Publications by authors named "Maleka Schenck"

16 Publications

  • Page 1 of 1

A covariate-constraint method to map brain feature space into lower dimensional manifolds.

Netw Neurosci 2021 1;5(1):252-273. Epub 2021 Mar 1.

Université Grenoble Alpes, CNRS, Inria, Grenoble, France.

Human brain connectome studies aim to both explore healthy brains, and extract and analyze relevant features associated with pathologies of interest. Usually this consists of modeling the brain connectome as a graph and using graph metrics as features. A fine brain description requires graph metrics computation at the node level. Given the relatively reduced number of patients in standard cohorts, such data analysis problems fall in the high-dimension, low-sample-size framework. In this context, our goal is to provide a machine learning technique that exhibits flexibility, gives the investigator an understanding of the features and covariates, allows visualization and exploration, and yields insight into the data and the biological phenomena at stake. The retained approach is dimension reduction in a manifold learning methodology; the originality is that the investigator chooses one (or several) reduced variables. The proposed method is illustrated in two studies. The first one addresses comatose patients; the second one compares young and elderly populations. The method sheds light on the differences between brain connectivity graphs using graph metrics and potential clinical interpretations of these differences.
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http://dx.doi.org/10.1162/netn_a_00176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935034PMC
March 2021

Acute-onset delirium in intensive care COVID patients: association of imperfect brain repair with foodborne micro-pollutants.

Eur J Neurol 2021 Feb 14. Epub 2021 Feb 14.

Plant Imaging and Mass Spectrometry, Institut de biologie moléculaire des plantes, CNRS, Strasbourg, France.

Background And Purpose: COVID-19 affects the brain in various ways, amongst which delirium is worrying. An assessment was made of whether a specific, long-lasting, COVID-19-related brain injury develops in acute respiratory distress syndrome patients after life-saving re-oxygenation.

Methods: Ten COVID+ patients (COVID+) with unusual delirium associated with neuroimaging suggestive of diffuse brain injury and seven controls with non-COVID encephalopathy were studied. The assessment took place when the intractable delirium started at weaning off ventilation support. Brain magnetic resonance imaging (MRI) was performed followed by standard cerebrospinal fluid (CSF) analyses and assessment of CSF erythropoietin concentrations (as a marker for the assessment of tissue repair), and of non-targeted CSF metabolomics using liquid chromatography high resolution mass spectrometry.

Results: Patients were similar as regards severity scores, but COVID+ were hospitalized longer (25 [11.75; 25] vs. 9 [4.5; 12.5] days, p = 0.03). On admission, but not at MRI and lumbar puncture performance, COVID+ were more hypoxic (p = 0.002). On MRI, there were leptomeningeal enhancement and diffuse white matter haemorrhages only in COVID+. In the latter, CSF erythropoietin concentration was lower (1.73 [1.6; 2.06] vs. 3.04 [2.9; 3.91] mIU/ml, p = 0.01), and CSF metabolomics indicated (a) increased compounds such as foodborne molecules (sesquiterpenes), molecules from industrialized beverages and micro-pollutants (diethanolamine); and (b) decreased molecules such as incomplete breakdown products of protein catabolism and foodborne molecules (glabridin). At 3-month discharge, fatigue, anxiety and depression as well as MRI lesions persisted in COVID+.

Conclusions: Some COVID+ are at risk of a specific delirium. Imperfect brain repair after re-oxygenation and lifestyle factors might influence long-lasting brain injuries in a context of foodborne micro-pollutants.
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http://dx.doi.org/10.1111/ene.14776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014494PMC
February 2021

Higher anticoagulation targets and risk of thrombotic events in severe COVID-19 patients: bi-center cohort study.

Ann Intensive Care 2021 Jan 25;11(1):14. Epub 2021 Jan 25.

Service de Médecine Intensive Réanimation, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France.

Background: Thromboprophylaxis of COVID-19 patients is a highly debated issue. We aimed to compare the occurrence of thrombotic/ischemic events in COVID-19 patients with acute respiratory distress syndrome (ARDS) treated with either prophylactic or therapeutic dosage of heparin. All patients referred for COVID-19 ARDS in two intensive care units (ICUs) from two centers of a French tertiary hospital were included in our cohort study. Patients were compared according to their anticoagulant treatment to evaluate the risk/benefit of prophylactic anticoagulation versus therapeutic anticoagulation. Medical history, symptoms, biological data and imaging were prospectively collected.

