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26 results on '"Isabelle Plu"'

1. Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis

Author

Joe-Elie Salem, Marie Bretagne, Baptiste Abbar, Sarah Leonard-Louis, Stéphane Ederhy, Alban Redheuil, Samia Boussouar, Lee S. Nguyen, Adrien Procureur, Frederic Stein, Charlotte Fenioux, Perrine Devos, Paul Gougis, Martin Dres, Alexandre Demoule, Dimitri Psimaras, Timothee Lenglet, Thierry Maisonobe, Marc Pineton De Chambrun, Guillaume Hekimian, Christian Straus, Jesus Gonzalez-Bermejo, David Klatzmann, Aude Rigolet, Perrine Guillaume-Jugnot, Nicolas Champtiaux, Olivier Benveniste, Nicolas Weiss, Samir Saheb, Philippe Rouvier, Isabelle Plu, Estelle Gandjbakhch, Mathieu Kerneis, Nadjib Hammoudi, Noel Zahr, Claudia Llontop, Capucine Morelot-Panzini, Lorenz Lehmann, Juan Qin, Javid J. Moslehi, Michelle Rosenzwajg, Thomas Similowski, and Yves Allenbach

Subjects
Myositis, Oncology and Carcinogenesis, Antineoplastic Agents, Myotoxicity, Respiratory Muscles, Abatacept, Myocarditis, Immunological, Rare Diseases, Oncology, Clinical Research, Humans, Immune Checkpoint Inhibitors, Lung
Abstract

Immune-checkpoint-inhibitor (ICI)–associated myotoxicity involves the heart (myocarditis) and skeletal muscles (myositis), which frequently occur concurrently and are highly fatal. We report the results of a strategy that included identification of individuals with severe ICI myocarditis by also screening for and managing concomitant respiratory muscle involvement with mechanical ventilation, as well as treatment with the CTLA4 fusion protein abatacept and the JAK inhibitor ruxolitinib. Forty cases with definite ICI myocarditis were included with pathologic confirmation of concomitant myositis in the majority of patients. In the first 10 patients, using recommended guidelines, myotoxicity-related fatality occurred in 60%, consistent with historical controls. In the subsequent 30 cases, we instituted systematic screening for respiratory muscle involvement coupled with active ventilation and treatment using ruxolitinib and abatacept. The abatacept dose was adjusted using CD86 receptor occupancy on circulating monocytes. The myotoxicity-related fatality rate was 3.4% (1/30) in these 30 patients versus 60% in the first quartile (P < 0.0001). These clinical results are hypothesis-generating and need further evaluation. Significance: Early management of respiratory muscle failure using mechanical ventilation and high-dose abatacept with CD86 receptor occupancy monitoring combined with ruxolitinib may be promising to mitigate high fatality rates in severe ICI myocarditis. See related commentary by Dougan, p. 1040. This article is highlighted in the In This Issue feature, p. 1027

Published
2023

2. Cerebral vasculitis due to Aspergillus spp. in immunocompromised patients: literature review

Author

Elie Haddad, Arnaud Fekkar, Sophie Bonnin, Natalia Shor, Danielle Seilhean, Isabelle Plu, Valérie Touitou, Véronique Leblond, Nicolas Weiss, Sophie Demeret, and Valérie Pourcher

Subjects
Microbiology (medical), Immunocompromised Host, Aspergillus, Infectious Diseases, Aspergillosis, Humans, General Medicine, Vasculitis, Central Nervous System, Retrospective Studies
Abstract

Invasive aspergillosis is a threat for immunocompromised patients. We present a case series of aggressive cerebral vasculitis caused by Aspergillus spp. infection in immunocompromised patients.We present a retrospective case series of three autopsy-proven invasive cerebral aspergillosis with diffuse vasculitis affecting large caliber cerebral vessels.Three patients were immunosuppressed: one on rituximab, one on corticosteroids, and one with a renal transplant. Two of these patients were diagnosed with cerebral aspergillosis on postmortem.Aspergillus cerebral vasculitis is a rare form of invasive aspergillosis that should be considered in an immunocompromised individual with suggestive lesions on imaging. It should be suspected as a possible cause of aseptic neutrophil meningitis.

Published
2022

3. First Case of Lethal Encephalitis in Western Europe Due to European Bat Lyssavirus Type 1

Author

Hervé Bourhy, Pascal Cozette, Béatrice Regnault, Anne Jamet, Mathilde Duchesne, Delphine Chrétien, Philippe Pérot, Vallat Jean-Michel, Danielle Seilhean, Marianne Leruez, Laurent Dacheux, Marc Eloit, Isabelle Plu, Eric Troadec, Bruno Evrard, Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris], Centre Collaborateur de l'OIE de Détection et identification chez l’homme des pathogènes animaux émergents et développement d’outils pour leur diagnostic / Collaborating Center for the Detection and identification in humans of emerging animal pathogens and development of tools for their diagnoses (CCOIE-OIECC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé Animale / World Animal Health Information System (OIE-WAHIS), Hôpital Dupuytren [CHU Limoges], Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], 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)-Centre National de la Recherche Scientifique (CNRS), Service de Neuropathologie [CHU Pitié Salpêtrière], 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), Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Centre National de Référence de la Rage - National Reference Center Rabies (CNR), Centre collaborateur de l'OMS - Rage / World Health Organization Collaboration Centres - Rabies (CC-OMS / WHO-CC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), École nationale vétérinaire d'Alfort (ENVA), This work was supported by Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant no. ANR-10-LABX-62-IBEID)., The authors thank Thomas Bigot for the use of the bioinformatic pipeline Microseek and Sarah Temmam, Yves Gaudin and Jennifer Richardson for helpful discussions, Laurent Magy, Thomas Daix, Bruno Francois, and Sophie Alain for reviewing the manuscript, Lauriane Kergoat and Simon Bonas for their excellent technical help, as well as Santé Publique France for the financial support of the National Reference Center for Rabies., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé Animale / World Animal Health Information System (OIE-WAHIS), 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)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université Paris Cité (UPCité), École nationale vétérinaire - Alfort (ENVA), Pérot, Philippe, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé Animale / World Organisation Animal Health [Paris] (OIE), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Microbiology (medical), [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Rabies, 030231 tropical medicine, Next Generation Sequencing, Context (language use), medicine.disease_cause, Virus, Mice, 03 medical and health sciences, 0302 clinical medicine, Chiroptera, Rhabdoviridae Infections, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Medicine, Lyssavirus, Metatranscriptomics, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology, business.industry, Rabies virus, medicine.disease, biology.organism_classification, Virology, 3. Good health, Europe, Titer, 030104 developmental biology, Infectious Diseases, European bat lyssavirus type 1, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Encephalitis, Antibody, business
Abstract

Background Inaccurate diagnosis of encephalitis is a major issue as immunosuppressive treatments can be deleterious in case of viral infection. The European bat lyssavirus type 1 (EBLV-1), a virus related to rabies virus, is endemic in European bats. No human case has yet been reported in Western Europe. A 59-year-old patient without specific past medical history died from encephalitis. A colony of bats lived in an outbuilding of his house. No diagnosis was made using standard procedures. Methods We used a next generation sequencing (NGS) based transcriptomic protocol to search for pathogens in autopsy samples (meninges and brain frontal lobe). Results were confirmed by polymerase chain reaction (PCR) and by antibody testing in serum. Immunochemistry was used to characterize inflammatory cells and viral antigens in brain lesions. Cells and mice were inoculated with brain extracts for virus isolation. Results The patient’s brain lesions were severe and diffuse in white and gray matter. Perivascular inflammatory infiltrates were abundant and rich in plasma cells. NGS identified European bat lyssavirus type 1a in brain, which was confirmed by PCR. A high titer of neutralizing antibodies was found in serum. No viral antigen was detected, and the virus could not be isolated by cell culture or by mouse inoculation. Conclusions The patient died from European bat lyssavirus type 1a infection. NGS was key to identifying this unexpected viral etiology in an epidemiological context that did not suggest rabies. People exposed to bats should be strongly advised to be vaccinated with rabies vaccines, which are effective against EBLV-1.

