41 results on '"Plu, Isabelle"'
Search Results
2. Normal meninges harbor oncogenic somatic mutations in meningioma-driver genes
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Boetto, Julien, Plu, Isabelle, Ducos, Yohan, Blouin, Antoine, Teranishi, Yu, Bizzotto, Sara, Kalamarides, Michel, and Peyre, Matthieu
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- 2023
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3. Cerebral vasculitis due to Aspergillus spp. in immunocompromised patients: literature review
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Haddad, Elie, Fekkar, Arnaud, Bonnin, Sophie, Shor, Natalia, Seilhean, Danielle, Plu, Isabelle, Touitou, Valérie, Leblond, Véronique, Weiss, Nicolas, Demeret, Sophie, and Pourcher, Valérie
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- 2022
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4. Neuro-Psychological Outcome of ICU-Admitted COVID-19 Patients Presenting With CNS Complications
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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
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- 2023
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5. Disturbances of brain cholesterol metabolism: A new excitotoxic process associated with status epilepticus
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Hanin, Aurélie, Baudin, Paul, Demeret, Sophie, Roussel, Delphine, Lecas, Sarah, Teyssou, Elisa, Damiano, Maria, Luis, David, Lambrecq, Virginie, Frazzini, Valerio, Decavèle, Maxens, Plu, Isabelle, Bonnefont-Rousselot, Dominique, Bittar, Randa, Lamari, Foudil, and Navarro, Vincent
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- 2021
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6. Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE).
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Hanin, Aurélie, Le Zhang, Huttner, Anita J., Plu, Isabelle, Mathon, Bertrand, Bielle, Franck, Navarro, Vincent, Hirsch, Lawrence J., and Hafler, David A.
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- 2024
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7. Terrorist explosive belt attacks: specific patterns of bone traumas
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Delannoy, Yann, Delabarde, Tania, Plu, Isabelle, Legrand, Laurence, Taccoen, Marc, Tracqui, Antoine, and Ludes, Bertrand
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- 2019
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8. Ultradeep sequencing reveals HIV-1 diversity and resistance compartmentalization during HIV-encephalopathy
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Giatsou, Eleni, Abdi, Basma, Plu, Isabelle, Desire, Nathalie, Palich, Romain, Calvez, Vincent, Seilhean, Danielle, Marcelin, Anne-Geneviève, and Jary, Aude
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- 2020
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9. 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?
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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)
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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)
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- 2023
10. CC17 group B Streptococcus exploits integrins for neonatal meningitis development
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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
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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 [...]
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- 2021
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11. Fatal Aβ cerebral amyloid angiopathy 4 decades after a dural graft at the age of 2 years
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Hervé, Dominique, Porché, Maximilien, Cabrejo, Lucie, Guidoux, Céline, Tournier-Lasserve, Elisabeth, Nicolas, Gaël, Adle-Biassette, Homa, Plu, Isabelle, Chabriat, Hugues, and Duyckaerts, Charles
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- 2018
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12. Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice
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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)
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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
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- 2022
13. Prevalence, patterns and outcomes of cardiac involvement in Erdheim–Chester disease.
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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
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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]
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- 2023
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14. The wide spectrum of COVID-19 neuropsychiatric complications within a multidisciplinary centre
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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]
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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
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- 2021
15. The neuroCEB brainbank: a brief history (15 years!) of neuropathology
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artaud botté, marie claire, Leclere-Turbant, Sabrina, Duyckaerts, C, Martin Negrier, Marie Laure, Letourneur, Franck, Plu, Isabelle, Boluda, Susana, Seilhean, Danielle, and neuro-ceb
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[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2021
16. Pearls & Oy-sters: Spinal Cord Candidiasis Linked to CARD9 Deficiency Masquerading as a Longitudinally Extensive Transverse Myelitis.
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Jeantin, Lina, Plu, Isabelle, Amador, Maria del Mar, Maillart, Elisabeth, Lanternier, Fanny, Pourcher, Valdrie, Davy, Vincent, and Pourcher, Valérie
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- 2022
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17. Induction of amyloid-β deposits from serially transmitted, histologically silent, Aβ seeds issued from human brains
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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)
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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.
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- 2020
18. Pregnancy, Cesarean, and Pheochromocytoma: A Case Report and Literature Review*
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Plu, Isabelle, Sec, Isabelle, Barrès, Denis, and Lecomte, Dominique
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- 2013
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19. First Case of Lethal Encephalitis in Western Europe Due to European Bat Lyssavirus Type 1.
