Tarek Sharshar

Université de Versailles Saint-Quentin, Versailles, Île-de-France, France

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Publications (157)593.45 Total impact

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    ABSTRACT: Experimental research has always been the cornerstone of pathophysiological and therapeutic advances in critical care medicine, where clinical observations and basic research mutually fed each other in a so-called translational approach. The objective of this review is to address the different aspects of translational research in the field of critical care medicine. We herein highlighted some demonstrative examples including the animal-to-human approach to study host-pathogen interactions, the human-to-animal approach for sepsis-induced immunosuppression, the still restrictive human approach to study critical illness-related neuromyopathy, and the technological developments to assess the microcirculatory changes in critically ill patients. These examples not only emphasize how translational research resulted in major improvements in the comprehension of the pathophysiology of severe clinical conditions and offered promising perspectives in critical care medicine but also point out the obstacles to translate such achievements into clinical practice.
    12/2015; 5(1). DOI:10.1186/s13613-015-0050-3
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    ABSTRACT: Glucose toxicity may play a crucial role in evoking neurologic complications of critical illness. We studied whether the neuropathological alterations in fatal human critical illness observed under hyperglycemia are present and can be attenuated by maintaining normoglycemia in a mouse model of prolonged sepsis induced by cecal ligation and puncture. Mice were randomized to moderate hyperglycemia (>8.3 mmol/l, n=8) or normoglycemia (4.4-6.7 mmol/l, n=8). After 5 days, hippocampus and frontal cortex from septic mice were compared with healthy controls (n=8). Blood glucose was 7.8±1.3 mmol/l in hyperglycemic and 6.1±0.7 mmol/l in normoglycemic critically ill mice (p=0.007). The percentage of damaged neurons was two-fold higher in frontal cortex (p=0.01) and hippocampus (p=0.06) of hyperglycemic ill mice than that of healthy mice. In frontal cortex, neuronal damage was attenuated under normoglycemia (p=0.04). Critical illness reduced astrocyte density and activation status 4-fold in hippocampus (p≤0.02), but not in frontal cortex, irrespective of glycemic control. Microglia were 2-4-fold more abundant in both brain areas of hyperglycemic critically ill mice (p≤0.002), but only in frontal cortex reduced in number with normoglycemia (p=0.0008). The density of apoptotic cells and abundance of carbonylated proteins were significantly higher than normal in frontal cortex of hyperglycemic ill mice only (p=0.05). In a mouse model of prolonged polymicrobial sepsis, remarkable neuropathological changes develop with neuronal damage, impaired astrocyte activation, increased microglia, apoptosis and accumulation of carbonylated proteins. These changes were partially prevented or attenuated when hyperglycemia was prevented with insulin. Frontal cortex appeared more vulnerable to hyperglycemic insults than hippocampus.
    Shock (Augusta, Ga.) 05/2015; DOI:10.1097/SHK.0000000000000403 · 2.73 Impact Factor
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    ABSTRACT: To characterize etiology, clinical course and outcomes of patients in prolonged refractory status epilepticus (PRSE) and looking for prognostic factors. Retrospective study conducted in patients hospitalized from January 1, 2001 to December 31, 2011 in 19 polyvalent intensive care units in French university and general hospitals. Patients were adults with a generalized convulsive refractory status epilepticus that lasted more than seven days, despite treatment including an anesthetic drug and mechanical ventilation. Patients with anoxic encephalopathy were excluded. Follow-up phone call was used to determine functional outcome using modified Rankin Scale (mRS) with mRS 0-3 defining good and mRS 4-6 poor outcome. 78 patients (35 female) were included. Median age was 57 years. Causes of status epilepticus were various, mainly including prior epilepsy (14.1%), CNS infection (12.8%), and stroke (12.8%). No etiology was found in 27 (34.6%) patients. PRSE was considered controlled in only 53 (67.9%) patients after a median duration of 17 (IQR 12-26) days. The median length of ICU stay was 28 (19-48) days. Forty-one (52.5%) patients died in the ICU, 26 from multiple organ failure, 8 from care withdrawal, 2 from sudden cardiac arrest, 1 from brain death and 4 from unknown causes. PRSE was previously resolved in 20 patients who died in the ICU. At one-year follow-up, there were 12 patients with good outcome and 58 with poor outcome and 8 lost of follow-up. On multivariate analysis, only vasopressor use was a predictor of poor outcome (OR 6.54; 95%CI 1.09-39.29; p = 0.04). Poor outcome was observed in about 80% of this population of PRSE. Most patients died from systemic complications linked to their ICU stay. Some patients can recover satisfactorily over time though we did not identify any robust factor of good outcome.
