Publications by authors named "Tarek Sharshar"

143 Publications

Free-Living Physical Activity and Sedentary Behaviour in Autoimmune Myasthenia Gravis: A Cross-Sectional Study.

J Neuromuscul Dis 2021 Apr 7. Epub 2021 Apr 7.

Bioingénierie, Tissus et Neuroplasticité, EA Université Paris-Est Créteil, Créteil, France.

Background: Muscle weakness and fatigability, the prominent symptoms of autoimmune myasthenia gravis (MG), impact negatively on daily function and quality of life (QoL). It is currently unclear as to what extent symptoms limit activity and whether physical activity (PA) behaviours are associated with reduced QoL.

Objectives: This study aimed to describe habitual PA patterns and explore relationships between PA metrics, clinical MG characteristics, and health-related QoL (HRQoL).

Methods: PA data from a trunk tri-axial accelerometer worn for seven days, was collected from females with generalized, stable MG and compared to control subjects. MG-specific evaluations, the six-minute walk test and knee extension strength were assessed in individuals with MG (IwMG). Mann-Whitney tests were used to study between-group differences. Spearman rank correlation coefficient was performed to explore relationships between variables.

Results: Thirty-three IwMG (mean (SD) age 45 (11) years) and 66 control subjects were included. IwMG perform less vigorous-intensity PA than control subjects (p = 0.001), spend more time sedentary (p = 0.02) and engage in less and shorter durations of moderate-vigorous-intensity PA (MVPA). For IwMG, habitual PA correlated positively with 6 min walking distance (rho = 0.387, p = 0.029) and negatively with body mass index (rho = -0.407, p = 0.019). We did not find any association between PA or sedentary behaviour and; HRQoL, symptom severity nor lower limb strength.

Conclusions: Individuals with stable MG perform less PA, at lower intensities, and are more inactive than controls individuals. Further research is warranted to understand factors influencing PA patterns in MG and whether interventions could be successful in increasing PA quantity and intensity in IwMG.
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http://dx.doi.org/10.3233/JND-210637DOI Listing
April 2021

Effect of early treatment with polyvalent immunoglobulin on acute respiratory distress syndrome associated with SARS-CoV-2 infections (ICAR trial): study protocol for a randomized controlled trial.

Trials 2021 Feb 28;22(1):170. Epub 2021 Feb 28.

GHU Paris Psychiatrie et neurosciences, Service de Neuroanesthésie Neuroréanimation, Paris, France.

Background: As of mid-June 2020, 7,500,000 people were infected with SARS-CoV-2 worldwide and 420,000 people died, mainly from coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). COVID-19-related ARDS is subject to a mortality rate of 50% and prolonged period of mechanical ventilation, with no specific pharmacological treatment currently available (Infection au nouveau Coronavirus (SARS-CoV-2), COVID-19, France et Monde. https://www.santepubliquefrance.fr/dossiers/coronavirus-covid-19 ). Because of its immunomodulatory action, we propose to evaluate the efficacy and safety of intravenous immunoglobulin (IVIG) administration in patients developing COVID-19-related ARDS.

Methods: The trial is a phase III double-blind, randomized, multicenter, parallel group, concurrent, controlled study in hospitalized participants with COVID-19 requiring mechanical ventilation using a sequential design. Participants in the treatment group will receive infusions of polyvalent immunoglobulin for 4 consecutive days, and the placebo group will receive an equivalent volume of sodium chloride 0.9% for the same duration. The primary outcome is the number of ventilator-free days up to the 28th day. Secondary objectives are to evaluate the effect of IVIG on (1) organ failure according to the Sequential Organ Failure Assessment (SOFA) score at 14 and 28 days, (2) lung injury score at 14 and 28 days, (3) the occurrence of grade 3 or 4 adverse events of IVIG, (4) length of intensive care unit (ICU) stay, (5) length of hospital stay, (6) functional outcomes at day 90 defined by the activities of daily living and instrumental activities of the daily living scales, and (7) 90-day survival. One hundred thirty-eight subjects will be randomized in a 1:1 ratio to IVIG or placebo groups (69 in each group), considering 90% power, alpha level 0.05 (two sides), and 0.67 effect size level.

Discussion: The ICAR trial investigates the effect of IVIG in COVID-19-related ARDS. We expect an increase in the survival rate and a reduction in the duration of mechanical ventilation, which is associated with significant morbidity.

Trial Registration: EudraCT 2020-001570-30. ClinicalTrials.gov NCT04350580 . Registered on 17 April 2020.
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http://dx.doi.org/10.1186/s13063-021-05118-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917531PMC
February 2021

The Burden of Mental Illness Among Survivors of Critical Care-Risk Factors and Impact on Quality of Life: A Multicenter Prospective Cohort Study.

Chest 2021 Feb 25. Epub 2021 Feb 25.

Post-graduation of Pulmonology-Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Background: Survivors of critical care may demonstrate mental health disorders in the months after discharge.

Research Question: What are risk factors for mental health disorders after ICU discharge and is there an association between the burden of mental illness and health-related quality of life (HRQoL)?

Study Design And Methods: Multicenter prospective cohort study that included 579 adult ICU survivors with an ICU stay of > 72 h in 10 ICUs.

Results: The outcomes were anxiety and depression assessed by the Hospital Anxiety and Depression Scale, posttraumatic stress disorder (PTSD) assessed by the Impact Event Scale 6, and HRQoL assessed by the Short Form 12 version 2. The 6-month prevalences of any mental health disorder were 36.2% (the prevalences of anxiety, depression, and PTSD were 24.2%, 20.9%, and 15.4%, respectively). ICU survivors with mental health disorders showed worse HRQoL scores in both physical and mental dimensions than those without. The higher the number of psychiatric syndromes manifested, the worse the mental dimension of HRQoL. Age of < 65 years (P = .009), history of depression (P = .009), anxiety (P = .003) and depression (P = .02) symptoms at ICU discharge, physical dependence (P = .01), and decreased physical functional status (P = .04) at 6 months were associated with anxiety. History of depression (P = .001), depression symptoms at ICU discharge (P < .001), and decreased physical functional status at 6 months (P = .01) were associated with depression. Depression symptoms at ICU discharge (P = .01), physical dependence (P = .01), and decreased physical functional status (P = .02) at 6 months were associated with PTSD.