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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
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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]
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- 2022
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20. Ethical issues raised by the introduction of payment for performance in France
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Saint-Lary, Olivier, Plu, Isabelle, and Naiditch, Michel
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- 2012
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21. Identification of Umbre Orthobunyavirus as a Novel Zoonotic Virus Responsible for Lethal Encephalitis in 2 French Patients with Hypogammaglobulinemia.
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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
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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]
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- 2021
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22. An overview of forensic operations performed following the terrorist attacks on November 13, 2015, in Paris.
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Tracqui, Antoine, Deguette, Céline, Delabarde, Tania, Delannoy, Yann, Plu, Isabelle, Sec, Isabelle, Hamza, Lilia, Taccoen, Marc, and Ludes, Bertrand
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TERRORISM ,CRUSH syndrome ,TERRORIST organizations ,BLAST injuries ,BOMBINGS ,AUTOPSY - Abstract
On the evening of November 13, 2015, the city of Paris and its surroundings was hit by a series of attacks committed by terrorist groups, using firearms and explosives. The final toll was 140 people deceased (130 victims and 10 terrorists or their relatives) and more than 413 injured, making these attacks the worst mass killings ever recorded in Paris in peacetime. This article presents the forensic operations carried out at the Medicolegal Institute of Paris (MLIP) following these attacks. A total of 68 autopsies of bodies or body fragments and 83 external examinations were performed within 7 days, and the overall forensic operations (including formal identification of the latest victims) were completed 10 days after the attacks. Over this period, 156 body presentations (some bodies were presented several times) were provided to families or relatives. Regarding the 130 civilian casualties, 129 died from firearm wounds and one died from blast injuries after an explosion. Of the 10 terrorists or their relatives who were killed, eight died from suicide bombing, one was shot by police and one died from crush injuries due to partial collapse of a building following the police raid against a terrorist's hideout after the attacks. All mass shootings were perpetrated with AK-47 or Zastava M70 assault rifles using 7.62 mm × 39 mm cartridges. In the case of ballistic injuries, death was most often obviously caused by craniocerebral injuries, extensive organ lacerations and/or massive haemorrhage. Among the terrorists killed by bombing, the lesion patterns were body transection, multiple amputations, extreme organ lacerations and the presence of foreign bodies owing to the shrapnel load (steel nuts, glass fragments) or the explosive charge fastening system of the devices. This discussion highlights the particular difficulties of interpretation encountered within the framework of ballistic injuries, a conclusion that should lead to a modest and realistic approach in these exceptional situations where forensic operations involve a very large number of victims in a constrained time. [ABSTRACT FROM AUTHOR]
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- 2020
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23. Terrorist attacks: cutaneous patterns of gunshot and secondary blast injuries.
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Delannoy, Yann, Plu, Isabelle, Sec, Isabelle, Delabarde, Tania, Taccoen, Marc, Tracqui, Antoine, and Ludes, Bertrand
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BLAST injuries ,TERRORISM ,PENETRATING wounds ,AUTOPSY ,PROJECTILES ,FORENSIC sciences - Abstract
Terrorist attacks have been on the rise. During the recent terrorist attacks in France, terrorists perpetrated their acts using weapons of war, as well as explosive charges. These two modes of action, when combined, can create skin lesions with similar macroscopic appearances, which can sometimes go unnoticed because of body fragmentation. A total of 68 autopsies, 83 external examinations, 140 standard radiographic examinations, and 49 computed tomography (CT) scans were performed over 7 days during the 2015 terrorist attacks in France. Bodies were injured by firearms and shrapnel-like projectiles. We analysed the clinical findings for the secondary blast cutaneous lesions from the explosive devices and compared these lesions with ballistic-related lesions to highlight that patterns can be macroscopically similar on external examination. Secondary blast injuries are characterised by penetrating trauma associated with materials added to explosive systems that are propelled by explosive air movement. These injuries are caused most often by small, shrapnel-like metallic objects, such as nails and bolts. Propulsion causes ballistic-type injuries that must be recognised and distinguished from those caused by firearm projectiles. Differentiating between these lesions is very difficult when using conventional criteria (size, shape, number and distribution on the body) with only external examination of corpses. This is why the particularities of these lesions must be further illustrated and then confirmed by complete autopsies and radiological and anatomopathological examinations. When occurring simultaneously in terrorist attacks, injuries caused by secondary blasts appear as cutaneous wound patterns that can be macroscopically very similar to those caused by firearm projectiles. The criteria usually found in the literature for distinguishing these two types of projectiles may be difficult to use. It is important in these difficult situations to benefit from systematic postmortem imaging. Systematic autopsy and then anatomopathological analyses of the orifices also help determine the cause of the wounds. [ABSTRACT FROM AUTHOR]
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- 2020
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24. Human subiculo-fornico-mamillary system in Alzheimer's disease: Tau seeding by the pillar of the fornix.