Results: One hundred and seventy-nine patients (73% men) were analyzed: 108 in prophylactic group and 71 in therapeutic group. Median age and SAPS II were 62 [IQR 51; 70] years and 47 [IQR 37; 63] points. ICU mortality rate was 17.3%. Fifty-seven patients developed clinically relevant thrombotic complications during their ICU stay, less frequently in therapeutic group (adjusted OR 0.38 [0.14-0.94], p = 0.04). The occurrences of pulmonary embolism (PE), deep vein thrombosis (DVT) and ischemic stroke were significantly lower in the therapeutic group (respective adjusted OR for PE: 0.19 [0.03-0.81]; DVT: 0.13 [0.01-0.89], stroke: 0.06 [0-0.68], all p < 0.05). The occurrence of bleeding complications was not significantly different between groups, neither were ICU length of stay or mortality rate. D-dimer levels were significantly lower during ICU stay, and aPTT ratio was more prolonged in the therapeutic group (p < 0.05).

Conclusion: Increasing the anticoagulation of severe COVID-19 patients to a therapeutic level might decrease thrombotic complications without increasing their bleeding risk.
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http://dx.doi.org/10.1186/s13613-021-00809-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829649PMC
January 2021

Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients.

J Infect Dis 2021 02;223(4):600-609

Service d'Imagerie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings.

Methods: The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed.

Results: Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%).

Conclusions: Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.
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http://dx.doi.org/10.1093/infdis/jiaa745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798956PMC
February 2021

Association of systemic secondary brain insults and outcome in patients with convulsive status epilepticus: A post hoc study of a randomized controlled trial.

Neurology 2020 11 10;95(18):e2529-e2541. Epub 2020 Sep 10.

From the Medical-Surgical Intensive Care Unit (C.F.), Hopital Paris Saint Joseph, Paris; IctalGroup (C.F., J.C., S.L.), Le Chesnay; Medical Intensive Care Unit (V.L.) and SBIM Biostatistics and Medical Information (M.R.-R., C.C.), Saint Louis University Hospital; Université Paris Diderot (M.R.-R., C.C.); ECSTRA Team (Epidémiologie Clinique et Statistiques pour la Recherche en Santé) (M.R.-R.), UMR 1153 INSERM, Université Paris Diderot, Sorbonne Paris Cité; Medical Intensive Care Unit (M.S.), Hôpital de Hautepierre, and Medical Intensive Care Unit (F.M.), Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg; Medical-Surgical Intensive Care Unit (J.C.), Centre Hospitalier de Melun; Anesthesiology and Critical Care Department (T.G.), Toulouse University Hospital, University Toulouse 3 Paul Sabatier; Medical-Surgical Intensive Care Unit (A.H.), Centre Hospitalier de Montreuil; Medical-Surgical Intensive Care Unit (C.G.), Centre Hospitalier du Mans, Le Mans; EA 7293 (F.M.), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Faculté de Médecine, Université de Strasbourg; Intensive Care Units (J.-Y.L.), Division of Anaesthesia, Intensive Care, Pain and Emergency Medicine, University Hospital of Nîmes; Medical Intensive Care Unit (B.M.), Lariboisiere University Hospital, APHP, Paris; Medical-Surgical Intensive Care Unit (H.M.), Centre Hospitalier Victor Dupouy, Argenteuil; Medical Intensive Care Unit (A.C.), Cochin University Hospital, Hopitaux Universitaires-Paris Centre, AP-HP; Paris Descartes University (A.C.), Sorbonne Paris Cité-Medical School; INSERM U970 (A.C.), Paris Cardiovascular Research Center; Intensive Care Department (S.L.), Centre Hospitalier de Versailles-Site André Mignot, Le Chesnay; and Université Paris-Saclay (S.L.), UVSQ, Inserm, CESP, Team DevPsy, Villejuif, France.

Objective: To evaluate the association between systemic factors (mean arterial blood pressure, arterial partial pressures of carbon dioxide and oxygen, body temperature, natremia, and glycemia) on day 1 and neurologic outcomes 90 days after convulsive status epilepticus.

Methods: This was a post hoc analysis of the Evaluation of Therapeutic Hypothermia in Convulsive Status Epilepticus in Adults in Intensive Care (HYBERNATUS) multicenter open-label controlled trial, which randomized 270 critically ill patients with convulsive status epilepticus requiring mechanical ventilation to therapeutic hypothermia (32°C-34°C for 24 hours) plus standard care or standard care alone between March 2011 and January 2015. The primary endpoint was a Glasgow Outcome Scale score of 5, defining a favorable outcome, 90 days after convulsive status epilepticus.

