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

Author

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

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

6. Neuro-Psychological Outcome of ICU-Admitted COVID-19 Patients Presenting With CNS Complications

Author

Pelle, Juliette, Nedelec, Thomas, Marois, Clémence, Delorme, Cecile, Corvol, Jean-Christophe, Delattre, Jean-Yves, Carvalho, Stephanie, Sagnes, Sandrine, Dubois, Bruno, Navarro, Vincent, Louapre, Celine, Stojkovic, Tanya, Idbaih, Ahmed, Rosso, Charlotte, Grabli, David, Gales, Ana Zenovia, Millet, Bruno, Rohaut, Benjamin, Bayen, Eleonore, Dupont, Sophie, Bruneteau, Gaelle, Lehericy, Stephane, Seilhean, Danielle, Durr, Alexandra, Lamari, Foudil, Houot, Marion, Brochard, Vanessa Batista, Lubetzki, Catherine, Seilhean, Danielle, Pradat-Diehl, Pascale, Rosso, Charlotte, Hoang-Xuan, Khe, Fontaine, Bertrand, Naccache, Lionel, Fossati, Philippe, Arnulf, Isabelle, Durr, Alexandra, Carpentier, Alexandre, Edel, Yves, Robain, Gilberte, Thoumie, Philippe, Degos, Bertrand, Sharshar, Tarek, Alamowitch, Sonia, Apartis-Bourdieu, Emmanuelle, Peretti, Charles-Siegried, Ursu, Renata, Dzierzynski, Nathalie, Bourron, Kiyoka Kinugawa, Belmin, Joel, Oquendo, Bruno, Pautas, Eric, Verny, Marc, Samson, Yves, Leder, Sara, Leger, Anne, Deltour, Sandrine, Baronnet, Flore, Bombois, Stephanie, Touat, Mehdi, Idbaih, Ahmed, Sanson, Marc, Dehais, Caroline, Houillier, Caroline, Laigle-Donadey, Florence, Psimaras, Dimitri, Alenton, Agusti, Younan, Nadia, Villain, Nicolas, Grabli, David, del Mar Amador, Maria, Bruneteau, Gaelle, Louapre, Celine, Mariani, Louise-Laure, Mezouar, Nicolas, Mangone, Graziella, Meneret, Aurelie, Hartmann, Andreas, Tarrano, Clement, Bendetowicz, David, Pradat, Pierre-François, Baulac, Michel, Sambin, Sara, Pichit, Phintip, Chochon, Florence, Hesters, Adele, Herlin, Bastien, Nguyen, An Hung, Procher, Valerie, Demoule, Alexandre, Morawiec, Elise, Mayaux, Julien, Faure, Morgan, Ewenczyk, Claire, Coarelli, Giulia, Heinzmann, Anna, Stojkovic, Tanya, Masingue, Marion, Bassez, Guillaume, Navarro, Vincent, An, Isabelle, Worbe, Yulia, Lambrecq, Virginie, Debs, Rabab, Musat, Esteban Munoz, Lenglet, Timothee, Lambrecq, Virginie, Hanin, Aurelie, Chougar, Lydia, Shor, Nathalia, Pyatigorskaya, Nadya, Galanaud, Damien, Leclercq, Delphine, Demeret, Sophie, Rohaut, Benjamin, Cao, Albert, Marois, Clemence, Weiss, Nicolas, Gassama, Salimata, Guennec, Loic Le, Degos, Vincent, Jacquens, Alice, Similowski, Thomas, Morelot-Panzini, Capucine, Rotge, Jean-Yves, Saudreau, Bertrand, Millet, Bruno, Pitron, Victor, Sarni, Nassim, Girault, Nathalie, Maatoug, Redwan, Leu, Smaranda, Bayen, Eleonore, Thivard, Lionel, Mokhtari, Karima, Plu, Isabelle, Gonçalves, Bruno, Bottin, Laure, Yger, Marion, Ouvrard, Gaelle, Haddad, Rebecca, Ketz, Flora, Lafuente, Carmelo, Oasi, Christel, Megabarne, Bruno, Herve, Dominique, Salman, Haysam, Rametti-Lacroux, Armelle, Chalançon, Alize, Herve, Anais, Royer, Hugo, Beauzor, Florence, Maheo, Valentine, Laganot, Christelle, Minelli, Camille, Fekete, Aurelie, Grine, Abel, Biet, Marie, Hilab, Rania, Besnard, Aurore, Bouguerra, Meriem, Goudard, Gwen, Houairi, Saida, Al-Youssef, Saba, Pires, Christine, Oukhedouma, Anissa, Siuda-Krzywicka, Katarzyna, Malkinson, Tal Seidel, Agguini, Hanane, Said, Safia, and Houot, Marion

Published
2023
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8. Supplementary Methods from Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis

Author

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

Published
2023
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9. Figure S2 from Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis

Author

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

Published
2023
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10. Table S3 from Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis

Author

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

Published
2023
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11. Data from Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis

Author

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

Published
2023
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15. Golgi localization of SARS-CoV-2 spike protein and interaction with furin in cerebral COVID-19 microangiopathy: a clue to the central nervous system involvement?