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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
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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]
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- 2020
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25. Increased prevalence of granulovacuolar degeneration in C9orf72 mutation.
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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
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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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26. Terrorist explosive belt attacks: specific patterns of bone traumas.
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Taccoen, Marc, Delannoy, Yann, Delabarde, Tania, Ludes, Bertrand, Plu, Isabelle, Legrand, Laurence, and Tracqui, Antoine
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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]
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- 2019
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27. « Opinion of healthcare workers in France about consent required for organ donation from deceased patients », poster, Dr.JC. Tortosa, D. Rodriguez-Arias, Pr.MF. Mamzer-Bruneel, E. Laforet, Dr.I. Plu, K. Bréhaux, Pr.H. Kreis, Dr.M. Wolf, Second Elpat Congress, Rotterdam, 17-20 april 2010
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Tortosa, Jean-Christophe, DAVID, RODRIGUES-ARIAS, Mamzer Bruneel, M.F., EMMANUELLE, LAFORET, Plu, Isabelle, Bréhaux, Karine, Kreis, Henri, Wolff, Manuel, brehaux, karine, Laboratoire Ethique Politique et Santé (EA 4569), and Université Paris Descartes - Paris 5 (UPD5)
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[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2010
28. Why Did Most French GPs Choose Not to Join the Voluntary National Pay-for-Performance Program?
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Saint-Lary, Olivier, Bernard, Erik, Sicsic, Jonathan, Plu, Isabelle, François-Purssell, Irène, and Franc, Carine
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PRIMARY care ,GENERAL practitioners ,MOTIVATION (Psychology) ,CROSS-sectional method ,PROFESSIONAL ethics ,MULTIVARIATE analysis - 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. [ABSTRACT FROM AUTHOR]
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- 2013
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29. Lack of early etiologic investigations in young sudden cardiac death.
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Sharifzadehgan, Ardalan, Gaye, Bamba, Bougouin, Wulfran, Narayanan, Kumar, Dumas, Florence, Karam, Nicole, Rischard, Julien, Plu, Isabelle, Waldmann, Victor, Algalarrondo, Vincent, Gandjbakhch, Estelle, Bruneval, Patrick, Beganton, Frankie, Alonso, Christine, Moubarak, Ghassan, Piot, Olivier, Lamhaut, Lionel, Jost, Daniel, Sideris, Georgios, and Mansencal, Nicolas
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CARDIAC arrest , *AUTOPSY , *TRAUMA registries , *CORONARY angiography , *INTENSIVE care units , *COMPUTED tomography , *EARLY diagnosis , *LONGITUDINAL method , *DISEASE complications - Abstract
Background: Since majority of sudden cardiac arrest (SCA) victims die in the intensive care unit (ICU), early etiologic investigations may improve understanding of SCA and targeted prevention.Methods: In this prospective, population-based registry all SCA admitted alive across the 48 hospitals of the Paris area were enrolled. We investigated the extent of early etiologic work-up among young SCD cases (<45 years) eventually dying within the ICU.Results: From May 2011 to May 2018, 4,314 SCA patients were admitted alive. Among them, 3,044 died in ICU, including 484 (15.9%) young patients. SCA etiology was established in 233 (48.1%) and remained unexplained in 251 (51.9%). Among unexplained (compared to explained) cases, coronary angiography (17.9 vs. 49.4%, P < 0.001), computed tomography scan (24.7 vs. 46.8%, P < 0.001) and trans-thoracic echocardiography (31.1 vs. 56.7%, P < 0.001) were less frequently performed. Only 22 (8.8%) patients with unexplained SCD underwent all three investigations. SCDs with unexplained status decreased significantly over the 7 years of the study period (from 62.9 to 35.2%, P = 0.005). While specialized TTE and CT scan performances have increased significantly, performance of early coronary angiography did not change. Autopsy, genetic analysis and family screening were performed in only 48 (9.9%), 5 (1.0%) and 14 cases (2.9%) respectively.Conclusions: More than half of young SCD dying in ICU remained etiologically unexplained; this was associated with a lack of early investigations. Improving early diagnosis may enhance both SCA understanding and prevention, including for relatives. Failure to identify familial conditions may result in other preventable deaths within these families. [ABSTRACT FROM AUTHOR]- Published
- 2022
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30. CC17 group B Streptococcus exploits integrins for neonatal meningitis development.