Published
2021

4. Pearlsamp; Oy-sters: Spinal Cord Candidiasis Linked to CARD9 Deficiency Masquerading as a Longitudinally Extensive Transverse Myelitis

Author

Lina Jeantin, Isabelle Plu, Maria del Mar Amador, Elisabeth Maillart, Fanny Lanternier, Valérie Pourcher, Vincent Davy, Institut Mutualiste de Montsouris (IMM), 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), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)

Subjects
Adult, Male, Antifungal Agents, [SDV]Life Sciences [q-bio], Candidiasis, Chronic Mucocutaneous, Candidiasis, Middle Aged, Myelitis, Transverse, CARD Signaling Adaptor Proteins, Spinal Cord, Adrenal Cortex Hormones, Humans, Neurology (clinical), Glucans
Abstract

Candida spp. myelopathies are very rare. We report a case of subacute longitudinally extensive transverse myelitis in an apparently immunocompetent 55-year-old man. After a negative infectious workup, corticosteroids and plasma exchange were initiated. Although there was a transient initial improvement, symptoms then worsened, and the lumbar puncture was repeated. Candida albicans was isolated in the CSF, and a diagnosis of spinal cord candidiasis was made. Gene panel sequencing for inborn immune deficiencies identified a homozygous disease-causing CARD9 variant. Despite antifungal treatment, necrotic myelitis, meningoencephalitis, and cerebral vasculitis developed. Fungal spinal cord infections can mimic inflammatory myelitis, and beta-D-glucan testing of both serum and CSF may help narrow down the diagnosis. In cases of severe or unexpected invasive Candida spp. infection, even adults and apparently immunocompetent patients should be screened for inborn immune deficiencies and CARD9 deficiency in particular.

Published
2022

5. Ultradeep sequencing reveals HIV-1 diversity and resistance compartmentalization during HIV-encephalopathy

Author

Nathalie Désiré, Isabelle Plu, Vincent Calvez, Romain Palich, Anne-Geneviève Marcelin, Eleni Giatsou, Danielle Seilhean, Basma Abdi, and Aude Jary

Subjects
AIDS Dementia Complex, Genotype, Anti-HIV Agents, Immunology, HIV Infections, Drug resistance, HIV Envelope Protein gp120, V3 loop, Biology, 03 medical and health sciences, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Drug Resistance, Viral, medicine, Humans, Immunology and Allergy, Amplified Fragment Length Polymorphism Analysis, Phylogeny, 030304 developmental biology, Genetics, 0303 health sciences, Phylogenetic tree, Reverse Transcriptase Polymerase Chain Reaction, High-Throughput Nucleotide Sequencing, medicine.disease, Reverse transcriptase, 3. Good health, Infectious Diseases, Anti-Retroviral Agents, Viral replication, Mutation, HIV-1, Viral hepatitis, 030217 neurology & neurosurgery
Abstract

OBJECTIVES To examine viral diversity and resistance mutations in different brain areas in cases of HIV-encephalopathy. DESIGN Twelve postmortem brain areas from three cases of possible or certain HIV-encephalopathy were analyzed. METHODS After amplification of the reverse transcriptase and the V3 loop region of the gp120 protein, ultradeep sequencing was performed with Illumina technology. Phylogenetic analysis was performed with Fastree v2.1 using the generalized time-reversible (GTR) model. Identification of resistant viral variants was performed on Geneious software, according to HIV-1 genotypic drug resistance interpretation's algorithms, 2018 administered by the French Agency for Research on AIDS and Viral Hepatitis. RESULTS Phylogenetic analysis revealed significant inter-regional and intra-regional diversity reflecting persistent HIV-1 viral replication in the different brain areas. Although some cerebral regions shared HIV-variants, most of them harbored a specific HIV-subpopulation reflecting HIV compartmentalization in the central nervous system. Furthermore, proportion and distribution of resistance mutations to nucleoside and non-nucleoside reverse transcriptase inhibitors differed among different brain areas of the same case suggesting that penetration of antiretroviral treatment may differ from one compartment to another. CONCLUSION This study, performed with a powerful sequencing technique, confirmed HIV compartmentalization in the central nervous system already shown by classical sequencing, suggesting that there are several reservoirs within the brain.

Published
2020

6. Memory CD4+ T-Cell Lymphocytic Angiopathy in Fatal Forms of COVID-19 Pulmonary Infection

Author

Amélie Guihot, Isabelle Plu, Cathia Soulié, Alice Rousseau, Cecilia Nakid-Cordero, Karim Dorgham, Christophe Parizot, Elena Litvinova, Julien Mayaux, Isabelle Malet, Paul Quentric, Béhazine Combadière, Christophe Combadière, Olivia Bonduelle, Lucille Adam, Pierre Rosenbaum, Alexandra Beurton, Patrice Hémon, Patrice Debré, Vincent Vieillard, Brigitte Autran, Danielle Seilhean, Frédéric Charlotte, Anne-Geneviève Marcelin, Guy Gorochov, Charles-Edouard Luyt, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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 VIEILLARD, Vincent

Subjects
Vasculitis, Adult, CD4-Positive T-Lymphocytes, SARS-CoV-2, [SDV]Life Sciences [q-bio], Immunology, COVID-19, Broncho-alveolar lavage (BAL), Autopsia, Pneumonia, CD8-Positive T-Lymphocytes, respiratory tract diseases, [SDV] Life Sciences [q-bio], T cell responses, Immunology and Allergy, Humans, Lung
Abstract

International audience; The immunopathological pulmonary mechanisms leading to Coronavirus Disease (COVID-19)-related death in adults remain poorly understood. Bronchoalveolar lavage (BAL) and peripheral blood sampling were performed in 74 steroid and non-steroid-treated intensive care unit (ICU) patients (23–75 years; 44 survivors). Peripheral effector SARS-CoV-2-specific T cells were detected in 34/58 cases, mainly directed against the S1 portion of the spike protein. The BAL lymphocytosis consisted of T cells, while the mean CD4/CD8 ratio was 1.80 in non-steroid- treated patients and 1.14 in steroid-treated patients. Moreover, strong BAL SARS-CoV-2 specific T-cell responses were detected in 4/4 surviving and 3/3 non-surviving patients. Serum IFN-γ and IL-6 levels were decreased in steroid-treated patients when compared to non-steroid treated patients. In the lung samples from 3 (1 non-ICU and 2 ICU) additional deceased cases, a lymphocytic memory CD4 T-cell angiopathy colocalizing with SARS-CoV-2 was also observed. Taken together, these data show that disease severity occurs despite strong antiviral CD4 T cell-specific responses migrating to the lung, which could suggest a pathogenic role for perivascular memory CD4 T cells upon fatal COVID-19 pneumonia.

Published
2021

7. Terrorist explosive belt attacks: specific patterns of bone traumas

Author

Yann Delannoy, Laurence Legrand, Isabelle Plu, Bertrand Ludes, Marc Taccoen, Antoine Tracqui, and Tania Delabarde

Subjects
Suicide bomber, Explosive material, Fractures, Multiple, Computer science, 010401 analytical chemistry, Explosions, Forensic Medicine, Fragmentation (weaponry), Computer security, computer.software_genre, 01 natural sciences, 0104 chemical sciences, Pathology and Forensic Medicine, 03 medical and health sciences, Identification (information), 0302 clinical medicine, Blast Injuries, Terrorism, Humans, 030216 legal & forensic medicine, computer
Abstract

In cases of terrorist bomb attacks, the issue of victim identification is the principal aim. For investigators and justice, terrorists must also be identified in a timely manner. The fragmentation of bodies caused by explosive devices however makes this operation difficult. The cases presented correspond to six autopsies of perpetrators carrying explosives. Their explosive belts produced different body sections on areas correlated with the location on the body of carrying explosive charges. Indeed, cross-sectional areas are the signature of the level of explosive devices on the body, and some fracture features through the damage of certain areas of constitutional weaknesses are specific elements to consider. These elements can allow a quick distinction between victims and terrorists, in order to assist in the medico-legal process of identification.

