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Early electrophysiological correlates of brain injury and outcome in comatose patients after cardiac arrest

Applicant Rossetti Andrea
Number 143780
Funding scheme Interdisciplinary projects
Research institution Service de Neurologie Département des Neurosciences Cliniques CHUV
Institution of higher education University of Lausanne - LA
Main discipline Neurology, Psychiatry
Start/End 01.03.2013 - 31.07.2016
Approved amount 281'312.00
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All Disciplines (2)

Discipline
Neurology, Psychiatry
Biomedical Engineering

Keywords (5)

Electroencephalography; Evoked potentials; Prognosis; Coma; Neuronal injury

Lay Summary (English)

Lead
Lay summary

Acute brain injury after cardiac arrest is a leading cause of severe coma and death. Recent advances in intensive care strategies (including therapeutic body cooling started immediately after the event and lasting 24 hours) have improved the outcome of these patients; however, several survivors experience long-lasting disability, with potentially devastating consequences for patients, relatives and health costs. The mechanisms of brain injury in this context are poorly understood; characterization of preserved neuronal circuits in early coma and their relation to long-term outcome are of outstanding importance.

Recently, our research group found that the variation of the electrical activity of the brain (measured through the electroencephalogram or EEG) to painful and sound stimulation within the first 72 hours is very informative of the outcome, and also correlates with the degree of neuronal injury. Furthermore, the analysis of EEG responses to standard and deviant sounds showed, surprisingly, a frequent preservation of the discrimination in early coma (the first 24 hours), and that an improvement of this discrimination during the following 24-48 hours seems to reliably predict awakening.

We hypothesize that the electrical activity of the brain measured early (even during cooling) is a robust predictor of neuronal injury and clinical outcome of comatose patients after cardiac arrest. We therefore aim at investigating the brain processing of sound stimuli during early coma, focusing on the electrical correlates of brain injury and consciousness recovery. We also aim at developing an objective EEG analysis that may be applied to each patient in this condition to inform on the quality of awakening at 6 months.

We will prospectively study with advanced EEG techniques (applied within 72 hours following the cardiac arrest) adult patients that are comatose after a cardiac arrest and treated with therapeutic cooling, and follow them for at least 6 months. Biological (blood parameters) and radiological (brain magnetic resonance imaging) markers will be used to estimate the degree of the acute neuronal injury. We will then associate the relationship between early brain electrical features and cognitive performance (neuropsychological examination) at 6 months, as well as with the early biological and radiological features.  

The successful completion of this multidisciplinary research (with the tight interplay of clinical neurophysiology, neuro-intensive care, neuropsychology, neuro-radiology, bio-engineering) has the potential to provide an important contribution to the understanding of the mechanisms leading to neuronal injury, and the prognostic determinants in acutely comatose patients.   