Author

Boluda, Susana, Mokhtari, Karima, Mégarbane, Bruno, Annane, Djillali, Mathon, Bertrand, Cao, Albert, Adam, Clovis, Androuin, Alexandre, Bielle, Franck, Brochier, Guy, Charlotte, Frédéric, Chougar, Lydia, El Hachimi, Khalid Hamid, Eloit, Marc, Haïk, Stéphane, Hervé, Dominique, Kasri, Amal, Leducq, Valentin, Lehéricy, Stéphane, Levavasseur, Etienne, Lobsiger, Christian, Lorin De La Grandmaison, Geoffroy, Malet, Isabelle, Malissin, Isabelle, Marot, Stéphane, Marty, Serge, Pérot, Philippe, Plu, Isabelle, Prigent, Annick, Stimmer, Lev, Potier, Marie-Claude, Marcelin, Anne-Geneviève, Delatour, Benoît, Duyckaerts, Charles, Seilhean, Danielle, 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), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Raymond Poincaré [Garches], Université Paris-Saclay, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-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), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL), Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris] (IP), Université Sorbonne Paris Nord, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), The authors thank the Cohort COVID-19 Neurosciences (CoCo Neurosciences) study supported by APHP and funded by the generous support of the Federation Internationale de l’Automobile (FIA), the FIA Foundation and donors of Paris Brain Institute – ICM. The research leading to these results has received funding from Sorbonne University (PathoCoV project) and from the program 'Investissements d’avenir' ANR-10- IAIHU-06. This work benefited from equipment and services from the CELIS cell culture core facility (Paris Brain Institute), a platform receiving support from ANR-10- IAIHU-06 and ANR-11-INBS-0011-NeurATRIS. We thank for targeted NGS sequencing the Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09), IBISA and the Illumina COVID-19 Projects’ offer., ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)

Subjects
Furin, Blood-brain barrier (BBB), Original Paper, Microangiopathy, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Neuro-Covid, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], COVID-19
Abstract

In a neuropathological series of 20 COVID-19 cases, we analyzed six cases (three biopsies and three autopsies) with multiple foci predominantly affecting the white matter as shown by MRI. The cases presented with microhemorrhages evocative of small artery diseases. This COVID-19 associated cerebral microangiopathy (CCM) was characterized by perivascular changes: arterioles were surrounded by vacuolized tissue, clustered macrophages, large axonal swellings and a crown arrangement of aquaporin-4 immunoreactivity. There was evidence of blood-brain-barrier leakage. Fibrinoid necrosis, vascular occlusion, perivascular cuffing and demyelination were absent. While no viral particle or viral RNA was found in the brain, the SARS-CoV-2 spike protein was detected in the Golgi apparatus of brain endothelial cells where it closely associated with furin, a host protease known to play a key role in virus replication. Endothelial cells in culture were not permissive to SARS-CoV-2 replication. The distribution of the spike protein in brain endothelial cells differed from that observed in pneumocytes. In the latter, the diffuse cytoplasmic labeling suggested a complete replication cycle with viral release, notably through the lysosomal pathway. In contrast, in cerebral endothelial cells the excretion cycle was blocked in the Golgi apparatus. Interruption of the excretion cycle could explain the difficulty of SARS-CoV-2 to infect endothelial cells in vitro and to produce viral RNA in the brain. Specific metabolism of the virus in brain endothelial cells could weaken the cell walls and eventually lead to the characteristic lesions of COVID-19 associated cerebral microangiopathy. Furin as a modulator of vascular permeability could provide some clues for the control of late effects of microangiopathy., Free Neuropathology, Vol. 4 (2023)

Published
2023

16. CC17 group B Streptococcus exploits integrins for neonatal meningitis development

Author

de Cambronne, Romain Deshayes, Fouet, Agnes, Picart, Amandine, Bourrel, Anne-Sophie, Anjou, Cyril, Bouvier, Guillaume, Candeias, Cristina, Bouaboud, Abdelouhab, Costa, Lionel, Boulay, Anne-Cecile, Cohen-Salmon, Martine, Plu, Isabelle, Rambaud, Caroline, Faurobert, Eva, Albiges-Rizo, Corinne, Tazi, Asmaa, Poyart, Claire, and Guignot, Julie

Subjects
Infants (Newborn) -- Diseases, Bacterial meningitis -- Genetic aspects -- Development and progression -- Care and treatment, Integrins -- Health aspects, Cell receptors -- Health aspects, Health care industry
Abstract

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 [alpha]5[beta]1 and [alpha]v[beta]3 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., Introduction In the early 1950s, because of the massive utilization of tetracyclines, Streptococcus agalactiae (group B Streptococcus, GBS) emerged worldwide as the most significant pathogen causing severe neonatal invasive infections [...]

Published
2021
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17. Prevalence, patterns and outcomes of cardiac involvement in Erdheim–Chester disease

Author

Azoulay, Lévi-Dan, primary, Bravetti, Marine, additional, Cohen-Aubart, Fleur, additional, Emile, Jean-François, additional, Seilhean, Danielle, additional, Plu, Isabelle, additional, Charlotte, Frédéric, additional, Waintraub, Xavier, additional, Carrat, Fabrice, additional, Amoura, Zahir, additional, Cluzel, Philippe, additional, and Haroche, Julien, additional

Published
2022
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18. Prevalence, patterns and outcomes of cardiac involvement in Erdheim–Chester disease.

