negative MRI and with PET considered normal not only on visual analysis but also on SPM. Results Among the 47 children, visual analysis succeeded detecting at least one hypometabolic area in 87% of the cases (interobserver kappa = 0.81). Regarding SPM analysis, the best compromise between sensitivity and specificity was obtained with a threshold of p less than 0.001 as an extent of more than 40 voxels. There was a significant concordance to detect hypometabolic areas between both SPM analyses [kappa (K) = 0.59; p < 0.005] and between both SPM and visual analyses (K = 0.45; p < 0.005), in symptomatic (K = 0.74; p < 0.005) as in cryptogenic patients (K = 0.26; p < 0.01). The pediatric pseudo-control group dramatically improved specificity (97% vs. 89%; p < 0.0001) by increasing the positive predictive value (86% vs. 65%). Sensitivity remained acceptable although it was not better (79% vs. 87%, p = 0.039). The main impact was to reduce by 41% the number of hypometabolic cortical artifacts detected by SPM, especially in the younger epileptic patients, which is a key point in clinical practice. Conclusions This age-matched pseudo-control group is a way to optimize SPM analysis of FDG-PET in children with epilepsy. It might also be considered for other brain pathologies in pediatrics in the future.
Published: 2013

21. First-line thrombectomy strategy for anterior large vessel occlusions: results of the prospective ETIS egistry

Author: Benjamin, Maïer, Stephanos, Finitsis, Romain, Bourcier, Panagiotis, Papanagiotou, Sébastien, Richard, Gaultier, Marnat, Igor, Sibon, Cyril, Dargazanli, Caroline, Arquizan, Raphael, Blanc, Michel, Piotin, Bertrand, Lapergue, Arturo, Consoli, Francois, Eugene, Stephane, Vannier, Suzana, Saleme, Francisco, Macian, Frédéric, Clarençon, Charlotte, Rosso, Olivier, Naggara, Guillaume, Turc, Alain, Viguier, Christophe, Cognard, Valerie, Wolff, Raoul, Pop, Mikael, Mazighi, Benjamin, Gory, Thomas, Ronziere, Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Aristotle University of Thessaloniki, Centre hospitalier universitaire de Nantes (CHU Nantes), Klinikum Bremen-Mitte, National and Kapodistrian University of Athens (NKUA), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de Neuro-Radiologie [Bordeaux] (DNR - Bordeaux), CHU Bordeaux [Bordeaux], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département de Neuroradiologie[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Département de neurologie [Montpellier], Service Neuroradiologie diagnostique et interventionnelle [Hôpital Foch], Hôpital Foch [Suresnes], Département de Radiologie [Rennes], Université de Rennes (UR), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Service de Neuroradiologie interventionnelle [CHU Limoges], CHU Limoges, Service de Neurologie [CHU Limoges], Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Sorbonne Paris Nord, Service d'Urgences Cérébro-Vasculaires [CHU Pitié-Salpêtrière], Service de Neurologie [CH Saint-Anne], Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurologie Vasculaire [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pôle Neurosciences [CHU Toulouse], Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Département de Neuroradiologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Chirurgie guidée par l'Image, and Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy]
Subjects: medicine.medical_specialty, MESH: Endovascular Procedures, medicine.medical_treatment, Arterial Occlusive Diseases, MESH: Stroke, Brain Ischemia, law.invention, Randomized controlled trial, Modified Rankin Scale, law, medicine.artery, Internal medicine, Stent, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, Device, MESH: Thrombectomy, Prospective Studies, Stroke, Ischemic Stroke, Retrospective Studies, Thrombectomy, MESH: Treatment Outcome, Catheter, MESH: Arterial Occlusive Diseases, MESH: Humans, Cerebral infarction, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Endovascular Procedures, MESH: Brain Ischemia, MESH: Retrospective Studies, General Medicine, Thrombolysis, medicine.disease, MESH: Prospective Studies, MESH: Stents, Treatment Outcome, Cardiology, Stents, Surgery, Neurology (clinical), Internal carotid artery, business, MESH: Ischemic Stroke
Abstract: BackgroundThe best recanalization strategy for mechanical thrombectomy (MT) remains unknown as no randomized controlled trial has simultaneously evaluated first-line stent retriever (SR) versus contact aspiration (CA) versus the combined approach (SR+CA).ObjectiveTo compare the efficacy and safety profiles of SR, CA, and SR+CA in patients with acute ischemic stroke (AIS) treated by MT.MethodsWe analyzed data of the Endovascular Treatment in Ischemic Stroke (ETIS) Registry, a prospective, multicenter, observational study of patients with AIS treated by MT. Patients with M1 and intracranial internal carotid artery (ICA) occlusions between January 2015 and March 2020 in 15 comprehensive stroke centers were included. We assessed the association of first-line strategy with favorable outcomes at 3 months (modified Rankin Scale score 0–2), successful recanalization rates (modified Thrombolysis In Cerebral Infarction (mTICI) 2b/3), and safety outcomes.ResultsWe included 2643 patients, 406 treated with SR, 1126 with CA, and 1111 with SR+CA. CA or SR+CA achieved more successful recanalization than SR for M1 occlusions (aOR=2.09, (95% CI 1.39 to 3.13) and aOR=1.69 (95% CI 1.12 to 2.53), respectively). For intracranial ICA, SR+CA achieved more recanalization than SR (aOR=2.52 (95% CI 1.32 to 4.81)), no differences were observed between CA and SR+CA. SR+CA was associated with lower odds of favorable outcomes compared with SR (aOR=0.63 (95% CI 0.44 to 0.90)) and CA (aOR=0.71 (95% CI 0.55 to 0.92)), higher odds of mortality at 3 months (aOR=1.56 (95% CI 1.22 to 2.0)) compared with CA, and higher odds of symptomatic intracranial hemorrhage (aOR=1.59 (95% CI 1.1 to 2.3)) compared with CA.ConclusionsDespite high recanalization rates, our results question the safety of the combined approach, which was associated with disability and mortality. Randomized controlled trials are needed to evaluate the efficacy and safety of these techniques.
Published: 2021

22. What animal models can tell us about long-term cognitive dysfunction following sepsis: A systematic review

Author: Fernando A. Bozza, Gabriela Ferreira de Medeiros, Cristiane Ritter, Felipe Dal-Pizzol, Alexandre de Oliveira, Monique Michels, Tarek Sharshar, Felipe Figueredo Savi, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Paris (UP)
Subjects: Cognitive Neuroscience, Radial maze, Water maze, Sepsis, 03 medical and health sciences, Behavioral Neuroscience, Cognition, 0302 clinical medicine, Cognitive Changes, Animals, Medicine, Memory impairment, Cognitive Dysfunction, 0501 psychology and cognitive sciences, 050102 behavioral science & comparative psychology, Fear conditioning, Maze Learning, ComputingMilieux_MISCELLANEOUS, business.industry, 05 social sciences, Sepsis-Associated Encephalopathy, medicine.disease, Disease Models, Animal, Neuropsychology and Physiological Psychology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Neuroscience, 030217 neurology & neurosurgery
Abstract: Survivors of sepsis often develop long-term cognitive impairments. This review aimed at exploring the results of the behavioral tools and tests which have been used to evaluate cognitive dysfunction in different animal models of sepsis. Two independent investigators searched for sepsis- and cognition-related keywords. 6323 publications were found, of which 355 were selected based on their title, and 226 of these were chosen based on manuscript review. LPS was used to induce sepsis in 171 studies, while CLP was used in 55 studies. Inhibitory avoidance was the most widely used method for assessing aversive memory, followed by fear conditioning and continuous multi-trial inhibitory avoidance. With regard to non-aversive memory, most studies used the water maze, open-field, object recognition, Y-maze, plus maze, and radial maze tests. Both CLP and LPS models of sepsis were effective in inducing short- and long-term behavioral impairment. Our findings help elucidate the mechanisms involved in the pathophysiology of sepsis-induced cognitive changes, as well as the available methods and tests used to study this in animal models.
Published: 2021

23. Benefit of mechanical thrombectomy in acute ischemic stroke related to calcified cerebral embolus

Author: Téodor Grand, Cyril Dargazanli, Chrysanthi Papagiannaki, Agnetha Bruggeman, Christoph Maurer, Gregory Gascou, Cédric Fauche, Romain Bourcier, Guillaume Tessier, Raphaël Blanc, Malek Ben Machaa, Gaultier Marnat, Xavier Barreau, Julien Ognard, Jean-Christophe Gentric, Charlotte Barbier, Benjamin Gory, Christine Rodriguez, Grégoire Boulouis, François Eugène, Pierre Thouant, Frederic Ricolfi, Kevin Janot, Denis Herbreteau, Omer Faruk Eker, Matteo Cappucci, Tomas Dobrocky, Markus Möhlenbruch, Theo Demerath, Marios Psychogios, Sebastian Fischer, Alessandro Cianfoni, Charles Majoie, Bart Emmer, Henk Marquering, Rémi Valter, Stéphanie Lenck, Kévin Premat, Jonathan Cortese, Didier Dormont, Nader-Antoine Sourour, Eimad Shotar, Yves Samson, Frédéric Clarençon, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Rouen, Normandie Université (NU), Amsterdam UMC - Amsterdam University Medical Center, Klinikum Augsburg, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre hospitalier universitaire de Nantes (CHU Nantes), Fondation Ophtalmologique Adolphe de Rothschild [Paris], CHU Bordeaux [Bordeaux], Service de Neuroradiologie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Bern University Hospital [Berne] (Inselspital), Heidelberg University Hospital [Heidelberg], University of Freiburg [Freiburg], University Hospital Basel [Basel], Universitätsklinikum Knappschaftskrankenhaus = University Hospital Knappschaftskrankenhaus [Bochum], University of Lugano, CHU Henri Mondor [Créteil], Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Neurovascular Disorders, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, ANS - Brain Imaging, and Radiology and nuclear medicine
Subjects: Adult, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Brain Ischemia, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, MESH: Thrombectomy, Radiology, Nuclear Medicine and imaging, Ischemic Stroke, Retrospective Studies, Thrombectomy, MESH: Treatment Outcome, MESH: Intracranial Embolism, MESH: Humans, Radiological and Ultrasound Technology, Clinical outcome, MESH: Brain Ischemia, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], MESH: Adult, MESH: Retrospective Studies, Calcified cerebral embolus, Treatment Outcome, Intracranial Embolism, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Reperfusion, Neurology (clinical), Mechanical thrombectomy, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, MESH: Ischemic Stroke
Abstract: Summary purpose: Mechanical thrombectomies (MT) in patients with large vessel occlusion (LVO) related to calcified cerebral embolus (CCE) have been reported, through small case series, being associated with low reperfusion rate and worse outcome, compared to regular MT. The purpose of the MASC (Mechanical Thrombectomy in Acute Ischemic Stroke Related to Calcified Cerebral Embolus) study was to evaluate the incidence of CCEs treated by MT and the effectiveness of MT in this indication. Methods: The MASC study is a retrospective multicentric (n = 37) national study gathering the cases of adult patients who underwent MT for acute ischemic stroke with LVO related to a CCE in France from January 2015 to November 2019. Reperfusion rate (mTICI ≥ 2B), complication rate and 90-day mRS were systematically collected. We then conducted a systematic review by searching for articles in PubMed, Cochrane Library, Embase and Google Scholar from January 2015 to March 2020. A meta-analysis was performed to estimate clinical outcome at 90 days, reperfusion rate and complications. Results: We gathered data from 35 patients. Reperfusion was obtained in 57% of the cases. Good clinical outcome was observed in 28% of the patients. The meta-analysis retrieved 136 patients. Reperfusion and good clinical outcome were obtained in 50% and 29% of the cases, respectively. Conclusion: The MASC study found worse angiographic and clinical outcomes compared to regular thrombectomies. Individual patient-based meta-analysis including the MASC findings shows a 50% reperfusion rate and a 29% of good clinical outcome.
Published: 2022

24. Place of the partial dopamine receptor agonist aripiprazole in the management of schizophrenia in adults: a Delphi consensus study

