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101. Probing ERP correlates of verbal semantic processing in patients with impaired consciousness

Author

Jean-Rémi King, Lionel Naccache, Benjamin Rohaut, N. Chausson, Imen El Karoui, Frédéric Faugeras, and Laurent D. Cohen

Subjects
Adult, Male, medicine.medical_specialty, genetic structures, Adolescent, Cognitive Neuroscience, Mismatch negativity, Experimental and Cognitive Psychology, Electroencephalography, Audiology, behavioral disciplines and activities, Developmental psychology, Behavioral Neuroscience, Young Adult, P3b, medicine, Semantic memory, Humans, Late positive component, Evoked Potentials, Aged, Cerebral Cortex, medicine.diagnostic_test, Minimally conscious state, Cognition, Middle Aged, medicine.disease, N400, Semantics, Acoustic Stimulation, Evoked Potentials, Auditory, Speech Perception, Consciousness Disorders, Female, Psychology, psychological phenomena and processes
Abstract

Our ability to identify covert cognitive abilities in non-communicating patients is of prime importance to improve diagnosis, to guide therapeutic decisions and to better predict their cognitive outcome. In the present study, we used a basic and rigorous paradigm contrasting pairs of words orthogonally. This paradigm enables the probing of semantic processing by comparing neural activity elicited by similar words delivered in various combinations. We describe the respective timing, topography and estimated cortical sources of two successive event-related potentials (ERP) components (N400 and late positive component (LPC)) using high-density EEG in conscious controls (N=20) and in minimally conscious (MCS; N=15) and vegetative states (VS; N=15) patients recorded at bedside. Whereas N400-like ERP components could be observed in the VS, MCS and conscious groups, only MCS and conscious groups showed a LPC response, suggesting that this late effect could be a potential specific marker of conscious semantic processing. This result is coherent with recent findings disentangling early and local non-conscious responses (e.g.: MMN in odd-ball paradigms, N400 in semantic violation paradigms) from late, distributed and conscious responses (e.g.: P3b to auditory rule violation) in controls and in patients with disorders of consciousness. However, N400 and LPC responses were not easily observed at the individual level, - even in conscious controls - , with standard ERP analyses, which is a limiting factor for its clinical use. Of potential interest, the only 3 patients presenting both significant N400 and LPC effects were MCS, and 2 of them regained consciousness and functional language abilities.

Published
2013

102. Single-trial decoding of auditory novelty responses facilitates the detection of residual consciousness

Author

Frédéric Faugeras, Alexandre Gramfort, E. Labyt, Stanislas Dehaene, Jean-Rémi King, Tristan A. Bekinschtein, Benjamin Rohaut, Catherine Wacongne, Jacobo D. Sitt, Lionel Naccache, I. El Karoui, Aaron Schurger, Laurent D. Cohen, Neuroimagerie cognitive - Psychologie cognitive expérimentale (UNICOG-U992), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Saclay (COmUE)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 Neurophysiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service NEUROSPIN (NEUROSPIN), 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, Laboratoire Traitement et Communication de l'Information (LTCI), Institut Mines-Télécom [Paris] (IMT)-Télécom Paris, Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Cognition and Brain Sciences Unit (MRC CBU), University of Cambridge [UK] (CAM), Sorbonne Université - Faculté de médecine Pitié Salpétrière, Chaire Psychologie cognitive expérimentale, Collège de France (CdF (institution)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 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), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Modelling brain structure, function and variability based on high-field MRI data (PARIETAL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Sorbonne Université - Faculté de médecine [CHU Pitié Salpétrière], Collège de France - Chaire Psychologie cognitive expérimentale, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Pitié-Salpêtrière], and IFR70-CHU Pitié-Salpêtrière [AP-HP]

Subjects
Adult, Male, medicine.medical_specialty, Consciousness, Cognitive Neuroscience, media_common.quotation_subject, Decoding, Mismatch negativity, Audiology, Electroencephalography, Article, Developmental psychology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Distraction, medicine, Humans, Unresponsive wakefulness syndrome, EEG, Minimally conscious state, 030304 developmental biology, media_common, 0303 health sciences, Computational neuroscience, Vegetative state, MEG, medicine.diagnostic_test, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SCCO.NEUR]Cognitive science/Neuroscience, Novelty, Brain, Magnetoencephalography, Contrast (statistics), [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Signal Processing, Computer-Assisted, Middle Aged, medicine.disease, Acoustic Stimulation, Neurology, Multivariate pattern classifier, Consciousness Disorders, Female, Psychology, 030217 neurology & neurosurgery
Abstract

International audience; Detecting residual consciousness in unresponsive patients is a major clinical concern and a challenge for theoretical neuroscience. To tackle this issue, we recently designed a paradigm that dissociates two electro-encephalographic (EEG) responses to auditory novelty. Whereas a local change in pitch automatically elicits a mismatch negativity (MMN), a change in global sound sequence leads to a late P300b response. The latter component is thought to be present only when subjects consciously perceive the global novelty. Unfortunately, it can be difficult to detect because individual variability is high, especially in clinical recordings. Here, we show that multivariate pattern classifiers can extract subject-specific EEG patterns and predict single-trial local or global novelty responses. We first validate our method with 38 high-density EEG, MEG and intracranial EEG recordings. We empirically demonstrate that our approach circumvents the issues associated with multiple comparisons and individual variability while improving the statistics. Moreover, we confirm in control subjects that local responses are robust to distraction whereas global responses depend on attention. We then investigate 104 vegetative state (VS), minimally conscious state (MCS) and conscious state (CS) patients recorded with high-density EEG. For the local response, the proportion of significant decoding scores (M = 60%) does not vary with the state of consciousness. By contrast, for the global response, only 14% of the VS patients' EEG recordings presented a significant effect, compared to 31% in MCS patients' and 52% in CS patients'. In conclusion, single-trial multivariate decoding of novelty responses provides valuable information in non-communicating patients and paves the way towards real-time monitoring of the state of consciousness.