Published
2018

8. Neuroinvasion of SARS-CoV-2 in human and mouse brain

Author

Aaron M. Ring, Akiko Iwasaki, Stéphane Haïk, Kai Zhang, Murat Gunel, Etienne Levavasseur, Alice Lu-Culligan, Yuki Yasumoto, Alba Sprado, Mia Madel Alfajaro, Shelli F. Farhadian, Tamas L. Horvath, Angeliki Louvi, Evelyn Ng, Orr-El Weizman, Syed Kazmi, Guilin Wang, John Wheeler, Jean-Leon Thomas, Craig B. Wilen, Shrikant Mane, Klara Szigeti-Buck, Nicolas Renier, Christopher Castaldi, Eric Song, Feimei Liu, Jaime Heltke, Yile Dai, Kaya Bilguvar, Benjamin Fontes, Neal G. Ravindra, Benjamin Israelow, Danielle Seilhean, Anita Huttner, Isabelle Plu, Ce Zhang, Peiwen Lu, David van Dijk, and Sophie Skriabine

Subjects
Male, 0301 basic medicine, Antagonists & inhibitors, Central nervous system, Immunology, Virus, Article, Infectious Disease and Host Defense, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Cerebrospinal fluid, In vivo, Interferon, Organoid, Animals, Humans, Medicine, Immunology and Allergy, Antibodies, Blocking, skin and connective tissue diseases, 030304 developmental biology, Cerebral Cortex, Neurons, 0303 health sciences, biology, SARS-CoV-2, business.industry, Respiratory disease, fungi, Respiratory infection, COVID-19, Human brain, Middle Aged, medicine.disease, 3. Good health, Organoids, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, biology.protein, Female, Angiotensin-Converting Enzyme 2, Antibody, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Neurological symptoms are frequently observed in COVID-19. Here, we examine the neuroinvasive potential of SARS-CoV-2 and demonstrate infection of neurons in three separate approaches: mouse model, human brain organoid, and autopsy of COVID-19 patients., Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2., Graphical Abstract

Published
2021
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9. CC17 group B Streptococcus exploits integrins for neonatal meningitis development

Author

Romain Deshayes de Cambronne, Lionel Costa, Caroline Rambaud, Martine Cohen-Salmon, Abdelouhab Bouaboud, Asmaa Tazi, Anne-Cécile Boulay, Anne-Sophie Bourrel, Agnès Fouet, Amandine Picart, Cristina Candeias, Claire Poyart, Julie Guignot, Guillaume Bouvier, Isabelle Plu, Cyril Anjou, Corinne Albiges-Rizo, Eva Faurobert, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Bioinformatique structurale - Structural Bioinformatics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Neuropathologie Raymond Escourolle, 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), Hôpital Raymond Poincaré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre national de Référence des Streptocoques (CNR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by Agence Nationale de la Recherche (ANR, grant StrepB2brain, ANR-17-CE15-0026-01). LC is a recipient of a postdoctoral fellowship from the ANR (StrepB2brain). ASB is a doctoral fellow funded by Université de Paris. RDDC was funded by FERCM., We are grateful to Pierre-Olivier Couraud (INSERM, Paris, France) for the gift of hCMEC/D3 cells, Alain Duperray for the gift of CHO-ICAM1 cells, Yoshikazu Takada for the gift of CHO-αvβ3 cells, and Glen Ulett for the gift of the GFP plasmid. We are extremely grateful to Nathalie Strazielle and Jean-François Ghersi-Egea from BIP (CRNL, Lyon, France) for choroid plexus isolation and helpful comments. We thank Matthieu Benard from the animal facility of the Institut Cochin and Marine Gaillard for their help with animal experiments and Thomas Guilbert and Fabienne Regnier for their help with brain slice clarification. We also thank the Imag’IC and HistIM core facilities of the Cochin Institute and Shaynoor Dramsi for anti-Srr1 antibody and for critical reading of the manuscript., ANR-17-CE15-0026,strepB2brain,Franchissement de la barrière hémato-méningée par le Streptocoque du groupe B hyper-virulent CC17(2017), Hôpitaux Universitaires Paris Centre (CHU Paris Centre), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Fouet, Agnès, Franchissement de la barrière hémato-méningée par le Streptocoque du groupe B hyper-virulent CC17 - - strepB2brain2017 - ANR-17-CE15-0026 - AAPG2017 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], 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 Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Group B Streptococcus, Integrins, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Clone (cell biology), medicine.disease_cause, Bacterial Adhesion, blood brain barrier (BBB), 0302 clinical medicine, Bacterial infections, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internalization, reproductive and urinary physiology, media_common, Infectious disease, Streptococcus, meningitis, General Medicine, 3. Good health, Srr2, Blood-Brain Barrier, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Meningitis, Research Article, integrin, media_common.quotation_subject, Integrin, Biology, Microbiology, Neonatal meningitis, Cell Line, Meningitis, Bacterial, Streptococcus agalactiae, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Streptococcal Infections, medicine, Animals, Humans, Receptors, Vitronectin, Adhesins, Bacterial, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Integrin alphaVbeta3, bacterial infections and mycoses, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Rats, Bacterial adhesin, 030104 developmental biology, Animals, Newborn, biology.protein, neonatal susceptibility, bacteria, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, CC17
Abstract

We are grateful to Pierre-Olivier Couraud (INSERM, Paris, France) for the gift of hCMEC/D3 cells, Alain Duperray for the gift of CHO-ICAM1 cells, Yoshikazu Takada for the gift of CHO-αvβ3 cells, and Glen Ulett for the gift of the GFP plasmid. We are extremely grateful to Nathalie Strazielle and Jean-François Ghersi-Egea from BIP (CRNL, Lyon, France) for choroid plexus isolation and helpful comments. We thank Matthieu Benard from the animal facility of the Institut Cochin and Marine Gaillard for their help with animal experiments and Thomas Guilbert and Fabienne Regnier for their help with brain slice clarification. We also thank the Imag’IC and HistIM core facilities of the Cochin Institute and Shaynoor Dramsi for anti-Srr1 antibody and for critical reading of the manuscript.; International audience; Group B Streptococcus (GBS) is the major cause of human neonatal infections. A single clone, designated CC17-GBS, accounts for more than 80% of meningitis cases, the most severe form of the infection. However, the events allowing blood-borne GBS to penetrate the brain remain largely elusive. In this study, we identified the host transmembrane receptors α5β1 and αvβ3 integrins as the ligands of Srr2, a major CC17-GBS-specific adhesin. Two motifs located in the binding region of Srr2 were responsible for the interaction between CC17-GBS and these integrins. We demonstrated in a blood-brain-barrier cellular model that both integrins contributed to the adhesion and internalization of CC17-GBS. Strikingly, both integrins were overexpressed during the postnatal period in the brain vessels of the blood-brain barrier and blood-cerebrospinal fluid barrier and contributed to juvenile susceptibility to CC17 meningitis. Finally, blocking these integrins decreased the ability of CC17-GBS to cross into the CNS of juvenile mice in an in vivo model of meningitis. Our study demonstrated that CC17-GBS exploits integrins in order to cross the brain vessels, leading to meningitis. Importantly, it provides host molecular insights into neonate's susceptibility to CC17-GBS meningitis, thereby opening new perspectives for therapeutic and prevention strategies of GBS-elicited meningitis.