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Deshayes de Cambronne, Romain, Fouet, Agnès, Picart, Amandine, Bourrel, Anne-Sophie, Anjou, Cyril, Bouvier, Guillaume, Candeias, Cristina, Bouaboud, Abdelouhab, Costa, Lionel, Boulay, Anne-Cécile, Cohen-Salmon, Martine, Plu, Isabelle, Rambaud, Caroline, Faurobert, Eva, Albiges-Rizo, Corinne, Tazi, Asmaa, Poyart, Claire, Guignot, Julie, and Albigès-Rizo, Corinne
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- *
STREPTOCOCCUS agalactiae , *INTEGRINS , *BLOOD-brain barrier , *MENINGITIS , *NEONATAL infections - 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 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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31. Low rates of immediate coronary angiography among young adults resuscitated from sudden cardiac arrest.
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Waldmann, Victor, Karam, Nicole, Rischard, Julien, Bougouin, Wulfran, Sharifzadehgan, Ardalan, Dumas, Florence, Narayanan, Kumar, Sideris, Georgios, Voicu, Sebastian, Gandjbakhch, Estelle, Jost, Daniel, Lamhaut, Lionel, Ludes, Bertrand, Plu, Isabelle, Beganton, Frankie, Wahbi, Karim, Varenne, Olivier, Megarbane, Bruno, Algalarrondo, Vincent, and Extramiana, Fabrice
- Subjects
- *
CORONARY angiography , *CARDIAC arrest , *CORONARY care units , *CORONARY disease , *ACUTE coronary syndrome , *HOSPITAL admission & discharge , *YOUNG adults - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2020
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32. Variant Creutzfeldt-Jakob Disease Diagnosed 7.5 Years after Occupational Exposure.
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Vlaicu, M. Bustuchina, Haïk, Stephane, Brandel, Jean-Philippe, Culeux, Audrey, Belondrade, Maxime, Bougard, Daisy, Grznarova, Katarina, Denouel, Angeline, Plu, Isabelle, Bouaziz-Amar, Elodie, Seilhean, Danielle, Levasseur, Michèle, and Haïk, Stéphane
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- *
CREUTZFELDT-Jakob disease , *BOVINE spongiform encephalopathy , *COVID-19 pandemic , *INFLAMMATORY bowel diseases , *STANDARD & Poor's 500 Index - Abstract
The article presents a case study about the variant Creutzfeldt-Jakob disease (CJD), plausibly related to accidental occupational exposure who diagnosed 7.5 Years after occupational exposure. It discusses that Magnetic resonance imaging showed an increased FLAIR signal in pulvinar and dorsomedial nuclei of thalami.
- Published
- 2020
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33. Mechanism of neurodegeneration mediated by clonal inflammatory microglia.
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Vicario R, Fragkogianni S, Pokrovskii M, Mayer C, Lopez-Rodrigo E, Hu Y, Ogishi M, Alberdi A, Baako A, Ay O, Plu I, Sazdovitch V, Heritier S, Cohen-Aubart F, Shor N, Miyara M, Nguyen-Khac F, Viale A, Idbaih A, Amoura Z, Rosenblum MK, Zhang H, Karnoub ER, Sashittal P, Jakatdar A, Iacobuzio-Donahue CA, Abdel-Wahab O, Tabar V, Socci ND, Elemento O, Diamond EL, Boisson B, Casanova JL, Seilhean D, Haroche J, Donadieu J, and Geissmann F
- Abstract
Langerhans cell Histiocytosis (LCH) and Erdheim-Chester disease (ECD) are clonal myeloid disorders, associated with MAP-Kinase activating mutations and an increased risk of neurodegeneration. Surprisingly, we found pervasive PU.1
+ microglia mutant clones across the brain of LCH and ECD patients with and without neurological symptoms, associated with microgliosis, reactive astrocytosis, and neuronal loss. The disease predominated in the grey nuclei of the rhombencephalon, a topography attributable to a local proliferative advantage of mutant microglia. Presence of clinical symptoms was associated with a longer evolution of the disease and a larger size of PU.1+ clones (p= 0.0003). Genetic lineage tracing of PU.1+ clones suggest a resident macrophage lineage or a bone marrow precursor origin depending on patients. Finally, a CSF1R-inhibitor depleted mutant microglia and limited neuronal loss in mice suggesting an alternative to MAPK inhibitors. These studies characterize a progressive neurodegenerative disease, caused by clonal proliferation of inflammatory microglia (CPIM), with a decade(s)-long preclinical stage of incipient disease that represent a therapeutic window for prevention of neuronal death., Competing Interests: Conflict of Interest. FG has performed consulting for Third Rock venture in the past. Targeted Sequencing was funded in part by a grant from Third Rock venture. FG and RV are inventors in MSKCC’s United States application or PCT international application number PCT/US2018/047964 filed on 8/24/2018 (KINASE MUTATION-ASSOCIATED NEURODEGENERATIVE DISORDERS)- Published
- 2024
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34. Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis.