Author: Llorca, Pierre-Michel, Nuss, Philippe, Fakra, Éric, Alamome, Isabelle, El-Hage, Wissam, Drapier, Dominique, Jardri, Renaud, Mouchabac, Stéphane, Rabbani, Marc, Simon, Nicolas, Vacheron, Marie-Noëlle, Azorin, Jean-Michel, CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Polyclinique de Limoges - Site Émailleurs-Colombier [Limoges], Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Guillaume Régnier [Rennes], Université de Rennes (UR), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Lundbeck SAS, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), and Malbec, Odile
Subjects: Adult, Delphi Technique, [SDV]Life Sciences [q-bio], Dopamine, Aripiprazole, Addiction, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Cognition, Pregnancy, Dopamine Agonists, Schizophrenia, Humans, Female, Negative symptoms, Clozapine
Abstract: Background Aripiprazole is a second-generation antipsychotic, efficacious in patients with schizophrenia during acute episodes. Due to its pharmacological profile, aripiprazole may be of interest in patients with specific clinical profiles who have not been studied extensively in randomised clinical trials. Objectives To capture experience with aripiprazole in everyday psychiatric practice using the Delphi method in order to inform decision-making on the use of aripiprazole for the treatment of patients with schizophrenia in clinical situations where robust evidence from clinical trials is lacking. Methods The scope of the survey was defined as the management of schizophrenia in adults. A systematic literature review was performed to identify the different clinical situations in which aripiprazole has been studied, and to describe the level of clinical evidence. Clinical profiles to include in the Delphi survey were selected if there was a clear interest in terms of medical need but uncertainty over the efficacy of aripiprazole. For each clinical profile retained, five to seven specific statements were generated and included in a questionnaire. The final 41-item questionnaire was proposed to a panel of 406 French psychiatrists with experience in the treatment of schizophrenia. Panellists rated their level of agreement using a Likert scale. A second round of voting on eleven items was organised to clarify points for which a consensus was not obtained in the first round. Results Five clinical profiles were identified in the literature review (persistent negative symptoms, pregnancy, cognitive dysfunction, addictive comorbidity and clozapine resistance). Sixty-two psychiatrists participated in the first round of the Delphi survey and 33 in the second round. A consensus was obtained for 11 out of 41 items in the first round and for 9/11 items in the second round. According to the panellists’ clinical experience, aripiprazole can be used as maintenance treatment for pregnant women, is relevant to preserve cognitive function and can be considered an option in patients with a comorbid addictive disorder or with persistent negative symptoms. Conclusion These findings may help physicians in choosing relevant ways to use aripiprazole and highlight areas where more research is needed to widen the evidence base.
Published: 2022

25. Comparing Two Neurodevelopmental Disorders Linked to CK2: Okur-Chung Neurodevelopmental Syndrome and Poirier-Bienvenu Neurodevelopmental Syndrome—Two Sides of the Same Coin?

Author: Demetra Ballardin, Jose M. Cruz-Gamero, Thierry Bienvenu, Heike Rebholz, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Danube Private University [Krems, Autriche] (DPU), and Martinez Rico, Clara
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, autism-spectrum disorders (ASD), OCNDS, POBINDS, CK2 (casein kinase II), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biochemistry, Genetics and Molecular Biology (miscellaneous), Molecular Biology, Biochemistry, NDD-neurodevelopmental disorder, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: In recent years, variants in the catalytic and regulatory subunits of the kinase CK2 have been found to underlie two different, yet symptomatically overlapping neurodevelopmental disorders, termed Okur-Chung neurodevelopmental syndrome (OCNDS) and Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). Both conditions are predominantly caused by de novo missense or nonsense mono-allelic variants. They are characterized by a generalized developmental delay, intellectual disability, behavioral problems (hyperactivity, repetitive movements and social interaction deficits), hypotonia, motricity and verbalization deficits. One of the main features of POBINDS is epilepsies, which are present with much lower prevalence in patients with OCNDS. While a role for CK2 in brain functioning and development is well acknowledged, these findings for the first time clearly link CK2 to defined brain disorders. Our review will bring together patient data for both syndromes, aiming to link symptoms with genotypes, and to rationalize the symptoms through known cellular functions of CK2 that have been identified in preclinical and biochemical contexts. We will also compare the symptomatology and elaborate the specificities that distinguish the two syndromes.
Published: 2022

26. Mortality in people with schizophrenia: a systematic review and meta‐analysis of relative risk and aggravating or attenuating factors

Author: Christoph U. Correll, Marco Solmi, Giovanni Croatto, Lynne Kolton Schneider, S. Christy Rohani‐Montez, Leanne Fairley, Nathalie Smith, István Bitter, Philip Gorwood, Heidi Taipale, Jari Tiihonen, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Donald and Barbara Zucker School of Medicine at Hofstra/Northwell [Hempstead, NY, USA], Zucker Hillside Hospital [Glen Oaks, NY, USA] (ZHH), University of Ottawa [Ottawa], The Ottawa Hospital, AULSS 3 Serenissima [Venice, Italy] (Mestre), WebMD Global LLC [London, UK], Semmelweis University [Budapest], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Karolinska Institutet [Stockholm], University of Eastern Finland, and Martinez Rico, Clara
Subjects: cardiovascular disease, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, clozapine, substance use disorder, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, long-acting injectable antipsychotics, Research Reports, mortality, Psychiatry and Mental health, antipsychotics, comorbidity, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, first-episode schizophrenia, Schizophrenia, psychosis, Pshychiatric Mental Health, physical health, suicide, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; People with schizophrenia die 15-20 years prematurely. Understanding mortality risk and aggravating/attenuating factors is essential to reduce this gap. We conducted a systematic review and random-effects meta-analysis of prospective and retrospective, nationwide and targeted cohort studies assessing mortality risk in people with schizophrenia versus the general population or groups matched for physical comorbidities or groups with different psychiatric disorders, also assessing moderators. Primary outcome was all-cause mortality risk ratio (RR); key secondary outcomes were mortality due to suicide and natural causes. Other secondary outcomes included any other specific-cause mortality. Publication bias, subgroup and meta-regression analyses, and quality assessment (Newcastle-Ottawa Scale) were conducted. Across 135 studies spanning from 1957 to 2021 (schizophrenia: N=4,536,447; general population controls: N=1,115,600,059; other psychiatric illness controls: N=3,827,955), all-cause mortality was increased in people with schizophrenia versus any non-schizophrenia control group (RR=2.52, 95% CI: 2.38-2.68, n=79), with the largest risk in first-episode (RR=7.43, 95% CI: 4.02-13.75, n=2) and incident (i.e., earlier-phase) schizophrenia (RR=3.52, 95% CI: 3.09-4.00, n=7) versus the general population. Specific-cause mortality was highest for suicide or injury-poisoning or undetermined non-natural cause (RR=9.76-8.42), followed by pneumonia among natural causes (RR=7.00, 95% CI: 6.79-7.23), decreasing through infectious or endocrine or respiratory or urogenital or diabetes causes (RR=3 to 4), to alcohol or gastrointestinal or renal or nervous system or cardio-cerebrovascular or all natural causes (RR=2 to 3), and liver or cerebrovascular, or breast or colon or pancreas or any cancer causes (RR=1.33 to 1.96). All-cause mortality increased slightly but significantly with median study year (beta=0.0009, 95% CI: 0.001-0.02, p=0.02). Individuals with schizophrenia
Published: 2022

27. Characterization of Depressive Symptoms Trajectories After Breast Cancer Diagnosis in Women in France

Author: Cécile Charles, Aurélie Bardet, Alicia Larive, Philip Gorwood, Nicolas Ramoz, Emilie Thomas, Alain Viari, Marina Rousseau-Tsangaris, Agnès Dumas, Gwenn Menvielle, Sibille Everhard, Anne-Laure Martin, Seyive-yvon-arnauld Gbenou, Julie Havas, Mayssam El-Mouhebb, Antonio Di Meglio, Fabrice André, Barbara Pistilli, Charles Coutant, Paul Cottu, Asma Mérimèche, Florence Lerebours, Olivier Tredan, Laurence Vanlemmens, Christelle Jouannaud, Christelle Levy, Ines Vaz-Luis, Stefan Michiels, Sarah Dauchy, Institut Bergonié [Bordeaux], UNICANCER, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut Curie [Paris], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut Curie - Saint Cloud (ICSC), Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut Jean Godinot [Reims], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Martinez Rico, Clara
Subjects: Male, Depression, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, Middle Aged, Cohort Studies, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Prevalence, Quality of Life, Humans, Female, Child
Abstract: International audience; Importance: Breast cancer (BC) diagnosis and treatment expose patients to a 5-fold higher risk of depression compared with the general population, with an estimated prevalence of 10% to 25%. A depressive episode in patients with BC has implications for the tolerance of and adherence to treatment, impairing quality of life and reducing life expectancy.Objective: To identify and characterize distinct longitudinal patterns of depressive symptoms in patients with BC from diagnosis to 3 years after treatment.Design, settings, and participants: The CANTO-DEePRESS (Deeper in the Understanding and Prevention of Depression in Breast Cancer Patients) cohort study included women in the French multicenter CANTO (CANcer TOxicities) cohort study (conducted between March 20, 2012 and December 11, 2018), who were 18 years or older with invasive stage I to III BC and no previous BC treatment. The study aimed to characterize toxicities over a 5-year period following stage I to III primary BC treatment. Assessments of depressive symptoms were performed on a subset of patients with available data at diagnosis and at least 2 other time points. All data were extracted from the CANTO database on October 1, 2020.Main outcomes and measures: The primary outcome was the level of depressive symptoms at each assessment time point measured with the Hospital Anxiety and Depression Scale and depression subscale at BC diagnosis and at 3 to 6, 12, and 36 months after the end of treatment. The group-based trajectory modeling was used to identify trajectory groups, and multinomial logistic regression models were used to characterize the following factors associated with trajectory group affiliation: demographic, socioeconomic, clinical, lifestyle, and quality-of-life data.Results: A total of 4803 women (mean [SD] age, 56.2 [11.2] years; 2441 patients [50.8%] with stage I BC) were included in the study. Six trajectory groups that described the heterogeneity in the expression of depressive symptoms were identified: noncases with no expression of symptoms (n = 2634 [54.8%]), intermediate worsening (1076 [22.4%]), intermediate improvement (480 [10.0%]), remission (261 [5.4%]), delayed occurrence (200 [4.2%]), and stable depression (152 [3.2%]). HADS-D scores at diagnosis were consistently associated with the 5 depressive trajectory group affiliations, with an estimated higher probability per point increase of experiencing subthreshold or clinically significant depressive symptoms between diagnosis and the 3 years after the end of BC treatment. The higher probabilities ranged from 1.49 (95% CI, 1.43-1.54) for the intermediate worsening group to 10.53 (95% CI, 8.84-12.55) for the stable depression group. Trajectory groups with depressive symptoms differed from the noncases group without symptoms by demographic and clinical factors, such as having dependent children, lower household income, cancer stage, family history of BC, previous psychiatric hospitalizations, obesity, smoking status, higher levels of fatigue, and depression at diagnosis.Conclusions and relevance: In this cohort study, nearly a third of patients with BC experienced temporary or lasting significant depressive symptoms during and after treatment. Improving early identification of women at risk of developing long-term or delayed depression is therefore critical to increase quality of life and overall survival. Subjected to validation, this study is an important first step toward personalized care of patients with BC at risk of depression.
Published: 2022

28. Zebrafish Melanoma-Derived Interstitial EVs Are Carriers of ncRNAs That Induce Inflammation

Author: Valentina Biagini, Federica Busi, Viviana Anelli, Emanuela Kerschbamer, Marta Baghini, Elena Gurrieri, Michela Notarangelo, Isabella Pesce, Guillaume van Niel, Vito G. D’Agostino, Marina Mione, University of Trento [Trento], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Martinez Rico, Clara
Subjects: Inflammation, RNA, Untranslated, P and MRP RNAse, danio rerio, exosomes/extracellular vesicles, long ncRNA, melanoma, Organic Chemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, Catalysis, Computer Science Applications, Inorganic Chemistry, Extracellular Vesicles, [SDV.CAN] Life Sciences [q-bio]/Cancer, Animals, Physical and Theoretical Chemistry, Molecular Biology, Melanoma, Spectroscopy, Zebrafish
Abstract: International audience; Extracellular vesicles (EVs) are membranous particles released by all cell types. Their role as functional carrier of bioactive molecules is boosted by cells that actively secrete them in biological fluids or in the intercellular space (interstitial EVs, iEVs). Here we have optimised a method for the isolation and characterization of zebrafish iEVs from whole melanoma tissues. Zebrafish melanoma iEVs are around 140 nm in diameter, as determined by nanoparticle tracking and transmission electron microscopy (TEM) analysis. Western blot analysis shows enrichment for CD63 and Alix in the iEV fraction, but not in melanoma cell lysates. Super resolution and confocal microscopy reveal that purified zebrafish iEVs are green fluorescent protein positive (GFP+), indicating that they integrate the oncogene GFP-HRASV12G used to induce melanoma in this model within their vesicular membrane or luminal content. Analysis of RNA-Seq data found 118 non-coding (nc)RNAs differentially distributed between zebrafish melanoma and their iEVs, with only 17 of them being selectively enriched in iEVs. Among these, the RNA components of RNAses P and MRP, which process ribosomal RNA precursors, mitochondrial RNAs, and some mRNAs, were enriched in zebrafish and human melanoma EVs, but not in iEVs extracted from brain tumours. We found that melanoma iEVs induce an inflammatory response when injected in larvae, with increased expression of interferon responsive genes, and this effect is reproduced by MRP- or P-RNAs injected into circulation. This suggests that zebrafish melanoma iEVs are a source of MRP- and P-RNAs that can trigger inflammation in cells of the innate immune system.
Published: 2022