Published
2021

10. Low rates of immediate coronary angiography among young adults resuscitated from sudden cardiac arrest

Author

Eloi Marijon, Daniel Jost, Florence Dumas, Lionel Lamhaut, Nicolas Lellouche, Christian Spaulding, Frankie Beganton, Sebastian Voicu, Bruno Mégarbane, Nicole Karam, David S. Celermajer, Olivier Varenne, Bertrand Ludes, Alain Cariou, Fabrice Extramiana, Antoine Lafont, Estelle Gandjbakhch, Kumar Narayanan, Julien Rischard, Vincent Algalarrondo, Karim Wahbi, Georgios Sideris, Isabelle Plu, on behalf Paris-SDEC investigators, Wulfran Bougouin, Xavier Jouven, Victor Waldmann, Ardalan Sharifzadehgan, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Privé Jacques Cartier [Massy], Service de médecine d'urgence [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lariboisière-Fernand-Widal [APHP], Service de Cardiologie [CHU Pitié-Salpêtrière], 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), Brigade de sapeurs pompiers de Paris (BSPP), SAMU 75 [Paris], CHU Necker - Enfants Malades [AP-HP], Service d'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP), Service de Cardiologie [CHU Cochin], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Unité de Soins Intensifs [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CCSD, Accord Elsevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Coronary angiography, Adult, Male, medicine.medical_specialty, Acute coronary syndrome, Paris, Adolescent, Epidemiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Emergency Nursing, Coronary Angiography, Coronary artery disease, Sudden cardiac death, Percutaneous coronary intervention, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Humans, Young adult, business.industry, 030208 emergency & critical care medicine, Sudden cardiac arrest, medicine.disease, Cardiac arrest, 3. Good health, [SDV] Life Sciences [q-bio], Death, Sudden, Cardiac, Emergency Medicine, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Out-of-Hospital Cardiac Arrest
Abstract

International audience; Aim: Coronary artery disease (CAD) has recently been emphasized as a major cause of sudden cardiac arrest (SCA) in young adults. We aim to assess the rate of immediate coronary angiography performance in young patients resuscitated from SCA.Methods: From May 2011 to May 2017, all cases of out-of-hospital SCA aged 18-40 years alive at hospital admission were prospectively included in 48 hospitals of the Great Paris area. Cardiovascular causes of SCA were centrally adjudicated, and management including immediate coronary angiography performance was assessed.Results: Out of 3579 SCA admitted alive, 409 (11.4%) patients were under 40 years of age (32.3 ± 6.2 years, 69.7% males), with 244 patients having a definite cause identified. Among those, CAD accounted for 72 (29.5%) cases, of which 64 (88.9%) were acute coronary syndromes. The rate of immediate coronary angiography was only 41.7% compared to 65.1% among those ≥40-years (P < 0.001). During the study period, while the rate of immediate coronary angiography increased from 60.5% to 70.3% (P < 0.001) in patients aged ≥40 years, the rate in patients aged less than 40 years remained stable (43.5% to 45.3%, P = 0.795). Patients younger than 40 years were significantly less likely to undergo immediate coronary angiography (OR = 0.34, 95% CI: 0.25-0.47), although early angiography was associated with survival at hospital discharge (OR = 2.68, 95% CI: 1.21-6.00).Conclusion: CAD is the first cause of SCA in young adults aged less than 40 years. The observed low rates of immediate coronary angiography suggest a missed opportunity for early intervention.

Published
2020

11. Identification of Umbre Orthobunyavirus as a Novel Zoonotic Virus Responsible for Lethal Encephalitis in 2 French Patients with Hypogammaglobulinemia

Author

Franck Bielle, Sophie Demeret, David Brassat, Philippe Pérot, Susana Boluda, Fabrice Bonneville, Charles Duyckaerts, Anne Huard de Verneuil, Grégory L'Ambert, Bertrand Mathon, Marie Bernadette Delisle, Delphine Chrétien, Jan Hellert, Karine Bollore, Vincent Foulongne, Isabelle Plu, Karima Mokhtari, Muriel Coulpier, Claire Fieschi, Patricia Gil, Edouard de Sousa Cunha, Thérèse Couderc, Marc Eloit, Marion Malphettes, Marie Flamand, Serafin Gutierrez, Carole Tamietti, Thomas Bigot, Danielle Seilhean, Sarah Temmam, Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris] (IP), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], 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), 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), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Etablissement français du don du sang [Montpellier], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Entente Interdépartementale pour la démoustication du littoral méditerranéen (EID), Virologie Structurale - Structural Virology, Virologie UMR1161 (VIRO), École nationale vétérinaire - Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre national de référence des Agents Transmissibles Non Conventionnels, Institut de Veille Sanitaire (INVS), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle Neurosciences [CHU Toulouse], Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], École nationale vétérinaire - Alfort (ENVA), This work was supported by the Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant number ANR-10-LABX-62-IBEID)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Pérot, Philippe, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Pasteur [Paris], Laboratoire de Neuropathologie Raymond Escourolle, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], École nationale vétérinaire d'Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Pôle neurosciences [Hôpital de Purpan - Toulouse], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), École nationale vétérinaire d'Alfort (ENVA), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Microbiology (medical), [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Orthobunyavirus, Culex, viruses, [SDE.MCG]Environmental Sciences/Global Changes, Population, Arbovirus, Virus, Serology, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Agammaglobulinemia, Umbre virus, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Culex pipiens, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, education, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, education.field_of_study, metatranscriptomics, biology, business.industry, biology.organism_classification, medicine.disease, Virology, 3. Good health, Europe, [SDE.MCG] Environmental Sciences/Global Changes, 030104 developmental biology, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Encephalitis, next-generation sequencing, France, business, 030217 neurology & neurosurgery
Abstract

Background Human encephalitis represents a medical challenge from a diagnostic and therapeutic point of view. We investigated the cause of 2 fatal cases of encephalitis of unknown origin in immunocompromised patients. Methods Untargeted metatranscriptomics was applied on the brain tissue of 2 patients to search for pathogens (viruses, bacteria, fungi, or protozoans) without a prior hypothesis. Results Umbre arbovirus, an orthobunyavirus never previously identified in humans, was found in 2 patients. In situ hybridization and reverse transcriptase–quantitative polymerase chain reaction (RT-qPCR) showed that Umbre virus infected neurons and replicated at high titers. The virus was not detected in cerebrospinal fluid by RT-qPCR. Viral sequences related to Koongol virus, another orthobunyavirus close to Umbre virus, were found in Culex pipiens mosquitoes captured in the south of France where the patients had spent some time before the onset of symptoms, demonstrating the presence of the same clade of arboviruses in Europe and their potential public health impact. A serological survey conducted in the same area did not identify individuals positive for Umbre virus. The absence of seropositivity in the population may not reflect the actual risk of disease transmission in immunocompromised individuals. Conclusions Umbre arbovirus can cause encephalitis in immunocompromised humans and is present in Europe.

Published
2020

12. Increased prevalence of granulovacuolar degeneration in C9orf72 mutation

Author

Charles Duyckaerts, Mari Yoshida, Susana Boluda, Gen Sobue, Yuichi Riku, Takashi Ando, Stéphanie Millecamps, Masahisa Katsuno, Isabelle Le Ber, Danielle Seilhean, François Salachas, Isabelle Plu, 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 [APHP]-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'éthique médicale et médecine légale (LEM), Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fédération des Maladies du Système Nerveux, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Department of neurology, The University of Tokyo, Department of Neuropathology, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Centre National de la Recherche Scientifique (CNRS), 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), The University of Tokyo (UTokyo), CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, Male, Pathology, TDP-43, [SDV]Life Sciences [q-bio], medicine.disease_cause, 0302 clinical medicine, C9orf72, Prevalence, Amyotrophic lateral sclerosis, Fisher's exact test, Inclusion Bodies, Neurons, Mutation, Granulovacuolar degeneration, DNA Repeat Expansion, Neurofibrillary Tangles, Frontotemporal lobar degeneration, Middle Aged, 3. Good health, DNA-Binding Proteins, symbols, Female, FTLD, medicine.medical_specialty, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, symbols.namesake, Dipeptide repeat, mental disorders, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Aged, C9orf72 Protein, business.industry, Amyotrophic Lateral Sclerosis, nutritional and metabolic diseases, Charged multivesicular body protein 2B, medicine.disease, nervous system diseases, 030104 developmental biology, Neurology (clinical), Frontotemporal Lobar Degeneration, ALS, business, 030217 neurology & neurosurgery
Abstract

International audience; Granulovacuolar degeneration (GVD) is usually found in Alzheimer's disease (AD) cases or in elderly individuals. Its severity correlates positively with the density of neurofibrillary tangles (NFTs). Mechanisms underlying GVD formation are unknown. We assessed the prevalence and distribution of GVD in cases with TDP-43-related frontotemporal lobar degeneration (FTLD-TDP) and amyotrophic lateral sclerosis (ALS-TDP). Consecutively autopsied cases with FTLD/ALS-TDP and C9orf72 mutations (FTLD/ALS-C9; N = 29), cases with FTLD/ALS-TDP without C9orf72 mutations (FTLD/ALS-nonC9; N = 46), and age-matched healthy controls (N = 40) were studied. The prevalence of GVD was significantly higher in the FTLD/ALS-C9 cases (26/29 cases) than in the FTLD/ALS-nonC9 cases (15/46 cases; Fisher exact test; p