Interpretation: The network of potential risk factors for mental illness among patients discharged from an ICU is complex and involves multiple factors (age, premorbid mental health, acute emotional stress, and physical impairment after ICU stay). The negative impact of the burden of mental illness on HRQoL among critical care survivors is of concern.
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http://dx.doi.org/10.1016/j.chest.2021.02.034DOI Listing
February 2021

Valproic Acid as an Adjuvant Treatment for Generalized Convulsive Status Epilepticus in Adults Admitted to Intensive Care Units: Protocol for a Double-Blind, Multicenter Randomized Controlled Trial.

JMIR Res Protoc 2021 Feb 24;10(2):e22511. Epub 2021 Feb 24.

Centre Hospitalier Poissy Saint Germain en Laye, Poissy, France.

Background: Generalized convulsive status epilepticus (GCSE) is a frequent medical emergency. GCSE treatment focuses on the administration of benzodiazepines followed by a second-line antiepileptic drug (AED). Despite this stepwise strategy, GCSE is not controlled in one-quarter of patients and is associated with protracted hospitalization, high mortality, and long-term disability. Valproic acid (VPA) is an AED with good tolerability and neuroprotective properties.

Objective: This study aims to demonstrate that administration of VPA as an adjuvant for first- and second-line treatment in GCSE can improve outcomes.

Methods: A multicenter, double-blind, randomized controlled trial was conducted, comparing VPA with a placebo in adults admitted to intensive care units (ICUs) for GCSE in France. GCSE was diagnosed by specifically trained ICU physicians according to standard criteria. All patients received standard of care, including a benzodiazepine and a second-line AED (not VPA), at the discretion of the treating medical team. In the intervention arm, VPA was administered intravenously at a loading dose of 30 mg/kg over 15 minutes, followed by a continuous infusion of 1 mg/kg/hour over the next 12 hours. In the placebo group, an identical intravenous administration of 0.9% saline was used. The primary outcome was the proportion of patients discharged alive from the hospital by day 15. Secondary outcomes were frequency of refractory and super refractory GCSE, ICU-related morbidity, adverse events related to VPA, and cognitive dysfunction at 3 months. Statistical analyses will be performed according to the intent-to-treat principle.

Results: The first patient was randomized on February 18, 2013, and the last patient was randomized on July 7, 2018. Of 248 planned patients, 98.7% (245/248) were enrolled across 20 ICUs. At present, data management is still ongoing, and all parties involved in the trial remain blinded.

Conclusions: The Valproic Acid as an Adjuvant Treatment for Generalized Convulsive Status Epilepticus (VALSE) trial will evaluate whether the use of VPA as an adjuvant for first- and second-line treatment in GCSE improves outcomes.

Trial Registration: ClinicalTrials.gov NCT01791868; https://clinicaltrials.gov/ct2/show/NCT01791868.

International Registered Report Identifier (irrid): DERR1-10.2196/22511.
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http://dx.doi.org/10.2196/22511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946594PMC
February 2021

Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis: A Randomized Clinical Trial.

JAMA Neurol 2021 Apr;78(4):426-433

General Intensive Care Unit, APHP, Raymond Poincaré Hospital, University of Versailles Saint-Quentin en Yvelines, Garches, France.

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.
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http://dx.doi.org/10.1001/jamaneurol.2020.5407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871208PMC
April 2021

What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review.

Neurotherapeutics 2021 Jan 6. Epub 2021 Jan 6.

Laboratoire de Neuropathologie Expérimentale, Institut Pasteur, 75015, Paris, France.

Lower sepsis mortality rates imply that more patients are discharged from the hospital, but sepsis survivors often experience sequelae, such as functional disability, cognitive impairment, and psychiatric morbidity. Nevertheless, the mechanisms underlying these long-term disabilities are not fully understood. Considering the extensive use of animal models in the study of the pathogenesis of neuropsychiatric disorders, it seems adopting this approach to improve our knowledge of postseptic psychiatric symptoms is a logical approach. With the purpose of gathering and summarizing the main findings of studies using animal models of sepsis-induced psychiatric symptoms, we performed a systematic review of the literature on this topic. Thus, 140 references were reviewed, and most of the published studies suggested a time-dependent recovery from behavior alterations, despite the fact that some molecular alterations persist in the brain. This review reveals that animal models can be used to understand the mechanisms that underlie anxiety and depression in animals recovering from sepsis.
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http://dx.doi.org/10.1007/s13311-020-00981-9DOI Listing
January 2021

What animal models can tell us about long-term cognitive dysfunction following sepsis: A systematic review.

Neurosci Biobehav Rev 2021 May 9;124:386-404. Epub 2020 Dec 9.

Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Brazil. Electronic address:

Survivors of sepsis often develop long-term cognitive impairments. This review aimed at exploring the results of the behavioral tools and tests which have been used to evaluate cognitive dysfunction in different animal models of sepsis. Two independent investigators searched for sepsis- and cognition-related keywords. 6323 publications were found, of which 355 were selected based on their title, and 226 of these were chosen based on manuscript review. LPS was used to induce sepsis in 171 studies, while CLP was used in 55 studies. Inhibitory avoidance was the most widely used method for assessing aversive memory, followed by fear conditioning and continuous multi-trial inhibitory avoidance. With regard to non-aversive memory, most studies used the water maze, open-field, object recognition, Y-maze, plus maze, and radial maze tests. Both CLP and LPS models of sepsis were effective in inducing short- and long-term behavioral impairment. Our findings help elucidate the mechanisms involved in the pathophysiology of sepsis-induced cognitive changes, as well as the available methods and tests used to study this in animal models.
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http://dx.doi.org/10.1016/j.neubiorev.2020.12.005DOI Listing
May 2021

Early abolition of cough reflex predicts mortality in deeply sedated brain-injured patients.

PeerJ 2020 26;8:e10326. Epub 2020 Nov 26.

Laboratory of Human Histopathology and Animal Models, Institut Pasteur, Paris, France.

Background: Deep sedation may hamper the detection of neurological deterioration in brain-injured patients. Impaired brainstem reflexes within the first 24 h of deep sedation are associated with increased mortality in non-brain-injured patients. Our objective was to confirm this association in brain-injured patients.