Published
2013

103. Neurology of consciousness impairments

Author

Lionel Naccache, Benjamin Rohaut, and Frédéric Faugeras

Subjects
medicine.medical_specialty, Neurology, media_common.quotation_subject, Neuropsychiatry, Orientation (mental), Event-related potential, Intensive care, Aphasia, Consciousness Disorders, medicine, Consciousness, medicine.symptom, Psychology, Psychiatry, Neuroscience, media_common
Published
2013

104. Event related potentials elicited by violations of auditory regularities in patients with impaired consciousness

Author

Louis Puybasset, Frédéric Faugeras, Lionel Naccache, Laurent D. Cohen, Benjamin Rohaut, Francis Bolgert, Nicolas Weiss, Tristan A. Bekinschtein, Damien Galanaud, Stanislas Dehaene, Claire Sergent, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cognition and Brain Sciences Unit (MRC CBU), University of Cambridge [UK] (CAM), Neuroimagerie cognitive - Psychologie cognitive expérimentale (UNICOG-U992), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Collège de France - Chaire Psychologie cognitive expérimentale, Collège de France (CdF (institution)), Cortex et Epilepsie [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Departement de Physiologie, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Service d'anesthésie-réanimation [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Fédération de neurologie 4, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Saclay (COmUE), Chaire Psychologie cognitive expérimentale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Saclay (COmUE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Collège de France (CDF (laboratoire)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Santoro, Giovanna

Subjects
Adult, Male, Patients, Adolescent, Consciousness, Cognitive Neuroscience, media_common.quotation_subject, Experimental and Cognitive Psychology, Electroencephalography, Auditory cortex, 050105 experimental psychology, Audition, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Event-related potential, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, 0501 psychology and cognitive sciences, In patient, media_common, Aged, Expectancy theory, Aged, 80 and over, Auditory Cortex, Vegetative state, medicine.diagnostic_test, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, 05 social sciences, Perspective (graphical), Cognition, Middle Aged, Acoustic Stimulation, Case-Control Studies, Evoked Potentials, Auditory, Consciousness Disorders, Female, Psychology, ERP, 030217 neurology & neurosurgery, Cognitive psychology
Abstract

International audience; Improving our ability to detect conscious processing in non communicating patients remains a major goal of clinical cognitive neurosciences. In this perspective, several functional brain imaging tools are currently under development. Bedside cognitive event-related potentials (ERPs) derived from the EEG signal are a good candidate to explore consciousness in these patients because: (1) they have an optimal time resolution within the millisecond range able to monitor the stream of consciousness, (2) they are fully non-invasive and relatively cheap, (3) they can be recorded continuously on dedicated individual systems to monitor consciousness and to communicate with patients, (4) and they can be used to enrich patients' autonomy through brain-computer interfaces. We recently designed an original auditory rule extraction ERP test that evaluates cerebral responses to violations of temporal regularities that are either local in time or global across several seconds. Local violations led to an early response in auditory cortex, independent of attention or the presence of a concurrent visual task, while global violations led to a late and spatially distributed response that was only present when subjects were attentive and aware of the violations. In the present work, we report the results of this test in 65 successive recordings obtained at bedside from 49 non-communicating patients affected with various acute or chronic neurological disorders. At the individual level, we confirm the high specificity of the 'global effect': only conscious patients presented this proposed neural signature of conscious processing. Here, we also describe in details the respective neural responses elicited by violations of local and global auditory regularities, and we report two additional ERP effects related to stimuli expectancy and to task learning, and we discuss their relations to consciousness.

Published
2012

105. [Persistent trigeminal artery]

Author

Cumurciuc R, Benjamin Rohaut, de Broucker F, and de Broucker T

Subjects
Incidental Findings, Basilar Artery, Circle of Willis, Humans, Female, Infarction, Middle Cerebral Artery, Cerebral Arteries, Carotid Artery, Internal, Magnetic Resonance Angiography, Aged, Cerebral Angiography
Published
2010

106. [Early complications after insertion of pacemaker]

Author

Aurélie, Méneret, Benjamin, Rohaut, and Claude, Bachmeyer

Subjects
Aged, 80 and over, Pacemaker, Artificial, Heparin, Bundle-Branch Block, Anticoagulants, Collateral Circulation, Thrombosis, Subclavian Vein, Echocardiography, Doppler, Intracranial Hemorrhage, Traumatic, Syncope, Electrocardiography, Echocardiography, Humans, Accidental Falls, Female
Published
2008

107. [Scurvy]

Author

Claude, Bachmeyer, Benjamin, Rohaut, Alain, Cazier, and Yves, Turc

Subjects
Male, Folic Acid, Time Factors, Treatment Outcome, Administration, Oral, Humans, Drug Therapy, Combination, Ascorbic Acid, Scurvy, Antioxidants, Aged
Published
2006