Published
2019

13. Seeding and propagation of lesions in neurodegenerative diseases: a new paradigm

Author

Charles. Duyckaerts, Danielle Seilhean, Véronique Sazdovitch, Isabelle Plu, Benoît Delatour, Marie-Claude Potier, Neurologie et thérapeutique expérimentale, IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), 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 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), Rousselle, Théo, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (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)-Centre National de la Recherche Scientifique (CNRS), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], Amyloid beta-Peptides, [SDV]Life Sciences [q-bio], alpha-Synuclein, Humans, Neurodegenerative Diseases, tau Proteins, Proteostasis Deficiencies
Abstract

International audience; Specific extracellular deposits, glial or neuronal inclusions help defining an ever increasing number of neurodegenerative diseases. Deposits or inclusions are aggregates of proteins: Aβ peptide and tau proteins in Alzheimer disease, a-synuclein in Parkinson disease, for instance. The protein that specifically accumulates in a given disease may be modified by a mutation that can increase its aggregability. Most often the sequence of the protein is normal. Misfolding, despite the protein normal sequence, is then considered the cause of the aggregation. The ubiquitin-proteasome system detects and eliminates misfolded proteins from the cell. Almost all the inclusions are indeed labeled by anti-ubiquitin antibodies, but, in neurodegenerative diseases, the system is unable to get rid of them. The large protein aggregates constituting the inclusions are poorly reactive. Their formation has been consi- dered a defense mechanism, protecting the cell against the toxic action of soluble oligomers that are, in that hypothesis, the real toxic agent, neutralized through aggregation. Soluble oligomers of Aβ peptide, tau or a-synuclein,for instance, have indeed been isolated and were shown to be toxic. In the prion hypothesis, the misfolded configuration may be passed from the misfolded to the normal protein by simple contact. There are indeed experimental evidences suggesting that this prion-like mechanism does occur in transgenic rodent models of Aβ, tau or a-synuclein pathology. This might be the explanation of thepropagation of the pathology through connections, observed in many neurodegenerative diseases. There is currently no epidemiological data suggesting a transmission of neurodegenerative diseases, comparable to the transmission of Creutzfeldt-Jakob or other prion diseases. The prion-like mechanisms of protein aggregation observed in the experimental animals or suspected through human neuropathology make that possibility not as remote as previously thought.

Published
2018

14. Characteristics and clinical assessment of unexplained sudden cardiac arrest in the real-world setting: focus on idiopathic ventricular fibrillation

Author

Victor, Waldmann, Wulfran, Bougouin, Nicole, Karam, Florence, Dumas, Ardalan, Sharifzadehgan, Estelle, Gandjbakhch, Vincent, Algalarrondo, Kumar, Narayanan, Alexandre, Zhao, Denis, Amet, Daniel, Jost, Guillaume, Geri, Lionel, Lamhaut, Frankie, Beganton, Bertrand, Ludes, Patrick, Bruneval, Isabelle, Plu, Françoise, Hidden-Lucet, Juliette, Albuisson, Thomas, Lavergne, Olivier, Piot, Christine, Alonso, Antoine, Leenhardt, Nicolas, Lellouche, Fabrice, Extramiana, Alain, Cariou, Xavier, Jouven, and Eloi, Marijon

Subjects
Adult, Male, Arrhythmias, Cardiac, Coronary Artery Disease, Middle Aged, Coronary Angiography, Magnetic Resonance Imaging, Electrocardiography, Death, Sudden, Cardiac, Cardiac Conduction System Disease, Echocardiography, Ventricular Fibrillation, Humans, Family, Female, Genetic Testing, Survivors, Cardiomyopathies, Out-of-Hospital Cardiac Arrest, Aged
Abstract

Recent studies have shown that in more than half of apparently unexplained sudden cardiac arrests (SCA), a specific aetiology can be unmasked by a careful evaluation. The characteristics and the extent to which such cases undergo a systematic thorough investigation in real-life practice are unknown.Data were analysed from an ongoing study, collecting all cases of out-of-hospital cardiac arrest in Paris area. Investigations performed during the index hospitalization or planned after discharge were gathered to evaluate the completeness of assessment of unexplained SCA. Between 2011 and 2016, among the 18 622 out-of-hospital cardiac arrests, 717 survivors (at hospital discharge) fulfilled the definition of cardiac SCA. Of those, 88 (12.3%) remained unexplained after electrocardiogram, echocardiography, and coronary angiography. Cardiac magnetic resonance imaging yielded the diagnosis in 25 (3.5%) cases, other investigations accounted for 14 (2.4%) additional diagnoses, and 49 (6.8%) patients were labelled as idiopathic ventricular fibrillation (IVF) (48.7 ± 15 years, 69.4% male). Among those labelled IVF, only 8 (16.3%) cases benefited from a complete workup (including pharmacological testing). Younger patients [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.80-22.26] and those admitted to university centres (OR 3.60, 95% CI 1.12-12.45) were more thoroughly investigated. Genetic testing and family screening were initiated in only 9 (18.4%) and 12 (24.5%) cases, respectively.Our findings suggest that complete investigations are carried out in a very low proportion of unexplained SCA. Standardized, systematic approaches need to be implemented to ensure that opportunities for specific therapies and preventive strategies (including relatives) are not missed.

Published
2017

15. Frontotemporal lobar degeneration: Diversity of FTLD lesions

Author

Franck Bielle, Isabelle Plu, Danielle Seilhean, and Charles Duyckaerts

Subjects
Pathology, medicine.medical_specialty, Semantic dementia, tau Proteins, Biology, Genetic Heterogeneity, Progranulins, Progressive nonfluent aphasia, C9orf72, mental disorders, medicine, Humans, nutritional and metabolic diseases, Frontotemporal lobar degeneration, medicine.disease, nervous system diseases, Multisystem proteinopathy, Basophilic, Phenotype, Tauopathies, Neurology, Intercellular Signaling Peptides and Proteins, RNA-Binding Protein FUS, Pick's disease, Neurology (clinical), Frontotemporal Lobar Degeneration, Neuroscience, Frontotemporal dementia
Abstract

Frontotemporal lobar degeneration (FTLD) is a heterogeneous group including both sporadic and familial diseases, characterized by a macroscopic alteration. It may correspond to various cognitive syndromes: behavioral variant of frontotemporal dementia (bvFTD), progressive nonfluent aphasia, and semantic dementia. The neuropathologic classification is now based on identification of the protein that accumulates in neurons and glia: Tau, TAR DNA Binding Protein 43 (TDP-43), and FUsed in Sarcoma (FUS). The disorders in which the corresponding proteins accumulate have been named FTLD-Tau, FTLD-TDP, and FTLD-FUS. FTLD-Tau includes sporadic cases (e.g. Pick's disease) and Tau mutations. FTLD-TDP are subdivided within four types (A, B, C, D) according to the shape and distribution of TDP-43 positive lesions within the associative frontal cortex. The FTLD-FUS group includes atypical FTLD with ubiquitinated lesions (FTLD-U), Neuronal Intermediate Filament Inclusion Disease (NIFID) and Basophilic Inclusion Body Disease (BIBD).

Published
2013

16. Pregnancy, Cesarean, and Pheochromocytoma: A Case Report and Literature Review

Author

Dominique Lecomte, Isabelle Sec, D. Barres, and Isabelle Plu

Subjects
Adult, Gestational hypertension, medicine.medical_specialty, endocrine system diseases, Adrenal Gland Neoplasms, Pulmonary Edema, Pheochromocytoma, Pathology and Forensic Medicine, Preeclampsia, Catecholamines, Fatal Outcome, Pregnancy, Genetics, medicine, Humans, Medical history, Intraoperative Complications, Forensic Pathology, Eclampsia, Cesarean Section, Obstetrics, business.industry, medicine.disease, Heart Arrest, Gestational diabetes, Anesthesia, Hypertension, Female, Maternal death, business
Abstract

A 43-year-old full-term pregnant woman (gravida 2, para 1, medical history of gestational diabetes mellitus) developed a sudden and malignant hypertension with hemoptysis, sweat, and tachycardia during a scheduled C-section. A dead newborn was delivered and was successfully resuscitated. The mother died after resistant cardiac arrest. Autopsy and pathological analyses revealed an acute pulmonary edema and a necrotic and hemorrhagic voluminous tumor of the left adrenal gland, which was a pheochromocytoma. Pheochromocytoma is a rare tumor of the adrenal glands which secretes catecholamines. In pregnant women, its symptoms can mimic gestational hypertension, preeclampsia or eclampsia, and gestational diabetes mellitus. The gestational diabetes mellitus was presumed to be a symptom of the pheochromocytoma, and cardiopulmonary failure the result from the necrosis of the tumor provoked by gravid uterus compression. From a medico-legal point of view, the tumor could not have been suspected during the pregnancy.