Methods: This was an observational prospective multicenter cohort study involving four neuro-intensive care units. We included acute brain-injured patients requiring deep sedation, defined by a Richmond Assessment Sedation Scale (RASS) < -3. Neurological assessment was performed at day 1 and included pupillary diameter, pupillary light, corneal and cough reflexes, and grimace and motor response to noxious stimuli. Pre-sedation Glasgow Coma Scale (GCS) and Simplified Acute Physiology Score (SAPS-II) were collected, as well as the cause of death in the Intensive Care Unit (ICU).

Results: A total of 137 brain-injured patients were recruited, including 70 (51%) traumatic brain-injured patients, 40 (29%) vascular (subarachnoid hemorrhage or intracerebral hemorrhage). Thirty patients (22%) died in the ICU. At day 1, the corneal (OR 2.69, = 0.034) and cough reflexes (OR 5.12, = 0.0003) were more frequently abolished in patients that died in the ICU. In a multivariate analysis, abolished cough reflex was associated with ICU mortality after adjustment to pre-sedation GCS, SAPS-II, RASS (OR: 5.19, 95% CI [1.92-14.1], = 0.001) or dose of sedatives (OR: 8.89, 95% CI [2.64-30.0], = 0.0004).

Conclusion: Early (day 1) cough reflex abolition is an independent predictor of mortality in deeply sedated brain-injured patients. Abolished cough reflex likely reflects a brainstem dysfunction that might result from the combination of primary and secondary neuro-inflammatory cerebral insults revealed and/or worsened by sedation.
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http://dx.doi.org/10.7717/peerj.10326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700733PMC
November 2020

Early mechanical ventilation in patients with Guillain-Barré syndrome at high risk of respiratory failure: a randomized trial.

Ann Intensive Care 2020 Sep 30;10(1):128. Epub 2020 Sep 30.

Medical Intensive Care Unit, Raymond Poincaré Teaching Hospital, 104 boulevard Raymond Poincaré, 92380, Garches, France.

Introduction: About 30% of patients with Guillain-Barré syndrome become ventilator dependent, of whom roughly 75% develop pneumonia. This trial aimed at assessing the impact of early mechanical ventilation (EMV) on pneumonia occurrence in GBS patients. We hypothesize that EMV will reduce the incidence of pneumonia.

Methods: This was a single centre, open-label, randomized controlled trial performed on two parallel groups. 50 intensive care unit adults admitted for Guillain-Barré syndrome and at risk for acute respiratory failure. Patients were randomized to early mechanical ventilation via face-mask or endotracheal intubation owing to the presence or absence of impaired swallowing (experimental arm), or to conventional care (control arm). The primary outcome was the incidence of pneumonia up to intensive care unit discharge (or 90 days, pending of which occurred first).

Findings: Twenty-five patients were randomized in each group. There was no significant difference between groups for the incidence of pneumonia (10/25 (40%) vs 9/25 (36%), P = 1). There was no significant difference between groups for the time to onset of pneumonia (P = 0.50, Gray test). During follow-up, there were 16/25 (64%) mechanically ventilated patients in the control group, and 25/25 (100%) in the experimental arm (P < 000·1). The time on ventilator was non-significantly shorter in the experimental arm (14 [7; 29] versus 21.5 [17.3; 35.5], P = 0.10). There were no significant differences between groups for length of hospital stay, neurological scores, the proportion of patients who needed tracheostomy, in-hospital death, or any serious adverse events.

Conclusions: In the present study including adults with Guillain-Barré syndrome at high risk of respiratory failure, we did not observe a prevention of pneumonia with early mechanical ventilation.

Trial Registration: ClinicalTrials.gov under the number NCT00167622. Registered 9 September 2005, https://clinicaltrials.gov/ct2/show/NCT00167622?cond=Guillain-Barre+Syndrome&cntry=FR&draw=2&rank=1.
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http://dx.doi.org/10.1186/s13613-020-00742-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525233PMC
September 2020

Association Between Anxiety and New Organ Failure, Independently of Critical Illness Severity and Respiratory Status: A Prospective Multicentric Cohort Study.

Crit Care Med 2020 10;48(10):1471-1479

1General Intensive Care Unit, APHP, Raymond Poincaré Hospital, University of Versailles Saint-Quentin en Yvelines, Garches, France. 2Perception and Memory Laboratory, Neuroscience Department, Institut Pasteur, Paris, France. 3General Intensive Care Unit, Sud-Essonne Hospital, Étampes, France. 4Centre d'Epidémiologie Clinique, Assistance Publique Hôpitaux de Paris, Hôtel Dieu Hospital, University Paris Descartes, Paris, France. 5General Intensive Care Unit, Institut Gustave Roussy Hospital, Villejuif, France. 6Department of Psychiatry, Sainte-Anne Hospital, Paris-Descartes University, Paris, France. 7Centre Hospitalier Sainte-Anne, Service Hospitalo-Universitaire, Faculté de Médecine Paris Descartes, Paris, France. 8Université Paris Descartes, Inserm Centre de Psychiatrie et Neurosciences, Laboratoire de Physiopathologie des maladies Psychiatriques, Paris, France. 9CNRS, GDR 3557, Institut de Psychiatrie, Paris, France. 10Department of Neuropathology, Sainte-Anne Hospital, Université de Paris, Paris, France. 11Laboratory of Critical Care, National Institute of Infectious Disease Evandro Chagas, Oswaldo Cruz Foundation, Ministry of Health, Rio de Janeiro, Brazil. 12D'Or Institute of Research and Education (IDOR), Rio de Janeiro, Brazil.

Objectives: Anxiety results from the anticipation of a threat and might be associated with poor outcome in the critically ill. This study aims at showing that anxiety at admission in critically ill patients is associated with new organ failure over the first 7 days of ICU hospitalization independently of baseline organ failure at admission.

Design: Prospective multicenter cohort study.

Setting: Three mixed ICU from April 2014 to December 2017.

Patients: Coma-, delirium-, and invasive mechanical ventilation-free patients admitted to the ICU were included.

Interventions: None.