Results: The 172 men and 93 women had a median age of 57 years (45-68 years). Among them, 130 (49%) had a history of epilepsy, and 59 (29%) had a primary brain insult. Convulsive status epilepticus was refractory in 86 (32%) patients, and total seizure duration was 67 minutes (35-120 minutes). The 90-day outcome was unfavorable in 126 (48%) patients. In multivariate analysis, none of the systemic secondary brain insults were associated with outcome; achieving an unfavorable outcome was associated with age >65 years (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.20-3.85; = 0.01), refractory convulsive status epilepticus (OR 2.00, 95% CI 1.04-3.85; = 0.04), primary brain insult (OR 2.00, 95% CI 1.02-4.00; = 0.047), and no bystander-witnessed seizure onset (OR 2.49, 95% CI 1.05-5.59; = 0.04).

Conclusions: In our population, systemic secondary brain insults were not associated with outcome in critically ill patients with convulsive status epilepticus.

Clinicaltrialsgov Identifier: NCT01359332.
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http://dx.doi.org/10.1212/WNL.0000000000010726DOI Listing
November 2020

Association of systemic secondary brain insults and outcome in patients with convulsive status epilepticus: A post hoc study of a randomized controlled trial.

Neurology 2020 11 10;95(18):e2529-e2541. Epub 2020 Sep 10.

From the Medical-Surgical Intensive Care Unit (C.F.), Hopital Paris Saint Joseph, Paris; IctalGroup (C.F., J.C., S.L.), Le Chesnay; Medical Intensive Care Unit (V.L.) and SBIM Biostatistics and Medical Information (M.R.-R., C.C.), Saint Louis University Hospital; Université Paris Diderot (M.R.-R., C.C.); ECSTRA Team (Epidémiologie Clinique et Statistiques pour la Recherche en Santé) (M.R.-R.), UMR 1153 INSERM, Université Paris Diderot, Sorbonne Paris Cité; Medical Intensive Care Unit (M.S.), Hôpital de Hautepierre, and Medical Intensive Care Unit (F.M.), Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg; Medical-Surgical Intensive Care Unit (J.C.), Centre Hospitalier de Melun; Anesthesiology and Critical Care Department (T.G.), Toulouse University Hospital, University Toulouse 3 Paul Sabatier; Medical-Surgical Intensive Care Unit (A.H.), Centre Hospitalier de Montreuil; Medical-Surgical Intensive Care Unit (C.G.), Centre Hospitalier du Mans, Le Mans; EA 7293 (F.M.), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Faculté de Médecine, Université de Strasbourg; Intensive Care Units (J.-Y.L.), Division of Anaesthesia, Intensive Care, Pain and Emergency Medicine, University Hospital of Nîmes; Medical Intensive Care Unit (B.M.), Lariboisiere University Hospital, APHP, Paris; Medical-Surgical Intensive Care Unit (H.M.), Centre Hospitalier Victor Dupouy, Argenteuil; Medical Intensive Care Unit (A.C.), Cochin University Hospital, Hopitaux Universitaires-Paris Centre, AP-HP; Paris Descartes University (A.C.), Sorbonne Paris Cité-Medical School; INSERM U970 (A.C.), Paris Cardiovascular Research Center; Intensive Care Department (S.L.), Centre Hospitalier de Versailles-Site André Mignot, Le Chesnay; and Université Paris-Saclay (S.L.), UVSQ, Inserm, CESP, Team DevPsy, Villejuif, France.

Objective: To evaluate the association between systemic factors (mean arterial blood pressure, arterial partial pressures of carbon dioxide and oxygen, body temperature, natremia, and glycemia) on day 1 and neurologic outcomes 90 days after convulsive status epilepticus.

Methods: This was a post hoc analysis of the Evaluation of Therapeutic Hypothermia in Convulsive Status Epilepticus in Adults in Intensive Care (HYBERNATUS) multicenter open-label controlled trial, which randomized 270 critically ill patients with convulsive status epilepticus requiring mechanical ventilation to therapeutic hypothermia (32°C-34°C for 24 hours) plus standard care or standard care alone between March 2011 and January 2015. The primary endpoint was a Glasgow Outcome Scale score of 5, defining a favorable outcome, 90 days after convulsive status epilepticus.