    Critical care (London, England) 04/2015; 19(1):199. DOI:10.1186/s13054-015-0914-9
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    ABSTRACT: Objective: To determine the prevalence, type, and significance of brain damage in critically ill patients with a primary non-neurological diagnosis developing acute brain dysfunction. Methods: This retrospective cohort study was performed at the Johns Hopkins University School of Medicine, an academic tertiary care hospital. Medical records were reviewed of 479 consecutive ICU patients who underwent brain MRI over a 2-year period. Patients were selected for analysis if MRI was obtained to evaluate an acute onset of brain dysfunction (altered mental status, seizures, and/or focal neurological deficit). Subjects with a history of a central nervous system disorder were excluded. The principal clinical endpoint was Glasgow Outcome Scale (GOS) assessed at discharge. MRI-defined brain abnormalities were classified according to type and location. Factors associated with MRI-defined abnormalities were assessed in uni- and multivariable models. Results: 146 patients met inclusion criteria (mean age 54±7years). Brain damage was detected in 130 patients (89%). The most prevalent lesions were white matter hyperintensities (104/146, 71%) and acute cerebral infarcts (59/146, 40%). In a multivariable model, lesions on brain MRI were independently associated with unfavorable outcome (GOS1-3 in 71% of patients with lesions vs. 44% in those without, p=0.007). No adverse events occurred in relation to transport and MRI scanning. Conclusions: In critically ill patients without known neurological disease who have brain dysfunction, MRI reveals an unexpectedly high burden of underlying brain damage, which is associated with unfavorable outcome. The results indicate that brain damage could be an important and under-recognized factor contributing to critical illness brain dysfunction.
    Neurocritical Care 02/2015; DOI:10.1007/s12028-015-0110-4 · 2.60 Impact Factor
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    ABSTRACT: Purpose Dysglycemia is a characteristic feature of critical illness associated with adverse outcome. Whether dysglycemia contributes to brain dysfunction during critical illness and long-term neurological complications is unclear. We give an overview of glucose metabolism in the brain and review the literature on critical illness-induced dysglycemia and the brain. Methods Medline database search using relevant search terms on dysglycemia, critical illness, acute brain injury/dysfunction, and randomized controlled trial. Results Hyperglycemia has been associated with deleterious effects on the nervous system. Underlying mechanisms in critical illness remain largely speculative and are often extrapolated from knowledge in diabetes mellitus. Increased hyperglycemia-induced blood–brain barrier permeability, oxidative stress, and microglia activation may play a role and compromise neuronal and glial cell integrity. Hypoglycemia is feared as critically ill patients cannot recognize or communicate hypoglycemic symptoms, which furthermore are masked by sedation and analgesia. However, observational data on the impact of brief hypoglycemia on the brain in critical illness are controversial. Secondary analysis of two large randomized studies suggested neuroprotection by strict glycemic control with insulin during intensive care, with lowered intracranial pressure, reduction of seizures, and better long-term rehabilitation in patients with isolated brain injury, and reduced incidence of critical illness polyneuromyopathy in the general critically ill patient population. Several subsequent studies failed to reproduce neurological benefit, likely explained by methodological issues, which include divergent achieved glucose levels and inaccurate glucose monitoring tools. Conclusions Preventing hyperglycemia during critical illness holds promise as a neuroprotective strategy to preserve brain cell viability and prevent acute brain dysfunction and long-term cognitive impairment in survivors.