Measurements And Main Results: "State anxiety" was assessed using the state component of the State-Trait Anxiety Inventory State. Severity of illness was measured using Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores. Primary endpoint was a composite of occurrence of death or new organ failure in the first 7 days after admission. Three hundred ninety-one patients were included; 159 of 391 women (40.7%); median age 63 years (49-74 yr); median Simplified Acute Physiology Score II 28 (19-37). Two hundred three out of 391 patients (51.9%) reported moderate to severe anxiety (State-Trait Anxiety Inventory State ≥ 40). One hundred two out of 391 patients (26.1%) developed a new organ failure. After adjustment to Simplified Acute Physiology Score II and Sequential Organ Failure Assessment, State-Trait Anxiety Inventory State greater than or equal to 40 was associated with the primary endpoint (odds ratio, 1.94; 95% CI, 1.18-3.18; p = 0.009) and respiratory failure. In post hoc analysis, State-Trait Anxiety Inventory State greater than or equal to 40 was associated with new organ failure independently and notably of respiratory status at admission (dyspnea-Visual Analogic Scale and PaCO2 ≥ 45 mm Hg).

Conclusions: Moderate to severe anxiety at ICU admission is associated with early occurrence of new organ failure in critically ill patients, independently of respiratory status and severity of critical illness. The causality link could be addressed in an interventional trial.
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http://dx.doi.org/10.1097/CCM.0000000000004495DOI Listing
October 2020

Long-Term Disabilities of Survivors of Out-of-Hospital Cardiac Arrest: The Hanox Study.

Chest 2021 Feb 20;159(2):699-711. Epub 2020 Jul 20.

Sorbonne Université, INSERM, UMRS_1166-ICAN Institute of Cardiometabolism and Nutrition, and Service de Médecine Intensive Réanimation, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris, France. Electronic address:

Background: Long-term outcomes of awakened survivors of out-of-hospital cardiac arrest (OHCA) are poorly known.

Research Question: What are the month (M) 18 outcomes of survivors of out-of-hospital cardiac arrest (OHCA) who awakened during the first 2 weeks' post-OHCA and their poor-outcome risk factors?

Study Design And Methods: All OHCA survivors with a Glasgow Coma Scale score ≥12 during the first 2 weeks' post-OHCA were enrolled in six ICUs and followed up at M3, M6, M12, and M18. The primary outcome measure was Glasgow Outcome Scale-Extended (GOS-E) score at M18. Secondary outcome measures included evaluation at M18 of neurologic, behavioral, and cognitive disabilities; health-related quality of life (HR-QOL), anxiety and depression; and poor-outcome risk factors (GOS-E score ≤ 6).

Results: Among the 139 included patients, 98 were assessable for the primary outcome measure. At M18, 64 (65%) had full recovery or minor disabilities (GOS-E score > 6), 18 (18%) had moderate disabilities but were autonomous for daily-life activities (GOS-E score = 6), 12 (12%) had poor autonomy (GOS-E score < 6 but > 1), and four had died. Percentages of patients with GOS-E scores > 6 increased significantly over the 18-month study period. At M18, no patients had major neurologic disabilities, 20% had cognitive disabilities, 32% had anxiety symptoms, 25% had depression symptoms, and their HR-QOL was impaired compared with a sex- and age-matched population. Low-flow time, Sequential Organ Failure Assessment score at admission, coma duration > 3 days after cardiac arrest, and mechanical ventilation on days 3 and 7 were associated with poor functional outcome.

Interpretation: Among patients who awoke (Glasgow Coma Scale score ≥12) in the 14 days following OHCA, 35% had moderate to severe disabilities or had died at M18. Interestingly, patients improved until M18 post-OHCA. Risk factors associated with poor functional outcome were low-flow time, clinical severity at ICU admission, prolonged coma duration, and mechanical ventilation.

Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02292147; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2020.07.022DOI Listing
February 2021

Randomized Controlled Study Evaluating Efficiency of Low Intensity Transcranial Direct Current Stimulation (tDCS) for Dyspnea Relief in Mechanically Ventilated COVID-19 Patients in ICU: The tDCS-DYSP-COVID Protocol.

Front Med (Lausanne) 2020 26;7:372. Epub 2020 Jun 26.

General Intensive Care Unit-Assistance Publique Hôpitaux de Paris, Raymond Poincaré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Inserm UMR 1173, Infection and Inflammation (2I), University of Versailles Saint-Quentin en Yvelines (UVSQ), Paris-Saclay University, Paris, France.

The severe respiratory distress syndrome linked to the new coronavirus disease (COVID-19) includes unbearable dyspneic suffering which contributes to the deterioration of the prognosis of patients in intensive care unit (ICU). Patients are put on mechanical ventilation to reduce respiratory suffering and preserve life. Despite this mechanical ventilation, most patients continue to suffer from dyspnea. Dyspnea is a major source of suffering in intensive care and one of the main factors that affect the prognosis of patients. The development of innovative methods for its management, especially non-drug management is more than necessary. In recent years, numerous studies have shown that transcranial direct current stimulation (tDCS) could modulate the perception of acute or chronic pain. In the other hand, it has been shown that the brain zones activated during pain and dyspnea are close and/or superimposed, suggesting that brain structures involved in the integration of aversive emotional component are shared by these two complex sensory experiences. Therefore, it can be hypothesized that stimulation by tDCS with regard to the areas which, in the case of pain have activated one or more of these brain structures, may also have an effect on dyspnea. In addition, our team recently demonstrated that the application of tDCS on the primary cortical motor area can modulate the excitability of the respiratory neurological pathways. Indeed, tDCS in anodal or cathodal modality reduced the excitability of the diaphragmatic cortico-spinal pathways in healthy subjects. We therefore hypothesized that tDCS could relieve dyspnea in COVID-19 patients under mechanical ventilation in ICU. This study was designed to evaluate effects of two modalities of tDCS (anodal and cathodal) vs. placebo, on the relief of dyspnea in COVID-19 patients requiring mechanical ventilation in ICU. This protocol is derived from the tDCS-DYSP-REA project registered on ClinicalTrials.gov NCT03640455. It will however be registered under its own NCT number.
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http://dx.doi.org/10.3389/fmed.2020.00372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332773PMC
June 2020

The Curing Coma Campaign: Framing Initial Scientific Challenges-Proceedings of the First Curing Coma Campaign Scientific Advisory Council Meeting.

Neurocrit Care 2020 08;33(1):1-12

Department of Neurology and Neurotherapeutics, University of Texas Southwestern, Dallas, TX, USA.