29. Dentate gyrus and hilus transection blocks seizure propagation and granule cell dispersion in a mouse model for mesial temporal lobe epilepsy

Author: Sophie Hamelin, Antoine Depaulis, Colin Deransart, Johan Pallud, Ute Häussler, Mélanie Langlois, Bertrand Devaux, Service de neurochirurgie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Centre Hospitalier Sainte-Anne, Experimental Epilepsy, Neurocenter, University of Freiburg [Freiburg], Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Deransart, Colin, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - Centre Hospitalier Sainte-Anne, and Université Joseph Fourier - Grenoble 1 (UJF) - CHU Grenoble - Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Kainic acid, Cognitive Neuroscience, Hippocampus, Hippocampal formation, Biology, Epileptogenesis, Neurosurgical Procedures, 03 medical and health sciences, Epilepsy, chemistry.chemical_compound, Mice, 0302 clinical medicine, Seizures, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030304 developmental biology, Neurons, 0303 health sciences, Kainic Acid, Dentate gyrus, Limbic lobe, medicine.disease, Granule cell dispersion, Mice, Inbred C57BL, Disease Models, Animal, chemistry, Epilepsy, Temporal Lobe, nervous system, Dentate Gyrus, Mossy Fibers, Hippocampal, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Epilepsy-associated changes of the anatomical organization of the dentate gyrus and hilus may play a critical role in the initiation and propagation of seizures in mesial temporal lobe epilepsy (MTLE). This study evaluated the role of longitudinal projections in the propagation of hippocampal paroxysmal discharges (HPD) in dorsal hippocampus by performing a selective transection in a mouse model for MTLE obtained by a single unilateral intrahippocampal injection of kainic acid (KA). Full transections of the dentate gyrus and hilus were performed in the transverse axis at 22 days after KA injection when spontaneous HPD were fully developed. They: (i) significantly reduced the occurrence of HPD; (ii) increased their duration at the KA injection site; (iii) abolished their spread along the longitudinal axis of the hippocampal formation and; (iv) limited granule cell dispersion (GCD) of the dentate gyrus posterior to the transection. These data suggest that: (i) longitudinal projections through the dentate gyrus and hilus are involved in HPD spread; (ii) distant hippocampal circuits participate in the generation and cessation of HPD and; (iii) GCD requires continuous HPD to develop, even when seizures are established. Our data reveal a critical role for longitudinal projections in the generation and spread of hippocampal seizures. © 2010 Wiley-Liss, Inc.
Published: 2010

30. Characterisation of early ultrastructural changes in the cerebral white matter of CADASIL small vessel disease using high‐pressure freezing/freeze‐substitution

Author: Nicolas Dupré, Rikesh M. Rajani, Guillaume van Niel, Valérie Domenga-Denier, Xavier Heiligenstein, Anne Joutel, Martinez Rico, Clara, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), and University of Vermont [Burlington]
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, small vessel disease, Histology, Freeze Substitution, inner tongue, Uranyl acetate, CADASIL, Corpus callosum, myelin splitting, Corpus Callosum, Pathology and Forensic Medicine, White matter, Mice, 03 medical and health sciences, chemistry.chemical_compound, Myelin, 0302 clinical medicine, Physiology (medical), medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Myelin Sheath, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Chemistry, CD68, high pressure freezing/freeze-substitution, medicine.disease, White Matter, Hyperintensity, 030104 developmental biology, medicine.anatomical_structure, Neurology, Freeze substitution, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; Aims: The objective of this study was to elucidate the early white matter changes in CADASIL small vessel disease.Methods: We used high-pressure freezing and freeze substitution (HPF/FS) in combination with high-resolution electron microscopy (EM), immunohistochemistry and confocal microscopy of brain specimens from control and CADASIL (TgNotch3R169C ) mice aged 4-15 months to study white matter lesions in the corpus callosum.Results: We first optimised the HPF/FS protocol in which samples were chemically prefixed, frozen in a sample carrier filled with 20% polyvinylpyrrolidone and freeze-substituted in a cocktail of tannic acid, osmium tetroxide and uranyl acetate dissolved in acetone. EM analysis showed that CADASIL mice exhibit significant splitting of myelin layers and enlargement of the inner tongue of small calibre axons from the age of 6 months, then vesiculation of the inner tongue and myelin sheath thinning at 15 months of age. Immunohistochemistry revealed an increased number of oligodendrocyte precursor cells, although only in older mice, but no reduction in the number of mature oligodendrocytes at any age. The number of Iba1 positive microglial cells was increased in older but not in younger CADASIL mice, but the number of activated microglial cells (Iba1 and CD68 positive) was unchanged at any age.Conclusion: We conclude that early WM lesions in CADASIL affect first and foremost the myelin sheath and the inner tongue, suggestive of a primary myelin injury. We propose that those defects are consistent with a hypoxic/ischaemic mechanism.
Published: 2021

31. Increased microglial activation in patients with Parkinson disease using [18F]-DPA714 TSPO PET imaging

Author: Marie Sarazin, Philippe Gervais, Matteo Tonietto, Julien Lagarde, Sonia Lavisse, Marie-Anne Peyronneau, Philippe Hantraye, Claire Thiriez, Philippe Remy, Catriona Wimberley, Olivier Barret, Sébastien Goutal, Michel Bottlaender, Bertrand Kuhnast, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité BioMaps (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche en NeuroImagerie Applicative Clinique et Translationnelle (UNIACT), Service NEUROSPIN (NEUROSPIN), Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), CHU Henri Mondor, This work was supported by France Parkinson (GAO 2008), ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), CHU Henri Mondor [Créteil], Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), CCSD, Accord Elsevier, and Infrastructures - Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences - - NeurATRIS2011 - ANR-11-INBS-0011 - INBS - VALID
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Disease, 03 medical and health sciences, 0302 clinical medicine, Neuroinflammation, In vivo, Internal medicine, Post-hoc analysis, Medicine, Dopamine transporter, Microglia, biology, business.industry, Neurodegeneration, medicine.disease, [SDV] Life Sciences [q-bio], Parkinson disease, PET, 030104 developmental biology, medicine.anatomical_structure, TSPO[$^{18}$F]-DPA714, Neurology, biology.protein, [(18)F]-DPA714, Neurology (clinical), Analysis of variance, Geriatrics and Gerontology, business, TSPO, 030217 neurology & neurosurgery
Abstract: International audience; Introduction: Increasing evidence suggests that neuroinflammation is active in Parkinson disease (PD) and contributes to neurodegeneration. This process can be studied in vivo with PET and radioligands targeting TSPO, upregulated in activated microglia. Initial PET studies investigating microglial activation in PD with the [11C]-PK11195 have provided inconclusive results. Here we assess the presence and distribution of neuroinflammatory response in PD patients using [18F]-DPA714 and to correlate imaging biomarkers to dopamine transporter imaging and clinical status.Methods: PD patients (n = 24, Hoehn and Yahr I-III) and 28 healthy controls were scanned with [18F]-DPA714 and [11C]-PE2I and analyzed. They were all genotyped for TSPO polymorphism. Regional binding parameters were estimated (reference Logan graphical approach with supervised cluster analysis). Impact of TSPO genotype was analyzed using Wilcoxon signed-rank test. Differences between groups were investigated using a two-way ANOVA and Tukey post hoc tests.Results: PD patients showed significantly higher [18F]-DPA714 binding compared to healthy controls bilaterally in the midbrain (p < 0.001), the frontal cortex (p = 0.001), and the putamen contralateral to the more clinically affected hemibody (p = 0.038). Microglial activation in these regions did not correlate with the severity of motor symptoms, disease duration nor putaminal [11C]-PE2I uptake. However, there was a trend toward a correlation between cortical TSPO binding and disease duration (p = 0.015 uncorrected, p = 0.07 after Bonferroni correction).Conclusion: [18F]-DPA714 binding confirmed that there is a specific topographic pattern of microglial activation in the nigro-striatal pathway and the frontal cortex of PD patients.Trial registration: Trial registration: INFLAPARK, NCT02319382. Registered 18 December 2014- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02319382.
Published: 2021

32. [Changes in spontaneous epileptic activity after selective intrahippocampal transection in a model of chronic mesial temporal lobe epilepsy]

Author: Pallud, Johan, Devaux, Bertrand, Depaulis, Antoine, Service de neurochirurgie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Centre Hospitalier Sainte-Anne, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Deransart, Colin, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - Centre Hospitalier Sainte-Anne, and Université Joseph Fourier - Grenoble 1 (UJF) - CHU Grenoble - Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Hippocampus, MESH : Hippocampus, Hippocampus, Neurosurgical Procedures, Mice, MESH : Chronic Disease, MESH : Mice, Excitatory Amino Acid Agonists, Kindling, Neurologic, Animals, MESH : Neuronal Plasticity, MESH: Animals, MESH: Neuronal Plasticity, MESH: Kindling, Neurologic, MESH: Mice, MESH : Kindling, Neurologic, MESH : Excitatory Amino Acid Agonists, Kainic Acid, Neuronal Plasticity, MESH: Chronic Disease, MESH: Neurosurgical Procedures, MESH : Neurosurgical Procedures, MESH: Kainic Acid, MESH : Disease Models, Animal, nervous system diseases, MESH : Epilepsy, Temporal Lobe, MESH : Kainic Acid, Disease Models, Animal, Epilepsy, Temporal Lobe, nervous system, Chronic Disease, MESH: Epilepsy, Temporal Lobe, MESH : Animals, MESH: Disease Models, Animal, MESH: Excitatory Amino Acid Agonists
Abstract: International audience; Drug-resistant mesial temporal lobe epilepsy with hippocampal sclerosis is associated with anatomical, ultrastructural and functional changes that facilitate generation and spread of epileptic seizures. Intrahippocampal circuits are modified in their transversal lamellar and longitudinal translamellar organization. Neuronal death and the neuroplasticity of surviving cells contribute to major phenomena: an increased hyperexcitability of the hippocampal formation and an increased synchronization of its principal cells. Selective disruption of the epileptic networks that are involved in mesial temporal lobe epilepsy may have a therapeutic effect. We present here the preliminary results of a selective intrahippocampal transection in a chronic model of mesial temporal lobe epilepsy after focal injection of kainic acid in adult mice. A complete transection of the hippocampal formation (including dentate gyrus and hippocampus proper, sparing the fimbria) results in a blockade of ictal activities spread from the generator, a reduction in their frequency and an increase in their duration. In contrast, after a transection sparing the dentate gyrus and hilus, no modification was noted. In this model of mesial temporal lobe epilepsy, longitudinally projecting axonal circuits of the dentate gyrus and hilus appear to be implicated in generation, propagation and interruption of ictal activities within hippocampal formation.
Published: 2008