    Intensive Care Medicine 12/2014; 41(2). DOI:10.1007/s00134-014-3577-0 · 5.54 Impact Factor
  • Djillali Annane, Tarek Sharshar
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    ABSTRACT: The modern era of sepsis management is characterised by a growing number of patients who survive in the short term and are discharged from hospital. Increasing evidence suggests that these survivors exhibit long-term neurological sequelae, particularly substantial declines in cognitive function. The exact prevalence and outcomes of these neuropsychological sequelae are unclear. The mechanisms by which sepsis induces cognitive dysfunction probably include vascular injuries and neuroinflammation that are mediated by systemic metabolism disorders and overwhelming inflammation, a disrupted blood-brain barrier, oxidative stress, and severe microglial activation, particularly within the limbic system. Interventions targeting the blood-brain barrier, glial activation, and oxidative stress have shown promise in prevention of cognitive dysfunction in various experimental models of sepsis. The next step should be to translate these favourable effects into positive clinical results. Copyright © 2014 Elsevier Ltd. All rights reserved.
    The Lancet Respiratory Medicine 11/2014; 3(1). DOI:10.1016/S2213-2600(14)70246-2
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    ABSTRACT: El síndrome de Guillain-Barré es la primera causa de parálisis aguda extensa en los países desarrollados desde la desaparición de la poliomielitis. Su diagnóstico se basa esencialmente en la clínica. Se trata de una patología evolutiva, por lo que una exploración neurológica minuciosa y repetida permite confirmar el diagnóstico y valorar su posible evolución y gravedad potencial. Las pruebas complementarias son útiles para descartar otras patologías, especialmente la meningorradiculitis, por punción lumbar, y la afectación medular, por resonancia magnética (RM). Un elemento esencial del tratamiento es la identificación del paciente con riesgo de desarrollar insuficiencia respiratoria aguda. Otro punto importante del tratamiento es la elección entre la plasmaféresis y la terapia con inmunoglobulinas intravenosas.
    11/2014; 40(4). DOI:10.1016/S1280-4703(14)68953-2
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    ABSTRACT: La sindrome di Guillain-Barré è la prima causa di paralisi acuta estensiva nei paesi industrializzati dopo la scomparsa della poliomielite. La sua diagnosi resta essenzialmente clinica. Dal momento che la malattia è evolutiva, un esame neurologico preciso e ripetuto permette, il più delle volte, di confermare la diagnosi e di giudicare l’evolutività e la potenziale gravità. Gli esami complementari sono utili soprattutto per escludere un’altra patologia, in particolare una meningoradicolite attraverso la puntura lombare e una lesione midollare attraverso una risonanza magnetica (RM). Un elemento essenziale della gestione è l’identificazione dei pazienti a rischio di sviluppare un’insufficienza respiratoria acuta. L’altro risvolto terapeutico è la scelta terapeutica tra gli scambi plasmatici e le immunoglobuline endovenose.
    11/2014; 19(4):1–7. DOI:10.1016/S1283-0771(14)68864-2
  • Annales Françaises d Anesthésie et de Réanimation 09/2014; 33:A168. DOI:10.1016/j.annfar.2014.07.282 · 0.84 Impact Factor
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    ABSTRACT: “Brain Disorders in Critical Illness”, edited by Robert Stevens, Tarek Sharshar and Wes Ely, offers an overview of critical illness brain dysfunction (delirium, coma, encephalopathy), a major problem in intensive care with potentially debilitating long-term consequences. Chapters on epidemiology, outcomes, relevant behavioral neurology and biological mechanisms of acute brain dysfunction are written by an interdiscplinary panel of leading experts in the field.