Coma and disordered consciousness are common manifestations of acute neurological conditions and are among the most pervasive and challenging aspects of treatment in neurocritical care. Gaps exist in patient assessment, outcome prognostication, and treatment directed specifically at improving consciousness and cognitive recovery. In 2019, the Neurocritical Care Society (NCS) launched the Curing Coma Campaign in order to address the "grand challenge" of improving the management of patients with coma and decreased consciousness. One of the first steps was to bring together a Scientific Advisory Council including coma scientists, neurointensivists, neurorehabilitationists, and implementation experts in order to address the current scientific landscape and begin to develop a framework on how to move forward. This manuscript describes the proceedings of the first Curing Coma Campaign Scientific Advisory Council meeting which occurred in conjunction with the NCS Annual Meeting in October 2019 in Vancouver. Specifically, three major pillars were identified which should be considered: endotyping of coma and disorders of consciousness, biomarkers, and proof-of-concept clinical trials. Each is summarized with regard to current approach, benefits to the patient, family, and clinicians, and next steps. Integration of these three pillars will be essential to the success of the Curing Coma Campaign as will expanding the "curing coma community" to ensure broad participation of clinicians, scientists, and patient advocates with the goal of identifying and implementing treatments to fundamentally improve the outcome of patients.
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http://dx.doi.org/10.1007/s12028-020-01028-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392933PMC
August 2020

Septic-Associated Encephalopathy: a Comprehensive Review.

Neurotherapeutics 2020 04;17(2):392-403

GHU Paris Psychiatrie et Neuroscience, Neurointensive Care and Neuroanesthesia Department, 1, rue Cabanis, 75014, Paris, France.

Septic-associated encephalopathy (SAE) is a key manifestation of sepsis, ranging from delirium to coma and occurring in up to 70% of patients admitted to the ICU. SAE is associated with higher ICU and hospital mortality, and also with poorer long-term outcomes, including cognitive and functional outcomes. The pathophysiology of SAE is complex, and it may involve neurotransmitter dysfunction, inflammatory and ischemic lesions to the brain, microglial activation, and blood-brain barrier dysfunction. Delirium (which is included in the SAE spectrum) is mostly diagnosed with validated scales in the ICU population. There is no established treatment for SAE; benzodiazepines should generally be avoided in this setting. Nonpharmacological prevention and management is key for treating SAE; it includes avoiding oversedation (mainly with benzodiazepines), early mobilization, and sleep promotion.
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http://dx.doi.org/10.1007/s13311-020-00862-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283452PMC
April 2020

Biomarker Panel to Differentiate Brain Injury From Brain Dysfunction in Patients With Sepsis-Associated Encephalopathy.

Crit Care Med 2020 May;48(5):e436-e437

Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Rostock, Rostock, Germany Queen Square Institute of Neurology, University College London, London, United Kingdom, and The National Hospital for Neurology and Neurosurgery, Moorfields Eye Hospital, London, United Kingdom, and Amsterdam UMC, Amsterdam, The Netherlands Neuro-anesthesiology and Intensive Care Medicine, Sainte-Anne Hospital, Paris-Descartes University, Paris, France, and Experimental neuropathology, Infection and epidemiology department, Institut Pasteur, Paris, France Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Vanderbilt University Medical Center, Nashville, TN, and Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, and Center for Health Services Research, The Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN, and Tennessee Valley Veterans Affairs Healthcare System, Geriatric Research Education and Clinical Center (GRECC), Nashville, TN Department of Anaesthesiology, University Hospital, LMU Munich, Munich, Germany.

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http://dx.doi.org/10.1097/CCM.0000000000004266DOI Listing
May 2020

Predictors of early postoperative epileptic seizures after awake surgery in supratentorial diffuse gliomas.

J Neurosurg 2020 Mar 13:1-10. Epub 2020 Mar 13.

1Department of Neurosurgery, Sainte-Anne Hospital, Paris.

Objective: Functional-based resection under awake conditions had been associated with a nonnegligible rate of intraoperative and postoperative epileptic seizures. The authors assessed the incidence of intraoperative and early postoperative epileptic seizures after functional-based resection under awake conditions.

Methods: The authors prospectively assessed intraoperative and postoperative seizures (within 1 month) together with clinical, imaging, surgical, histopathological, and follow-up data for 202 consecutive diffuse glioma adult patients who underwent a functional-based resection under awake conditions.

Results: Intraoperative seizures occurred in 3.5% of patients during cortical stimulation; all resolved without any procedure being discontinued. No predictor of intraoperative seizures was identified. Early postoperative seizures occurred in 7.9% of patients at a mean of 5.1 ± 2.9 days. They increased the duration of hospital stay (p = 0.018), did not impact the 6-month (median 95 vs 100, p = 0.740) or the 2-year (median 100 vs 100, p = 0.243) postoperative Karnofsky Performance Status score and did not impact the 6-month (100% vs 91.4%, p = 0.252) or the 2-year (91.7 vs 89.4%, p = 0.857) postoperative seizure control. The time to treatment of at least 3 months (adjusted OR [aOR] 4.76 [95% CI 1.38-16.36], p = 0.013), frontal lobe involvement (aOR 4.88 [95% CI 1.25-19.03], p = 0.023), current intensity for intraoperative mapping of at least 3 mA (aOR 4.11 [95% CI 1.17-14.49], p = 0.028), and supratotal resection (aOR 6.24 [95% CI 1.43-27.29], p = 0.015) were independently associated with early postoperative seizures.

Conclusions: Functional-based resection under awake conditions can be safely performed with a very low rate of intraoperative and early postoperative seizures and good 6-month and 2-year postoperative seizure outcomes. Intraoperatively, the use of the lowest current threshold producing reproducible responses is mandatory to reduce seizure occurrence intraoperatively and in the early postoperative period.
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http://dx.doi.org/10.3171/2020.1.JNS192774DOI Listing
March 2020

Brainstem dysfunction in critically ill patients.

Crit Care 2020 01 6;24(1). Epub 2020 Jan 6.

Department of Neuro-ICU, GHU-Paris, Paris-Descartes University, Paris, France.

