Tarek Sharshar

Assistance Publique – Hôpitaux de Paris, Lutetia Parisorum, Île-de-France, France

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Publications (138)562.84 Total impact

  • Robert D. Stevens, Tarek Sharshar, E Wesley Ely
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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
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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; · 5.17 Impact Factor
  • Critical care medicine 02/2014; 42(2):485-6. · 6.37 Impact Factor
  • The Lancet Neurology 01/2014; 13(6):534–536. · 23.92 Impact Factor
  • Bernard De Jonghe, Tarek Sharshar, Hervé Outin
    European Journal of Intensive Care Medicine 11/2013; · 5.17 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; · 2.87 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. · 4.72 Impact Factor
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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.
    09/2013: pages 219-228; , ISBN: 9781107029194
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    ABSTRACT: We investigated effects of transcranial direct-current stimulation (tDCS) on the diaphragmatic corticospinal pathways in healthy human. Anodal, cathodal, and sham tDCS were randomly applied upon the left diaphragmatic motor cortex in twelve healthy right-handed men. Corticospinal pathways excitability was assessed by means of transcranial magnetic stimulation (TMS) elicited motor-evoked-potential (MEP). For each tDCS condition, MEPs were recorded before (Pre) tDCS then after 10minutes (Post1, at tDCS discontinuation in the anodal and cathodal sessions) and 20minutes (Post2). As result, both anodal and cathodal tDCS significantly decreased MEP amplitude of the right hemidiaphragm at both Post1 and Post2, versus Pre. MEP amplitude was unchanged versus Pre during the sham condition. The effects of cathodal and anodal tDCS applied to the diaphragm motor cortex differ from those observed during tDCS of the limb motor cortex. These differences may be related to specific characteristics of the diaphragmatic corticospinal pathways as well as to the diaphragm's functional peculiarities compared with the limb muscles.
    Respiratory Physiology & Neurobiology 08/2013; · 2.05 Impact Factor
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    ABSTRACT: Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood--brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke's encephalopathy. Modulation of microglial activation, prevention of blood--brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors.
    Annals of intensive care. 05/2013; 3(1):15.
  • Nicolas Adam, Eric Magalhaes, Tarek Sharshar
    Critical care medicine 04/2013; 41(4):1162-3. · 6.37 Impact Factor
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    ABSTRACT: Sepsis is a major cause of mortality and morbidity in intensive care units (ICU). Acute and longterm brain dysfunctions have been demonstrated both in experimental models and septic patients. Sepsis-associated encephalopathy (SAE) is an early and frequent manifestation, but is under diagnosed, due to the absence of specific biomarkers and to confounding factors such as sedatives used in the ICU. SAE may have acute and long-term consequences including development of autonomic dysfunction, delirium and cognitive impairment. The mechanisms of SAE involve mitochondrial and vascular dysfunctions, oxidative stress, neurotransmission disturbances, inflammation and cell death. Here we review specific evidence that links bioenergetics, mitochondrial dysfunction and oxidative stress in the setting of brain dysfunctions associated to sepsis.
    Shock (Augusta, Ga.) 03/2013; · 2.87 Impact Factor
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    ABSTRACT: The scientific community has agreed upon developing accurate monitoring of tissue perfusion and oxygenation to improve the management of subjects with sepsis. This pilot study aimed to investigate the feasibility of targeting tissue oxygen saturation (StO(2)) in addition to the currently recommended resuscitation goals, central venous pressure, mean arterial pressure and central venous oxygen saturation, in patients with severe sepsis or septic shock. A pilot, single-centre, randomised, non-blinded trial recruited 30 subjects with severe sepsis upon intensive care unit admission at an academic medical centre in France. Subjects were randomly assigned to a 6 h resuscitation strategy following the Surviving Sepsis Campaign guidelines with (experimental) or without (control) StO(2). StO(2) was measured over several muscles (masseter, deltoid and pectoral or thenar muscles), and a StO(2) above 80 % over at least 2 muscles was the therapeutic goal. The primary outcome was evaluated as follows: 7-day mortality or worsening of SOFA score between day 7 and study onset, i.e., DSOFA > 0). Thirty subjects were included in the study over a period of 40 weeks. Fifteen subjects were included in each group. Monitoring of StO(2) over three areas was performed in the experimental group. However, measures over the pectoral muscle provided poor results. At study day 7, there were 5/15 (33.3 %) subjects who died or had a DSOFA > 0 in the experimental arm and 4/15 (26.6 %) who died or had a DSOFA > 0 in the control arm (p = 1.00). This pilot study was the first randomised controlled trial using an algorithm derived from the SSC recommendations, which included StO(2) as a treatment goal. However, the protocol showed no clear trend for or against targeting StO(2).
    International Journal of Clinical Monitoring and Computing 02/2013;
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    ABSTRACT: Systemic infection is often revealed by or associated with brain dysfunction, which is characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological signs. Its pathophysiology involves an ischemic process, secondary to impairment of cerebral perfusion and its determinants and a neuroinflammatory process that includes endothelial activation, alteration of the blood-brain barrier and passage of neurotoxic mediators. Microcirculatory dysfunction is common to these two processes. This brain dysfunction is associated with increased mortality, morbidity and long-term cognitive disability. Its diagnosis relies essentially on neurological examination that can lead to specific investigations, including electrophysiological testing or neuroimaging. In practice, cerebrospinal fluid analysis is indisputably required when meningitis is suspected. Hepatic, uremic or respiratory encephalopathy, metabolic disturbances, drug overdose, sedative or opioid withdrawal, alcohol withdrawal delirium or Wernicke's encephalopathy are the main differential diagnoses. Currently, treatment consists mainly of controlling sepsis. The effects of insulin therapy and steroids need to be assessed. Various drugs acting on sepsis-induced blood-brain barrier dysfunction, brain oxidative stress and inflammation have been tested in septic animals but not yet in patients.
    Expert Review of Anticancer Therapy 02/2013; 11(2):211-21. · 3.22 Impact Factor
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    ABSTRACT: Critically ill patients are frequently at risk of neurological dysfunction as a result of primary neurological conditions or secondary insults. Determining which aspects of brain function are affected and how best to manage the neurological dysfunction can often be difficult and is complicated by the limited information that can be gained from clinical examination in such patients and the effects of therapies, notably sedation, on neurological function. Methods to measure and monitor brain function have evolved considerably in recent years and now play an important role in the evaluation and management of patients with brain injury. Importantly, no single technique is ideal for all patients and different variables will need to be monitored in different patients; in many patients, a combination of monitoring techniques will be needed. Although clinical studies support the physiologic feasibility and biologic plausibility of management based on information from various monitors, data supporting this concept from randomized trials are still required.
    Critical care (London, England) 01/2013; 17(1):201. · 4.72 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 01/2013; 8(11):e80190. · 3.73 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 12/2012; 186(11):1192. · 11.04 Impact Factor
  • Neurophysiologie Clinique/Clinical Neurophysiology 06/2012; 42(4):252. · 2.55 Impact Factor
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    ABSTRACT: Chronic obstructive pulmonary disease is associated with altered cortical excitability. The relevance of this to the need for non-invasive ventilation is not known. We assessed the diaphragm response to transcranial magnetic stimulation in terms of motor threshold and latency as well as assessing intracortical excitability using paired stimulation in eight long-term users and six non-users of home ventilation with COPD. Overall, intracortical facilitation was strongly correlated with inspiratory muscle strength (r2 0.72, p<0.001) whereas intracortical inhibition was correlated with PaCO2 (r2 0.51, p=0.01). The two groups did not differ in motor evoked potential or latency, nor in the excitability of intracortical inhibitory or facilitatory circuits assessed using paired stimulation. The acute effect of isocapnic non-invasive ventilation was studied in six established ventilator users. Diaphragm motor evoked potential fell but there was no effect on intracortical facilitation or inhibition, implying an effect of neuromechanical feedback at brainstem or spinal level.
    Respiratory Physiology & Neurobiology 05/2012; 183(1):41-7. · 2.05 Impact Factor
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    ABSTRACT: Although preventing excessive hyperglycemia during critical illness may provide clinical neuroprotection, it remains debated whether normoglycemia is without risk for the brain. To address this question, we compared the neuropathological alterations in microglia, astrocytes, and neurons, with uncontrolled hyperglycemia, moderately controlled hyperglycemia, and normoglycemia during human critical illness. We further investigated the time course in an animal model. We analyzed brain specimens from patients who died in the intensive care unit and from critically ill rabbits randomized to hyper- or normoglycemia. PATIENTS/OTHER PARTICIPANTS: We compared 10 critically ill patients randomized to normoglycemia (104 ±9 mg/dl) or moderate hyperglycemia (173 ±32 mg/dl), and five patients with uncontrolled hyperglycemia (254 ±83 mg/dl) with 16 controls (out of hospital sudden deaths). Critically ill rabbits were randomized to hyperglycemia (315 ±32 mg/dl) or normoglycemia (85 ±13 mg/dl) and studied after 3 and 7 d. Insulin was infused to control blood glucose. Patients with uncontrolled hyperglycemia showed 3.7-6-fold increased microglial activation, 54-95% reduced number and activation of astrocytes, more than 9-fold increased neuronal and glial apoptosis, and a 1.5-2-fold increase in damaged neurons in hippocampus and frontal cortex (all P ≤ 0.05). Most of these abnormalities were attenuated with moderate hyperglycemia and virtually absent with normoglycemia. Frontal cortex of hyperglycemic rabbits that had been critically ill for 3 d only revealed microglial activation, followed after 7 d by astrocyte and neuronal abnormalities similar to those observed in patients, all prevented by normoglycemia. Preventing hyperglycemia with insulin during critical illness reduced neuropathological abnormalities, with microglial activation being the earliest preventable event. Whether these pathological findings associate with neurological outcome remains unknown.
    The Journal of clinical endocrinology and metabolism 03/2012; 97(6):2113-23. · 6.50 Impact Factor