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Salem JE, Bretagne M, Abbar B, Leonard-Louis S, Ederhy S, Redheuil A, Boussouar S, Nguyen LS, Procureur A, Stein F, Fenioux C, Devos P, Gougis P, Dres M, Demoule A, Psimaras D, Lenglet T, Maisonobe T, De Chambrun MP, Hekimian G, Straus C, Gonzalez-Bermejo J, Klatzmann D, Rigolet A, Guillaume-Jugnot P, Champtiaux N, Benveniste O, Weiss N, Saheb S, Rouvier P, Plu I, Gandjbakhch E, Kerneis M, Hammoudi N, Zahr N, Llontop C, Morelot-Panzini C, Lehmann L, Qin J, Moslehi JJ, Rosenzwajg M, Similowski T, and Allenbach Y
- Subjects
- Humans, Immune Checkpoint Inhibitors therapeutic use, Abatacept therapeutic use, Myotoxicity complications, Myotoxicity drug therapy, Respiratory Muscles pathology, Myocarditis drug therapy, Antineoplastic Agents, Immunological therapeutic use, Myositis drug therapy, Myositis complications, Myositis pathology
- 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., (©2023 American Association for Cancer Research.)
- Published
- 2023
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35. 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?
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Boluda S, Mokhtari K, Mégarbane B, Annane D, Mathon B, Cao A, Adam C, Androuin A, Bielle F, Brochier G, Charlotte F, Chougar L, El Hachimi KH, Eloit M, Haïk S, Hervé D, Kasri A, Leducq V, Lehéricy S, Levavasseur E, Lobsiger C, Lorin de La Grandmaison G, Malet I, Malissin I, Marot S, Marty S, Pérot P, Plu I, Prigent A, Stimmer L, Potier MC, Marcelin AG, Delatour B, Duyckaerts C, and Seilhean D
- 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.
- Published
- 2023
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36. Memory CD4+ T-Cell Lymphocytic Angiopathy in Fatal Forms of COVID-19 Pulmonary Infection.
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Guihot A, Plu I, Soulié C, Rousseau A, Nakid-Cordero C, Dorgham K, Parizot C, Litvinova E, Mayaux J, Malet I, Quentric P, Combadière B, Combadière C, Bonduelle O, Adam L, Rosenbaum P, Beurton A, Hémon P, Debré P, Vieillard V, Autran B, Seilhean D, Charlotte F, Marcelin AG, Gorochov G, and Luyt CE
- Subjects
- Adult, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Humans, Lung, SARS-CoV-2, COVID-19, Pneumonia
- Abstract
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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guihot, Plu, Soulié, Rousseau, Nakid-Cordero, Dorgham, Parizot, Litvinova, Mayaux, Malet, Quentric, Combadière, Combadière, Bonduelle, Adam, Rosenbaum, Beurton, Hémon, Debré, Vieillard, Autran, Seilhean, Charlotte, Marcelin, Gorochov and Luyt.)
- Published
- 2022
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37. Neuroinvasion of SARS-CoV-2 in human and mouse brain.