The brainstem conveys sensory and motor inputs between the spinal cord and the brain, and contains nuclei of the cranial nerves. It controls the sleep-wake cycle and vital functions via the ascending reticular activating system and the autonomic nuclei, respectively. Brainstem dysfunction may lead to sensory and motor deficits, cranial nerve palsies, impairment of consciousness, dysautonomia, and respiratory failure. The brainstem is prone to various primary and secondary insults, resulting in acute or chronic dysfunction. Of particular importance for characterizing brainstem dysfunction and identifying the underlying etiology are a detailed clinical examination, MRI, neurophysiologic tests such as brainstem auditory evoked potentials, and an analysis of the cerebrospinal fluid. Detection of brainstem dysfunction is challenging but of utmost importance in comatose and deeply sedated patients both to guide therapy and to support outcome prediction. In the present review, we summarize the neuroanatomy, clinical syndromes, and diagnostic techniques of critical illness-associated brainstem dysfunction for the critical care setting.
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http://dx.doi.org/10.1186/s13054-019-2718-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945639PMC
January 2020

Early and Late Mortality Following Discharge From the ICU: A Multicenter Prospective Cohort Study.

Crit Care Med 2020 01;48(1):64-72

Intensive Care Unit, Hospital Moinhos de Vento (HMV), Porto Alegre, Brazil.

Objectives: To identify the frequency, causes, and risk factors of early and late mortality among general adult patients discharged from ICUs.

Design: Multicenter, prospective cohort study.

Setting: ICUs of 10 tertiary hospitals in Brazil.

Patients: One-thousand five-hundred fifty-four adult ICU survivors with an ICU stay greater than 72 hours for medical and emergency surgical admissions or greater than 120 hours for elective surgical admissions.

Interventions: None.

Measurements And Main Results: The main outcomes were early (30 d) and late (31 to 365 d) mortality. Causes of death were extracted from death certificates and medical records. Twelve-month cumulative mortality was 28.2% (439 deaths). The frequency of early mortality was 7.9% (123 deaths), and the frequency of late mortality was 22.3% (316 deaths). Infections were the leading cause of death in both early (47.2%) and late (36.4%) periods. Multivariable analysis identified age greater than or equal to 65 years (hazard ratio, 1.65; p = 0.01), pre-ICU high comorbidity (hazard ratio, 1.59; p = 0.02), pre-ICU physical dependence (hazard ratio, 2.29; p < 0.001), risk of death at ICU admission (hazard ratio per 1% increase, 1.008; p = 0.03), ICU-acquired infections (hazard ratio, 2.25; p < 0.001), and ICU readmission (hazard ratio, 3.76; p < 0.001) as risk factors for early mortality. Age greater than or equal to 65 years (hazard ratio, 1.30; p = 0.03), pre-ICU high comorbidity (hazard ratio, 2.28; p < 0.001), pre-ICU physical dependence (hazard ratio, 2.00; p < 0.001), risk of death at ICU admission (hazard ratio per 1% increase, 1.010; p < 0.001), and ICU readmission (hazard ratios, 4.10, 4.17, and 1.82 for death between 31 and 60 days, 61 and 90 days, and greater than 90 days after ICU discharge, respectively; p < 0.001 for all comparisons) were associated with late mortality.

Conclusions: Infections are the main cause of death after ICU discharge. Older age, pre-ICU comorbidities, pre-ICU physical dependence, severity of illness at ICU admission, and ICU readmission are associated with increased risk of early and late mortality, while ICU-acquired infections are associated with increased risk of early mortality.
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http://dx.doi.org/10.1097/CCM.0000000000004024DOI Listing
January 2020

Small vessel disease in patients with subarachnoid hemorrhage: Prevalence and associations with vasospasm occurrence, severity and clinical outcomes.

Neuroradiol J 2019 Dec 30;32(6):438-444. Epub 2019 Sep 30.

Service d'Imagerie Morphologique et Fonctionnelle, Centre Hospitalier Sainte-Anne, Paris, France.

Purpose: Investigating the associations between cerebral small vessel disease (cSVD) burden and cerebral vasospasm (CVS), delayed cerebral ischemia (DCI) and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH).

Methods: Consecutive aSAH patients with initial (<7 days after onset) and 3-month follow-up brain magnetic resonance imaging (MRI) and clinical evaluation at 6 months were included. The cSVD burden score was built using MRI criteria. CVS was defined according to transcranial Doppler examination and computed tomography (CT) or digital subtraction angiography. DCI was defined by the appearance of hyperintense fluid-attenuated inversion recovery lesions, with territorial or cortico-subcortical distribution, between initial MRI and 3-month MRI. The modified Rankin scale of ≤2 at 6 months was considered a favorable outcome. Using univariate and multivariable analyses, we investigated the associations between cSVD and CVS, DCI and clinical outcome.

Results: A total of 113 patients were included in the study sample (median age 49.1 years (IQR 42.1-60.8), 70/113 females). The burden of cSVD was mild with a median of 0 (IQR 0-1). When comparing patients with no/mild versus those with moderate/severe cSVD burden, we did not find a univariable difference regarding vasospasm occurrence (60% versus 46.1%,  = 0.54), DCI (20.2% versus 23%,  = 0.66) or favorable outcome at 3 months (94% versus 83.3%,  = 0.20). There was a univariable trend towards more frequent favorable outcome in patients with no/milde white matter hyperintensities versus those with moderate/severe white matter hyperintensities (92% versus 85%, p = 0.09). In multivariable models, cSVD markers were not associated with CVS occurrence and severity, DCI or clinical outcome.

Conclusions: In patients with mild aSAH, the burden of cSVD as assessed by MRI is minimal and is not associated with CVS, DCI or clinical outcome.
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http://dx.doi.org/10.1177/1971400919877470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856992PMC
December 2019

Microglial production of quinolinic acid as a target and a biomarker of the antidepressant effect of ketamine.

Brain Behav Immun 2019 10 28;81:361-373. Epub 2019 Jun 28.

Institut Pasteur, Experimental Neuropathology Unit, Infection and Epidemiology Department, Paris, France; Service Hospitalo Universitaire, Centre Hospitalier Sainte-Anne, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France. Electronic address:

Major depressive disorder is a complex multifactorial condition with a so far poorly characterized underlying pathophysiology. Consequently, the available treatments are far from satisfactory as it is estimated that up to 30% of patients are resistant to conventional treatment. Recent comprehensive evidence has been accumulated which suggests that inflammation may be implied in the etiology of this disease. Here we investigated ketamine as an innovative treatment strategy due to its immune-modulating capacities. In a murine model of LPS-induced depressive-like behavior we demonstrated that a single dose of ketamine restores the LPS-induced depressive-like alterations. These behavioral effects are associated with i/ a reversal of anxiety and reduced self-care, ii/ a decrease in parenchymal cytokine production, iii/ a modulation of the microglial reactivity and iv/ a decrease in microglial quinolinic acid production that is correlated with plasmatic peripheral production. In a translational approach, we show that kynurenic acid to quinolinic acid ratio is a predictor of ketamine response in treatment-resistant depressed patients and that the reduction in quinolinic acid after a ketamine infusion is a predictor of the reduction in MADRS score. Our results suggest that microglia is a key therapeutic target and that quinolinic acid is a biomarker of ketamine response in major depressive disorder.
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http://dx.doi.org/10.1016/j.bbi.2019.06.033DOI Listing
October 2019

Update in Neurocritical Care: a summary of the 2018 Paris international conference of the French Society of Intensive Care.