    07/2014; Cambridge University Press., ISBN: 9781107029194
  • The Lancet Neurology 06/2014; 13(6):534–536. DOI:10.1016/S1474-4422(14)70064-X · 21.82 Impact Factor
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    ABSTRACT: Many patients admitted to the intensive care unit (ICU) have pre-existing or acquired neurological disorders which significantly affect their short-term and long-term outcomes. The ESICM NeuroIntensive Care Section convened an expert panel to establish a pragmatic approach to neurological examination (NE) of the critically ill patient. The group conducted a comprehensive review of published studies on the NE of patients with coma, delirium, seizures and neuromuscular weakness in critically ill patients. Quality of data was rated as high, moderate, low, or very low, and final recommendations as strong, weak, or best practice. The group made the following recommendations: (1) NE should be performed in all patients admitted to ICUs; (2) NE should include an assessment of consciousness and cognition, brainstem function, and motor function; (3) sedation should be managed to maximize the clinical detection of neurological dysfunction, except in patients with reduced intracranial compliance in whom withdrawal of sedation may be deleterious; (4) the need for additional tests, including neurophysiological and neuroradiological investigations, should be guided by the NE; (5) selected features of the NE have prognostic value which should be considered in well-defined patient populations.
    European Journal of Intensive Care Medicine 02/2014; 40(4). DOI:10.1007/s00134-014-3214-y · 5.54 Impact Factor
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    Critical care medicine 02/2014; 42(2):485-6. DOI:10.1097/CCM.0000000000000007 · 6.15 Impact Factor
  • Bernard De Jonghe, Tarek Sharshar, Hervé Outin
    European Journal of Intensive Care Medicine 11/2013; 40(2). DOI:10.1007/s00134-013-3157-8 · 5.54 Impact Factor
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    ABSTRACT: Vasopressin (AVP) secretion during an osmotic challenge is frequently altered in the immediate post-acute phase of septic shock. We sought to determine if this response is still altered in patients recovering from septic shock. Prospective interventional study. Intensive care unit (ICU) at Raymond Poincaré and Etampes Hospitals. Normonatremic patients at least 5 days post discontinuation of catecholamines given for a septic shock. Osmotic challenge involved infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 minutes. Plasma AVP levels were measured 15 minutes before the infusion and then every 30 minutes for two hours. Non-responders were defined as those with a slope of the relation between AVP and plasma sodium levels less than < 0.5 ng/mEq. Among the 30 included patients, 18 (60%) were non-responders. Blood pressure and plasma sodium and brain natriuretic peptide levels were similar in both responders and non-responders during the course of the test. Critical illness severity, hemodynamic alteration, electrolyte disturbances, treatment and outcome did not differ between the two groups. Responders had more severe gas exchange abnormality. Thirst perception was significantly diminished in non-responders. The osmotic challenge was repeated in 4 non-responders several months after discharge and the abnormal response persisted. More than half of patients recovering from septic shock have an alteration of osmoregulation characterised by a dramatic decrease in vasopressin secretion and thirst perception during osmotic challenge. The mechanisms of this alteration but also of the relationship between haematosis and normal response remain to be elucidated.
    PLoS ONE 11/2013; 8(11):e80190. DOI:10.1371/journal.pone.0080190 · 3.53 Impact Factor
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    ABSTRACT: SUMMARY The role of Campylobacter jejuni as the triggering agent of Guillain-Barré syndrome (GBS) has not been reassessed since the end of the 1990s in France. We report that the number of C. jejuni-related GBS cases increased continuously between 1996 and 2007 in the Paris region (mean annual increment: 7%, P = 0·007).
    Epidemiology and Infection 10/2013; 142(8):1-5. DOI:10.1017/S095026881300263X · 2.49 Impact Factor
  • Clinical Neurophysiology 10/2013; 124(10):e112. DOI:10.1016/j.clinph.2013.04.177 · 2.98 Impact Factor
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    ABSTRACT: Sepsis-associated brain dysfunction has been linked to white matter lesions (leucoencephalopathy) and ischemic stroke. Our objective was to assess the prevalence of brain lesions in septic shock patients requiring magnetic resonance imaging (MRI) for an acute neurological change. Seventy-one septic shock patients were included in a prospective observational study. Patients underwent daily neurological examination. Brain MRI was obtained in patients who developed focal neurological deficit, seizure, coma, or delirium. Electroencephalogy was performed in case of coma, delirium or seizure. Leucoencephalopathy was graded and considered present when white matter lesions were either confluent or diffuse. Patient outcome was evaluated at 6 months using the Glasgow Outcome Scale (GOS). We included 71 patients with a median age of 65 yrs (56-76) and new simplified acute physiology score (SAPS II) at admission of 49 (38-60). MRI was indicated upon focal neurological sign in 13 (18%), seizure in 7 (10%), coma in 33 (46%) and delirium in 35 (49%). MRI was normal in 37 patients (52%) and showed cerebral infarcts in 21(29%), leucoencephalopathy in 15 (21%), and mixed lesions in 6 (8%). EEG malignant pattern was more frequent in patients with ischemic stroke or leukoencephalopathy. Ischemic stroke was independently associated with disseminated intravascular coagulation (DIC), focal neurological signs, increased mortality and worse GOS at six months. Brain MRI in septic shock patients who developed acute brain dysfunction can reveal leukoencephalopathy and ischemic stroke, which is associated with DIC and increased mortality.