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Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, and Iwasaki A
- Subjects
- Animals, Disease Models, Animal, Female, Humans, Male, Mice, Middle Aged, Organoids metabolism, Organoids pathology, Organoids virology, Angiotensin-Converting Enzyme 2 antagonists & inhibitors, Angiotensin-Converting Enzyme 2 metabolism, Antibodies, Blocking chemistry, COVID-19 metabolism, COVID-19 pathology, Cerebral Cortex metabolism, Cerebral Cortex pathology, Cerebral Cortex virology, Neurons metabolism, Neurons pathology, Neurons virology, SARS-CoV-2 metabolism
- Abstract
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., Competing Interests: Disclosures: M. Gunel reported personal fees from AI Therapeutics outside the submitted work; and reported, "AI Therapeutics is currently sponsoring a clinical trial for a therapeutic, which has no relevance for this study, in COVID-19. I am the Chief Scientific Advisor to AI Therapeutics." C.B. Wilen reported personal fees from ZymoResearch outside the submitted work; in addition, C.B. Wilen had a patent for compounds and compositions for treating, ameliorating, and/or preventing SARS-CoV-2 infection and/or complications thereof pending. S. Haik reported a patent to Method for treating prion diseases (PCT/EP 2019/070457) pending. A. Iwasaki reported "other" from RIGImmune and grants from Spring Discovery during the conduct of the study; in addition, A. Iwasaki had a patent to 14/776,463 pending, a patent for a T cell-based immunotherapy for central nervous system viral infections and tumors pending, and a patent to manipulation of meningeal lymphatic vasculature for brain and CNS tumor therapy pending. No other disclosures were reported., (© 2021 Song et al.)
- Published
- 2021
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38. Neuroinvasion of SARS-CoV-2 in human and mouse brain.
- Author
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Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, and Iwasaki A
- Abstract
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 whether the virus can infect the brain, or what the consequences of CNS infection are. 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 the infected and neighboring neurons. However, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. Finally, in brain autopsy from patients who died of COVID-19, we detect SARS-CoV-2 in the cortical neurons, and note pathologic features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2.
- Published
- 2020
- Full Text
- View/download PDF
39. Variant Creutzfeldt-Jakob Disease Diagnosed 7.5 Years after Occupational Exposure.
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Brandel JP, Vlaicu MB, Culeux A, Belondrade M, Bougard D, Grznarova K, Denouel A, Plu I, Bouaziz-Amar E, Seilhean D, Levasseur M, and Haïk S
- Subjects
- Accidents, Occupational, Adult, Animals, Brain diagnostic imaging, Brain pathology, Brain Chemistry, Creutzfeldt-Jakob Syndrome diagnosis, Creutzfeldt-Jakob Syndrome transmission, Fatal Outcome, Female, Humans, Laboratory Personnel, Magnetic Resonance Imaging, Methionine genetics, Mice, Mice, Transgenic, Prion Proteins blood, Prion Proteins cerebrospinal fluid, Creutzfeldt-Jakob Syndrome etiology, Occupational Exposure adverse effects, Occupational Injuries complications, Prion Proteins analysis, Wounds, Stab complications
- Published
- 2020
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- View/download PDF
40. Characteristics and clinical assessment of unexplained sudden cardiac arrest in the real-world setting: focus on idiopathic ventricular fibrillation.
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Waldmann V, Bougouin W, Karam N, Dumas F, Sharifzadehgan A, Gandjbakhch E, Algalarrondo V, Narayanan K, Zhao A, Amet D, Jost D, Geri G, Lamhaut L, Beganton F, Ludes B, Bruneval P, Plu I, Hidden-Lucet F, Albuisson J, Lavergne T, Piot O, Alonso C, Leenhardt A, Lellouche N, Extramiana F, Cariou A, Jouven X, and Marijon E
- Subjects
- Adult, Aged, Arrhythmias, Cardiac complications, Arrhythmias, Cardiac diagnosis, Cardiac Conduction System Disease complications, Cardiac Conduction System Disease diagnosis, Cardiomyopathies complications, Cardiomyopathies diagnosis, Coronary Angiography, Coronary Artery Disease complications, Coronary Artery Disease diagnosis, Echocardiography, Electrocardiography, Family, Female, Genetic Testing, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Survivors, Ventricular Fibrillation complications, Ventricular Fibrillation genetics, Death, Sudden, Cardiac etiology, Out-of-Hospital Cardiac Arrest etiology, Ventricular Fibrillation diagnosis
- Abstract
Aims: 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., Methods and Results: 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., Conclusion: 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
- 2018
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41. Seeding and propagation of lesions in neurodegenerative diseases: a new paradigm.
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Duyckaerts C, Seilhean D, Sazdovitch V, Plu I, Delatour B, and Potier MC
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- Amyloid beta-Peptides metabolism, Humans, alpha-Synuclein metabolism, tau Proteins metabolism, Neurodegenerative Diseases metabolism, Proteostasis Deficiencies metabolism
- Abstract
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
- 2015
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