Ann Intensive Care 2019 Apr 16;9(1):47. Epub 2019 Apr 16.

Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles (ULB), Route de Lennik, 808, 1070, Brussels, Belgium.

The 2018 Paris Intensive Care symposium entitled "Update in Neurocritical Care" was organized in Paris, June 21-22, 2018, under the auspices of the French Intensive Care Society. This 2-day post-graduate educational symposium comprised several chapters, aiming first to provide all-board intensivists with current standards for the clinical assessment of altered consciousness states (including coma and delirium) and peripheral nervous system in critically ill patients, monitoring of brain function (specifically, electro-encephalography) and best practices for sedation-analgesia-delirium management. An update on the treatment of specific severe brain pathologies-including ischaemic/haemorrhagic stroke, cerebral venous thrombosis, hypoxic-ischaemic brain injury, immune-mediated and infectious encephalitis and refractory status epilepticus-was also provided. Finally, we discuss how to approach some difficult decisions, namely the role of decompressive craniectomy and prognostication models in patients with head injury. For each chapter, the scope of the present review was to provide important issues and key messages, provide most recent and relevant literature in the field, and briefly describe new developments in the field.
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http://dx.doi.org/10.1186/s13613-019-0523-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468018PMC
April 2019

Tailored multicomponent program for discomfort reduction in critically ill patients may decrease post-traumatic stress disorder in general ICU survivors at 1 year.

Intensive Care Med 2019 02 30;45(2):223-235. Epub 2019 Jan 30.

Unité de recherche CEReSS-EA3279, Aix-Marseille Université, Marseille, France.

Purpose: Reducing discomfort in the intensive care unit (ICU) should have a positive effect on long-term outcomes. This study assessed whether a tailored multicomponent program for discomfort reduction was effective in reducing post-traumatic stress disorder (PTSD) symptoms at 1 year in general ICU survivors.

Methods: This study is a prospective observational comparative effectiveness cohort study involving 30 ICUs. It was an extension of the IPREA3 study, a cluster-randomized controlled trial designed to assess the efficacy of a tailored multicomponent program to reduce discomfort in critically ill patients. The program included assessment of ICU-related self-perceived discomforts, immediate and monthly feedback to the healthcare team, and site-specific tailored interventions. The exposure was the implementation of this program. The eligible patients were exposed versus unexposed general adult ICU survivors. The prevalence of substantial PTSD symptoms at 1 year was assessed based on the Impact of Event Scale-Revised (IES-R).

Results: Of the 1537 ICU survivors included in the study, 475 unexposed patients and 344 exposed patients had follow-up data at 1 year: 57 (12.0%) and 21 (6.1%) presented with PTSD at 1 year, respectively (p = 0.004). Considering the clustering and after adjusting for age, gender, McCabe classification, and ICU-related self-perceived overall discomfort score, exposed patients were significantly less likely than unexposed patients to have substantial PTSD symptoms at 1 year (p = 0.015).

Conclusions: Implementation of a tailored multicomponent program in the ICU that has proved to be effective for reducing self-perceived discomfort in general adult ICU survivors also reduced the prevalence of substantial PTSD symptoms at 1 year.

Trial Registration: ClinicalTrials.gov identifier NCT02762409.
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http://dx.doi.org/10.1007/s00134-018-05511-yDOI Listing
February 2019

The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy - A prospective, pilot observational study.

PLoS One 2019 24;14(1):e0211184. Epub 2019 Jan 24.

Department of Anesthesiology and Intensive Care Medicine, University Medical Center Rostock, Rostock, Germany.

Sepsis-associated encephalopathy (SAE) contributes to mortality and neurocognitive impairment of sepsis patients. Neurofilament (Nf) light (NfL) and heavy (NfH) chain levels as biomarkers for neuroaxonal injury were not evaluated in cerebrospinal fluid (CSF) and plasma of patients with sepsis-associated encephalopathy (SAE) before. We conducted a prospective, pilot observational study including 20 patients with septic shock and five patients without sepsis serving as controls. The assessment of SAE comprised a neuropsychiatric examination, electroencephalography (EEG), magnetic resonance imaging (MRI) and delirium screening methods including the confusion assessment method for the ICU (CAM-ICU) and the intensive care delirium screening checklist (ICDSC). CSF Nf measurements in sepsis patients and longitudinal plasma Nf measurements in all participants were performed on days 1, 3 and 7 after study inclusion. Plasma NfL levels increased in sepsis patients over time (p = 0.0063) and remained stable in patients without sepsis. Plasma NfL values were significantly higher in patients with SAE (p = 0.011), significantly correlated with the severity of SAE represented by ICDSC values (R = 0.534, p = 0.022) and correlated with a poorer functional outcome after 100 days (R = -0.535, p = 0.0003). High levels of CSF Nf were measured in SAE patients. CSF NfL levels were higher in non-survivors (p = 0.012) compared with survivors and correlated with days until death (R = -0.932, p<0.0001) and functional outcome after 100 days (R = -0.749, p<0.0001). The present study showed for the first time that Nf levels provide complementary prognostic information in SAE patients indicating a higher chance of death and poorer functional/cognitive outcome in survivors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211184PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345472PMC
October 2019

Quality of life after intensive care unit: a multicenter cohort study protocol for assessment of long-term outcomes among intensive care survivors in Brazil.

Rev Bras Ter Intensiva 2018 Oct-Dec;30(4):405-413. Epub 2019 Jan 10.

Centro de Tratamento Intensivo Adulto, Hospital Moinhos de Vento - Porto Alegre (RS), Brasil.

Objective: To establish the prevalence of physical, cognitive and psychiatric disabilities, associated factors and their relationship with the qualities of life of intensive care survivors in Brazil.