Results: The 172 men and 93 women had a median age of 57 years (45-68 years). Among them, 130 (49%) had a history of epilepsy, and 59 (29%) had a primary brain insult. Convulsive status epilepticus was refractory in 86 (32%) patients, and total seizure duration was 67 minutes (35-120 minutes). The 90-day outcome was unfavorable in 126 (48%) patients. In multivariate analysis, none of the systemic secondary brain insults were associated with outcome; achieving an unfavorable outcome was associated with age >65 years (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.20-3.85; = 0.01), refractory convulsive status epilepticus (OR 2.00, 95% CI 1.04-3.85; = 0.04), primary brain insult (OR 2.00, 95% CI 1.02-4.00; = 0.047), and no bystander-witnessed seizure onset (OR 2.49, 95% CI 1.05-5.59; = 0.04).

Conclusions: In our population, systemic secondary brain insults were not associated with outcome in critically ill patients with convulsive status epilepticus.

Clinicaltrialsgov Identifier: NCT01359332.
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http://dx.doi.org/10.1212/WNL.0000000000010726DOI Listing
November 2020

Neurologic and neuroimaging findings in patients with COVID-19: A retrospective multicenter study.

Neurology 2020 09 17;95(13):e1868-e1882. Epub 2020 Jul 17.

From the Hôpitaux Universitaires de Strasbourg (S.K., F.L., S.B., F.-D.A., T.W.), Service d'imagerie 2, Hôpital de Hautepierre; Engineering Science, Computer Science and Imaging Laboratory (S.K., N.M.), UMR 7357, University of Strasbourg-CNRS; Service de Neurologie (M. Anheim), Hôpitaux Universitaires de Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (M. Anheim), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch; Fédération de Médecine Translationnelle de Strasbourg (M. Anheim), Université de Strasbourg; Hôpitaux universitaires de Strasbourg (H.M., F.M., J.H.), Service de Médecine Intensive Réanimation, Nouvel Hôpital Civil; INSERM (French National Institute of Health and Medical Research) (H.M., F.M.), UMR 1260, Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg; Médecine Intensive-Réanimation (M.S., F.S.), Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg; Service de Neuroradiologie (H.O., F.B., J.M.), Hôpitaux Civils de Colmar; Service d'Imagerie (A. Khalil, A.G.), Unité de Neuroradiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat Claude Bernard; Université Paris Diderot (A. Khalil), Paris; Service de Neurologie (S. Carré, C.L.), Centre Hospitalier de Haguenau; Service de Radiologie (M. Alleg), Centre Hospitalier de Haguenau; Service de Neuroradiologie, (E.S., R.A., F.Z.) Hôpital Central, CHU de Nancy; CHIC Unisanté (L.J., P.N., Y.T.M.), Hôpital Marie Madeleine, Forbach; Neuroimaging Department (G.H., J. Benzakoun, C.O., G. Boulouis, M.E.-G., B.K.), GHU Paris Psychiatrie et Neurosciences, Hôpital Sainte-Anne, Université de Paris, INSERM U1266, F-75014; CHU Rennes (J.-C.F., B.C.-N.), Department of Neuroradiology; CHU Rennes (A.M.), Medical Intensive Care Unit; Department of Neuroradiology (P.-O.C., F.R., P.T.), University Hospital of Dijon, Hôpital François Mitterrand; Service de Radiologie (C.B.), CHU de Saint-Etienne; Service de Réanimation (X.F.), CH de Roanne; Service de Neuroradiologie (G.F., S.S.), CHU de Limoges; Radiology Department (I.d.B., G. Bornet), Hôpital Privé d'Antony; Department of Diagnostic and Interventional Neuroradiology (H.D.), University Hospital, Nantes; Neuroradiology Department (J. Berge), CHU de Bordeaux; Service de Neuroradiologie (A. Kazémi), CHU de Lille; Assistance Publique Hôpitaux de Paris (N.P.), Service de Neuroradiologie, Hôpital Pitié-Salpêtrière; Sorbonne Université (N.P.), Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, F-75013; Service de Neuroradiologie Diagnostique (A.L.), Foundation A. Rothschild Hospital, Paris; EA CHIMERE 7516 (J.-M.C.), Université de Picardie Jules Verne; Service de NeuroRadiologie, pôle Imagerie Médicale, Centre Hospitalo-Universitaire d'Amiens; Hôpitaux Universitaires de Strasbourg (P.-E.Z., M.M.), UCIEC, Pôle d'Imagerie, Strasbourg; Observatoire Français de la Sclérose en Plaques (J.-C.B.), Lyon; Nephrology and Transplantation Department (S. Caillard), Hôpitaux Universitaires de Strasbourg; Inserm UMR S1109 (S. Caillard), LabEx Transplantex, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg; Hôpitaux Universitaires de Strasbourg (O.C., P.M.M.), Service d'Anesthésie-Réanimation, Nouvel Hôpital Civil; Hôpitaux Universitaires de Strasbourg (S.F.-K.), Laboratoire de Virologie Médicale; Radiology Department (M.O.), Nouvel Hôpital Civil, Strasbourg University Hospital; CHU de Strasbourg (N.M.), Service de Santé Publique, GMRC, F-67091 Strasbourg; Immuno-Rhumatologie Moléculaire (S.F.-K., J.H.), INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg; MRI Center (F.C.), Centre Hospitalier Lyon Sud, Hospices Civils de Lyon; and Université Lyon 1 (F.C.), CREATIS-LRMN, CNRS/UMR/5220-INSERM U630, Villeurbanne, France.