109. Complications précoces après pose de pacemaker

Author

Aurélie Méneret, Claude Bachmeyer, and Benjamin Rohaut

Subjects
medicine.medical_specialty, business.industry, medicine, General Medicine, business, Complication, Surgery
Published
2009

110. Sarcoïdose mimant une polyarthrite rhumatoïde

Author

Benjamin Rohaut and Claude Bachmeyer

Subjects
medicine.medical_specialty, business.industry, medicine, General Medicine, Sarcoidosis, Splenic disease, Differential diagnosis, medicine.disease, business, Dermatology
Published
2006

111. C - 9 Méningo-encéphalites avec mouvements anormaux

Author

Benjamin Rohaut, B. Garcin, V. Denys, C. Laage, Francis Bolgert, and S. Demeret

Subjects
Neurology, Neurology (clinical)
Abstract

Introduction Nous rapportons ici cinq cas de meningo-encephalites avec mouvements anormaux, dont la presentation et l’evolution ont ete remarquablement similaires, sans agent causal retrouve. Observations Cinq patientes âgees de 24 a 38 ans presenterent un tableau de meningo-encephalite, febrile dans 4 cas, au decours immediat d’un episode infectieux des voies aeriennes superieures dans 3 cas. Le tableau neurologique initial associait une confusion, avec troubles d’allure psychiatrique puis alteration de la vigilance, et des crises epileptiques. Les mouvements anormaux involontaires etaient de survenue precoce (2 cas) ou retardee apres le reveil des patientes (3 cas) ; ils debutaient et predominaient au niveau de la face, mais atteignaient egalement les membres. Ces mouvements etaient de type choreo-athetosique (noyaux gris centraux) ou myoclonies squelettiques (tronc cerebral). Leur importance necessitait une sedation profonde et prolongee avec maintien en reanimation. Chez toutes les patientes, on retrouvait : une meningite lymphocytaire, une IRM cerebrale normale, des ondes lentes diffuses sans signes critiques a l’EEG ; le bilan etiologique infectieux, auto-immun, neoplasique etait negatif. La biopsie cerebrale realisee dans un cas evoquait une encephalite virale. L’evolution se deroula sur plusieurs mois, avec disparition complete des mouvements anormaux involontaires, mais persistance de sequelles neuropsychologiques d’intensite moderee a severe. Discussion Aux cotes des encephalites virales avec atteinte de la substance grise (type HSV1), des encephalites post-infectieuses avec atteinte de la substance blanche (type ADEM), il existe des encephalites avec atteinte predominante des regions profondes, noyaux gris centraux et tronc cerebral, dont le mecanisme peut-etre infectieux, auto-immun post-infectieux ou paraneoplasique, mais le plus souvent sans etiologie retrouvee. Cette entite mal circonscrite merite d’etre revisitee. Conclusion Nous rapportons cinq cas adultes de meningo-encephalites avec atteinte des regions profondes, caracterisees par l’existence de mouvements anormaux involontaires, de presentation et d’evolution tres similaire.

Published
2007

112. Lichen planus: an unusual cause of oesophageal stricture

Author

O Danne, Benjamin Rohaut, L. Blum, Claude Bachmeyer, B. Petitjean, and B Benchaa

Subjects
medicine.medical_specialty, Infectious Diseases, Oesophageal stricture, business.industry, medicine, Dentistry, Dermatology, business
Published
2007

113. Human consciousness is supported by dynamic complex patterns of brain signal coordination

Author

Enzo Tagliazucchi, Nicholas D. Schiff, Charlotte Martial, Adrian M. Owen, Henning U. Voss, Benjamin Rohaut, Lionel Naccache, Athena Demertzi, Federico Raimondo, Davinia Fernández-Espejo, Stanislas Dehaene, Pablo Barttfeld, Steven Laureys, Jacobo D. Sitt, Gustavo Deco, Université de Liège, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Research), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Instituto de Física de Buenos Aires (IFIBA), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Ciencias Exactas y Naturales [Buenos Aires] (FCEyN), Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA), Université Paris-Sud - Paris 11 (UP11), Chaire Psychologie cognitive expérimentale, Collège de France (CdF (institution)), Universitat Pompeu Fabra [Barcelona] (UPF), Institució Catalana de Recerca i Estudis Avançats (ICREA), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), University of Birmingham [Birmingham], University of Western Ontario (UWO), Columbia University [New York], Weill Medical College of Cornell University [New York], 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), Collège de France - Chaire Psychologie cognitive expérimentale, Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universitat Pompeu Fabra [Barcelona], Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Neuroimagerie cognitive (LCogn), and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, purl.org/becyt/ford/1 [https], 0302 clinical medicine, Neural Pathways, Psychology, Research Articles, ComputingMilieux_MISCELLANEOUS, media_common, 0303 health sciences, Brain Mapping, Multidisciplinary, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, medicine.diagnostic_test, Unconsciousness, SciAdv r-articles, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Brain, Cognition, Middle Aged, Magnetic Resonance Imaging, Dynamics, Neurology, Female, medicine.symptom, Research Article, Mental image, Adult, Consciousness, Cognitive Neuroscience, media_common.quotation_subject, Neuroimaging, Brain damage, 03 medical and health sciences, medicine, Connectome, Humans, 030304 developmental biology, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neurosciences, purl.org/becyt/ford/1.3 [https], Covert, Functional magnetic resonance imaging, Neuroscience, 030217 neurology & neurosurgery
Abstract