33. Uncinate fasciculus fiber tracking in mesial temporal lobe epilepsy. Initial findings

Author: D. Le Bihan, Catherine Oppenheim, J.-F. Mangin, Y. Cointepas, F. Semah, Sebastian Rodrigo, C. Poupon, Narly Golestani, Francine Chassoux, Jean-François Meder, service de neuroradiologie [Paris], Hôpital Sainte-Anne, Commissariat à l'Energie Atomique, Direction des Sciences du Vivant, Département de Recherche Médicale, Service Hospitalier Frédéric Joliot, Service de Neurochirurgie, Hôpital Saint-Anne, Institut d'imagerie neurofonctionnelle ( IIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -ENST-Assistance publique - Hôpitaux de Paris (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -École des hautes études en sciences sociales ( EHESS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Traitement et Communication de l'Information ( LTCI ), Télécom ParisTech-Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Imagerie et de Spectroscopie ( LRMN ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratoire de Neuroimagerie Assistée par Ordinateur ( LNAO ), Service Hospitalier Frédéric Joliot ( SHFJ ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Center for Neuroscience and Behavioral Medicine, Children's National Medical Center, Human Brain Research Center [Kyoto] ( HBRC ), Kyoto University [Kyoto], Service NEUROSPIN ( NEUROSPIN ), National Institutes of Health [Bethesda] ( NIH ), IFR de Neuroimagerie Fonctionnelle ( IFR 49 ), DIMF, Université Paris Descartes - Paris 5 ( UPD5 ) -Centre Hospitalier Sainte-Anne, Service de neuroradiologie [Paris], Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut d'imagerie neurofonctionnelle (IIN), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École des hautes études en sciences sociales (EHESS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Ecole Nationale Supérieure des Télécommunications (ENST)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Traitement et Communication de l'Information (LTCI), Télécom ParisTech-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Neuroimagerie Assistée par Ordinateur (LNAO), Human Brain Research Center [Kyoto] (HBRC), Kyoto University, Service NEUROSPIN (NEUROSPIN), National Institutes of Health [Bethesda] (NIH), IFR de Neuroimagerie Fonctionnelle (IFR 49), Université Paris Descartes - Paris 5 (UPD5)-Centre Hospitalier Sainte-Anne, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure des Télécommunications (ENST)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École des hautes études en sciences sociales (EHESS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-ENST-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École des hautes études en sciences sociales (EHESS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH: Hippocampus, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, MESH: Frontal Lobe, MESH : Hippocampus, Hippocampus, Nerve Fibers, Myelinated, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, MESH : Neural Pathways, Reference Values, Neural Pathways, Image Processing, Computer-Assisted, MESH : Anisotropy, MESH : Female, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, MESH: Energy Metabolism, MESH: Reference Values, General Medicine, Human brain, Anatomy, MESH : Adult, MESH : Diffusion Magnetic Resonance Imaging, MESH: Image Processing, Computer-Assisted, Temporal Lobe, Frontal Lobe, MESH: Nerve Fibers, Myelinated, medicine.anatomical_structure, MESH: Epilepsy, Temporal Lobe, MESH : Imaging, Three-Dimensional, Female, Radiology, MESH : Image Processing, Computer-Assisted, Adult, medicine.medical_specialty, Adolescent, MESH : Male, Uncinate fasciculus, MESH: Imaging, Three-Dimensional, MESH: Diffusion Magnetic Resonance Imaging, MESH : Dominance, Cerebral, Insular cortex, MESH : Reference Values, behavioral disciplines and activities, Temporal lobe, White matter, 03 medical and health sciences, Imaging, Three-Dimensional, MESH : Adolescent, MESH : Nerve Fibers, Myelinated, Fractional anisotropy, medicine, Humans, MESH: Temporal Lobe, MESH : Frontal Lobe, Radiology, Nuclear Medicine and imaging, Ictal, Dominance, Cerebral, MESH : Temporal Lobe, MESH: Adolescent, Hippocampal sclerosis, Sclerosis, MESH: Humans, business.industry, MESH: Neural Pathways, MESH : Humans, MESH: Adult, MESH: Dominance, Cerebral, medicine.disease, MESH: Male, MESH : Sclerosis, MESH : Energy Metabolism, MESH : Epilepsy, Temporal Lobe, Diffusion Magnetic Resonance Imaging, Epilepsy, Temporal Lobe, nervous system, MESH: Anisotropy, Anisotropy, MESH: Sclerosis, business, Energy Metabolism, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; In temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), ictal discharge spread to the frontal and insulo-perisylvian cortex is commonly observed. The implication of white matter pathways in this propagation has not been investigated. We compared diffusion tensor imaging (DTI) measurements along the uncinate fasciculus (UF), a major tract connecting the frontal and temporal lobes, in patients and controls. Ten right-handed patients referred for intractable TLE due to a right HS were investigated on a 1.5-T MR scanner including a DTI sequence. All patients had interictal fluorodeoxyglucose PET showing an ipsilateral temporal hypometabolism associated with insular and frontal or perisylvian hypometabolism. The controls consisted of ten right-handed healthy subjects. UF fiber tracking was performed, and its fractional anisotropy (FA) values were compared between patients and controls, separately for the right and left UF. The left-minus-right FA UF asymmetry index was computed to test for intergroup differences. Asymmetries were found in the control group with right-greater-than-left FA. This asymmetrical pattern was lost in the patient group. Right FA values were lower in patients with right HS versus controls. Although preliminary, these findings may be related to the preferential pathway of seizure spread from the mesial temporal lobe to frontal and insulo-perisylvian areas.
Published: 2007

34. French validation of the Sexual Addiction Screening Test (SAST-Fr)

Author: Paul Brunault, Servane Barrault, Christian Réveillère, K G Hegbe, Robert Courtois, Département de Psychologie, Université de Tours, Service d’Addictologie « Moreau de Tours » [CH Sainte-Anne - APHP], Centre Hospitalier Sainte Anne [Paris]-GHU Paris Psychiatrie & Neurosciences, Qualité de vie et Santé psychologique [Tours] (QualiPsy - E.E. 1901), Université de Tours (UT), Clinique Psychiatrique Universitaire [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Reveillere, Christian
Subjects: Sexual Addiction Screening Test-version française (SAST-Fr), Sexual addiction, [SHS.PSY]Humanities and Social Sciences/Psychology, Assessment, Addiction sexuelle, Qualités psychométriques, medicine.disease, 030227 psychiatry, [SHS.PSY] Humanities and Social Sciences/Psychology, Psychometric properties, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Arts and Humanities (miscellaneous), Sexual Addiction Screening Test (SAST), [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Évaluation, medicine, Psychology, Humanities, ComputingMilieux_MISCELLANEOUS
Abstract: Introduction. – The Sexual Addiction Screening Test (SAST) is one of the most frequently used tools on the international level for assessing sexual addiction. This study aimed to translate the English version of the SAST, and adapt and test the psychometric properties of its French version (the SAST-Fr) by establishing its factor structure, internal consistency and convergent validity.Methods. – Three hundred ninety eight voluntary participants were recruited online through specialized forums. Participants completed a sociodemographic questionnaire, the SAST-Fr and the diagnostic criteria of sexual addiction proposed by Goodman. We tested the psychometric properties of SAST-Fr through an exploratory factorial analysis, especially its internal consistency, using the Kuder-Richardson alpha (KR-20) given that the items were dichotomous. We also performed correlation analyses of Bravais-Pearson on numerical variables. Finally, we studied the predictive validity of Goodman’s score in predicting SAST-Fr criteria using a ROC (Receiver Operating Characteristics) analysis., Introduction. – Le SAST (Sexual Addiction Screening Test) est l’un des outils les plus fréquemment utilisés sur un plan international pour évaluer l’addiction sexuelle. L’objectif de cette étude est de traduire la version anglophone du SAST, d’adapter et d’analyser les qualités psychométriques de sa version francophone (le SAST-Fr) et la validité convergente de cette dernière.Méthodes. – Notre étude a porté sur 398 sujets recrutés sur internet grâce à des forums spécialisés. Nous avons proposé à ces derniers un questionnaire incluant des données sociodémographiques, le SASTFr et les critères d’addiction sexuelle selon Goodman. Nous avons testé les qualités psychométriques du SAST-Fr à travers une analyse factorielle exploratoire, notamment sa consistance interne à l’aide du coefficient Kuder-Richardson (KR-20). Nous avons effectué des analyses de corrélations de Bravais Pearson sur les variables numériques. Enfin, nous avons étudié la validité prédictive du score de Goodman dans la prédiction des critères du SAST-Fr, à travers une analyse ROC (Receiver Operating Characteristics). Résultats. – L’âge moyen des participants était de 29,08 ans (f 11,30) incluant 54 % de femmes (n = 215). L’analyse statistique montre que le SAST-Fr possède une structure mono-factorielle expliquant 31 % de la variance, une excellente consistance interne (KR-20 = 0,90). Les scores aux items du SAST-Fr sont fortement corrélés à ceux des critères de Goodman (r = 0,79 ; p < 0,001).Conclusion. – Nos résultats indiquent que le SAST-Fr possède des propriétés psychométriques proches de la version originale anglophone. Il est un outil fiable et valide, qui facilite le repérage des symptômes de l’addiction sexuelle.
Published: 2020

35. LAMP2A regulates the loading of proteins into exosomes

Author: José C. Ramalho, Ana Sofia Carvalho, Henrique Girão, Petra Pintado, Paulo Pereira, Ana Soares, Joao Vasco Ferreira, Guillaume van Niel, Rune Matthiesen, Hans Christian Beck, Catarina Máximo Carvalho, Mónica Zuzarte, Maria Helena Cardoso, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Centro de Estudos de Doenças Crónicas (CEDOC), Martinez Rico, Clara, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Odense University Hospital (OUH), University of Coimbra [Portugal] (UC), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Endosome, BIOGENESIS, Cell Communication, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Exosomes, Exosome, Extracellular Vesicles, SYNTENIN, Lysosomal-Associated Membrane Protein 2, TSG101, LYSOSOMES, Transcription factor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, EXTRACELLULAR VESICLE, Multidisciplinary, Endosomal Sorting Complexes Required for Transport, Chemistry, DEGRADATION, Microvesicles, Autophagic Punctum, Cell biology, Cytosol, HIF1A, Membrane protein, SECRETION, Signal Transduction
Abstract: Exosomes are extracellular vesicles of endosomal origin released by virtually all cell types across metazoans. Exosomes are active vehicles of intercellular communication and can transfer lipids, RNAs and proteins between different cells, tissues or organs. However, the mechanisms that regulate the selective loading of cytosolic proteins into these vesicles are still largely unknow. Here we describe a mechanism whereby proteins containing a pentapeptide sequence, biochemically related to the KFERQ-motif, are loaded into a subpopulation of exosomes in a process that is dependent on the membrane protein LAMP2A. Moreover, this mechanism is independent of the ESCRT machinery components TSG101 and VPS4b and dependent on HSC70, CD63, Alix, Syntenin-1, Rab31 and ceramides. The transcription factor and master regulator of hypoxia HIF1A is loaded into exosomes by this mechanism to transport hypoxia signaling to normoxic cells. Additionally, by tagging fluorescent proteins with KFERQ-like sequences we were able to follow inter-organ transfer of exosomes in zebrafish larvae. Our findings identify LAMP2A as a key component in exosome biogenesis while opening new avenues for exosome engineering by allowing the loading of bioactive proteins by tagging them with KFERQ-like motifs.
Published: 2022

36. A Phosphosite Mutant Approach on LRRK2 Links Phosphorylation and Dephosphorylation to Protective and Deleterious Markers, Respectively

Author: Antoine Marchand, Alessia Sarchione, Panagiotis S. Athanasopoulos, Hélène Bauderlique-Le Roy, Liesel Goveas, Romain Magnez, Matthieu Drouyer, Marco Emanuele, Franz Y. Ho, Maxime Liberelle, Patricia Melnyk, Nicolas Lebègue, Xavier Thuru, R. Jeremy Nichols, Elisa Greggio, Arjan Kortholt, Thierry Galli, Marie-Christine Chartier-Harlin, Jean-Marc Taymans, Cell Biochemistry, CHU Lille, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Groningen [Groningen], Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Stanford University, Università degli Studi di Padova = University of Padua (Unipd), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Martinez Rico, Clara, ANR-16-CE16-0012,MeTDePaDi,Défauts de Traffic Membranaire dans la Maladie de Parkinson(2016), and ANR-20-CE16-0008,Synapark,Evaluation de l'implication de la fonction transcriptionnelle de la parkine dans le contrôle de l'alpha-synucléïne in vitro, in vivo et dans le sang de patients atteints de la Maladie de Parkinson(2020)
Subjects: LRRK2, phosphorylation, Parkinson’s disease, lysosome, RABs, [SDV]Life Sciences [q-bio], Parkinson's disease, Parkinson Disease, General Medicine, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, nervous system diseases, [SDV] Life Sciences [q-bio], Lysosome, Phosphorylation, Humans, Lysosomes, Signal Transduction
Abstract: International audience; The Leucine Rich Repeat Kinase 2 (LRRK2) gene is a major genetic determinant of Parkinson's disease (PD), encoding a homonymous multi-domain protein with two catalytic activities, GTPase and Kinase, involved in intracellular signaling and trafficking. LRRK2 is phosphorylated at multiple sites, including a cluster of autophosphorylation sites in the GTPase domain and a cluster of heterologous phosphorylation sites at residues 860 to 976. Phosphorylation at these latter sites is found to be modified in brains of PD patients, as well as for some disease mutant forms of LRRK2. The main aim of this study is to investigate the functional consequences of LRRK2 phosphorylation or dephosphorylation at LRRK2's heterologous phosphorylation sites. To this end, we generated LRRK2 phosphorylation site mutants and studied how these affected LRRK2 catalytic activity, neurite outgrowth and lysosomal physiology in cellular models. We show that phosphorylation of RAB8a and RAB10 substrates are reduced with phosphomimicking forms of LRRK2, while RAB29 induced activation of LRRK2 kinase activity is enhanced for phosphodead forms of LRRK2. Considering the hypothesis that PD pathology is associated to increased LRRK2 kinase activity, our results suggest that for its heterologous phosphorylation sites LRRK2 phosphorylation correlates to healthy phenotypes and LRRK2 dephosphorylation correlates to phenotypes associated to the PD pathological processes.
Published: 2022
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37. Functional connectivity correlates of reduced goal-directed behaviors in behavioural variant frontotemporal dementia