Author

Azoulay, Lévi-Dan, Bravetti, Marine, Cohen-Aubart, Fleur, Emile, Jean-François, Seilhean, Danielle, Plu, Isabelle, Charlotte, Frédéric, Waintraub, Xavier, Carrat, Fabrice, Amoura, Zahir, Cluzel, Philippe, and Haroche, Julien

Subjects
CARDIAC magnetic resonance imaging, ERDHEIM-Chester disease, CARDIAC tamponade, PERICARDIAL effusion, CORONARY artery disease
Abstract

Aims Cardiac involvement of Erdheim–Chester disease (ECD), a rare L group histiocytosis, has been reported to be associated with poor outcomes, but systematic studies are lacking. The present study aimed to investigate the prevalence, clinical features, imaging features, and prognosis of cardiac involvement in ECD in a large series. Methods and results All patients with ECD who underwent cardiac magnetic resonance (CMR) imaging between 2003 and 2019 at a French tertiary center were retrospectively included. Primary outcome was all-cause mortality. Secondary outcomes were pericarditis, cardiac tamponade, conduction disorders, device implantation and coronary artery disease (CAD). A total of 200 patients were included [63 (54–71) years, 30% female, 58% BRAFV600E mutated]. Median follow-up was 5.5 years (3.3–9 years). On CMR, right atrioventricular sulcus infiltration was observed in 37% of patients, and pericardial effusion was seen in 24% of patients. In total, 8 patients (4%) had pericarditis (7 acute, 1 constrictive), 10 patients (5%) had cardiac tamponade, 5 patients (2.5%) had ECD-related high-degree conduction disorders, and 45 patients (23%) had CAD. Overall, cardiac involvement was present in 96 patients (48%) and was associated with BRAFV600E mutation [Odds ratio (OR) = 7.4, 95% confidence interval (CI) (3.5–16.8), P < 0.001] and ECD-related clinical events [OR = 5, 95%CI (1.5–21.2), P = 0.004] but not with lower survival in multivariate analysis [adjusted hazard ratio (HR) = 1.4, 95% CI (0.8–2.5), P = 0.2]. Conclusion Cardiac involvement is present in nearly half of ECD patients and is associated with BRAFV600E mutation and complications (pericarditis, cardiac tamponade, and conduction disorders) but not with lower survival. [ABSTRACT FROM AUTHOR]

Published
2023
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20. Lack of early etiologic investigations in young sudden cardiac death

Author

Sharifzadehgan, Ardalan, primary, Gaye, Bamba, additional, Bougouin, Wulfran, additional, Narayanan, Kumar, additional, Dumas, Florence, additional, Karam, Nicole, additional, Rischard, Julien, additional, Plu, Isabelle, additional, Waldmann, Victor, additional, Algalarrondo, Vincent, additional, Gandjbakhch, Estelle, additional, Bruneval, Patrick, additional, Beganton, Frankie, additional, Alonso, Christine, additional, Moubarak, Ghassan, additional, Piot, Olivier, additional, Lamhaut, Lionel, additional, Jost, Daniel, additional, Sideris, Georgios, additional, Mansencal, Nicolas, additional, Deye, Nicolas, additional, Voicu, Sebastian, additional, Megarbane, Bruno, additional, Geri, Guillaume, additional, Vieillard-Baron, Antoine, additional, Lellouche, Nicolas, additional, Extramiana, Fabrice, additional, Wahbi, Karim, additional, Varenne, Olivier, additional, Cariou, Alain, additional, Jouven, Xavier, additional, and Marijon, Eloi, additional

Published
2022
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23. Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice

Author

Lam, Suzanne, Hérard, Anne-Sophie, Boluda, Susana, Petit, Fanny, Eddarkaoui, Sabiha, Cambon, Karine, Letournel, Franck, Martin-Négrier, Marie-Laure, Faisant, Maxime, Godfraind, Catherine, Boutonnat, Jean, Maurage, Claude-Alain, Deramecourt, Vincent, Duchesne, Mathilde, Meyronet, David, Fenouil, Tanguy, de Paula, André Mauès, Rigau, Valérie, Vandenbos-Burel, Fanny, Seilhean, Danielle, Duyckaerts, Charles, Plu, Isabelle, Chiforeanu, Dan Christian, Laquerrière, Annie, Marguet, Florent, Lannes, Béatrice, Lhermitte, Benoît, Picq, Jean-Luc, Buée, Luc, Haïk, Stéphane, Dhenain, Marc, 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), and 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)

Subjects
Mice, Cellular and Molecular Neuroscience, Amyloid beta-Peptides, Alzheimer Disease, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Animals, Brain, Humans, Neurofibrillary Tangles, Plaque, Amyloid, tau Proteins, Neurology (clinical), Pathology and Forensic Medicine
Abstract

Alzheimer's disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Three types of tau lesions occur in the form of neuropil threads, neurofibrillary tangles, and neuritic plaques i.e. tau aggregates within neurites surrounding Aβ deposits. The cascade of events linking these lesions and synaptic or memory impairments are still debated. Intracerebral infusion of human AD brain extracts in Aβ plaque-bearing mice that do not overexpress pathological tau proteins induces tau pathologies following heterotopic seeding of mouse tau protein. There is however little information regarding the downstream events including synaptic or cognitive repercussions of tau pathology induction in these models. In the present study, human AD brain extracts (ADbe) and control-brain extracts (Ctrlbe) were infused into the hippocampus of Aβ plaque-bearing APPswe/PS1dE9 mice. Memory, synaptic density, as well as Aβ plaque and tau aggregate loads, microgliosis, astrogliosis at the inoculation site and in connected regions (perirhinal/entorhinal cortex) were evaluated 4 and 8 months post-inoculation. ADbe inoculation produced the following effects: (i) memory deficit; (ii) increased Aβ plaque deposition in proximity to the inoculation site; (iii) tau pathology induction; (iv) appearance of neuropil threads and neurofibrillary tangles next to the inoculation site with a spreading to connected regions. Neuritic plaque pathology was detected in both ADbe- and Ctrlbe-inoculated animals but ADbe inoculation increased the severity close to and at distance of the inoculation site. (v) Finally, ADbe inoculation reduced synaptic density in the vicinity to the inoculation site and in connected regions as the perirhinal/entorhinal cortex. Synaptic impairments were correlated with increased severity of neuritic plaques but not to other tau lesions or Aβ lesions, suggesting that neuritic plaques are a culprit for synaptic loss. Synaptic density was also associated with microglial load. Graphical abstract