Dynamic patterns of brain activity at rest distinguish conscious and unconscious states in humans., Adopting the framework of brain dynamics as a cornerstone of human consciousness, we determined whether dynamic signal coordination provides specific and generalizable patterns pertaining to conscious and unconscious states after brain damage. A dynamic pattern of coordinated and anticoordinated functional magnetic resonance imaging signals characterized healthy individuals and minimally conscious patients. The brains of unresponsive patients showed primarily a pattern of low interareal phase coherence mainly mediated by structural connectivity, and had smaller chances to transition between patterns. The complex pattern was further corroborated in patients with covert cognition, who could perform neuroimaging mental imagery tasks, validating this pattern’s implication in consciousness. Anesthesia increased the probability of the less complex pattern to equal levels, validating its implication in unconsciousness. Our results establish that consciousness rests on the brain’s ability to sustain rich brain dynamics and pave the way for determining specific and generalizable fingerprints of conscious and unconscious states.

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

Author

Sharshar, Tarek, Porcher, Raphaël, Asfar, Pierre, Grimaldi, Lamiae, Jabot, Julien, Argaud, Laurent, Lebert, Christine, Bollaert, Pierre Édouard, Harlay, Marie Line, Chillet, Patrick, Maury, Éric, Santoli, Francesco, Blanc, Pascal, Sonneville, Romain, Vu, Dinh Chuyen, Rohaut, Benjamin, Mazeraud, Aurélien, Alvarez, Jean Claude, Navarro, Vincent, Clair, Bernard, Outin, Hervé D., Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Hôtel-Dieu [Paris], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Lorraine (UL), Hôpital de Hautepierre [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital de Châlons-en-Champagne, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Hôpital Robert Ballanger [Aulnay-sous-Bois], Centre Hospitalier René Dubos [Pontoise], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier d'Etampes, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [Garches], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], and Valse investigators and for the Groupe d’Explorations Neurologiques en Reanimation (GENER): Laurent Argaud, Eric Azabou, François Beloncle, Omar Ben-Hadj, Pascal Blanc, Pierre-Edouard Bollaert, Francis Bolgert, Lila Bouadma, Patrick Chillet, Bernard Clair, Philippe Corne, Raphaël Clere-Jehl, Martin Cour, Arielle Crespel, Véronique Déiler, Jean Dellamonica, Sophie Demeret, Marie-Line Harley, Matthieu Henry-Lagarrigue, Julien Jabot, Nicholas Heming, Romain Hernu, Achille Kouatchet, Christine Lebert, Nicolas Lerolle, Eric Maury, Sophie Letrou, Aurélien Mazeraud, Alain Mercat, Satar Mortaza, Bruno Mourvillier, Hervé Outin, Catherine Paugham-Burtz, Marc Pierrot, Marion Provent, Benjamin Rohaut, Sylvie De La Salle, François Santoli, Maleka Schenk, Shidasp Siami, Vincent Souday, Tarek Sharshar, Romain Sonneville, Jean-François Timsit, Marie Thuong, Nicolas Weiss

Subjects
[SDV]Life Sciences [q-bio], Generalised convulsive status epilepticus, Valproic acid, Intensive care unit, Critical Care and Intensive Care Medicine, Seizure
Abstract

Background Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20–40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE. Methods This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90. Results A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89–1.19); p = 0.58]. There were no between-group differences for secondary outcomes. Conclusions VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15. Trial registration No. NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

Published
2023

115. Herpes Simplex Virus Encephalitis With Initial Negative Polymerase Chain Reaction in the Cerebrospinal Fluid: Prevalence, Associated Factors, and Clinical Impact

Author

Etienne, de Montmollin, Claire, Dupuis, Pierre, Jaquet, Benjamine, Sarton, Charline, Sazio, Vincent, Susset, Marie, Conrad, Laurent, Argaud, Sophie, Demeret, Jean Marc, Tadié, François, Barbier, Michel, Wolff, Jean-François, Timsit, Benoit, Visseaux, Romain, Sonneville, Guillaume, Franchineau, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, CHU Bordeaux [Bordeaux], Centre Hospitalier Métropole Savoie [Chambéry], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Régional d'Orléans (CHRO), GHU Paris Psychiatrie et Neurosciences, Université Paris Cité (UPCité), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), ENCEPHALITICA Study Group: Julien Marechal, Bruno Mourvillier, Frederic Dailler, Fabrice Bruneel, Alexandre Lautrette, Emmanuel Novy, Bertrand Guidet, François Mateos, Clément Brault, Quentin Maestraggi, Keyvan Razazi, Jean-Pierre Quenot, Aurélie Joret, Albrice Levrat, Alexandre Massri, Alexandre Robert, Damien Contou, Jean-Paul Mira, Sarah Benghanem, Gaudry Stephane, Guillaume Voiriot, Asael Berger, Vincent Das, Nicolas Engrand, Martin Murgier, Shidasp Siami, Sami Hraiech, Eric Mariotte, Claire Ragot, Annabelle Stoclin, Pierre Trouiller, Mathieu Schmidt, Benjamin Rohaut, Guillaume Franchineau., CarMeN, laboratoire, 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), CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
[SDV] Life Sciences [q-bio], Critical Illness, [SDV]Life Sciences [q-bio], Prevalence, Acyclovir, Humans, Simplexvirus, Encephalitis, Herpes Simplex, Critical Care and Intensive Care Medicine, Polymerase Chain Reaction, Cerebrospinal Fluid
Abstract