Author: Valérie Godefroy, Bénédicte Batrancourt, Sylvain Charron, Arabella Bouzigues, David Bendetowicz, Guilhem Carle, Armelle Rametti-Lacroux, Stéphanie Bombois, Emmanuel Cognat, Raffaella Migliaccio, Richard Levy, Martinez Rico, Clara, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144))
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Histology, Resting-state functional connectivity, General Neuroscience, Apathy, fMRI, Brain, Ecological design, Magnetic Resonance Imaging, Cognition, Goal-directed behavior, Frontotemporal Dementia, Parietal Lobe, Humans, Anatomy, Goals, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: INTRODUCTION: We explored the resting state functional connectivity correlates of apathy assessed as a multidimensional construct, using behavioral metrics, in behavioral variant frontotemporal dementia (bvFTD).METHODS: We recorded the behavior of 20 bvFTD patients and 16 healthy controls (HC) in a close-to-real-life situation including a free phase (FP – in which actions were self-initiated) and a guided phase (GP – in which initiation of actions was facilitated by external guidance). We investigated the activity time and walking episode features as quantifiers of apathy. We used the means ((FP+GP)/2) and the differences (FP-GP) calculated for these metrics as well as measures by questionnaires to extract apathy dimensions by factor analysis. We assessed two types of connectivity measures (local low-frequency signal power and distant seed-based functional connectivity) and explored their relationship with extracted apathy dimensions. RESULTS: Apathy in bvFTD was associated with lower time spent in activity combined with walking episodes of higher frequency, lower acceleration and higher duration. Using these behavioral metrics and apathy measures by questionnaires, we disentangled two dimensions: the global reduction of goal-directed behaviors and the specific deficit of selfinitiation. Global apathy was associated with lower resting state activity within prefrontal cortex and lower connectivity of salience network hubs while the decrease in self-initiation was related to increased connectivity of parietal default-mode network hubs. DISCUSSION: Through a new dimensional approach of apathy, we dissociated the functional connectivity correlates of global apathy and self-initiation deficit. This contributes to better understand the role of functional networks in the production of goal-directed behaviors.
Published: 2022

38. Off-label drug database

Author: Emanuelle Advenier-Iakovlev, Ilan Zana, Catherine Letord, Stéfan Jacques Darmoni, Marie-Odile Krebs, Julien Grosjean, Catherine Duclos, Jean Charlet, Letord, Catherine, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, CHU Rouen, Normandie Université (NU), Département d'Informatique Médicale (D2IM), Normandie Université (NU)-Normandie Université (NU), Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI)
Subjects: Drug, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], Health professionals, Database, Computer science, media_common.quotation_subject, Context (language use), [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Off-label use, computer.software_genre, [INFO.INFO-CL]Computer Science [cs]/Computation and Language [cs.CL], [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Mode (computer interface), [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [INFO.INFO-CL] Computer Science [cs]/Computation and Language [cs.CL], [INFO.INFO-IR]Computer Science [cs]/Information Retrieval [cs.IR], [INFO.INFO-DB] Computer Science [cs]/Databases [cs.DB], [INFO.INFO-DL]Computer Science [cs]/Digital Libraries [cs.DL], [INFO.INFO-IR] Computer Science [cs]/Information Retrieval [cs.IR], Medical prescription, [INFO.INFO-DL] Computer Science [cs]/Digital Libraries [cs.DL], computer, media_common
Abstract: BackgroundMany drugs are still being prescribed in a “off-label mode” and especially in psychiatry. Off-label prescription situations may vary depending on several factors and such practice is not well identifiable in the literature. Methods: A new public academic drug database has been recently created and is able to contain off-label indications, especially in psychiatry in the context of the PSYHAMM French research project. For each situation, bibliographic references have been collected to make the scientific information available to all. Results: this new off-label drug database contains more than 18,154 lines. It is freely available at https://www.hetop.eu/hetop/medicaments. Several off-label usages have been formally described and the system is extensible to all drugs and all specialties. Conclusion: An off-label drug database can be a valuable tool for health professionals and students.
Published: 2022

39. Telemedicine in French Memory Clinics During the COVID-19 Pandemic

Author: Alexandre Morin, Thibaut Pressat-Laffouilhere, Marie Sarazin, Julien Lagarde, Carole Roue-Jagot, Pauline Olivieri, Claire Paquet, Emmanuel Cognat, Julien Dumurgier, Florence Pasquier, Thibaut Lebouvier, Matthieu Ceccaldi, Olivier Godefroy, Olivier Martinaud, Julien Grosjean, Aline Zarea, David Maltête, David Wallon, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), GHU AP-HP Centre Université de Paris, Université Sorbonne Paris Cité (USPC), Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Lariboisière-Fernand-Widal [APHP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Lille, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, Neuropsychologie et imagerie de la mémoire humaine (NIMH), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'informatique biomédicale [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Service de neurologie [Rouen], Université de Rouen Normandie (UNIROUEN), DESSAIVRE, Louise, 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), and Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE)
Subjects: SARS-CoV-2, General Neuroscience, [SDV]Life Sciences [q-bio], COVID-19, General Medicine, Telemedicine, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Clinical Psychology, Treatments in dementia, Communicable Disease Control, Psychoactive drugs, Humans, Geriatrics and Gerontology, Pandemics, Alzheimer’s disease
Abstract: International audience; This multicenter study was conducted in French memory clinics during the first COVID-2019 lockdown (March-May 2020). The objective was to evaluate the effect of a telemedicine consultation on treatment modification in dementia care. Among 874 patients who had a telemedicine consultation, 103 (10.7%) had treatment modifications, in particular those living with a relative or diagnosed with Alzheimer's disease. A control group of patients referred March-May 2019 was also included. Treatment modification rate was similar between periods with an adjusted percentage difference of -4% (p = 0.27). Telemedicine consultations allowed treatment modifications with only a minor short-term negative impact on therapeutic strategies.
Published: 2022

40. Small vessel disease and collaterals in ischemic stroke patients treated with thrombectomy

Author: Géraud Forestier, Rémi Agbonon, Nicolas Bricout, Wagih Benhassen, Guillaume Turc, Martin Bretzner, Marco Pasi, Joseph Benzakoun, Pierre Seners, Thomas Personnic, Laurence Legrand, Denis Trystram, Christine Rodriguez-Regent, Andreas Charidimou, Natalia S. Rost, Serge Bracard, Frédéric Clarençon, Omer F. Eker, Norbert Nighoghossian, Charlotte Cordonnier, Catherine Oppenheim, Olivier Naggara, Hilde Henon, Grégoire Boulouis, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Dupuytren [CHU Limoges], GHU Paris Psychiatrie et Neurosciences, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurochirurgie [CHU Pitié-Salpêtrière], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lyon, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CarMeN, laboratoire, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Aged, 80 and over, Male, Collateral circulation, Radiological and Ultrasound Technology, [SDV]Life Sciences [q-bio], Cerebral small vessel disease, Middle Aged, Brain Ischemia, Stroke, [SDV] Life Sciences [q-bio], Magnetic resonance imaging, Neurology, Cerebral Small Vessel Diseases, Humans, Female, Radiology, Nuclear Medicine and imaging, Prospective Studies, Neurology (clinical), Aged, Ischemic Stroke, Retrospective Studies, Thrombectomy
Abstract: International audience; BACKGROUND AND PURPOSE: To determine the influence of the cerebral small vessel disease (SVD) burden on collateral recruitment in patients treated with mechanical thrombectomy (MT) for anterior circulation acute ischemic stroke (AIS). METHODS: Patients with AIS due to large vessel occlusion (LVO) from the Thrombectomie des Artères Cérébrales (THRACE) trial and prospective cohorts from 2 academic comprehensive stroke centers treated with MT were pooled and retrospectively analyzed. Collaterals' adequacy was assessed using the American Society of Interventional and Therapeutic Radiology/Society of Interventional Radiology (ASITN/SIR) score on initial digital subtraction angiography and dichotomized as good (3,4) versus poor (0-2) collaterals. The SVD burden was rated with the global SVD score on MRI. Multivariable logistic regression analyses were used to determine relationships between SVD and ASITN/SIR scores. RESULTS: A total of 312 participants were included (53.2% males, mean age 67.8 ± 14.9 years). Two hundred and seven patients had poor collaterals (66.4%), and 133 (42.6%) presented with any SVD signature. In multivariable analysis, patients demonstrated worse leptomeningeal collaterality with increasing SVD burden before and after adjustment for SVD risk factors (adjusted odds ratio [aOR] 0.69; 95%CI [0.52-0.89] and aOR 0.66; 95%CI [0.5-0.88], respectively). Using individual SVD markers, poor collaterals were significantly associated with the presence of lacunes (aOR 0.40, 95% CI [0.20-0.79]). CONCLUSION: Our study provides evidence that in patients with AIS due to LVO treated with MT, the burden of SVD assessed by pre-treatment MRI is associated with poorer recruitment of leptomeningeal collaterals.
Published: 2022

41. Should Patients With Acute Minor Ischemic Stroke With Isolated Internal Carotid Artery Occlusion Be Thrombolysed?

Author: Naouel Boulenoir, Guillaume Turc, Adrien Ter Schiphorst, Mirjam R. Heldner, Davide Strambo, Nadia Laksiri, Isabelle Girard Buttaz, Jérémie Papassin, Igor Sibon, Nicolas Chausson, Patrik Michel, Charlotte Rosso, Frédéric Bourdain, Chantal Lamy, David Weisenburger-Lile, Pierre Agius, Marion Yger, Michael Obadia, Denis Sablot, Nicolas Legris, Simon Jung, Sara Pilgram-Pastor, Hilde Henon, Lucy Bernardaud, Caroline Arquizan, Jean-Claude Baron, Pierre Seners, Wagih Ben Hassen, Bertrand Lapergue, Ludovic Lucas, Didier Leys, Frédéric Philippeau, Omar Bennani, Laura Mechtouff, Frédéric Klapczynski, Olivier Detante, Vincent Costalat, Gioia Mione, Sébastien Gazzola, Séverine Debiais, Serkan Cakmak, Valer Grigoras, Christian Denier, Didier Smadja, François Mounier-Vehier, Roxane Peres, Laurent Spelle, Nicolas Bricout, Serge Bracard, Aude Triquenot, Aïcha Lyoubi, Jean-Philippe Cottier, Duc-Long Duong, Camille Ollivier, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département de Neurologie [Hôpital Sainte-Anne - APHP] (Paris CB2 2QQ), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), GHU Paris Psychiatrie et Neurosciences, 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), Université de Montpellier (UM), Université de Lausanne = University of Lausanne (UNIL), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Grenoble, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Bordeaux [Bordeaux], Centre Hospitalier Sud Francilien, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neurologie - Côte Basque, Centre Hospitalier de la Côte Basque (CHCB), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Hôpital Foch [Suresnes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier de Saint-Nazaire, CHU Saint-Antoine [AP-HP], Infrastructure de recherche clinique en psychiatrie adulte [ICM Paris] (iCRIN psychiatrie), 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 du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Saint Jean de Perpignan, Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Saint-Anne (GHU Paris), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)
Subjects: Advanced and Specialized Nursing, Carotid Artery Diseases, carotid artery, anticoagulant, 360 Soziale Probleme, Sozialdienste, Anticoagulants, Arterial Occlusive Diseases, Thrombosis, embolism, Brain Ischemia, Stroke, Treatment Outcome, Fibrinolytic Agents, thrombus, internal, Humans, Thrombolytic Therapy, Neurology (clinical), Cardiology and Cardiovascular Medicine, 610 Medizin und Gesundheit, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Carotid Artery, Internal, Ischemic Stroke, Retrospective Studies, Thrombectomy
Abstract: Background: We recently reported a worrying 30% rate of early neurological deterioration (END) occurring within 24 hours following intravenous thrombolysis (IVT) in minor stroke with isolated internal carotid artery occlusion (ie, without additional intracranial occlusion), mainly due to artery-to-artery embolism. Here, we hypothesize that in this setting IVT—as compared to no-IVT—may foster END, in particular by favoring artery-to-artery embolism from thrombus fragmentation. Methods: From a large multicenter retrospective database, we compared minor stroke (National Institutes of Health Stroke Scale score 7d ) and 3-month modified Rankin Scale score 0 to 1. Results: Overall, 189 patients were included (IVT=95; antithrombotics=94 [antiplatelets, n=58, anticoagulants, n=36]) from 34 centers. END within 24 hours and END 7d occurred in 46 (24%) and 60 (32%) patients, respectively. Baseline clinical and radiological variables were similar between the 2 groups, except significantly higher National Institutes of Health Stroke Scale (median 3 versus 2) and shorter onset-to-imaging (124 versus 149min) in the IVT group. END within 24 hours was more frequent following IVT (33% versus 16%, adjusted hazard ratio, 2.01 [95% CI, 1.07–3.92]; P =0.03), driven by higher odds of artery-to-artery embolism (20% versus 9%, P =0.09). However, END 7d and 3-month modified Rankin Scale score of 0 to 1 did not significantly differ between the 2 groups (END 7d : adjusted hazard ratio, 1.29 [95% CI, 0.75–2.23]; P =0.37; modified Rankin Scale score of 0–1: adjusted odds ratio, 1.1 [95% CI, 0.6–2.2]; P =0.71). END 7d occurred earlier in the IVT group: median imaging-to-END 2.6 hours (interquartile range, 1.9–10.1) versus 20.4 hours (interquartile range, 7.8–34.4), respectively, P Conclusions: In our population of minor strokes with iICAO, although END rate at 7 days and 3-month outcome were similar between the 2 groups, END—particularly END due to artery-to-artery embolism—occurred earlier following IVT. Prospective studies are warranted to further clarify the benefit/risk profile of IVT in this population.
Published: 2022
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42. Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial

Author: Urs Fischer, Johannes Kaesmacher, Daniel Strbian, Omer Eker, Christoph Cognard, Patricia S Plattner, Lukas Bütikofer, Pasquale Mordasini, Sandro Deppeler, Vitor M Pereira, Jean François Albucher, Jean Darcourt, Romain Bourcier, Guillon Benoit, Chrysanthi Papagiannaki, Ozlem Ozkul-Wermester, Gerli Sibolt, Marjaana Tiainen, Benjamin Gory, Sébastien Richard, Jan Liman, Marielle Sophie Ernst, Marion Boulanger, Charlotte Barbier, Laura Mechtouff, Liqun Zhang, Gaultier Marnat, Igor Sibon, Omid Nikoubashman, Arno Reich, Arturo Consoli, Bertrand Lapergue, Marc Ribo, Alejandro Tomasello, Suzana Saleme, Francisco Macian, Solène Moulin, Paolo Pagano, Guillaume Saliou, Emmanuel Carrera, Kevin Janot, María Hernández-Pérez, Raoul Pop, Lucie Della Schiava, Andreas R Luft, Michel Piotin, Jean Christophe Gentric, Aleksandra Pikula, Waltraud Pfeilschifter, Marcel Arnold, Adnan H Siddiqui, Michael T Froehler, Anthony J Furlan, René Chapot, Martin Wiesmann, Paolo Machi, Hans-Christoph Diener, Zsolt Kulcsar, Leo H Bonati, Claudio L Bassetti, Mikael Mazighi, David S Liebeskind, Jeffrey L Saver, Jan Gralla, Angelika Alonso, Caroline Arquizan, Xavier Barreau, Rémy Beaujeux, Daniel Behme, Tobias Boeckh-Behrens, Christian Boehme, Martí Boix, Grégoire Boulouis, Nicolas Bricout, Nicolas Broc, Carlo W. Cereda, Emmanuel Chabert, Tae-Hee Cho, Alessandro Cianfoni, Vincent Costalat, Christian Denier, Frederico Di Maria, Richard du Mesnil de Rochemont, Patricia Fearon, Anna Ferrier, Sebastian Fischer, Maxime Gauberti, Marie Gaudron, Laetitia Gimenez, Christoph Globas, Michael Görtler, Mayank Goyal, Ruediger Hilker-Roggendorf, Michael D. Hill, Vi Tuan Hua, Lisa Humbertjean, Olav Jansen, Simon Jung, Georg Kägi, Michael E. Kelly, Ilka Kleffner, Michael Knoflach, Krassen Nedeltchev, Lars Udo Krause, Kimmo Lappalainen, Margaux Lefebvre, Joe Leyon, Liang Liao, Jean-Sebastien Liegey, Christian Loehr, Patrik Michel, Stefania Nannoni, Patrick Nicholson, Lorena Nico, Michael Obadia, Julien Ognard, Ayokunle Ogungbemi, Jean-Marc Olivot, Simon Escalard, Marco Pasi, Lissa Peeling, Jane Perez, Martina Petersen, Eike Piechowiak, Roberto Raposo, Silja Räty, Sarah C. Reitz, Sebastià Remollo, Luca Remonda, Ian Rennie, Manuel Requena, Alexander Riabikin, Roberto Riva, Aymeric Rouchaud, Andrea Rosi, Marta Rubiera, Laurent Spelle, Marlena Schnieder, Joanna D. Schaafsma, Tilman Schubert, Jörg B. Schulz, Mohammed Siddiqui, Sébastien Soize, Michael Sonnberger, Emmanuel Touze, Aude Triquenot, Guillaume Turc, Lucy Vieira, Wagih Ben Hassen, Judith N. Wagner, Katrin Wasser, Johannes Weber, Holger Wenz, David Weisenburger-Lile, Fritz Wodarg, Valérie Wolff, Silke Wunderlich, University of Bern, Bern University Hospital [Berne] (Inselspital), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Service de neuroradiologie [Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Toulouse [Toulouse], Département de Neuro-Radiologie [Bordeaux] (DNR - Bordeaux), CHU Bordeaux [Bordeaux], University of Toronto, Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Radiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service de neurologie [Rouen], Helsinki University Hospital [Finland] (HUS), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], University Medical Center Göttingen (UMG), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Interférométrie, In situ et Instrumentation pour la Microscopie Electronique (CEMES-I3EM), Centre d'élaboration de matériaux et d'études structurales (CEMES), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Hôpital Foch [Suresnes], Institut de Ciencies del Cosmos (ICCUB), Universitat de Barcelona (UB), Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Environnement, Bioénergie, Microalgues et Plantes (EBMP), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Département de Neuroradiologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Lille, University hospital of Zurich [Zurich], Fondation Ophtalmologique Adolphe de Rothschild [Paris], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toronto Western Hospital, Frankfurt University Hospital, University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Case Western Reserve University [Cleveland], Alfried Krupp Krankenhaus [Essen], Geneva University Hospitals and Geneva University, Institute of Medical Informatics, Biometrics and Epidemiology [ Essen, Germany] (IMIBE), University Hospital Basel [Basel], University of Basel (Unibas), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), University of California (UC), SWIFT DIRECT Collaborators: Angelika Alonso, Caroline Arquizan, Xavier Barreau, Rémy Beaujeux, Daniel Behme, Tobias Boeckh-Behrens, Christian Boehme, Martí Boix, Grégoire Boulouis, Nicolas Bricout, Nicolas Broc, Carlo W Cereda, Emmanuel Chabert, Tae-Hee Cho, Alessandro Cianfoni, Vincent Costalat, Christian Denier, Frederico Di Maria, Richard du Mesnil de Rochemont, Patricia Fearon, Anna Ferrier, Sebastian Fischer, Maxime Gauberti, Marie Gaudron, Laetitia Gimenez, Christoph Globas, Michael Görtler, Mayank Goyal, Ruediger Hilker-Roggendorf, Michael D Hill, Vi Tuan Hua, Lisa Humbertjean, Olav Jansen, Simon Jung, Georg Kägi, Michael E Kelly, Ilka Kleffner, Michael Knoflach, Krassen Nedeltchev, Lars Udo Krause, Kimmo Lappalainen, Margaux Lefebvre, Joe Leyon, Liang Liao, Jean-Sebastien Liegey, Christian Loehr, Patrik Michel, Stefania Nannoni, Patrick Nicholson, Lorena Nico, Michael Obadia, Julien Ognard, Ayokunle Ogungbemi, Jean-Marc Olivot, Simon Escalard, Marco Pasi, Lissa Peeling, Jane Perez, Martina Petersen, Eike Piechowiak, Roberto Raposo, Silja Räty, Sarah C Reitz, Sebastià Remollo, Luca Remonda, Ian Rennie, Manuel Requena, Alexander Riabikin, Roberto Riva, Aymeric Rouchaud, Andrea Rosi, Marta Rubiera, Laurent Spelle, Marlena Schnieder, Joanna D Schaafsma, Tilman Schubert, Jörg B Schulz, Mohammed Siddiqui, Sébastien Soize, Michael Sonnberger, Emmanuel Touze, Aude Triquenot, Guillaume Turc, Lucy Vieira, Wagih Ben Hassen, Judith N Wagner, Katrin Wasser, Johannes Weber, Holger Wenz, David Weisenburger-Lile, Fritz Wodarg, Valérie Wolff, Silke Wunderlich., Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), St George’s University Hospitals, Vall d'Hebron University Hospital [Barcelona], and CarMeN, laboratoire
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], General Medicine, 610 Medicine & health
Abstract: Background Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. Methods In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0.9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. Findings Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7 .3%, 95% CI -16.6 to 2.1, lower limit of one-sided 95% CI -15.1%, crossing the non-inferiority margin of - 12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy ( risk difference -1.0%, 95% CI -4.8 to 2 .7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [ 91%] of 201 vs 199 [96%] of 207, risk difference -5.1%, 95% CI -10.2 to 0. 0, p=0.047). Interpretation Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
Published: 2022

43. Off-Label Use of Tenecteplase for the Treatment of Acute Ischemic Stroke A Systematic Review and Meta-analysis

Author: Katsanos, Aristeidis H, Psychogios, Klearchos, Turc, Guillaume, Sacco, Simona, de Sousa, Diana Aguiar, De Marchis, Gian Marco, Palaiodimou, Lina, Filippou, Dimitrios K, Ahmed, Niaz, Sarraj, Amrou, Menon, Bijoy K, Tsivgoulis, Georgios, Martinez Rico, Clara, McMaster University [Hamilton, Ontario], Metropolitan Hospital [Piraeus, Greece] (MH), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), University of L'Aquila [Italy] (UNIVAQ), Lusófona University [Lisbon], University of Basel (Unibas), National and Kapodistrian University of Athens (NKUA), Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], The University of Texas Health Science Center at Houston (UTHealth), University of Calgary, and The University of Tennessee Health Science Center [Memphis] (UTHSC)
Subjects: Stroke, Observational Studies as Topic, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Tenecteplase, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Off-Label Use, General Medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Brain Ischemia, Ischemic Stroke
Abstract: International audience; Importance: Tenecteplase is being evaluated as an alternative thrombolytic agent for the treatment of acute ischemic stroke (AIS) within ongoing randomized clinical trials (RCTs). In addition, nonrandomized clinical experiences with off-label use of tenecteplase vs alteplase for AIS treatment are being published.Objective: To evaluate the available evidence on the safety and efficacy of intravenous tenecteplase compared with intravenous alteplase provided by nonrandomized studies.Data sources: Eligible studies were identified by searching MEDLINE and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 12, 2021. This meta-analysis used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal.Study selection: Nonrandomized studies (prospective or retrospective) comparing intravenous tenecteplase (at any dose) with intravenous alteplase in patients with AIS were included in the analysis.Data extraction and synthesis: The crude odds ratios (ORs) and 95% CIs were calculated for the association of tenecteplase vs alteplase with the outcomes of interest and adjusted ORs were extracted if provided. Estimates using random-effects models were pooled.Main outcomes and measures: The primary outcome was the probability of good functional outcome (modified Rankin scale [mRS] score, 0-2) at 90 days.Results: Six studies were identified including a total of 1820 patients (618 [34%] treated with tenecteplase). Patients receiving tenecteplase had higher odds of 3-month good functional outcome (crude odds ratio [OR], 1.22; 95% CI, 0.90-1.66; adjusted OR, 1.60, 95% CI, 1.08-2.37), successful recanalization (crude OR, 2.82; 95% CI, 1.12-7.10; adjusted OR, 2.38; 95% CI, 1.18-4.81), and early neurological improvement (crude OR, 4.88; 95% CI, 2.03-11.71; adjusted OR, 7.60; 95% CI, 1.97-29.41). No significant differences were detected in 3-month excellent functional outcome proportions (mRS score 0-1; crude OR, 1.53; 95% CI, 0.81-2.91; adjusted OR, 2.51; 95% CI, 0.66- 9.49), symptomatic intracranial hemorrhage (crude OR, 0.97; 95% CI, 0.44-2.16; adjusted OR, 1.16; 95% CI, 0.13-10.50), or parenchymal hematoma (crude OR, 1.20; 95% CI, 0.24-5.95).Conclusions and relevance: Evidence from nonrandomized studies suggests tenecteplase is as safe as alteplase and potentially associated with improved functional outcomes compared with alteplase. Based on these findings, enrollment in the ongoing RCTs appears to be appropriate.
Published: 2022