Published
2022

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

Author

Guihot, Amélie, primary, Plu, Isabelle, additional, Soulié, Cathia, additional, Rousseau, Alice, additional, Nakid-Cordero, Cecilia, additional, Dorgham, Karim, additional, Parizot, Christophe, additional, Litvinova, Elena, additional, Mayaux, Julien, additional, Malet, Isabelle, additional, Quentric, Paul, additional, Combadière, Béhazine, additional, Combadière, Christophe, additional, Bonduelle, Olivia, additional, Adam, Lucille, additional, Rosenbaum, Pierre, additional, Beurton, Alexandra, additional, Hémon, Patrice, additional, Debré, Patrice, additional, Vieillard, Vincent, additional, Autran, Brigitte, additional, Seilhean, Danielle, additional, Charlotte, Frédéric, additional, Marcelin, Anne-Geneviève, additional, Gorochov, Guy, additional, and Luyt, Charles-Edouard, additional

Published
2022
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27. The wide spectrum of COVID-19 neuropsychiatric complications within a multidisciplinary centre

Author

Delorme, Cécile, Houot, Marion, Rosso, Charlotte, Carvalho, Stéphanie, Nedelec, Thomas, Maatoug, Redwan, Pitron, Victor, Gassama, Salimata, Sambin, Sara, Bombois, Stéphanie, Herlin, Bastien, Ouvrard, Gaëlle, Bruneteau, Gaëlle, Hesters, Adèle, Gales, Ana Zenovia, Millet, Bruno, Lamari, Foudil, Lehericy, Stéphane, Navarro, Vincent, Rohaut, Benjamin, Demeret, Sophie, Maisonobe, Thierry, Yger, Marion, Degos, Bertrand, Mariani, Louise-Laure, Bouche, Christophe, Dzierzynski, Nathalie, Oquendo, Bruno, Ketz, Flora, Nguyen, An-Hung, Kas, Aurélie, Lubetzki, Catherine, Delattre, Jean-Yves, Corvol, Jean-Christophe, Fontaine, Bertrand, Thoumie, Philippe, Sharshar, Tarek, Alamowitch, Sonia, Apartis-Bourdieu, Emmanuelle, Peretti, Charles-Siegried, Ursu, Renata, Bourron, Kiyoka Kinugawa, Belmin, Joel, Pautas, Eric, Verny, Marc, Samson, Yves, Leder, Sara, Leger, Anne, Deltour, Sandrine, Baronnet, Flore, Touat, Mehdi, Sanson, Marc, Dehais, Caroline, Houillier, Caroline, Laigle-Donadey, Florence, Psimaras, Dimitri, Alenton, Agusti, Younan, Nadia, Villain, Nicolas, Del Mar Amador, Maria, Mezouar, Nicolas, Mangone, Graziella, Meneret, Aurelie, Hartmann, Andreas, Tarrano, Clement, Bendetowicz, David, Pradat, Pierre-François, Baulac, Michel, Pichit, Phintip, Chochon, Florence, Nguyen, An Hung, Porcher, Valerie, Demoule, Alexandre, Morawiec, Elise, Mayaux, Julien, Faure, Morgan, Ewenczyk, Claire, Coarelli, Giulia, Heinzmann, Anna, Masingue, Marion, Bassez, Guillaume, An, Isabelle, Worbe, Yulia, Lambrecq, Virginie, Debs, Rabab, Musat, Esteban Munoz, Lenglet, Timothee, Hanin, Aurelie, Chougar, Lydia, Shor, Nathalia, Pyatigorskaya, Nadya, Galanaud, Damien, Leclercq, Delphine, Cao, Albert, Marois, Clemence, Weiss, Nicolas, Le Guennec, Loic, Degos, Vincent, Jacquens, Alice, Similowski, Thomas, Morelot-Panzini, Capucine, Rotge, Jean-Yves, Saudreau, Bertrand, Sarni, Nassim, Girault, Nathalie, Leu, Smaranda, Thivard, Lionel, Mokhtari, Karima, Plu, Isabelle, Gonçalves, Bruno, Bottin, Laure, Haddad, Rebecca, Lafuente, Carmelo, Oasi, Christel, Megabarne, Bruno, Herve, Dominique, Salman, Haysam, Rametti-Lacroux, Armelle, Chalançon, Alize, Herve, Anais, Royer, Hugo, Beauzor, Florence, Maheo, Valentine, Laganot, Christelle, Minelli, Camille, Fekete, Aurelie, Grine, Abel, Biet, Marie, Hilab, Rania, Besnard, Aurore, Bouguerra, Meriem, Goudard, Gwen, Houairi, Saida, Al-Youssef, Saba, Pires, Christine, Oukhedouma, Anissa, Siuda-Krzywicka, Katarzyna, Malkinson, Tal Seidel, Agguini, Hanane, Said, Safia, Gales, Ana, Brochard, Vanessa, Bourron, Kiyoka, Nguyen, An, Musat, Esteban, Malkinson, Tal, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de psychiatrie adulte [CHU Pitié-Salpêtière], CHU Pitié-Salpêtrière [AP-HP], Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Service de Neuroradiologie [CHU Pitié-Salpêtrière], Service de Neurophysiologie [CHU Pitié-Salpêtrière], Service des Soins Intensifs [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Gériatrique [CHU Pitié-Salpêtrière], Service d'Activités cliniques [CHU Pitié-Salpêtrière], Service de médecine nucléaire [CHU Pitié-Salpétrière], Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre de Recherche en Myologie, and Service de gériatrie [CHU Pitié-Salpêtrière]