International audience; OBJECTIVES: To describe the prevalence, associated factors, and clinical impact of an initial negative herpes simplex virus (HSV) polymerase chain reaction (PCR) in critically ill patients with PCR-proven HSV encephalitis. DESIGN: Retrospective multicenter study from 2007 to 2017. SETTING: Forty-seven French ICUs. PATIENTS: Critically ill patients admitted to the ICU with possible/probable acute encephalitis and a positive cerebrospinal fluid (CSF) PCR for HSV. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 273 patients with a median Glasgow Coma Scale score of 9 (6-12) at ICU admission. CSF HSV PCR was negative in 11 cases (4%), exclusively in lumbar punctures (LPs) performed less than 4 days after symptoms onset. Patients with an initial negative PCR presented with more frequent focal neurologic signs (4/11 [36.4%] vs 35/256 [13.7%]; p = 0.04) and lower CSF leukocytosis (4 cells/mm3 [3-25 cells/mm3] vs 52 cells/mm3 [12-160 cells/mm3]; p \textless 0.01). An initial negative PCR was associated with an increased delay between LP and acyclovir treatment (3 d [2-7 ] vs 0 d [0-0 d]; p \textless 0.01) and was independently associated with a poor neurologic outcome at hospital discharge (modified Rankin Scale score ≥ 4) (adjusted odds ratio, 9.89; 95% CI, 1.18-82.78). CONCLUSIONS: In severe herpes simplex encephalitis, initial negative CSF HSV PCR occurred in 4% of cases and was independently associated with worse neurologic outcome at hospital discharge. In these patients, a systematic multimodal diagnostic approach including early brain MRI and EEG will help clinicians avoid delayed acyclovir initiation or early inappropriate discontinuation.

Published
2022

116. Characteristics, management, and prognosis of elderly patients with COVID-19 admitted in the ICU during the first wave: insights from the COVID-ICU study