Objective: To describe neuroimaging findings and to report the epidemiologic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with neurologic manifestations.

Methods: In this retrospective multicenter study (11 hospitals), we included 64 patients with confirmed COVID-19 with neurologic manifestations who underwent a brain MRI.

Results: The cohort included 43 men (67%) and 21 women (33%); their median age was 66 (range 20-92) years. Thirty-six (56%) brain MRIs were considered abnormal, possibly related to severe acute respiratory syndrome coronavirus. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurologic manifestation, followed by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from that of other patients with abnormal brain imaging: the former less frequently had acute respiratory distress syndrome ( = 0.006) and more frequently had corticospinal tract signs ( = 0.02). Patients with encephalitis were younger ( = 0.007), whereas agitation was more frequent for patients with leptomeningeal enhancement ( = 0.009).

Conclusions: Patients with COVID-19 may develop a wide range of neurologic symptoms, which can be associated with severe and fatal complications such as ischemic stroke or encephalitis. In terms of meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology seems to involve an immune or inflammatory process given the presence of signs of inflammation in both CSF and neuroimaging but the lack of virus in CSF.

Clinicaltrialsgov Identifier: NCT04368390.
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http://dx.doi.org/10.1212/WNL.0000000000010112DOI Listing
September 2020

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.

Radiology 2020 11 16;297(2):E242-E251. Epub 2020 Jun 16.

From the Hôpitaux Universitaires de Strasbourg, Service d'Imagerie 2, Hôpital de Hautepierre, Strasbourg, France (S.K.).

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were () positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, () severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, () neurologic manifestations, and () abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student test or Wilcoxon test. < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.
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http://dx.doi.org/10.1148/radiol.2020202222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301613PMC
November 2020

Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial.

Lancet Respir Med 2017 03 15;5(3):180-190. Epub 2017 Feb 15.

Institut für anesthesiologische Pathophysiologie und Verfahrensentwicklung, Universitätklinikum Ulm, Ulm, Germany.

Background: There is insufficient research into the use of mechanical ventilation with increased inspiratory oxygen concentration (FiO) and fluid resuscitation with hypertonic saline solution in patients with septic shock. We tested whether these interventions are associated with reduced mortality.

Methods: This two-by-two factorial, multicentre, randomised, clinical trial (HYPERS2S) recruited patients aged 18 years and older with septic shock who were on mechanical ventilation from 22 centres in France. Patients were randomly assigned 1:1:1:1 to four groups by a computer generated randomisation list stratified by site and presence or absence of acute respiratory distress syndrome by use of permuted blocks of random sizes. Patients received, in an open-labelled manner, mechanical ventilation either with FiO at 1·0 (hyperoxia) or FiO set to target an arterial haemoglobin oxygen saturation of 88-95% (normoxia) during the first 24 h; patients also received, in a double-blind manner, either 280 mL boluses of 3·0% (hypertonic) saline or 0·9% (isotonic) saline for fluid resuscitation during the first 72 h. The primary endpoint was mortality at day 28 after randomisation in the intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT01722422.