Subjects
Pediatrics, medicine.medical_specialty, encephalitis, Encephalopathy, Context (language use), law.invention, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Intensive care, medicine, Critical illness polyneuropathy, Biological Psychiatry, 030304 developmental biology, 0303 health sciences, business.industry, AcademicSubjects/SCI01870, COVID-19, medicine.disease, encephalopathy, Comorbidity, Intensive care unit, 3. Good health, Psychiatry and Mental health, Neurology, Observational study, Original Article, AcademicSubjects/MED00310, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, critical illness neuropathy, 030217 neurology & neurosurgery, Encephalitis
Abstract

A variety of neuropsychiatric complications has been described in association with Covid-19 infection. Large scale studies presenting a wider picture of these complications and their relative frequency are lacking. The objective of our study was to describe the spectrum of neurological and psychiatric complications in patients with Covid-19 seen in a multidisciplinary hospital center over six months. We conducted a retrospective, observational study on all patients showing neurological or psychiatric symptoms in the context of Covid-19 seen in the medical and university neuroscience department of Assistance Publique Hopitaux de Paris -Sorbonne University. We collected demographic data, comorbidities, symptoms and severity of Covid-19 infection, neurological and psychiatric symptoms, neurological and psychiatric examination data and, when available, results from CSF analysis, MRI, EEG and EMG. A total of 249 Covid-19 patients with a de novo neurological or psychiatric manifestation were included in the database and 245 were included in the final analyses. One-hundred fourteen patients (47%) were admitted to the intensive care unit and 10 (4%) died. The most frequent neuropsychiatric complications diagnosed were encephalopathy (43%), critical illness polyneuropathy and myopathy (26%), isolated psychiatric disturbance (18%), and cerebrovascular disorders (16%). No patients showed CSF evidence of SARS-CoV-2. Encephalopathy was associated with older age and higher risk of death. Critical illness neuromyopathy was associated with an extended stay in the intensive care unit. The majority of these neuropsychiatric complications could be imputed to critical illness, intensive care and systemic inflammation, which contrasts with the paucity of more direct SARS-CoV-2-related complications or post-infection disorders., Graphical Abstract Graphical Abstract

Published
2021

28. The neuroCEB brainbank: a brief history (15 years!) of neuropathology

Author

artaud botté, marie claire, Leclere-Turbant, Sabrina, Duyckaerts, C, Martin Negrier, Marie Laure, Letourneur, Franck, Plu, Isabelle, Boluda, Susana, Seilhean, Danielle, and neuro-ceb

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2021

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

Author

Regnault, Béatrice, primary, Evrard, Bruno, additional, Plu, Isabelle, additional, Dacheux, Laurent, additional, Troadec, Eric, additional, Cozette, Pascal, additional, Chrétien, Delphine, additional, Duchesne, Mathilde, additional, Vallat, Jean-Michel, additional, Jamet, Anne, additional, Leruez, Marianne, additional, Pérot, Philippe, additional, Bourhy, Hervé, additional, Eloit, Marc, additional, and Seilhean, Danielle, additional

Published
2021
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32. Identification d’un nouvel arbovirus neurotrope en France : le virus Umbre

Author

Pérot, Philippe, Bielle, Franck, Bigot, Thomas, Foulongne, Vincent, Bolloré, Karine, Chrétien, Delphine, Gil, Patricia, Gutierrez, Serafin, L'Ambert, Grégory, Mokhtari, Karima, Hellert, Jan, Flamand, Marie, Tamietti, Carole, Coulpier, Muriel, Huard de Verneuil, Anne, Temmam, Sarah, Couderc, Thérèse, De Sousa Cunha, Edouard, Boluda, Susana, Plu, Isabelle, Delisle, Marie Bernadette, Bonneville, Fabrice, Brassat, David, Fieschi, Claire, Malphettes, Marion, Duyckaerts, Charles, Mathon, Bertrand, Demeret, Sophie, Seilhean, Danielle, Eloit, Marc, Pérot, Philippe, Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris] (IP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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], 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)-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), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Immunologie clinique [CHU St-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre national de référence des Agents Transmissibles Non Conventionnels, Institut de Veille Sanitaire (INVS), École nationale vétérinaire - Alfort (ENVA), Institut Pasteur [Paris], Laboratoire de Neuropathologie Raymond Escourolle, 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 et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), 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), Service d'anatomie et cytologie pathologiques [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Neuroradiologie Diagnostique et Thérapeutique [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], Service de Neurochirurgie [CHU Pitié-Salpêtrière], and École nationale vétérinaire d'Alfort (ENVA)