Author

Dres, Martin, Hajage, David, Lebbah, Said, Kimmoun, Antoine, Pham, Tai, Béduneau, Gaëtan, Combes, Alain, Mercat, Alain, Guidet, Bertrand, Demoule, Alexandre, Schmidt, Matthieu, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hôpital Bicêtre, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Groupe de Recherche sur le Handicap Ventilatoire et Neurologique (GRHVN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), CHU Saint-Antoine [AP-HP], COVID-ICU investigators: Alain Mercat, Pierre Asfar, François Beloncle, Julien Demiselle, Tài Pham, Arthur Pavot, Xavier Monnet, Christian Richard, Alexandre Demoule, Martin Dres, Julien Mayaux, Alexandra Beurton, Cédric Daubin, Richard Descamps, Aurélie Joret, Damien Du Cheyron, Frédéric Pene, Jean-Daniel Chiche, Mathieu Jozwiak, Paul Jaubert, Guillaume Voiriot, Muriel Fartoukh, Marion Teulier, Clarisse Blayau, Erwen L'Her, Cécile Aubron, Laetitia Bodenes, Nicolas Ferriere, Johann Auchabie, Anthony Le Meur, Sylvain Pignal, Thierry Mazzoni, Jean-Pierre Quenot, Pascal Andreu, Jean-Baptiste Roudau, Marie Labruyère, Saad Nseir, Sébastien Preau, Julien Poissy, Daniel Mathieu, Sarah Benhamida, Rémi Paulet, Nicolas Roucaud, Martial Thyrault, Florence Daviet, Sami Hraiech, Gabriel Parzy, Aude Sylvestre, Sébastien Jochmans, Anne-Laure Bouilland, Mehran Monchi, Marc Danguy des Déserts, Quentin Mathais, Gwendoline Rager, Pierre Pasquier, Reignier Jean, Seguin Amélie, Garret Charlotte, Canet Emmanuel, Jean Dellamonica, Clément Saccheri, Romain Lombardi, Yanis Kouchit, Sophie Jacquier, Armelle Mathonnet, Mai-AhnNay, Isabelle Runge, Frédéric Martino, Laure Flurin, Amélie Rolle, Michel Carles, Rémi Coudroy, Arnaud W Thille, Jean-Pierre Frat, Maeva Rodriguez, Pascal Beuret, Audrey Tientcheu, Arthur Vincent, Florian Michelin, Marie Anne Melone, Maxime Gauzi, Arnaud Guilbert, Geoffrey Kouadri, Valérie Gissot, Stéphan Ehrmann, Charlotte Salmon Gandonniere, Djlali Elaroussi, Agathe Delbove, Yannick Fedun, Julien Huntzinger, Eddy Lebas, Grâce Kisoka, Céline Grégoire, Stella Marchetta, Bernard Lambermont, Laurent Argaud, Thomas Baudry, Pierre-Jean Bertrand, Auguste Dargent, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Cédric Darreau, Alexis Ferre, Antoine Gros, Guillaume Lacave, Fabrice Bruneel, Mathilde Neuville, Jérôme Devaquet, Guillaume Tachon, Richard Gallot, Riad Chelha, Arnaud Galbois, Anne Jallot, Ludivine Chalumeau Lemoine, Khaldoun Kuteifan, Valentin Pointurier, Louise-Marie Jandeaux, Joy Mootien, Charles Damoisel, Benjamin Sztrymf, Matthieu Schmidt, Alain Combes, Juliette Chommeloux, Charles Edouard Luyt, Frédérique Schortgen, Leon Rusel, Camille Jung, Florent Gobert, Damien Vimpere, Lionel Lamhaut, Bertrand Sauneuf, Liliane Charrrier, Julien Calus, Isabelle Desmeules, Benoît Painvin, Jean-Marc Tadie, Vincent Castelain, Baptiste Michard, Jean-Etienne Herbrecht, Mathieu Baldacini, Nicolas Weiss, Sophie Demeret, Clémence Marois, Benjamin Rohaut, Pierre-Henri Moury, Anne-Charlotte Savida, Emmanuel Couadau, Mathieu Série, Nica Alexandru, Cédric Bruel, Candice Fontaine, Sonia Garrigou, Juliette Courtiade Mahler, Maxime Leclerc, Michel Ramakers, Pierre Garçon, Nicole Massou, Ly Van Vong, Juliane Sen, Nolwenn Lucas, Franck Chemouni, Annabelle Stoclin, Alexandre Avenel, Henri Faure, Angélie Gentilhomme, Sylvie Ricome, Paul Abraham, Céline Monard, Julien Textoris, Thomas Rimmele, Florent Montini, Gabriel Lejour, Thierry Lazard, Isabelle Etienney, Younes Kerroumi, Claire Dupuis, Marine Bereiziat, Elisabeth Coupez, François Thouy, Clémet Hoffmann, Nicolas Donat, Violaine Muller, Thibault Martinez, Antoine Kimmoun, Audrey Jacquot, Matthieu Mattei, Bruno Levy, Ramin Ravan, Loïc Dopeux, Jean-Mathias Liteaudon, Delphine Roux, Brice Rey, Radu Anghel, Deborah Schenesse, Vincent Gevrey, Jermy Castanera, Philippe Petua, Benjamin Madeux, Otto Hartman, Michael Piagnerelli, Anne Joosten, Cinderella Noel, Patrick Biston, Thibaut Noel, Gurvan L E Bouar, Messabi Boukhanza, Elsa Demarest, Marie-France Bajolet, Nathanaël Charrier, Audrey Quenet, Cécile Zylberfajn, Nicolas Dufour, Buno Mégarbane, SqébastianVoicu, Nicolas Deye, Isabelle Malissin, François Legay, Matthieu Debarre, Nicolas Barbarot, Pierre Fillatre, Bertrand Delord, Thomas Laterrade, Tahar Saghi, Wilfried Pujol, Pierre Julien Cungi, Pierre Esnault, Mickael Cardinale, Vivien Hong Tuan Ha, Grégory Fleury, Marie-Ange Brou, Daniel Zafimahazo, David Tran-Van, Patrick Avargues, Lisa Carenco, Nicolas Robin, Alexandre Ouali, Lucie Houdou, Christophe Le Terrier, Noémie Suh, Steve Primmaz, Jérome Pugin, Emmanuel Weiss, Tobias Gauss, Jean-Denis Moyer, Catherine Paugam Burtz, Béatrice La Combe, Rolland Smonig, Jade Violleau, Pauline Cailliez, Jonathan Chelly, Antoine Marchalot, Cécile Saladin, Christelle Bigot, Pierre-Marie Fayolle, Jules Fatséas, Amr Ibrahim, Dabor Resiere, Rabih Hage, Clémentine Cholet, Marie Cantier, Pierre Trouiler, Philippe Montravers, Brice Lortat-Jacob, Sebastien Tanaka, Alexy