    Critical care (London, England) 09/2013; 17(5):R204. DOI:10.1186/cc12899
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    Raoul Sutter, Tarek Sharshar, Robert D Stevens
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    ABSTRACT: Neurological assessment of critically ill patients requires physical examination although coexisting cognitive impairment, sedative or paralytic medication, endotracheal intubation, mechanical ventilation, neuromuscular weakness, injuries or surgery involving extracranial tissues may limit sensitivity and specificity of findings. Notwithstanding these constraints, neurological signs and syndromes are valuable indicators of severity of illness and prognosis. Common neurologic syndromes in ICU patients include disturbances in the level of arousal and in cognition, delirium, seizures, generalized weakness, and focal neurological deficits. Whenever possible, neurological examination should include an assessment of mental status, attention, cranial nerves, motor and sensory findings. If there is persisting diagnostic uncertainty additional testing should be sought. Computed tomography of the head should be obtained whenever there is a new onset of seizures, focal neurologic deficits, alteration of mental status or loss of consciousness which are not immediately reversible or explainable. Magnetic resonance imaging has greater sensitivity for demyelinating and inflammatory diseases, hyperacute ischemic stroke, microhemorrhagic lesions, anoxic-ischemic damage, and disorders affecting the white matter and the brainstem. Electroencephalography is needed if seizures or status epilepticus are suspected as a cause or consequence of acute brain dysfunction. Somatosensory evoked potentials, best studied in patients with anoxic brain injury may help with prognostication following cardiac arrest. Electromyography and nerve conduction velocities should be obtained when neuromuscular weakness is severe or cannot be assessed clinically.
    Brain Disorders in Critical Illness, 1 edited by Robert D Stevens, Tarek Sharshar, E Wesley Ely, 09/2013: chapter Diagnosis of Brain Dysfunction: pages 219-228; Cambridge University Press., ISBN: 9781107029194
  • Annales Françaises d Anesthésie et de Réanimation 09/2013; 32:A249. DOI:10.1016/j.annfar.2013.07.466 · 0.84 Impact Factor

Publication Stats

3k Citations
593.45 Total Impact Points


  • 2005–2015
    • Université de Versailles Saint-Quentin
      Versailles, Île-de-France, France
  • 2010–2014
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 1998–2013
    • Hôpital Raymond-Poincaré – Hôpitaux universitaires Paris Ile-de-France Ouest
      Garches, Île-de-France, France
    • Pierre and Marie Curie University - Paris 6
      • Centre de recherche des Cordeliers - UMR_S 872
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Imperial College London
      • Molecular Medicine
      Londinium, England, United Kingdom
  • 2009
    • Johns Hopkins University
      • Department of Anesthesiology and Critical Care Medicine
      Baltimore, MD, United States
  • 2004–2009
    • Hôpital de Poissy Saint Germain en Laye
      Saint-Germain, Île-de-France, France
    • King's College London
      • Division of Asthma, Allergy and Lung Biology
      Londinium, England, United Kingdom
  • 2004–2007
    • Royal Brompton and Harefield NHS Foundation Trust
      • Respiratory Medicine
      Harefield, England, United Kingdom
  • 2006
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 2003
    • King's College Hospital NHS Foundation Trust
      Londinium, England, United Kingdom