Published
2013

17. [Modern biology, imagery and forensic medicine: contributions and limitations in examination of skeletal remains]

Author

Dominique, Lecomte, Isabelle, Plu, and Alain, Froment

Subjects
Adult, Male, Sex Characteristics, Time Factors, Anthropometry, Radiometric Dating, DNA, Forensic Medicine, Body Height, Bone and Bones, Imaging, Three-Dimensional, Blood Stains, Age Determination by Skeleton, Cause of Death, Face, Image Processing, Computer-Assisted, Forensic Anthropology, Humans, Female, Child, Tomography, X-Ray Computed, Skeleton
Abstract

Forensic examination is often requested when skeletal remains are discovered. Detailed visual observation can provide much information, such as the human or animal origin, sex, age, stature, and ancestry, and approximate time since death. New three-dimensional imaging techniques can provide further information (osteometry, facial reconstruction). Bone chemistry, and particularly measurement of stable or unstable carbon and nitrogen isotopes, yields information on diet and time since death, respectively. Genetic analyses of ancient DNA are also developing rapidly. Although seldom used in a judicial context, these modern anthropologic techniques are nevertheless available for the most complex cases.

Published
2013

18. [Migrants' health, the experience of a network providing access to healthcare]

Author

Sophie, Emery, Isabelle, Plu, Jean-Julien, Atsou, Catherine, Suarez, and Christian, Hervé

Subjects
Patient Care Team, Primary Care Nursing, Chronic Disease, Emigrants and Immigrants, Humans, Interdisciplinary Communication, France, Cooperative Behavior, Cultural Competency, Vulnerable Populations, Health Services Accessibility
Abstract

Migrants form a heterogeneous population which requires specific medical-social care. Networks providing access to healthcare are one of the solutions enabling migrants to benefit from curative and preventative primary care.

Published
2011

20. [Fetuses born lifeless: new representations and new rights.]

Author

Grégoire, Moutel, Michèle, Goussot-Souchet, Isabelle, Plu, Marion, Pierre, Thomas, Leclercq, Jean-Christophe, Coffin, Nathalie, Duchange, Laboratoire d'éthique médicale et médecine légale (LEM), Université Paris Descartes - Paris 5 (UPD5)-Réseau Inserm de Recherche en éthique médicale, Unité d'accès aux soins et droits des patients, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Corentin Celton [Issy-les-Moulineaux], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de médecine de l'enfant et de l'adolescent, hôpital Sud, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Duchange, Nathalie, Laboratoire d'éthique médicale et médecine légale ( LEM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Réseau Inserm de Recherche en éthique médicale, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpital Corentin Celton [Issy-les-Moulineaux], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], and Hôpital Sud

Subjects
Human Rights, Pregnancy, Infant, Newborn, Humans, [ SDV.ETH ] Life Sciences [q-bio]/Ethics, Female, France, Registries, Stillbirth, [SDV.ETH] Life Sciences [q-bio]/Ethics, [SDV.ETH]Life Sciences [q-bio]/Ethics
Abstract

International audience; A february-2008 rule about << children born lifeless >> stressed that << every fetus born lifeless >> could be registered at the General Register Office. This rule, which was followed in 2009 by the implementation of new procedures to deal with dead fetuses, highlighted that this topic is more and more becoming an important public issue. The rights for parents to choose has now been recognized, bringing about new questions for health professionals. Another point is which symbolism is to be given to dead fetuses to alleviate couples' suffering, without being too ideological, i.e. seeing fetuses as persons. This change also makes professionals reconsider public health system priorities, and this at a very particular time. Indeed, as parent mourning has now been made easier through registration at the General Register Office, there has not been any rule yet linking national epidemiological registration and fetal death in France. double dagger.

Published
2010

21. Ethical issues arising from the requirement to sign a consent form in palliative care

Author

Irène Purssell-François, Isabelle Plu, Grégoire Moutel, Christian Hervé, Françoise Ellien, Service de médecine légale (Institut médico-légal et Unité médico-judiciaire) (CHU de Dijon), Centre Hospitalier Universitaire de Dijon (CHU Dijon), Laboratoire d'éthique médicale et médecine légale (LEM), Université Paris Descartes - Paris 5 (UPD5), Réseau SPES, Réseau Soins Palliatifs Essonne Sud, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and Duchange, Nathalie

Subjects
Health (social science), Palliative care, Attitude of Health Personnel, education, MEDLINE, Legislation, Article, Consent Forms, 03 medical and health sciences, 0302 clinical medicine, Arts and Humanities (miscellaneous), Nursing, 030502 gerontology, Health care, Medicine, Humans, 030212 general & internal medicine, Physician-Patient Relations, Ethical issues, business.industry, Health Policy, Palliative Care, Sign (semiotics), Continuity of Patient Care, Patient Acceptance of Health Care, [SDV.ETH] Life Sciences [q-bio]/Ethics, 3. Good health, [SDV.ETH]Life Sciences [q-bio]/Ethics, Issues, ethics and legal aspects, Guardian, Psychological aspects, France, 0305 other medical science, business
Abstract

International audience; French healthcare networks aim to help healthcare workers to take care of patients by improving cooperation, coordination and the continuity of care. When applied to palliative care in the home, they facilitate overall care including medical, social and psychological aspects. French legislation in 2002 required that an information document explaining the functioning of the network should be given to patients when they enter a healthcare network. The law requires that this document be signed. Ethical issues arise from this legislation with regard to the validity of the signature of dying patients. Signature of the consent form by a guardian or trustee, a designated person--the Person of Trust--transforms the doctor-patient relationship into a triangular doctor-patient-third-party relationship.

Published
2008

22. Ethical issues arising from the requirement to provide written information in palliative care

Author

Christian Hervé, Irène Purssell-François, Grégoire Moutel, Isabelle Plu, Cécile Manaouil, Nathanael Lapidus, Françoise Ellien, Laboratoire d'éthique médicale et médecine légale (LEM), Université Paris Descartes - Paris 5 (UPD5), Service de médecine légale (Institut médico-légal et Unité médico-judiciaire) (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Consultation de Médecine Légale, CHU Amiens-Picardie, and Duchange, Nathalie

Subjects
Palliative care, Legislation, Disclosure, Disease, 03 medical and health sciences, 0302 clinical medicine, Nursing, Informed consent, Health care, Humans, Medicine, physician patient relationship, Ethics, Medical, healthcare networks, 030212 general & internal medicine, Physician-Patient Relations, Terminal Care, palliative care, Ethical issues, business.industry, informed consent, Sign (semiotics), General Medicine, Continuity of Patient Care, [SDV.ETH] Life Sciences [q-bio]/Ethics, ethics, 3. Good health, [SDV.ETH]Life Sciences [q-bio]/Ethics, Anesthesiology and Pain Medicine, 030220 oncology & carcinogenesis, France, Psychological aspects, business
Abstract

French Healthcare Networks aim to help healthcare workers take care of patients by improving co-operation, co-ordination and the continuity of care. When applied to palliative care in the home, they facilitate overall care, including medical, social and psychological aspects. French legislation in 2002 required that an information document explaining the functioning of the Network should be given to patients when they enter a Healthcare Network. Ethical problems arise from this legislation with regard to providing terminal patients with explicit information upon their entry into the palliative phase of the disease, and requiring them to sign the document. It highlights the limitations of this practice, and the gap between the legislation and the nature of the physician-patient relationship in palliative care.