Tran Dinh, Jacques Duranteau, Anatole Harrois, Guillaume Dubreuil, Marie Werner, Anne Godier, Sophie Hamada, Diane Zlotnik, Hélène Nougue, Armand Mekontso-Dessap, Guillaume Carteaux, Keyvan Razazi, Nicolas De Prost, Nicolas Mongardon, Olivier Langeron, Eric Levesque, Arié Attias, Charles de Roquetaillade, Benjamin G Chousterman, Alexandre Mebazaa, Etienne Gayat, Marc Garnier, Emmanuel Pardo, Lea Satre-Buisson, Christophe Gutton, Elise Yvin, Clémence Marcault, Elie Azoulay, Michael Darmon, Hafid Ait Oufella, Geoffroy Hariri, Tomas Urbina, Sandie Mazerand, Nicholas Heming, Francesca Santi, Pierre Moine, Djillali Annane, Adrien Bouglé, Edris Omar, Aymeric Lancelot, Emmanuelle Begot, Gaétan Plantefeve, Damien Contou, Hervé Mentec, Olivier Pajot, Stanislas Faguer, Olivier Cointault, Laurence Lavayssiere, Marie-Béatrice Nogier, Matthieu Jamme, Claire Pichereau, Jan Hayon, Hervé Outin, François Dépret, Maxime Coutrot, Maité Chaussard, Lucie Guillemet, Pierre Goffin, Romain Thouny, Julien Guntz, Laurent Jadot, Romain Persichini, Vanessa Jean-Michel, Hugues Georges, Thomas Caulier, Gaël Pradel, Marie-Hélène Hausermann, ThiMy Hue Nguyen-Valat, Michel Boudinaud, Emmanuel Vivier, Sylvène Rosseli, Gaël Bourdin, Christian Pommier, Marc Vinclair, Simon Poignant, Sandrine Mons, Wulfran Bougouin, Franklin Bruna, Quentin Maestraggi, Christian Roth, Laurent Bitker, François Dhelft, Justine Bonnet-Chateau, Mathilde Filippelli, Tristan Morichau-Beauchant, Stéphane Thierry, Charlotte Le Roy, Mélanie Saint Jouan, Bruno Goncalves, Aurélien Mazeraud, Matthieu Daniel, Tarek Sharshar, Cyril Cadoz, RostaneGaci, Sébastien Gette, Guillaune Louis, Sophe-Caroline Sacleux, Marie-Amélie Ordan, Aurélie Cravoisy, Marie Conrad, Guilhem Courte, Sébastien Gibot, Younès Benzidi, Claudia Casella, Laurent Serpin, Jean-Lou Setti, Marie-Catherine Besse, Anna Bourreau, Jérôme Pillot, Caroline Rivera, Camille Vinclair, Marie-Aline Robaux, Chloé Achino, Marie-Charlotte Delignette, Tessa Mazard, Frédéric Aubrun, Bruno Bouchet, Aurélien Frérou, Laura Muller, Charlotte Quentin, Samuel Degoul, Xavier Stihle, Claude Sumian, Nicoletta Bergero, Bernard Lanaspre, Hervé Quintard, Eve Marie Maiziere, Pierre-Yves Egreteau, Guillaume Leloup, Florin Berteau, Marjolaine Cottrel, Marie Bouteloup, Matthieu Jeannot, Quentin Blanc, Julien Saison, Isabelle Geneau, Romaric Grenot, Abdel Ouchike, Pascal Hazera, Anne-Lyse Masse, Suela Demiri, Corinne Vezinet, Elodie Baron, Deborah Benchetrit, Antoine Monsel, Grégoire Trebbia, Emmanuelle Schaack, Raphaël Lepecq, Mathieu Bobet, Christophe Vinsonneau, Thibault Dekeyser, Quentin Delforge, Imen Rahmani, Bérengère Vivet, Jonathan Paillot, Lucie Hierle, Claire Chaignat, Sarah Valette, Benoït Her, Jennifier Brunet, Mathieu Page, Fabienne Boiste, Anthony Collin, Florent Bavozet, Aude Garin, Mohamed Dlala, Kais Mhamdi, Bassem Beilouny, Alexandra Lavalard, Severine Perez, Benoit Veber, Pierre-Gildas Guitard, Philippe Gouin, Anna Lamacz, Fabienne Plouvier, Bertrand P Delaborde, Aïssa Kherchache, Amina Chaalal, Jean-Damien Ricard, Marc Amouretti, Santiago Freita-Ramos, Damien Roux, Jean-Michel Constantin, Mona Assefi, Marine Lecore, Agathe Selves, Florian Prevost, Christian Lamer, Ruiying Shi, Lyes Knani, Sébastien PiliFloury, Lucie Vettoretti, Michael Levy, Lucile Marsac, Stéphane Dauger, Sophie Guilmin-Crépon, Hadrien Winiszewski, Gael Piton, Thibaud Soumagne, Gilles Capellier, Jean-Baptiste Putegnat, Frédérique Bayle, Maya Perrou, Ghyslaine Thao, Guillaume Géri, Cyril Charron, Xavier Repessé, Antoine Vieillard-Baron, Mathieu Guilbart, Pierre-Alexandre Roger, Sébastien Hinard, Pierre-Yves Macq, Kevin Chaulier, Sylvie Goutte, Patrick Chillet, Anaïs Pitta, Barbara Darjent, Amandine Bruneau, Sigismond Lasocki, Maxime Leger, Soizic Gergaud, Pierre Lemarie, Nicolas Terzi, Carole Schwebel, Anaïs Dartevel, Louis-Marie Galerneau, Jean-Luc Diehl, Caroline Hauw-Berlemont, Nicolas Péron, Emmanuel Guérot, Abolfazl Mohebbi Amoli, Michel Benhamou, Jean-Pierre Deyme, Olivier Andremont, Diane Lena, Julien Cady, Arnaud Causeret, Arnaud De La Chapelle, Christophe Cracco, Stéphane Rouleau, David Schnell, Camille Foucault, Cécile Lory, Thibault Chapelle, Vincent Bruckert, Julie Garcia, Abdlazize Sahraoui, Nathalie Abbosh, Caroline Bornstain, Pierre Pernet, Florent Poirson, Ahmed Pasem, Philippe Karoubi, Virginie Poupinel, Caroline Gauthier, François Bouniol, Philippe Feuchere, Florent Bavozet, Anne Heron, Serge Carreira, Malo Emery, Anne Sophie Le Floch, Luana Giovannangeli, Nicolas Herzog, Christophe Giacardi, Thibaut Baudic, Chloé Thill, Said Lebbah, Jessica Palmyre, Florence Tubach, David Hajage, Nicolas Bonnet, Nathan Ebstein, Stéphane Gaudry, Yves Cohen, Julie Noublanche, Olivier Lesieur, Arnaud Sément, Isabel Roca-Cerezo, Michel Pascal, Nesrine Sma, Gwenhaël Colin, Jean-Claude Lacherade, Gauthier Bionz, Natacha Maquigneau, Pierre Bouzat, Michel Durand, Marie-Christine Hérault, Jean-Francois Payen, and dres, martin