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
How Do You Feel? Subjective Perception of Recovery as a Reliable Surrogate of Cognitive and Functional Outcome in Cardiac Arrest Survivors
Juan Elsa, De Lucia Marzia, Beaud Valérie, Oddo Mauro, Rusca Marco, Viceic Dragana, Clarke Stephanie, Rossetti Andrea O. (2018), How Do You Feel? Subjective Perception of Recovery as a Reliable Surrogate of Cognitive and Functional Outcome in Cardiac Arrest Survivors, in Critical Care Medicine, 46(4), e286-e293.
Electroencephalography Predicts Poor and Good Outcomes After Cardiac ArrestA Two-Center Study*
Rossetti Andrea O., Tovar Quiroga Diego F., Juan Elsa, Novy Jan, White Roger D., Ben-Hamouda Nawfel, Britton Jeffrey W., Oddo Mauro, Rabinstein Alejandro A. (2017), Electroencephalography Predicts Poor and Good Outcomes After Cardiac ArrestA Two-Center Study*, in Critical Care Medicine, 45(7), e674-e682.
Evidence of trace conditioning in comatose patients revealed by the reactivation of EEG responses to alerting sounds
Juan E Nguepnjo Nguissi NA Tzovara A Viceic D Rusca M Oddo M Rossetti AO DeLucia M (2016), Evidence of trace conditioning in comatose patients revealed by the reactivation of EEG responses to alerting sounds, in Neuroimage, 141, 530-541.
Neurological prognostication of outcome in patients in coma after cardiac arrest
Rossetti AO Rabinstein AA Oddo M (2016), Neurological prognostication of outcome in patients in coma after cardiac arrest, in Lancet Neurol, 15, 597.
Prediction of awakening from hypothermic post anoxic coma based on auditory discrimination
Tzovara A Rossetti AO Juan E Suys T Viceic D Rusca M Oddo M DeLucia M (2016), Prediction of awakening from hypothermic post anoxic coma based on auditory discrimination, in Ann Neurol, 79, 748.
Prediction of cognitive outcome based on the progression of auditory discrimination during coma
Juan E DeLucia M Tzovara A Beaud V Oddo M Clarke S Rossetti AO (2016), Prediction of cognitive outcome based on the progression of auditory discrimination during coma, in Resuscitation, 106, 89.
Standardized EEG interpretation accurately predicts prognosis after cardiac arrest
Westhall E Rossetti AO van Rotselaar AF Weseberg Kjaer T Horn J Ullen S et al. (2016), Standardized EEG interpretation accurately predicts prognosis after cardiac arrest, in Neurology, 86, 1482.
Clinical evolution after a non-reactive hypothermic EEG after cardiac arrest
Juan E Novy J Suys T Oddo M Rossetti AO (2015), Clinical evolution after a non-reactive hypothermic EEG after cardiac arrest, in Neurocrit Care, 22, 403.
EEG as an Indicator of Cerebral Functioning in Postanoxic Coma
Juan E Kaplan PW Oddo M Rossetti AO (2015), EEG as an Indicator of Cerebral Functioning in Postanoxic Coma, in J Clin Neurophysiol, 32, 465.
EEG for outcome prediction after cardiac arrest: when the quest for optimization needs standardization
Rossetti AO (2015), EEG for outcome prediction after cardiac arrest: when the quest for optimization needs standardization, in Int Care Med, 41, 1321.
EEG reactivity to pain in comatose patients: Importance of the stimulus type
Testsou S Novy J Oddo M Rossetti AO (2015), EEG reactivity to pain in comatose patients: Importance of the stimulus type, in Resuscitation, 97, 34.
Interrater variability of EEG interpretation in comatose cardiac arrest patients
Westhall E Rosen I Rossetti AO van Rotselaar AF Kjaer TW Friberg H et al. (2015), Interrater variability of EEG interpretation in comatose cardiac arrest patients, in Clin Neurophysiol, 126, 2397.
Neural detection of complex sound sequences in the absence of consciousness
Tzovara A Simonin A Oddo M Rossetti AO DeLucia M (2015), Neural detection of complex sound sequences in the absence of consciousness, in Brain, 138, 1160.
Reply: Neural detection of complex sound sequences or of statistical regularities in the absence of consciousness?
Tzovara A Simonin A Oddo M Rossetti AO DeLucia M (2015), Reply: Neural detection of complex sound sequences or of statistical regularities in the absence of consciousness?, in Brain, 138, e396.
Should Postanoxic Status Epilepticus be Treated Aggressively?-No!
Rossetti AO (2015), Should Postanoxic Status Epilepticus be Treated Aggressively?-No!, in J Clin Neurophysiol, 32, 447.
Automated Analysis of Background EEG and Reactivity During Therapeutic Hypothermia in Comatose Patients after Cardiac Arrest
Noirhomme Q Lehembre R Zulay del Rosario L Lesenfants D Luxen A Laureys S Oddo M Rossetti AO (2014), Automated Analysis of Background EEG and Reactivity During Therapeutic Hypothermia in Comatose Patients after Cardiac Arrest, in Clin EEG Neurosci, 45, 6.
Contemporary approach to neurologic prognostication of coma after cardiac arrest
Nawfel Ben-Hamouda MD , Fabio S. Taccone MD PhD , Andrea O. Rossetti MD , and Mauro Oddo M (2014), Contemporary approach to neurologic prognostication of coma after cardiac arrest, in Chest, 146(5), 1375.
Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia
Oddo M Rossetti AO (2014), Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia, in Crit Care Med, 42, 1340.
Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design
Westhall E Rosen I Rossetti AO van Rotselaar AF Kjaer TW Horn J et al. (2014), Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design, in BMC Neurology, 14, 159.
Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine
Sandroni C Cariou A, Cavallaro F Cronberg T Friberg H Hoedemakers C Horn J Nolan JP Rossetti (2014), Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine, in Int Care Med, 85, 1779.
Robust discrimination between EEG responses to categories of environmental sounds in early coma
Cossy N Tzovara A Simonin A Rossetti AO DeLucia M (2014), Robust discrimination between EEG responses to categories of environmental sounds in early coma, in Frontiers in Psychology, 5, 155.
Clinical outcome after a reactive hypothermic EEG following cardiac arrest
Tsetsou S Oddo M Rossetti AO (2013), Clinical outcome after a reactive hypothermic EEG following cardiac arrest, in Neurocrit Care, 19, 283.