Subjects
[SDV.EE]Life Sciences [q-bio]/Ecology, environment, métagénomique, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, moustiques, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], encéphalites, orthobunyavirus, [SDV.EE] Life Sciences [q-bio]/Ecology, environment, arbovirus, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], NGS, Umbre virus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], virologie, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
Abstract

International audience; Notre laboratoire a mis en place une collaboration avec le laboratoire de neuropathologie de l’hôpital de la Pitié-Salpêtrière pour explorer une série post-mortem de cas d’encéphalites humaines d’étiologie inconnue par un séquençage NGS profond et non ciblé du transcriptome, à la recherche de séquences de pathogènes. Le virus Umbre, un virus du genre orthobunyavirus, a été identifié chez deux patients immunodéprimés décédés en 2013 et 2019. Le virus infecte des neurones du cortex cérébral, la moelle épinière et le foie. Le virus Umbre a été décrit initialement dans les années 1950 dans des populations de moustiques Culex en zone Asie Pacifique, mais n’avait auparavant ni été isolé chez des mammifères (dont l’homme), ni détecté en Europe. Cette infection par le virus Umbre chez deux patients français, dont l’un vivait dans la région Occitanie et n’avait jamais voyagé en dehors de France métropolitaine, et l’autre avait fait une croisière en méditerranée avant l’apparition des symptômes, nous a amené à rechercher l’origine de la contamination dans des moustiques. Une investigation réalisée en partenariat avec le CIRAD de Montpellier et l’EID Méditerranée a permis d’identifier des séquences du genre orthobunyavirus très proches du virus Umbre dans des moustiques Culex de Camargue. Une enquête sérologique par un test développé à l’Institut Pasteur sur une population du sud de la France composée d’environ 300 personnes « contrôles » et d’une vingtaine de cas « encéphalites » n’a pas mis en évidence de réponse anticorps contre le virus Umbre. Ce résultat suggère que la fréquence de l’infection dans la population générale est au plus faible, ce qui ne reflète donc pas le risque pour les personnes immunodéprimées. Cette découverte d’un nouvel arbovirus responsable d’encéphalite, et son existence en France, présente un intérêt particulier en matière de santé publique.

Published
2021

33. Induction of amyloid-β deposits from serially transmitted, histologically silent, Aβ seeds issued from human brains

Author

Herard, Anne-Sophie, Petit, Fanny, Gary, Charlotte, Guillermier, Martine, Boluda, Susana, Garin, Clément, Lam, Suzanne, Dhenain, Marc, Letournel, Franck, Martin-Negrier, Marie-Laure, Faisant, Maxime, Godfraind, Catherine, Maurage, Claude-Alain, Deramecourt, Vincent, Duchesne, Mathilde, Meyronnet, David, Maues De Paula, André, Rigau, Valérie, Burel-Vandenbos, Fanny, Duyckaerts, Charles, Seilhean, Danielle, Plu, Isabelle, Milin, Serge, Chiforeanu, Dan Christian, Laquerriere, Annie, Lannes, Béatrice, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neuropathologie Raymond Escourolle, 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 Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), France-Alzheimer Association, Fondation Vaincre Alzheimer, CEA bottom-up program, NeurATRIS - ANR-11-INBS-0011, Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), 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), 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), and Institut des Neurosciences de Montpellier (INM)

Subjects
Genetically modified mouse, Pathology, medicine.medical_specialty, Amyloid, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Iatrogenic Disease, Mice, Transgenic, Plaque, Amyloid, Endogeny, Context (language use), Hippocampal formation, β-amyloid pathology, Hippocampus, lcsh:RC346-429, Pathology and Forensic Medicine, Lesion, Amyloid beta-Protein Precursor, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, Presenilin-1, medicine, Animals, Humans, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, 0303 health sciences, Amyloid beta-Peptides, Tissue Extracts, Chemistry, Research, Amyloidosis, Brain, Human brain, Alzheimer's disease, medicine.disease, Immunohistochemistry, Disease Models, Animal, medicine.anatomical_structure, Neurology (clinical), medicine.symptom, Aβ transmission, Alzheimer’s disease, 030217 neurology & neurosurgery
Abstract

In humans, iatrogenic transmission of cerebral amyloid-β (Aβ)-amyloidosis is suspected following inoculation of pituitary-derived hormones or dural grafts presumably contaminated with Aβ proteins as well as after cerebral surgeries. Experimentally, intracerebral inoculation of brain homogenate extracts containing misfolded Aβ can seed Aβ deposition in transgenic mouse models of amyloidosis or in non-human primates. The transmission of cerebral Aβ is governed by the host and by the inoculated samples. It is critical to better characterize the propensities of different hosts to develop Aβ deposition after contamination by an Aβ-positive sample as well as to better assess which biological samples can transmit this lesion. Aβ precursor protein (huAPPwt) mice express humanized non-mutated forms of Aβ precursor protein and do not spontaneously develop Aβ or amyloid deposits. We found that inoculation of Aβ-positive brain extracts from Alzheimer patients in these mice leads to a sparse Aβ deposition close to the alveus 18 months post-inoculation. However, it does not induce cortical or hippocampal Aβ deposition. Secondary inoculation of apparently amyloid deposit-free hippocampal extracts from these huAPPwt mice to APPswe/PS1dE9 mouse models of amyloidosis enhanced Aβ deposition in the alveus 9 months post-inoculation. This suggests that Aβ seeds issued from human brain samples can persist in furtive forms in brain tissues while maintaining their ability to foster Aβ deposition in receptive hosts that overexpress endogenous Aβ. This work emphasizes the need for high-level preventive measures, especially in the context of neurosurgery, to prevent the risk of iatrogenic transmission of Aβ lesions from samples with sparse amyloid markers.