Publication Stats

2k Citations
562.84 Total Impact Points

Institutions

  • 2010–2014
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • Hôpital Ambroise Paré – Hôpitaux universitaires Paris Ile-de-France Ouest
      Billancourt, Île-de-France, France
  • 2005–2014
    • Université de Versailles Saint-Quentin
      Versailles, Île-de-France, France
  • 2004–2013
    • Hôpital de Poissy Saint Germain en Laye
      Saint-Germain, Île-de-France, France
  • 2004–2012
    • Imperial College London
      Londinium, England, United Kingdom
  • 2011
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire de Lyon
      • Service de Neurologie
      Lyon, Rhone-Alpes, France
  • 2009–2011
    • Johns Hopkins University
      • Department of Anesthesiology and Critical Care Medicine
      Baltimore, MD, United States
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 1998–2010
    • Hôpital Raymond-Poincaré – Hôpitaux universitaires Paris Ile-de-France Ouest
      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
  • 2008
    • Centre Médico-Chirurgicale de Tronquières
      Aurillac, Auvergne, France
  • 2004–2006
    • Royal Brompton and Harefield NHS Foundation Trust
      Harefield, England, United Kingdom
  • 2003
    • King's College Hospital NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2001
    • Université de Vincennes - Paris 8
      Saint-Denis, Île-de-France, France
  • 1999
    • Université Paris-Est Créteil Val de Marne - Université Paris 12
      • Faculty of medicine
      Créteil, Île-de-France, France