Findings: Between Nov 3, 2012, and June 13, 2014, 442 patients were recruited and assigned to a treatment group (normoxia [n=223] or hyperoxia [n=219]; isotonic [n=224] or hypertonic [n=218]). The trial was stopped prematurely for safety reasons. 28 day mortality was recorded for 434 patients; 93 (43%) of 217 patients had died in the hyperoxia group versus 77 (35%) of 217 patients in the normoxia group (hazard ratio [HR] 1·27, 95% CI 0·94-1·72; p=0·12). 89 (42%) of 214 patients had died in the hypertonic group versus 81 (37%) of 220 patients in the isotonic group (HR 1·19, 0·88-1·61; p=0·25). We found a significant difference in the overall incidence of serious adverse events between the hyperoxia (185 [85%]) and normoxia groups (165 [76%]; p=0·02), with a clinically relevant doubling in the hyperoxia group of the number of patients with intensive care unit-acquired weakness (24 [11%] vs 13 [6%]; p=0·06) and atelectasis (26 [12%] vs 13 [6%]; p=0·04) compared with the normoxia group. We found no statistical difference for serious adverse events between the two saline groups (p=0·23).

Interpretation: In patients with septic shock, setting FiO to 1·0 to induce arterial hyperoxia might increase the risk of mortality. Hypertonic (3%) saline did not improve survival.

Funding: The French Ministry of Health.
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http://dx.doi.org/10.1016/S2213-2600(17)30046-2DOI Listing
March 2017

Hypothermia for Neuroprotection in Convulsive Status Epilepticus.

N Engl J Med 2016 12;375(25):2457-2467

From the Medical-Surgical Intensive Care Unit (S.L., V. Laurent, J.H.-G., B.P., S.M., J.-P.B.) and the Neurology and Stroke Department (F.P.), Centre Hospitalier de Versailles-Site André Mignot, Versailles, INSERM Unité 970 (Team 4), Paris Cardiovascular Research Center (S.L., A.C.), the Medical Intensive Care Unit (V. Lemiale, E.C., E.A.) and Department of Biostatistics and Medical Information (M.R.-R.), Saint Louis University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), the Medical Intensive Care Unit, Cochin University Hospital, Hopitaux Universitaires-Paris Centre, AP-HP (F.D., G.G., N.M., A.C.), the Medical Intensive Care Unit (I.M.) and Neurophysiology Department (Y.-R.T.-D.), Lariboisière University Hospital, AP-HP, INSERM Unité 1153 (ECSTRA Team), Université Paris Diderot, Sorbonne Paris Cité (M.R.-R.), and Paris Descartes University, Sorbonne Paris Cité-Medical School (A.C.), Paris, the Medical Intensive Care Unit, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg (M. Schenck), and the Medical Intensive Care Unit, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, and Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, Université de Strasbourg (J.B.-H.), Strasbourg, the Medical-Surgical Intensive Care Unit, Centre Hospitalier de Melun, Melun (J.C.), the Anesthesiology and Critical Care Department, Toulouse University Hospital, University Toulouse 3 Paul Sabatier, Toulouse (M. Srairi), the Medical-Surgical Intensive Care Unit, Centre Hospitalier de Montreuil, Montreuil (A.H.), the Medical-Surgical Intensive Care Unit, Centre Hospitalier du Mans, Le Mans (T.R.), the Intensive Care Units, Division of Anesthesia, Intensive Care, Pain, and Emergency Medicine, University Hospital of Nîmes, Nîmes (B.L.), and the Medical-Surgical Intensive Care Unit, Centre Hospitalier Victor Dupouy, Argenteuil (M.T.) - all in France.

Background: Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus.

Methods: In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90.

Results: A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval [CI], 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group.

Conclusions: In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).
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http://dx.doi.org/10.1056/NEJMoa1608193DOI Listing
December 2016

Resting-state networks distinguish locked-in from vegetative state patients.

Neuroimage Clin 2016 6;12:16-22. Epub 2016 Jun 6.

ICube, UMR 7357, UdS, CNRS, Fédération de médecine translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France; Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), France; Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Purpose: Locked-in syndrome and vegetative state are distinct outcomes from coma. Despite their differences, they are clinically difficult to distinguish at the early stage and current diagnostic tools remain insufficient. Since some brain functions are preserved in locked-in syndrome, we postulated that networks of spontaneously co-activated brain areas might be present in locked-in patients, similar to healthy controls, but not in patients in a vegetative state.

Methods: Five patients with locked-in syndrome, 12 patients in a vegetative state and 19 healthy controls underwent a resting-state fMRI scan. Individual spatial independent component analysis was used to separate spontaneous brain co-activations from noise. These co-activity maps were selected and then classified by two raters as either one of eight resting-state networks commonly shared across subjects or as specific to a subject.