44. European Stroke Organisation (ESO) guidelines on mobile stroke units for prehospital stroke management

Author: Silke Walter, Heinrich J Audebert, Aristeidis H Katsanos, Karianne Larsen, Simona Sacco, Thorsten Steiner, Guillaume Turc, Georgios Tsivgoulis, Martinez Rico, Clara, Saarland University Medical Center [Homburg, Germany] (SUMC), Berlin Institute of Health (BIH), Humboldt University Of Berlin, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], McMaster University [Hamilton, Ontario], National and Kapodistrian University of Athens (NKUA), University of Oslo (UiO), University of L'Aquila [Italy] (UNIVAQ), Heidelberg University Hospital [Heidelberg], Universitätsklinikum Frankfurt, GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), and The University of Tennessee Health Science Center [Memphis] (UTHSC)
Subjects: thrombolysis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Guidelines, prehospital, stroke, Mobile Stroke Unit, large vessel occlusion, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), cardiovascular diseases, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cardiology and Cardiovascular Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The safety and efficacy of mobile stroke units (MSUs) in prehospital stroke management has recently been investigated in different clinical studies. MSUs are ambulances equipped with a CT scanner, point-of-care lab, telemedicine and are staffed with a stroke specialised medical team. This European Stroke Organisation (ESO) guideline provides an up-to-date evidence-based recommendation to assist decision-makers in their choice on using MSUs for prehospital management of suspected stroke, which includes patients with acute ischaemic stroke (AIS), intracranial haemorrhage (ICH) and stroke mimics. The guidelines were developed according to the ESO standard operating procedure and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and aggregated data meta-analyses of the literature, assessed the quality of the available evidence and made specific recommendations. Expert consensus statements are provided where sufficient evidence was not available to provide recommendations based on the GRADE approach. We found moderate evidence for suggesting MSU management for patients with suspected stroke. The patient group diagnosed with AIS shows an improvement of functional outcomes at 90 days, reduced onset to treatment times and increased proportion receiving IVT within 60 min from onset. MSU management might be beneficial for patients with ICH as MSU management was associated with a higher proportion of ICH patients being primarily transported to tertiary care stroke centres. No safety concerns (all-cause mortality, proportion of stroke mimics treated with IVT, symptomatic intracranial bleeding and major extracranial bleeding) could be identified for all patients managed with a MSU compared to conventional care. We suggest MSU management to improve prehospital management of suspected stroke patients.
Published: 2022

45. Perfusion Imaging to Select Patients with Large Ischemic Core for Mechanical Thrombectomy

Author: François Zhu, Aymeric Rouchaud, Wagih Benhassen, Joseph Benzakoun, Kevin Janot, Jean François Hak, Florent Gariel, Lili Detraz, Gaultier Marnat, Cyril Dargazanli, Gregoire Boulouis, Charline Perot, Basile Kerleroux, Romain Bourcier, Géraud Forestier, Dimitri Daly-Eraya, Johannes Kaesmacher, Pasquale Mordasini, Benjamin Gory, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], CHU Limoges, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Bern University Hospital [Berne] (Inselspital), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Martinez Rico, Clara
Subjects: medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, [SDV]Life Sciences [q-bio], 610 Medicine & health, Perfusion scanning, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, Internal medicine, Medicine, Acute stroke, Endovascular treatment, 030212 general & internal medicine, Prospective cohort study, Thrombectomy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Ischemic stroke, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Odds ratio, Perfusion imaging, Confidence interval, [SDV] Life Sciences [q-bio], lcsh:RC666-701, Cardiology, Original Article, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Perfusion, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Cohort study
Abstract: Background and Purpose Patients with acute ischemic stroke, proximal vessel occlusion and a large ischemic core at presentation are commonly not considered for mechanical thrombectomy (MT). We tested the hypothesis that in patients with baseline large infarct cores, identification of remaining penumbral tissue using perfusion imaging would translate to better outcomes after MT.Methods This was a multicenter, retrospective, core lab adjudicated, cohort study of adult patients with proximal vessel occlusion, a large ischemic core volume (diffusion weighted imaging volume ≥70 mL), with pre-treatment magnetic resonance imaging perfusion, treated with MT (2015 to 2018) or medical care alone (controls; before 2015). Primary outcome measure was 3-month favorable outcome (defined as a modified Rankin Scale of 0–3). Core perfusion mismatch ratio (CPMR) was defined as the volume of critically hypo-perfused tissue (Tmax >6 seconds) divided by the core volume. Multivariable logistic regression models were used to determine factors that were independently associated with clinical outcomes. Outputs are displayed as adjusted odds ratio (aOR) and 95% confidence interval (CI).Results A total of 172 patients were included (MT n=130; Control n=42; mean age 69.0±15.4 years; 36% females). Mean core-volume and CPMR were 102.3±36.7 and 1.8±0.7 mL, respectively. As hypothesized, receiving MT was associated with increased probability of favorable outcome and functional independence, as CPMR increased, a difference becoming statistically significant above a mismatch-ratio of 1.72. Similarly, receiving MT was also associated with favorable outcome in the subgroup of 74 patients with CPMR >1.7 (aOR, 8.12; 95% CI, 1.24 to 53.11; P=0.028). Overall (prior to stratification by CPMR) 73 (42.4%) patients had a favorable outcome at 3 months, with no difference amongst groups.Conclusions In patients currently deemed ineligible for MT due to large infarct ischemic cores at baseline, CPMR identifies a subgroup strongly benefiting from MT. Prospective studies are warranted.
Published: 2020

46. The identification, assessment and management of difficult-to-treat depression: An international consensus statement

Author: Allan H. Young, Gin S Malhi, RH McAllister-Williams, Eduard Vieta, Philip Gorwood, Afzal Javed, Peter Falkai, Andrew Papadopoulos, A. J. Rush, Celso Arango, Jair C. Soares, Malcolm Hopwood, Pierre Blier, Koen Demyttenaere, Siegfried Kasper, Martinez Rico, Clara, Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Instituto de Investigación Sanitaria Gregorio Marañón [Madrid, Spain] ( IiSGM), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), University of Ottawa [Ottawa], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Ludwig Maximilian University [Munich] (LMU), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Melbourne, University of Warwick [Coventry], Medizinische Universität Wien = Medical University of Vienna, The University of Sydney, Royal North Shore Hospital (RNSH), The University of Texas Health Science Center at Houston (UTHealth), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), King‘s College London, South London and Maudsley NHS Foundation Trust, Somerset Partnership NHS Foundation Trust, Duke University [Durham], Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Duke-NUS Medical School [Singapore], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: VAGUS NERVE-STIMULATION, TRANSCRANIAL MAGNETIC STIMULATION, medicine.medical_specialty, Consensus, 2016 CLINICAL GUIDELINES, SEROTONIN REUPTAKE INHIBITORS, medicine.medical_treatment, Clinical Neurology, GENERALIZED ANXIETY DISORDER, Difficult-to-treat depression, Depressive Disorder, Treatment-Resistant, DOUBLE-BLIND, 03 medical and health sciences, POSTTRAUMATIC-STRESS-DISORDER, 0302 clinical medicine, Pharmacotherapy, Diagnosis, medicine, Humans, Symptom control, COGNITIVE-BEHAVIORAL THERAPY, Intensive care medicine, Neurostimulation, Psychiatry, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Science & Technology, Conceptualization, Depression, Clinical management, business.industry, Treatment options, MAJOR DEPRESSION, medicine.disease, 3. Good health, 030227 psychiatry, Psychotherapy, Psychiatry and Mental health, Clinical Psychology, Management implications, Quality of Life, TREATMENT-RESISTANT DEPRESSION, Neurosciences & Neurology, Treatment-resistant depression, business, Life Sciences & Biomedicine, Psychosocial, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: BACKGROUND: Many depressed patients are not able to achieve or sustain symptom remission despite serial treatment trials - often termed "treatment resistant depression". A broader, perhaps more empathic concept of "difficult-to-treat depression" (DTD) was considered. METHODS: A consensus group discussed the definition, clinical recognition, assessment and management implications of the DTD heuristic. RESULTS: The group proposed that DTD be defined as "depression that continues to cause significant burden despite usual treatment efforts". All depression management should include a thorough initial assessment. When DTD is recognized, a regular reassessment that employs a multi-dimensional framework to identify addressable barriers to successful treatment (including patient-, illness- and treatment-related factors) is advised, along with specific recommendations for addressing these factors. The emphasis of treatment, in the first instance, shifts from a goal of remission to optimal symptom control, daily psychosocial functional and quality of life, based on a patient-centred approach with shared decision-making to enhance the timely consideration of all treatment options (including pharmacotherapy, psychotherapy, neurostimulation, etc.) to optimize outcomes when sustained remission is elusive. LIMITATIONS: The recommended definition and management of DTD is based largely on expert consensus. While DTD would seem to have clinical utility, its specificity and objectivity may be insufficient to define clinical populations for regulatory trial purposes, though DTD could define populations for service provision or phase 4 trials. CONCLUSIONS: DTD provides a clinically useful conceptualization that implies a search for and remediation of specific patient-, illness- and treatment obstacles to optimizing outcomes of relevance to patients. ispartof: Journal of Affective Disorders vol:267 pages:264-282 ispartof: location:Netherlands status: published
Published: 2020

47. An epidemiology report for primary central nervous system tumors in adolescents and young adults: a nationwide population-based study in France, 2008–2013

Author: Luc Bauchet, Didier Frappaz, Valérie Rigau, Johan Pallud, Brigitte Trétarre, Amélie Darlix, Sam Ng, Sonia Zouaoui, Faiza Bessaoud, Hélène Mathieu-Daudé, Thomas Roujeau, Alexandre Roux, Dominique Figarella-Branger, Fabienne Bauchet, Department of Biomolecular Engineering, University of California [Santa Cruz] (UC Santa Cruz), University of California (UC)-University of California (UC), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'épidémiologie, Groupe de neuro-oncologie du Languedoc Roussillon, FRANCIM, Réseau des registres français du cancer, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service d’Anatomie Pathologique et de Neuropathologie, APHM, Hôpital de la Timone, Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Surgical oncology Centre Léon Bérard, Centre Léon Bérard [Lyon], Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], Neurochirurgie [Hôpital Gui de Chauliac], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], University of California [Santa Cruz] (UCSC), University of California-University of California, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Service de Neurochirurgie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Adult, Male, Cancer Research, Pediatrics, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Population, Brain tumor, Neuropathology, Central Nervous System Neoplasms, Young Adult, 03 medical and health sciences, Age Distribution, 0302 clinical medicine, Biopsy, Epidemiology, medicine, Humans, Young adult, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, medicine.diagnostic_test, Brain Neoplasms, business.industry, Incidence, Editorials, Histology, medicine.disease, 3. Good health, Europe, Oncology, 030220 oncology & carcinogenesis, Female, France, Neurology (clinical), Neurosurgery, business, 030217 neurology & neurosurgery
Abstract: Background Primary central nervous system tumors (PCNST) among adolescents and young adults (AYA, 15–39 y) have rarely been reported. We present a nationwide report of PCNST histologically confirmed in the French AYA population between 2008 and 2013. Methods Patients were identified through the French Brain Tumor Database (FBTDB), a national dataset that includes prospectively all histologically confirmed cases of PCNST in France. Patients aged 15 to 39 years with histologically confirmed PCNST diagnosed between 2008 and 2013 were included. For each of the 143 histological subtypes of PCNST, crude rates, sex, surgery, and age distribution were provided. To enable international comparisons, age-standardized incidence rates were adjusted to the world-standard, European, and USA populations. Results For 6 years, 9661 PCNST (males/females: 4701/4960) were histologically confirmed in the French AYA population. The overall crude rate was 8.15 per 100 000 person-years. Overall, age-standardized incidence rates were (per 100 000 person-years, population of reference: world/Europe/USA): 7.64/8.07/8.21, respectively. Among patients aged 15–24 years, the crude rate was 5.13 per 100 000. Among patients aged 25–39 years, the crude rate was 10.10 per 100 000. Age-standardized incidence rates were reported for each of the 143 histological subtypes. Moreover, for each histological subtype, data were detailed by sex, age, type of surgery (surgical resection or biopsy), and cryopreserved samples. Conclusion These data represent an exhaustive report of all histologically confirmed cases of PCNST with their frequency and distribution in the French AYA population in 2008–2013. For the first time in this age group, complete histological subtypes and rare tumor identification are detailed.
Published: 2019