Subjects
[SDV] Life Sciences [q-bio], Acute respiratory distress syndrome, Frailty, [SDV]Life Sciences [q-bio], Old patients, COVID-19, Intensive care unit, Mortality, Intubation
Abstract

International audience; Abstract Background The COVID-19 pandemic is a heavy burden in terms of health care resources. Future decision-making policies require consistent data on the management and prognosis of the older patients (> 70 years old) with COVID-19 admitted in the intensive care unit (ICU). Methods Characteristics, management, and prognosis of critically ill old patients (> 70 years) were extracted from the international prospective COVID-ICU database. A propensity score weighted-comparison evaluated the impact of intubation upon admission on Day-90 mortality. Results The analysis included 1199 (28% of the COVID-ICU cohort) patients (median [interquartile] age 74 [72–78] years). Fifty-three percent, 31%, and 16% were 70–74, 75–79, and over 80 years old, respectively. The most frequent comorbidities were chronic hypertension (62%), diabetes (30%), and chronic respiratory disease (25%). Median Clinical Frailty Scale was 3 (2–3). Upon admission, the PaO 2 /FiO 2 ratio was 154 (105–222). 740 (62%) patients were intubated on Day-1 and eventually 938 (78%) during their ICU stay. Overall Day-90 mortality was 46% and reached 67% among the 193 patients over 80 years old. Mortality was higher in older patients, diabetics, and those with a lower PaO 2 /FiO 2 ratio upon admission, cardiovascular dysfunction, and a shorter time between first symptoms and ICU admission. In propensity analysis, early intubation at ICU admission was associated with a significantly higher Day-90 mortality (42% vs 28%; hazard ratio 1.68; 95% CI 1.24–2.27; p

Published
2021

117. Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis

Author

Sharshar, Tarek, Porcher, Raphaël, Demeret, Sophie, Tranchant, Christine, Gueguen, Antoine, Eymard, Bruno, Nadaj-Pakleza, Aleksandra, Spinazzi, Marco, Grimaldi, Lamiae, Birnbaum, Simone, Friedman, Diane, Clair, Bernard, Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP), Centre Hospitalier Sainte Anne [Paris], Hôpital Hôtel-Dieu [Paris], Université Paris Descartes - Paris 5 (UPD5), 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), Sorbonne Université (SU), CHU Strasbourg, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Ambroise Paré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Hôpital Raymond Poincaré [AP-HP], and MYACOR Study Group: Philippe Aegerter, Djillali Annane, Anne-Catherine Aubé-Nathier, Francis Bolgert, Marie Fleury, Marie-Christine Durand, Pierre-Marie Gonnaud, Catherine Goulon-Goeau, Olivier Gout, Frédéric Lofaso, Christophe Marcel, Vivien Pautot, Isabelle Penisson-Besnier, Hélène Prigent, Benjamin Rohaut, Christophe Vial, Nicolas Weiss

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

International audience; Importance: The tapering of prednisone therapy in generalized myasthenia gravis (MG) presents a therapeutic dilemma; however, the recommended regimen has not yet been validated.Objective: To compare the efficacy of the standard slow-tapering regimen of prednisone therapy with a rapid-tapering regimen.Design: From June 1, 2009, to July 31, 2013, a multicenter, parallel, single-blind randomized trial was conducted to compare 2 regimens of prednisone tapering. Data analysis was conducted from February 18, 2019, to January 23, 2020. A total of 2291 adults with a confirmed diagnosis of moderate to severe generalized MG at 7 specialized centers in France were assessed for eligibility.Interventions: The slow-tapering arm included a gradual increase of the prednisone dose to 1.5 mg/kg every other day and a slow decrease once minimal manifestation status of MG was attained. The rapid-tapering arm consisted of immediate high-dose daily administration of prednisone, 0.75 mg/kg, followed by an earlier and rapid decrease once improved MG status was attained. Azathioprine, up to a maximum dose of 3 mg/kg/d, was prescribed for all participants.Main outcomes and measures: The primary outcome was attainment of minimal manifestation status of MG without prednisone at 12 months and without clinical relapse at 15 months. Intention-to-treat analysis was conducted.Results: Of the 2291 patients assessed, 2086 did not fulfill the inclusion criteria, 87 declined to participate, and 1 patient registered after trial closure. A total of 117 patients (58 in the slow-tapering arm and 59 in the rapid-tapering arm) were selected for inclusion by MG specialists and were randomized. The population included 62 men (53%); median age was 65 years (interquartile range, 35-69 years). The proportion of patients having met the primary outcome was higher in the rapid- vs slow-tapering arm (23 [39%] vs 5 [9%]), with a risk ratio of 3.61 (95% CI, 1.64-7.97; P < .001) after adjusting for center and thymectomy. The rapid-tapering regimen allowed sparing of a mean of 1898 mg (95% CI, -3121 to -461 mg) of prednisone over 1 year (ie, 5.3 mg/d per patient, P = .03). The number of serious adverse events did not differ significantly between the slow- vs rapid-tapering group (13 [22%] vs 21 [36%], P = .15).Conclusions and relevance: In patients with moderate to severe generalized MG who require high-dose prednisone with azathioprine therapy, rapid tapering of prednisone appears to be feasible, well tolerated, and associated with a good outcome.Trial registration: ClinicalTrials.gov Identifier: NCT00987116.

Published
2021

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