Collaboration

Group / person Country
Types of collaboration
Unité de Neuroradiologie , CHUV, Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Coma Science Group, Liège Belgium (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Awards

Title Year
Best Poster (Neurointensive care) European Academy of Neurology meeting 2014, Istanbul (TR) 2014

Associated projects

Number Title Start Funding scheme
169379 Impact on clinical outcome of continuous EEG monitoring in patients with disorders of consciousness: a randomized controlled trial 01.05.2017 Project funding
189969 PETITION - PET for InTensive Care units and Innovative protON therapy 01.09.2020 Sinergia

Abstract

Background: Acute brain injury after cardiac arrest (hypoxic-ischemic encephalopathy, HIE) is a leading cause of coma and consequent morbidity and mortality in humans. Recent advances in intensive care and neuroprotective strategies (including induced hypothermia) have substantially reduced mortality. However, a number of survivors experience significant long-term functional and cognitive disability, with potentially devastating consequences for patients, relatives and health costs. The exact mechanisms of HIE have been poorly studied, and long-term brain tissue and cognitive sequelae are not well known. Further characterization of preserved neuronal processes in early HIE stages, and their relation to long-term prognosis, are of outstanding importance for health care and related costs. Data from our group show that analysis of early (<72 hours) neural response (reactivity) to painful stimulation assessed through electroencephalography (EEG) significantly improves the prognostic accuracy of acute coma after HIE. Importantly, we found a strong correlation between EEG background reactivity and neuronal injury after HIE. Furthermore, using auditory evoked potentials during a mismatch negativity paradigm, we analyzed EEG based on a multivariate decoding algorithm allowing automatic quantification of neural auditory discrimination at a single-patient level. Our preliminary findings show, for the first time, preserved auditory processing after acute coma, and an improvement of auditory discrimination during the early phase of acute coma seems to be 100% predictive of awakening. This supports further investigations to examine if this novel multimodal EEG approach - combining EEG reactivity with multivariate quantification of auditory responses - correlates with neuronal injury and outcome.Hypothesis and study aim: We hypothesize that multimodal EEG is a strong predictor of neuronal injury, tissue loss and functional/cognitive outcome in coma after HIE. We aim at investigating functional brain processing of auditory stimuli during early coma, focusing on mechanisms of consciousness and on brain electrophysiological correlates of acute brain injury and consciousness recovery. We also aim at developing early quantitative EEG analyses at single-patient level to associate multimodal EEG with cognitive outcome and activities of daily living at 6 months. Methods: Prospective cohort of comatose adults after HIE with therapeutic hypothermia, studied with multimodal EEG (including painful and auditory stimulations), followed for 6 months. Estimation of acute neuronal injury will be performed by measuring serum-neuron-specific enolase (NSE), and of chronic tissue loss by MRI voxel-based morphometry).Primary endpoint: Association between early multimodal EEG variables with cognitive performance (neuropsychological examination) of survivors at 6 months. Secondary endpoints: association between early multimodal EEG variables with serum NSE (all patients), and structural damage (MRI) (survivors at 6 months). Impact: a) Better understanding of the pathophysiology of HIE; b) improved early prediction of cognitive outcome after HIE leading to improvement of quality of care and public health costs; c) since HIE after global brain ischemia is considered as a “homogeneous” form of acute brain injury, this project will provide a solid platform for studying other forms of coma after acute brain injury, such as subarachnoid hemorrhage or traumatic brain injury. Overall, successful completion of the proposed multidisciplinary research (with the interplay of clinical neurophysiology, neuro-intensive care, neuropsychology, neuro-radiology, bio-engineering) has the potential to provide an important contribution to the understanding of the pathobiology and prognostic determinants of acute coma in humans.
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