48. Tau-PET imaging predicts cognitive decline and brain atrophy progression in early Alzheimer's disease

Author: Julien Lagarde, Pauline Olivieri, Matteo Tonietto, Cecile Tissot, Isabelle Rivals, Philippe Gervais, Fabien Caillé, Martin Moussion, Michel Bottlaender, Marie Sarazin, GHU Paris Psychiatrie et Neurosciences, Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), McGill University = Université McGill [Montréal, Canada], Equipe de Statistique Appliquée (UMRS 1158) (ESA), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Centre Hospitalier Saint-Anne (GHU Paris)
Subjects: Amyloid beta-Peptides, Brain, CSF, tau Proteins, Alzheimer's disease, Psychiatry and Mental health, PET, Alzheimer Disease, Positron-Emission Tomography, Humans, Surgery, Cognitive Dysfunction, Neurology (clinical), tau Subject Categories Biomarkers, Atrophy, Alzheimer's disease CSF PET plasma tau Subject Categories Biomarkers Neuroscience, plasma, [PHYS.PHYS.PHYS-DATA-AN]Physics [physics]/Physics [physics]/Data Analysis, Statistics and Probability [physics.data-an], Biomarkers, Neuroscience
Abstract: ObjectivesTo explore whether regional tau binding measured at baseline is associated with the rapidity of Alzheimer’s disease (AD) progression over 2 years, as assessed by the decline in specified cognitive domains, and the progression of regional brain atrophy, in comparison with amyloid-positron emission tomography (PET), MRI and cerebrospinal fluid (CSF) biomarkers.MethodsThirty-six patients with AD (positive CSF biomarkers and amyloid-PET) and 15 controls underwent a complete neuropsychological assessment, 3T brain MRI, [11C]-PiB and [18F]-flortaucipir PET imaging, and were monitored annually over 2 years, with a second brain MRI after 2 years. We used mixed effects models to explore the relations between tau-PET, amyloid-PET, CSF biomarkers and MRI at baseline and cognitive decline and the progression of brain atrophy over 2 years in patients with AD.ResultsBaseline tau-PET was strongly associated with the subsequent cognitive decline in regions that are usually associated with each cognitive domain. No significant relationship was observed between the cognitive decline and initial amyloid load, regional cortical atrophy or CSF biomarkers. Baseline tau tracer binding in the superior temporal gyrus was associated with subsequent atrophy in an inferomedial temporal volume of interest, as was the voxelwise tau tracer binding with subsequent cortical atrophy in the superior temporal, parietal and frontal association cortices.ConclusionsThese results suggest that tau tracer binding is predictive of cognitive decline in AD in domain-specific brain areas, which provides important insights into the interaction between tau burden and neurodegeneration, and is of the utmost importance to develop new prognostic markers that will help improve the design of therapeutic trials.
Published: 2021

49. L’imagerie in vivo: Un outil incontournable pour mieux comprendre la biologie des vésicules extracellulaires

Author: Bécot, Anaïs, Corona, Maribel Lara, van Niel, Guillaume, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; Les vésicules extracellulaires interviennent dans un nombre croissant de processus physiopathologiques et constituent des outils cliniques prometteurs pour le diagnostic et le traitement de diverses maladies. Leur petite taille a longtemps entravé leur étude in situ, ce qui a limité leur caractérisation in vivo et leur utilisation en clinique. Les avancées récentes en imagerie permettent à présent d’examiner et de suivre les vésicules extracellulaires dans différents modèles animaux, en temps réel et à l’échelle de la vésicule unique. Le poisson zèbre apparaît notamment comme un organisme modèle pertinent pour explorer le cycle de vie de ces vésicules in vivo et évaluer leurs potentialités thérapeutiques.
Published: 2021

50. Thrombectomy Complications in Large Vessel Occlusions: Incidence, Predictors, and Clinical Impact in the ETIS Registry

Author: Ngankou, Emmanuel Happi, Gory, Benjamin, Marnat, Gaultier, Richard, Sébastien, Bourcier, Romain, Sibon, Igor, Dargazanli, Cyril, Arquizan, Caroline, Maïer, Benjamin, Blanc, Raphaël, Lapergue, Bertrand, Consoli, Arturo, Vannier, Stéphane, Spelle, Laurent, Denier, Christian, Boulanger, Marion, Gauberti, Maxime, Saleme, Suzana, Macian, Francisco, Clarençon, Frédéric, Rosso, Charlotte, Naggara, Olivier, Turc, Guillaume, Ozkul-Wermester, Ozlem, Papagiannaki, Chrysanthi, Viguier, Alain, Cognard, Christophe, Lebras, Anthony, Evain, Sarah, Wolff, Valérie, Pop, Raoul, Timsit, Serge, Gentric, Jean Christophe, Bourdain, Frédéric, Veunac, Louis, Eugène, François, Finitsis, Stephanos Nikolaos, Piotin, Michel, Redjem, Hocine, Escalard, Simon, Dessilles, Jean Philippe, Delvoye, François, Smajda, Stanislas, Solène, Hebert, Mazighi, Mikael, Obadia, Mikael, Sabben, Candice, Seners, Pierre, Raynouard, Igor, Corabianu, Ovide, de Broucker, Thomas, Manchon, Eric, Taylor, Guillaume, Maacha, Malek Ben, Thion, Laurie Anne, Lecler, Augustin, Savatovsjy, Julien, Hospital, Foch, Wang, Adrien, Evrard, Serge, Tchikviladze, Maya, Ajili, Nadia, Weisenburgerlile, David, Gorza, Lucas, Buard, Géraldine, Coskun, Oguzhan, Di Maria, Federico, Rodesh, Georges, Zimatore, Sergio, Leguen, Morgan, Gratieux, Julie, Pico, Fernando, Rakotoharinandrasana, Haja, Tassan, Philippe, Poll, Roxanna, Marinier, Sylvie, Gariel, Florent, Barreau, Xavier, Berge, Jerome, Menegon, Patrice, Lucas, Ludovic, Olindo, Stéphane, Renou, Pauline, Sagnier, Sharmila, Poli, Mathilde, Debruxelles, Sabrina, Rouanet, François, Tourdias, Thomas, Liegey, Jean Sebastien, Briau, Pierre, Pangon, Nicolas, Detraz, Lili, Daumas-Duport, Benjamin, Alexandre, Pierre Louis, Roy, Monica, Lenoble, Cédric, Desal, Hubert Armand, Guillon, Benoît, de Gaalon, Solène, Preterre, Cécile, Bracard, Serge, Anxionnat, René, Braun, Marc, Derelle, Anne Laure, Romain, Tonnelet, Liao, Liang, Zhu, François, Schmitt, Emmanuelle, Planel, Sophie, Humbertjean, Lisa, Mione, Gioia, Lacour, Jean Christophe, Riou-Comte, Nolwenn, Audibert, Gérard, Voicu, Marcela, Alb, Lionel, Reitter, Marie, Brezeanu, Madalina, Masson, Agnès, Tabarna, Adriana, Podar, Iona, Guy, Sarah, Bechiri, Fatiha, Bourst, Pauline, Macian-Montoro, Francisco, Saleme, Suzanna, Mounayer, Charbel, Rouchaud, Aymeric, Gimenez, Laetitia, Cosnard, Alexandre, Costalat, Vincent, Gascou, Grégory, Lefèvre, Pierre Henri, Derraz, Imad, Riquelme, Carlos, Gaillard, Nicolas, Mourand, Isabelle, Corti, Lucas, Cagnazzo, Federico, ter Schiphorst, Adrien, Ferré, Jean-Christophe, Raoult, Hélène, Ronziere, Thomas, Lassale, Maria, Paya, Christophe, Gauvrit, Jean Yves, Tracol, Clément, Langnier-Lemercier, Sophie, Maurice, Axelle, Cochennec, Sabrina, Pinault, Mélanie, Shotar, Eimad, Sourour, Nader Antoine, Lenck, Stéphanie, Premat, Kévin, Anne Léger, Yves Samson, Crozier, Sophie, Baronnet, Flore, Alamowitch, Sonia, Bottin, Laure, Yger, Marion, Degos, Vincent, Chassin, Olivier, Chalumeau, Vanessa, Caroff, Jildaz, Venditti, Laura, Sarov, Mariana, Legris, Nicolas, Hassen, Wagih Ben, Boulouis, Grégoire, Rodriguez-Régent, Christine, Trystram, Denis, Kerleroux, Basile, Domigo, Valérie, Lamy, Catherine, Birchenall, Julia, Isabel, Clothilde, Lun, François, Januel, Anne Christine, Olivot, Jean Marc, Fontaine, Louis, Raposo, Nicolas, Bonneville, Fabrice, Albucher, Jean François, Calviere, Lionel, Darcourt, Jean, Bellanger, Guillaume, Tall, Philippe, Touzé, Emmanuel, Barbier, Charlotte, Schneckenburger, Romain, Cogez, Julien, Guettier, Sophie, Ognard, Julien, Merrien, François Mathias, Wermester, Ozlem Ozku, Massardier, Evelyne Guégan, Triquenot, Aude Bagan, Lefebvre, Margeaux, Bernady, Patricia, Lagoarde-Segot, Laurent, Cailliez, Hélène, Higue, David, Quenardelle, Véronique, Lauer, Valérie, Gheoca, Roxana, Pierre-Paul, Irène Nora, Beaujeux, Remy, Mihoc, Dan, Manisor, Monica, Pottecher, Julien, Meyer, Alain, Chamaraux-Tran, Thiên Nga, Le Bras, Anthony, Le Guen, Arnaud, Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Bordeaux [Bordeaux], Service de neurologie [CHRU Nancy], Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre hospitalier universitaire de Nantes (CHU Nantes), Neuroradiologie [Hôpital Gui de Chauliac], Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service Neuroradiologie diagnostique et interventionnelle [Hôpital Foch], Hôpital Foch [Suresnes], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Neurologie [CHU Rennes], CHU Pontchaillou [Rennes], Service de Neuroradiologie [CHU de Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neurologie [Le Kremlin Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Départment de Neuroradiologie [CHU Caen], Service de Neuroradiologie interventionnelle [CHU Limoges], CHU Limoges, Service de Neurologie [CHU Limoges], CHU Pitié-Salpêtrière [AP-HP], Service de Neurologie [CH Saint-Anne], Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de Neuroradiologie [CHU Rouen], Normandie Université (NU)-Normandie Université (NU), Neurologie Vasculaire [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de radiologie [Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Département de Neuroradiologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service de Neurologie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Neuroradiologie [Brest], Neurologie - Côte Basque, Centre Hospitalier de la Côte Basque (CHCB), Aristotle University of Thessaloniki, Neuroimagerie: méthodes et applications (Empenn), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)
Subjects: Male, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Embolism, Large vessel, Dissection (medical), Brain ischemia, Postoperative Complications, Risk Factors, Thromboembolism, medicine, Humans, Registries, Aged, Ischemic Stroke, Thrombectomy, Advanced and Specialized Nursing, business.industry, Incidence (epidemiology), Dissection, Incidence, Endovascular Procedures, Middle Aged, medicine.disease, Surgery, Cerebrovascular Disorders, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background and Purpose: Procedural complications in thrombectomy for large vessel occlusions of the anterior circulation are not well described. We investigated the incidence, risk factors, and clinical implications of thrombectomy complications in daily clinical practice. Methods: We used data from the ongoing prospective multicenter observational Endovascular Treatment in Ischemic Stroke Registry in France. The present study is a retrospective analysis of 4029 stroke patients with anterior large vessel occlusions treated with thrombectomy between January 2015 and May 2020 in 18 centers. We systematically collected procedural data, incidence of embolic complications, perforations and dissections, clinical outcome at 90 days, and hemorrhagic complications. Results: Procedural complications occurred in 7.99% (95% CI, 7.17%–8.87%), and embolus to a new territory (ENT) was the most frequent (5.2%). Predictors of ENTs were terminal carotid/tandem occlusion (odds ratio [OR], 5 [95% CI, 2.03–12.31]; P P =0.006). ENTs were associated to worse clinical outcomes (90-day modified Rankin Scale score, 0–2; adjusted OR, 0.4 [95% CI, 0.25–0.63]; P P P =0.011). Perforations occurred in 1.69% (95% CI, 1.31%–2.13%). Predictors of perforations were terminal carotid/tandem occlusions (39.7% versus 27.6%; P =0.028). 40.7% of patients died at 90 days, and the overall rate of poor outcome was 74.6% in case of perforation. Dissections occurred in 1.46% (95% CI, 1.11%–1.88%) and were more common in younger patients (median age, 64.2 versus 70.2 years; P =0.002). Dissections did not affect the clinical outcome at 90 days. Besides dissection, complications were independent of the thrombectomy technique. Conclusions: Thrombectomy complication rate is not negligible, and ENTs were the most frequent. ENTs and perforations were associated with disability and mortality, and terminal carotid/tandem occlusions were a risk factor. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03776877.
Published: 2021

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