Methods: A prospective multicenter cohort study is currently being conducted at 10 adult medical-surgical intensive care units representative of the 5 Brazilian geopolitical regions. Patients aged ≥ 18 years who are discharged from the participating intensive care units and stay 72 hours or more in the intensive care unit for medical or emergency surgery admissions or 120 hours or more for elective surgery admissions are consecutively included. Patients are followed up for a period of one year by means of structured telephone interviews conducted at 3, 6 and 12 months after discharge from the intensive care unit. The outcomes are functional dependence, cognitive dysfunction, anxiety and depression symptoms, posttraumatic stress symptoms, health-related quality of life, rehospitalization and long-term mortality.

Discussion: The present study has the potential to contribute to current knowledge of the prevalence and factors associated with postintensive care syndrome among adult intensive care survivors in Brazil. In addition, an association might be established between postintensive care syndrome and health-related quality of life.
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http://dx.doi.org/10.5935/0103-507X.20180063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334490PMC
May 2019

Dysglycemia and Neurologic Outcome in Mechanically Ventilated Patients With Guillain-Barré Syndrome.

Crit Care Med 2019 03;47(3):e227-e233

Department of neuro-anesthesiology and intensive care medicine, Sainte-Anne teaching hospital, Paris-Descartes University, Paris, France.

Objectives: Acute respiratory failure is a frequent complication of Guillain-Barré syndrome, associated with high morbidity and mortality. Adjuvant treatments are needed to improve the outcome of Guillain-Barré syndrome. Since dysglycemia is a risk factor for development of axonal polyneuropathy in critically ill patients and since insulin therapy may be neuroprotective, we sought to explore the association between dysglycemia and neurologic status in Guillain-Barré syndrome patients.

Design: Retrospective study.

Setting: Single-center study.

Interventions: All plasma levels of glycemia measured by enzymatic technique as well as capillary glycemia were collected in a cohort of mechanically ventilated Guillain-Barré syndrome patients. Insulin administration and dysglycemia were correlated to neurologic status at discharge defined by disability grade and arm grade.

Measurements And Main Results: In a multivariate analysis, disability grade and arm grade at ICU discharge were independently and inversely correlated with mean blood glucose. Disability grade and arm grade did not correlate with any other dysglycemic variables or with insulin administration or length of stay.

Conclusions: In the present study, we found that neurologic disability at ICU discharge correlated with dysglycemia in mechanically ventilated Guillain-Barré syndrome patients. These finding indicates that dysglycemia may delay motor recovery and impact the functional outcome of Guillain-Barré syndrome. Blood glucose control might be an adjuvant therapy for improving Guillain-Barré syndrome recovery.
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http://dx.doi.org/10.1097/CCM.0000000000003635DOI Listing
March 2019

Marathons and myasthenia gravis: a case report.

BMC Neurol 2018 Sep 18;18(1):145. Epub 2018 Sep 18.

Institute of Myology, GH Pitié-Salpêtrière (AP-HP), Bd de l'Hôpital, 75651, Paris Cedex 13, France.

Background: The cardinal symptoms of auto-immune myasthenia gravis are fatigue and weakness. Endurance events such as marathon running would seem incompatible with this chronic disease. Many patients stop sport altogether. There is limited literature of patients with auto-immune myasthenia gravis undergoing regular endurance exercise.

Case Presentation: We report the case of a 36-year-old female who began long-distance running whilst experiencing initial symptoms of myasthenia gravis. She was diagnosed with auto-immune myasthenia gravis and whilst advised to stop all sport, her way of fighting and living with this chronic and unpredictable disease was to continue running to maintain a healthy body and mind. Despite suffering from ocular, bulbar and localized limb fatigability, she managed to complete multiple marathons and achieve disease stability with cholinesterase inhibitors.

Conclusions: Marathon and half-marathon running lead to distinct changes in mediators of inflammation in an exercise-dose-dependent manner. Despite symptoms of weakness and fatigue in certain muscles in myasthenia gravis, physical exertion remains possible and may not worsen symptoms as demonstrated in this case and recent studies. The immunomodulatory role of exercise could be considered in this case however this hypothesis remains to be confirmed in future studies with quantitative data.
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http://dx.doi.org/10.1186/s12883-018-1150-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142625PMC
September 2018

Value and mechanisms of EEG reactivity in the prognosis of patients with impaired consciousness: a systematic review.

Crit Care 2018 08 2;22(1):184. Epub 2018 Aug 2.

Department of Neuro-Intensive Care Medicine, Sainte-Anne Hospital, Paris-Descartes University, Paris, France.

Background: Electroencephalography (EEG) is a well-established tool for assessing brain function that is available at the bedside in the intensive care unit (ICU). This review aims to discuss the relevance of electroencephalographic reactivity (EEG-R) in patients with impaired consciousness and to describe the neurophysiological mechanisms involved.

Methods: We conducted a systematic search of the term "EEG reactivity and coma" using the PubMed database. The search encompassed articles published from inception to March 2018 and produced 202 articles, of which 42 were deemed relevant, assessing the importance of EEG-R in relationship to outcomes in patients with impaired consciousness, and were therefore included in this review.

Results: Although definitions, characteristics and methods used to assess EEG-R are heterogeneous, several studies underline that a lack of EEG-R is associated with mortality and unfavorable outcome in patients with impaired consciousness. However, preserved EEG-R is linked to better odds of survival. Exploring EEG-R to nociceptive, auditory, and visual stimuli enables a noninvasive trimodal functional assessment of peripheral and central sensory ascending pathways that project to the brainstem, the thalamus and the cerebral cortex. A lack of EEG-R in patients with impaired consciousness may result from altered modulation of thalamocortical loop activity by afferent sensory input due to neural impairment. Assessing EEG-R is a valuable tool for the diagnosis and outcome prediction of severe brain dysfunction in critically ill patients.

Conclusions: This review emphasizes that whatever the etiology, patients with impaired consciousness featuring a reactive electroencephalogram are more likely to have a favorable outcome, whereas those with a nonreactive electroencephalogram are prone to having an unfavorable outcome. EEG-R is therefore a valuable prognostic parameter and warrants a rigorous assessment. However, current assessment methods are heterogeneous, and no consensus exists. Standardization of stimulation and interpretation methods is needed.
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http://dx.doi.org/10.1186/s13054-018-2104-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091014PMC
August 2018