Results: The numbers of spontaneous co-activity maps, total resting-state networks, and resting-state networks underlying high-level cognitive activity were shown to differentiate controls and locked-in patients from patients in a vegetative state. Analyses of each common resting-state network revealed that the default mode network accurately distinguished locked-in from vegetative-state patients. The frontoparietal network also had maximum specificity but more limited sensitivity.

Conclusions: This study reinforces previous reports on the preservation of the default mode network in locked-in syndrome in contrast to vegetative state but extends them by suggesting that other networks might be relevant to the diagnosis of locked-in syndrome. The aforementioned analysis of fMRI brain activity at rest might be a step in the development of a diagnostic biomarker to distinguish locked-in syndrome from vegetative state.
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http://dx.doi.org/10.1016/j.nicl.2016.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913176PMC
November 2017

Magnetic Resonance Imaging of Cerebral Aspergillosis: Imaging and Pathological Correlations.

PLoS One 2016 20;11(4):e0152475. Epub 2016 Apr 20.

Département de Neuroradiologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Cerebral aspergillosis is associated with a significant morbidity and mortality rate. The imaging data present different patterns and no full consensus exists on typical imaging characteristics of the cerebral lesions. We reviewed MRI findings in 21 patients with cerebral aspergillosis and correlated them to the immune status of the patients and to neuropathological findings when tissue was available. The lesions were characterized by their number, topography, and MRI signal. Dissemination to the brain resulted from direct spread from paranasal sinuses in 8 patients, 6 of them being immunocompetent. Hematogenous dissemination was observed in 13 patients, all were immunosuppressed. In this later group we identified a total of 329 parenchymal abscesses involving the whole brain with a predilection for the corticomedullary junction. More than half the patients had a corpus callosum lesion. Hemorrhagic lesions accounted for 13% and contrast enhancement was observed in 61% of the lesions. Patients with hematogenous dissemination were younger (p = 0.003), had more intracranial lesions (p = 0.0004) and had a higher 12-week mortality rate (p = 0.046) than patients with direct spread from paranasal sinuses. Analysis of 12 aneurysms allowed us to highlight two distinct situations. In case of direct spread from the paranasal sinuses, aneurysms are saccular and located on the proximal artery portions, while the hematogenous dissemination in immunocompromised patients is more frequently associated with distal and fusiform aneurysms. MRI is the exam of choice for cerebral aspergillosis. Number and type of lesions are different according to the mode of dissemination of the infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152475PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838310PMC
August 2016

Effect of Noninvasive Ventilation vs Oxygen Therapy on Mortality Among Immunocompromised Patients With Acute Respiratory Failure: A Randomized Clinical Trial.

JAMA 2015 Oct;314(16):1711-9

Hôpital d'Avicenne, APHP, Bobigny, France.

Importance: Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure. However, its effectiveness for this indication remains unclear.

Objective: To determine whether early noninvasive ventilation improved survival in immunocompromised patients with nonhypercapnic acute hypoxemic respiratory failure.

Design, Setting, And Participants: Multicenter randomized trial conducted among 374 critically ill immunocompromised patients, of whom 317 (84.7%) were receiving treatment for hematologic malignancies or solid tumors, at 28 intensive care units (ICUs) in France and Belgium between August 12, 2013, and January 2, 2015.

Interventions: Patients were randomly assigned to early noninvasive ventilation (n = 191) or oxygen therapy alone (n = 183).

Main Outcomes And Measures: The primary outcome was day-28 mortality. Secondary outcomes were intubation, Sequential Organ Failure Assessment score on day 3, ICU-acquired infections, duration of mechanical ventilation, and ICU length of stay.

Results: At randomization, median oxygen flow was 9 L/min (interquartile range, 5-15) in the noninvasive ventilation group and 9 L/min (interquartile range, 6-15) in the oxygen group. All patients in the noninvasive ventilation group received the first noninvasive ventilation session immediately after randomization. On day 28 after randomization, 46 deaths (24.1%) had occurred in the noninvasive ventilation group vs 50 (27.3%) in the oxygen group (absolute difference, -3.2 [95% CI, -12.1 to 5.6]; P = .47). Oxygenation failure occurred in 155 patients overall (41.4%), 73 (38.2%) in the noninvasive ventilation group and 82 (44.8%) in the oxygen group (absolute difference, -6.6 [95% CI, -16.6 to 3.4]; P = .20). There were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays.