Published
2007

23. [Domestic violence: what are the difficulties for practitioners? Analysis of interviews among 19 practitioners within a town-hospital care network aimed at a global approach of patients]

Author

Irène, François, Grégoire, Moutel, Isabelle, Plu, Isabelle, Fauriel, and Christian, Hervé

Subjects
Adult, Male, Domestic Violence, Health Knowledge, Attitudes, Practice, Health Care Surveys, Humans, Physicians, Family, Female, France, Middle Aged, Practice Patterns, Physicians'
Abstract

Using a qualitative approach of medical practice, the aim of this study was to specify the difficulties and pitfalls that practitioners are confronted with regarding persons suffering from domestic violence.Nineteen practitioners agreed to participate in an assessment of their attitude towards the recognition and management of domestic violence. These practitioners were aware of the medico-social dimension of their practice. A questionnaire was proposed during an interview conducted in all participants by the same investigator. The interviews were reviewed and analysed by two assessors. In the case of discordance, a second reading was made so that a consensus could be reached.The interview lasted a mean of 40 minutes. The practitioners interviewed (11 men and 8 women) were 29 to 60 years old and had practiced for 6 months to 36 years. They all knew of such violence, notably through its physical impact, but this did not permit them to recognise all the forms of violence. The medico-legal tools at their disposal are not clearly understood and are often not adapted to the demands of their female patients.The notion of global management required in such cases must be developed and specified in medical training, because the recognition and management of "battered women" is a question of personal dignity.

Published
2005

24. Why Did Most French GPs Choose Not to Join the Voluntary National Pay-for-Performance Program?

Author

Jonathan Sicsic, Isabelle Plu, Olivier Saint-Lary, Erik Bernard, Carine Franc, and Irène François-Purssell

Subjects
Adult, Male, Attitude of Health Personnel, media_common.quotation_subject, education, lcsh:Medicine, Pay for performance, Primary care, Nursing, General Practitioners, Risk Factors, Surveys and Questionnaires, Perception, Humans, Medicine, Marketing, lcsh:Science, Reimbursement, Incentive, Reimbursement, Aged, media_common, Multidisciplinary, Primary Health Care, business.industry, lcsh:R, Middle Aged, Cross-Sectional Studies, Incentive, Turnover, Global Positioning System, Female, lcsh:Q, France, business, Medical ethics, Research Article
Abstract

BACKGROUND: In 2009, a voluntary pay for performance (P4P) scheme for primary care physicians was introduced in France through the 'Contract for Improving Individual Practice' (CAPI). Although the contract could be interrupted at any time and without any penalty, two-thirds of French general practitioners chose not to participate. We studied what factors motivated general practitioners not to subscribe to the P4P contract, and particularly their perception of the ethical risks that may be associated with adhering to a CAPI. METHOD: A cross-sectional survey among French general practitioners using an online questionnaire based on focus group discussion results. Descriptive and multivariate statistical analyses with logistic regression. RESULTS: A sample of 1,016 respondents, representative of French GPs. The variables that were associated with the probability of not signing a CAPI were "discomfort that patients were not informed of the signing of a P4P contract by their doctors" (OR = 8.24, 95% CI = 4.61-14.71), "the risk of conflicts of interest" (OR = 4.50, 95% CI = 2.42-8.35), "perceptions by patients that doctors may risk breaching professional ethics" (OR = 4. 35, 95% CI = 2.43-7.80) and "the risk of excluding the poorest patients" (OR = 2.66, 95% CI = 1.53-4.63). CONCLUSION: The perception of ethical risks associated with P4P may have hampered its success. Although the CAPI was extended to all GPs in 2012, our results question the relevance of the program itself by shedding light on potential adverse effects.

Published
2013

25. Transmission of amyloid-beta and tau pathologies is associated with cognitive impairments in a primate

Author

Charles Duyckaerts, Martine Guillermier, Stéphane Haïk, Fanny Petit, Marc Dhenain, Suzanne Lam, Jean-Luc Picq, Anne-Sophie Hérard, Luc Buée, Susana Boluda, Sabiha Eddarkaoui, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-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-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)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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), Excellence Laboratory LabEx DISTALZ, Université de Lille, CHU Lille, Fonctionnement et Dysfonctionnement Cognitifs : Les âges de la vie (DysCo), Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN), Brain Bank Neuro-C. E. B. Neuropathology Network: Franck Letournel, Marie-Laure Martin-Négrier, Maxime Faisant, Catherine Godfraind, Jean Boutonnat, Claude-Alain Maurage, Vincent Deramecourt, Mathilde Duchesne, David Meyronet, Tanguy Fenouil, André Mauès de Paula, Valérie Rigau, Fanny Vandenbos-Burel, Danielle Seilhean, Charles Duyckaerts, Susana Boluda, Isabelle Plu, Dan Christian Chiforeanu, Annie Laquerrière, Florent Marguet, Béatrice Lannes, Benoît Lhermitte, 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)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), BUEE, Luc, Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pathology, medicine.medical_specialty, Tau pathology, Amyloid beta, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Iatrogenic Disease, tau Proteins, Cerebral atrophy, Corpus callosum, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, Cortex (anatomy), medicine, Animals, Humans, Transmission, Cognitive Dysfunction, Cognitive decline, RC346-429, 030304 developmental biology, 0303 health sciences, Amyloid beta-Peptides, biology, business.industry, Research, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Brain, Human brain, Alzheimer's disease, medicine.disease, Entorhinal cortex, 3. Good health, medicine.anatomical_structure, Posterior cingulate, biology.protein, Prion, Neurology. Diseases of the nervous system, Neurology (clinical), Amyloid-β pathology, Cheirogaleidae, business, 030217 neurology & neurosurgery
Abstract

Amyloid-β (Aβ) pathology transmission has been described in patients following iatrogenic exposure to compounds contaminated with Aβ proteins. It can induce cerebral Aβ angiopathy resulting in brain hemorrhages and devastating clinical impacts. Iatrogenic transmission of tau pathology is also suspected but not experimentally proven. In both scenarios, lesions were detected several decades after the putatively triggering medico-surgical act. There is however little information regarding the cognitive repercussions in individuals who do not develop cerebral hemorrhages. In the current study, we inoculated the posterior cingulate cortex and underlying corpus callosum of young adult primates (Microcebus murinus) with either Alzheimer’s disease or control brain extracts. This led to widespread Aβ and tau pathologies in all of the Alzheimer-inoculated animals following a 21-month-long incubation period (n = 12) whereas none of the control brain extract-inoculated animals developed such lesions (n = 6). Aβ deposition affected almost all cortical regions. Tau pathology was also detected in Aβ-deposit-free regions distant from the inoculation sites (e.g. in the entorhinal cortex), while some regions adjacent, but not connected, to the inoculation sites were spared (e.g. the occipital cortex). Alzheimer-inoculated animals developed cognitive deficits and cerebral atrophy compared to controls. These pathologies were induced using two different batches of Alzheimer brain extracts. This is the first experimental demonstration that tau can be transmitted by human brain extracts inoculations in a primate. We also showed for the first time that the transmission of widespread Aβ and tau pathologies can be associated with cognitive decline. Our results thus reinforce the need to organize a systematic monitoring of individuals who underwent procedures associated with a risk of Aβ and tau iatrogenic transmission. They also provide support for Alzheimer brain-inoculated primates as relevant models of Alzheimer pathology.