Published
2020

34. CC17 group B Streptococcus exploits integrins for neonatal meningitis development

Author

Deshayes de Cambronne, Romain, primary, Fouet, Agnès, additional, Picart, Amandine, additional, Bourrel, Anne-Sophie, additional, Anjou, Cyril, additional, Bouvier, Guillaume, additional, Candeias, Cristina, additional, Bouaboud, Abdelouhab, additional, Costa, Lionel, additional, Boulay, Anne-Cécile, additional, Cohen-Salmon, Martine, additional, Plu, Isabelle, additional, Rambaud, Caroline, additional, Faurobert, Eva, additional, Albigès-Rizo, Corinne, additional, Tazi, Asmaa, additional, Poyart, Claire, additional, and Guignot, Julie, additional

Published
2021
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35. First Case of Lethal Encephalitis in Western Europe Due to European Bat Lyssavirus Type 1.

Author

Regnault, Béatrice, Evrard, Bruno, Plu, Isabelle, Dacheux, Laurent, Troadec, Eric, Cozette, Pascal, Chrétien, Delphine, Duchesne, Mathilde, Vallat, Jean-Michel, Jamet, Anne, Leruez, Marianne, Pérot, Philippe, Bourhy, Hervé, Eloit, Marc, and Seilhean, Danielle

Subjects
RNA virus infections, CAUSES of death, IMMUNOCHEMISTRY, VIRAL antigens, SEQUENCE analysis, IMMUNOGLOBULINS, VIRAL encephalitis, BATS, AUTOPSY, INFLAMMATION, RNA viruses, POLYMERASE chain reaction, MIDDLE age
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. [ABSTRACT FROM AUTHOR]

Published
2022
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36. Neuroinvasion of SARS-CoV-2 in human and mouse brain

Author

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

Published
2021
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39. Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure

Author

Brandel, Jean-Philippe, primary, Vlaicu, M. Bustuchina, additional, Culeux, Audrey, additional, Belondrade, Maxime, additional, Bougard, Daisy, additional, Grznarova, Katarina, additional, Denouel, Angeline, additional, Plu, Isabelle, additional, Bouaziz-Amar, Elodie, additional, Seilhean, Danielle, additional, Levasseur, Michèle, additional, and Haïk, Stéphane, additional

Published
2020
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41. Neuroinvasion of SARS-CoV-2 in human and mouse brain

Author

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

Published
2020
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42. Identification of Umbre Orthobunyavirus as a Novel Zoonotic Virus Responsible for Lethal Encephalitis in 2 French Patients with Hypogammaglobulinemia

Author

Pérot, Philippe, primary, Bielle, Franck, additional, Bigot, Thomas, additional, Foulongne, Vincent, additional, Bolloré, Karine, additional, Chrétien, Delphine, additional, Gil, Patricia, additional, Gutiérrez, Serafín, additional, L’Ambert, Grégory, additional, Mokhtari, Karima, additional, Hellert, Jan, additional, Flamand, Marie, additional, Tamietti, Carole, additional, Coulpier, Muriel, additional, Huard de Verneuil, Anne, additional, Temmam, Sarah, additional, Couderc, Thérèse, additional, De Sousa Cunha, Edouard, additional, Boluda, Susana, additional, Plu, Isabelle, additional, Delisle, Marie Bernadette, additional, Bonneville, Fabrice, additional, Brassat, David, additional, Fieschi, Claire, additional, Malphettes, Marion, additional, Duyckaerts, Charles, additional, Mathon, Bertrand, additional, Demeret, Sophie, additional, Seilhean, Danielle, additional, and Eloit, Marc, additional

Published
2020
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43. Low rates of immediate coronary angiography among young adults resuscitated from sudden cardiac arrest

Author

Waldmann, Victor, primary, Karam, Nicole, additional, Rischard, Julien, additional, Bougouin, Wulfran, additional, Sharifzadehgan, Ardalan, additional, Dumas, Florence, additional, Narayanan, Kumar, additional, Sideris, Georgios, additional, Voicu, Sebastian, additional, Gandjbakhch, Estelle, additional, Jost, Daniel, additional, Lamhaut, Lionel, additional, Ludes, Bertrand, additional, Plu, Isabelle, additional, Beganton, Frankie, additional, Wahbi, Karim, additional, Varenne, Olivier, additional, Megarbane, Bruno, additional, Algalarrondo, Vincent, additional, Extramiana, Fabrice, additional, Lellouche, Nicolas, additional, Celermajer, David S., additional, Spaulding, Christian, additional, Lafont, Antoine, additional, Cariou, Alain, additional, Jouven, Xavier, additional, and Marijon, Eloi, additional

Published
2020
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45. Identification of Umbre Orthobunyavirus as a Novel Zoonotic Virus Responsible for Lethal Encephalitis in 2 French Patients with Hypogammaglobulinemia.