Conclusions And Relevance: Among immunocompromised patients admitted to the ICU with hypoxemic acute respiratory failure, early noninvasive ventilation compared with oxygen therapy alone did not reduce 28-day mortality. However, study power was limited.

Trial Registration: clinicaltrials.gov Identifier: NCT01915719.
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http://dx.doi.org/10.1001/jama.2015.12402DOI Listing
October 2015

Outcomes in critically ill patients with systemic rheumatic disease: a multicenter study.

Chest 2015 Oct;148(4):927-935

Medical Intensive Care Unit, Saint-Louis Teaching Hospital, Paris. Electronic address:

Background: Patients with systemic rheumatic diseases (SRDs) may require ICU management for SRD exacerbation or treatment-related infections or toxicities.

Methods: This was an observational study at 10 university-affiliated ICUs in France. Consecutive patients with SRDs were included. Determinants of ICU mortality were identified through multivariable logistic analysis.

Results: Three hundred sixty-three patients (65.3% women; median age, 59 years [interquartile range, 42-70 years]) accounted for 381 admissions. Connective tissue disease (primarily systemic lupus erythematosus) accounted for 66.1% of SRDs and systemic vasculitides for 26.2% (chiefly antineutrophil cytoplasm antibodies-associated vasculitides). SRDs were newly diagnosed in 43 cases (11.3%). Direct admission to the ICU occurred in 143 cases (37.9%). Reasons for ICU admissions were infection (39.9%), SRD exacerbation (34.4%), toxicity (5.8%), or miscellaneous (19.9%). Respiratory involvement was the leading cause of admission (56.8%), followed by shock (41.5%) and acute kidney injury (42.2%). Median Sequential Organ Failure Assessment (SOFA) score on day 1 was 5 (3-8). Mechanical ventilation was required in 57% of cases, vasopressors in 33.9%, and renal replacement therapy in 28.1%. ICU mortality rate was 21.0% (80 deaths). Factors associated with ICU mortality were shock (OR, 3.77; 95% CI, 1.93-7.36), SOFA score at day 1 (OR, 1.19; 95% CI, 1.10-1.30), and direct admission (OR, 0.52; 95% CI, 0.28-0.97). Neither comorbidities nor SRD characteristics were associated with survival.

Conclusions: In patients with SRDs, critical care management is mostly needed only in patients with a previously known SRD; however, diagnosis can be made in the ICU for 12% of patients. Infection and SRD exacerbation account for more than two-thirds of these situations, both targeting chiefly the lungs. Direct admission to the ICU may improve outcomes.
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http://dx.doi.org/10.1378/chest.14-3098DOI Listing
October 2015

[Localized tamponade: a rare cause of cardiac arrest of sudden onset].

Presse Med 2014 Mar 17;43(3):323-5. Epub 2014 Jan 17.

CHRU de Strasbourg, hôpital de Hautepierre, services de réanimation médicale et de radiologie, 67000 Strasbourg, France.

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http://dx.doi.org/10.1016/j.lpm.2013.06.030DOI Listing
March 2014

Hubs of brain functional networks are radically reorganized in comatose patients.

Proc Natl Acad Sci U S A 2012 Dec 26;109(50):20608-13. Epub 2012 Nov 26.

Centre National de Recherche Scientifique, Grenoble Image Parole Signal Automatique, 38402 Grenoble, France.

Human brain networks have topological properties in common with many other complex systems, prompting the following question: what aspects of brain network organization are critical for distinctive functional properties of the brain, such as consciousness? To address this question, we used graph theoretical methods to explore brain network topology in resting state functional MRI data acquired from 17 patients with severely impaired consciousness and 20 healthy volunteers. We found that many global network properties were conserved in comatose patients. Specifically, there was no significant abnormality of global efficiency, clustering, small-worldness, modularity, or degree distribution in the patient group. However, in every patient, we found evidence for a radical reorganization of high degree or highly efficient "hub" nodes. Cortical regions that were hubs of healthy brain networks had typically become nonhubs of comatose brain networks and vice versa. These results indicate that global topological properties of complex brain networks may be homeostatically conserved under extremely different clinical conditions and that consciousness likely depends on the anatomical location of hub nodes in human brain networks.
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http://dx.doi.org/10.1073/pnas.1208933109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528500PMC
December 2012