Published
2021

26. Association of Clinical, Biological, and Brain Magnetic Resonance Imaging Findings With Electroencephalographic Findings for Patients With COVID-19

Author

Virginie, Lambrecq, Aurélie, Hanin, Esteban, Munoz-Musat, Lydia, Chougar, Salimata, Gassama, Cécile, Delorme, Louis, Cousyn, Alaina, Borden, Maria, Damiano, Valerio, Frazzini, Gilles, Huberfeld, Frank, Landgraf, Vi-Huong, Nguyen-Michel, Phintip, Pichit, Aude, Sangare, Mario, Chavez, Capucine, Morélot-Panzini, Elise, Morawiec, Mathieu, Raux, Charles-Edouard, Luyt, Pierre, Rufat, Damien, Galanaud, Jean-Christophe, Corvol, Catherine, Lubetzki, Benjamin, Rohaut, Sophie, Demeret, Nadya, Pyatigorskaya, Lionel, Naccache, Vincent, Navarro, Safia, Said, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], 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)-Centre National de la Recherche Scientifique (CNRS), Service de Neurophysiologie [CHU Pitié-Salpêtrière], 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 Neuroradiologie [CHU Pitié-Salpêtrière], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Cardiologie [CHU Pitié-Salpêtrière], Service de Département d'Information Médicale [CHU Pitié-Salpêtrière] (DIM), Unité fonctionnelle d'épilepsie [CHU Pitié-Salpêtrière], 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], Institut du Cerveau = Paris Brain Institute (ICM), 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)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département Médico-Universitaire Neurosciences [Sorbonne Université] (DMU Neurosciences), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Département Médico-Universitaire réanimation anesthésie médecine péri-opératoire [Sorbonne Université] (DMU DREAM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Groupe de recherche clinique en anesthésie réanimation médecine périopératoire [CHU Pitié-Salpétrière] (GRC ARPE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), Centre de référence des épilepsies rares [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)-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], Cohort COVID-19 Neurosciences (CoCo Neurosciences) Study Group: Jean-Yves Delattre, Stephanie Carvalho, Sandrine Sagnes, Bruno Dubois, Celine Louapre, Tanya Stojkovic, Ahmed Idbaih, Charlotte Rosso, David Grabli, Ana Zenovia Gales, Bruno Millet, Eleonore Bayen, Sophie Dupont, Gaelle Bruneteau, Stephane Lehericy, Danielle Seilhean, Alexandra Durr, Aurelie Kas, Foudil Lamari, Marion Houot, Vanessa Batista Brochard, Pascale Pradat-Diehl, Khe Hoang-Xuan, Bertrand Fontaine, Philippe Fossati, Isabelle Arnulf, Alexandre Carpentier, Yved Edel, Anna Luisa Di Stefano, Gilberte Robain, Philippe Thoumie, Bertrand Degos, Tarek Sharshar, Sonia Alamowitch, Emmanuelle Apartis-Bourdieu, Charles-Siegried Peretti, Renata Ursu, Nathalie Dzierzynski, Kiyoka Kinugawa Bourron, Joel Belmin, Bruno Oquendo, Eric Pautas, Marc Verny, Yves Samson, Sara Leder, Anne Leger, Sandrine Deltour, Flore Baronnet, Stéphanie Bombois, Mehdi Touat, Caroline Dehais, Caroline Houillier, Florence Laigle-Donadey, Dimitri Psimaras, Agusti Alentorn, Nadia Younan, Nicolas Villain, Maria Del Mar Amador, Louise-Laure Mariani, Nicolas Mezouar, Graziella Mangone, Aurélie Meneret, Andreas Hartmann, Clément Tarrano, David Bendetowicz, Pierre-Francois Pradat, Michel Baulac, Sara Sambin, Florence Chochon, Adele Hesters, Bastien Herlin, An Hung Nguyen, Valérie Procher, Alexandre Demoule, Julien Mayaux, Morgane Faure, Claire Ewenczyk, Giulia Coarelli, Anna Heinzmann, Perrine Charles, Marion Masingue, Guillaume Bassez, Isabelle An, Yulia Worbe, Rabab Debs, Timothee Lenglet, Natalia Shor, Delphine Leclercq, Albert Cao, Clémence Marois, Nicolas Weiss, Loic Le Guennec, Vincent Degos, Alice Jacquens, Thomas Similowski, Jean-Yves Rotge, Bertrand Saudreau, Victor Pitron, Nassim Sarni, Nathalie Girault, Redwan Maatoug, Smaranda Leu, Lionel Thivart, Karima Mokhtari, Isabelle Plu, Bruno Goncalves, Laure Bottin, Marion Yger, Gaelle Ouvrard, Rebecca Haddad, Flora Ketz, Carmelo Lafuente, Christel Oasi, Bruno Megarbane, Dominique Herve, Haysam Salman, Armelle Rametti-Lacroux, Alize Chalancon, Anais Herve, Hugo Royer, Florence Beauzor, Valentine Maheo, Christelle Laganot, Camille Minelli, Aurélie Fekete, Abel Grine, Marie Biet, Rania Hilab, Aurore Besnard, Meriem Bouguerra, Gwen Goudard, Saida Houairi, Saba Al-Youssef, Christine Pires, Anissa Oukhedouma, Katarzyna Siuda-Krzywicka, Tal Seidel Malkinson, Hanane Agguini, Hassen Douzane Agguini, Safia Said, Raux, Mathieu, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and HAL-SU, Gestionnaire

Subjects
Male, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Brain Diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Research, [SDV]Life Sciences [q-bio], COVID-19, Electroencephalography, Middle Aged, Magnetic Resonance Imaging, Cohort Studies, [SDV] Life Sciences [q-bio], Online Only, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Electronic Health Records, Humans, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Original Investigation
Abstract

Key Points Question Can electroencephalography (EEG), combined with clinical, biological, and magnetic resonance imaging (MRI) analyses, help to better characterize patients with neurologic coronavirus disease 2019 (COVID-19) and diagnose specific COVID-19–related encephalopathy? Findings Neurologic manifestations, biological findings, EEG findings, and brain MRI images were analyzed in a cohort study of 78 adult patients with COVID-19. Nine patients had no identified cause of brain injury, as revealed by biological and MRI findings; their injury was defined as COVID-19–related encephalopathy. Meaning This study suggests that, although neurologic manifestations, EEG findings, and MRI findings may appear heterogeneous and nonspecific, multimodal monitoring may better identify patients with COVID-19–related encephalopathy and guide treatment strategy., Importance There is evidence of central nervous system impairments associated with coronavirus disease 2019 (COVID-19) infection, including encephalopathy. Multimodal monitoring of patients with COVID-19 may delineate the specific features of COVID-19–related encephalopathy and guide clinical management. Objectives To investigate clinical, biological, and brain magnetic resonance imaging (MRI) findings in association with electroencephalographic (EEG) features for patients with COVID-19, and to better refine the features of COVID-19–related encephalopathy. Design, Setting, and Participants This retrospective cohort study conducted in Pitié-Salpêtrière Hospital, Paris, France, enrolled 78 hospitalized adults who received a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and underwent EEG between March 30 and June 11, 2020. Exposures Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription–polymerase chain reaction assay or, in the case of associated pneumonia, on a computed tomography scan of the chest. Main Outcomes and Measures Data on the clinical and paraclinical features of the 78 patients with COVID-19 were retrieved from electronic patient records. Results Of 644 patients who were hospitalized for COVID-19, 78 (57 men [73%]; mean [SD] age, 61 [12] years) underwent EEG. The main indications for EEG were delirium, seizure-like events, and delayed awakening in the intensive care unit after stopping treatment with sedatives. Sixty-nine patients showed pathologic EEG findings, including metabolic-toxic encephalopathy features, frontal abnormalities, periodic discharges, and epileptic activities. Of 57 patients who underwent brain MRI, 41 showed abnormalities, including perfusion abnormalities, acute ischemic lesions, multiple microhemorrhages, and white matter–enhancing lesions. Fifty-five patients showed biological abnormalities, including dysnatremia, kidney failure, and liver dysfunction, the same day as the EEG. The results of cerebrospinal fluid analysis were negative for SARS-Cov-2 for all tested patients. Nine patients who had no identifiable cause of brain injury outside COVID-19 were further isolated; their brain injury was defined as COVID-19–related encephalopathy. They represented 1% (9 of 644) of patients with COVID-19 requiring hospitalization. Six of these 9 patients had movement disorders, 7 had frontal syndrome, 4 had brainstem impairment, 4 had periodic EEG discharges, and 3 had MRI white matter–enhancing lesions. Conclusions and Relevance The results from this cohort of patients hospitalized with COVID-19 suggest there are clinical, EEG, and MRI patterns that could delineate specific COVID-19–related encephalopathy and guide treatment strategy., This cohort study investigates clinical, biological, and brain magnetic resonance imaging (MRI) findings in association with electroencephalographic (EEG) features for patients with coronavirus disease 2019 (COVID-19) and refines the features of COVID-19–related encephalopathy.

Published
2021

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