Author

Pérot, Philippe, Bielle, Franck, Bigot, Thomas, Foulongne, Vincent, Bolloré, Karine, Chrétien, Delphine, Gil, Patricia, Gutiérrez, Serafín, L'Ambert, Grégory, Mokhtari, Karima, Hellert, Jan, Flamand, Marie, Tamietti, Carole, Coulpier, Muriel, Verneuil, Anne Huard de, Temmam, Sarah, Couderc, Thérèse, Cunha, Edouard De Sousa, Boluda, Susana, and Plu, Isabelle

Subjects
ENCEPHALITIS viruses, REVERSE transcriptase polymerase chain reaction, BRAIN, EPIDEMIC encephalitis, IMMUNOCOMPROMISED patients, SERODIAGNOSIS, ZOONOSES, AGAMMAGLOBULINEMIA, GENE expression profiling, IN situ hybridization, POLYMERASE chain reaction, CEREBROSPINAL fluid, MOSQUITOES, INFECTIOUS disease transmission
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. [ABSTRACT FROM AUTHOR]

Published
2021
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48. Human subiculo-fornico-mamillary system in Alzheimer's disease: Tau seeding by the pillar of the fornix.

Author

Thierry, Manon, Boluda, Susana, Delatour, Benoît, Marty, Serge, Seilhean, Danielle, Brainbank Neuro-CEB Neuropathology Network, Letournel, Franck, Martin-Négrier, Marie-Laure, Chapon, Françoise, Godfraind, Catherine, Maurage, Claude-Alain, Deramecourt, Vincent, Meyronnet, David, Streichenberger, Nathalie, de Paula, André Maues, Rigau, Valérie, Vandenbos-Burel, Fanny, Duyckaerts, Charles, Plu, Isabelle, and Milin, Serge

Subjects
NEUROFIBRILLARY tangles, ALZHEIMER'S disease, ELECTRON microscopy, AXONS
Abstract

In Alzheimer's disease (AD), Tau and Aβ aggregates involve sequentially connected regions, sometimes distantly separated. These alterations were studied in the pillar of the fornix (PoF), an axonal tract, to analyse the role of axons in their propagation. The PoF axons mainly originate from the subicular neurons and project to the mamillary body. Forty-seven post-mortem cases at various Braak stages (Tau) and Thal phases (Aβ) were analysed by immunohistochemistry. The distribution of the lesions showed that the subiculum was affected before the mamillary body, but neither Tau aggregation nor Aβ deposition was consistently first. The subiculum and the mamillary body contained Gallyas positive neurofibrillary tangles, immunolabelled by AT8, TG3, PHF1, Alz50 and C3 Tau antibodies. In the PoF, only thin and fragmented threads were observed, exclusively in the cases with neurofibrillary tangles in the subiculum. The threads were made of Gallyas negative, AT8 and TG3 positive Tau. They were intra-axonal and devoid of paired helical filaments at electron microscopy. We tested PoF homogenates containing Tau AT8 positive axons in a Tau P301S biosensor HEK cell line and found a seeding activity. There was no Aβ immunoreactivity detected in the PoF. We could follow microcryodissected AT8 positive axons entering the mamillary body; contacts between Tau positive endings and Aβ positive diffuse or focal deposits were observed in CLARITY-cleared mamillary body. In conclusion, we show that non-fibrillary, hyperphosphorylated Tau is transported by the axons of the PoF from the subiculum to the mamillary body and has a seeding activity. Either Tau aggregation or Aβ accumulation may occur first in this system: this inconstant order is incompatible with a cause-and-effects relationship. However, both pathologies were correlated and intimately associated, indicating an interaction of the two processes, once initiated. [ABSTRACT FROM AUTHOR]

Published
2020
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49. Increased prevalence of granulovacuolar degeneration in C9orf72 mutation.

Author

Riku, Yuichi, Duyckaerts, Charles, Boluda, Susana, Plu, Isabelle, Le Ber, Isabelle, Millecamps, Stéphanie, Salachas, François, Brainbank NeuroCEB Neuropathology Network, Letournel, Franck, Martin-Négrier, Marie-Laure, Chapon, Françoise, Godfraind, Catherine, Maurage, Claude-Alain, Deramecourt, Vincent, Meyronet, David, Streichenberger, Nathalie, Maues de Paula, André, Rigau, Valérie, Vandenbos-Burel, Fanny, and Milin, Serge

Subjects
AMYOTROPHIC lateral sclerosis, NEUROFIBRILLARY tangles, FRONTOTEMPORAL lobar degeneration, CASEIN kinase, FISHER exact test, ALZHEIMER'S disease, DEGENERATION (Pathology)
Abstract

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 < 2×10−6) or in the control group (12/40 individuals; p < 1×10−6). Average Braak stages and ages of death were not significantly different among the groups. The CA2 sector was most frequently affected in the FTLD/ALS-C9 group, whereas the CA1/subiculum was the most vulnerable area in the other groups. Extension of GVD correlated with the clinical duration of the disease in the FTLD/ALS-C9 cases but not in the FTLD/ALS-nonC9 cases. The GVD-containing neurons frequently had dipeptide repeat (DPR) protein inclusions. GVD granules labeled with antibodies directed against charged multivesicular body protein 2B or casein kinase 1δ were attached to DPR inclusions within GVD. Our results suggest that development of GVD and DPR inclusions is related to common pathogenic mechanisms and that GVD is not only associated with NFTs seen in AD cases or aging individuals. [ABSTRACT FROM AUTHOR]

Published
2019
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50. Terrorist explosive belt attacks: specific patterns of bone traumas.

Author

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

Subjects
BONE injuries, SUICIDE bombings, TERRORISM, FORENSIC medicine, FORENSIC anthropology, SOFT tissue injuries
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. [ABSTRACT FROM AUTHOR]

Published
2019
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