Postanoxic electrographic status epilepticus and serum biomarkers of brain injury

AIM: To explore if electrographic status epilepticus (ESE) after cardiac arrest causes additional secondary brain injury reflected by serum levels of two novel biomarkers of brain injury: neurofilament light chain (NfL) originating from neurons and glial fibrillary acidic protein (GFAP) from glial cells. METHODS: Simplified continuous EEG (cEEG) and serum levels of NfL and GFAP, sampled at 24, 48 and 72 h after cardiac arrest, were collected during the Target Temperature Management (TTM)-trial. Two statistical methods were used: multivariable regresssion analysis; and a matched control group of patients without ESE matched for early predictors of poor neurological outcome. RESULTS: 128 patients had available biomarkers and cEEG. Twenty-six (20%) patients developed ESE, the majority (69%) within 24 h. ESE was an independent predictor of elevated serum NfL (p < 0.001) but not of serum GFAP (p = 0.16) at 72 h after cardiac arrest. Compared to a control group matched for early predictors of poor neurological outcome, patients who developed ESE had higher levels of serum NfL (p = 0.03) and GFAP (p = 0.04) at 72 h after cardiac arrest. CONCLUSION: ESE after cardiac arrest is associated with higher levels of serum NfL which may suggest increased secondary neuronal injury compared to matched patients without ESE but similar initial brain injury. Associations with GFAP reflecting glial injury are less clear. The study design cannot exclude imperfect matching or other mechanisms of secondary brain injury contributing to the higher levels of biomarkers of brain injury seen in the patients with ESE

Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design.

BACKGROUND: Electroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest, but its value is limited by varying definitions of pathological patterns and by inter-rater variability. The American Clinical Neurophysiology Society (ACNS) has recently proposed a standardized EEG-terminology for critical care to address these limitations. METHODS/DESIGN: In the TTM-trial, 399 post cardiac arrest patients who remained comatose after rewarming underwent a routine EEG. The presence of clinical seizures, use of sedatives and antiepileptic drugs during the EEG-registration were prospectively documented. DISCUSSION: A well-defined terminology for interpreting post cardiac arrest EEGs is critical for the use of EEG as a prognostic tool. TRIAL REGISTRATION: The TTM-trial is registered at ClinicalTrials.gov (NCT01020916)

Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review.

To assess the ability of clinical examination, blood biomarkers, electrophysiology, or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict poor neurological outcome, defined as death, vegetative state, or severe disability (CPC 3-5) at hospital discharge/1 month or later, in comatose adult survivors from cardiac arrest (CA). PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews (January 2013-April 2020) were searched. Sensitivity and false-positive rate (FPR) for each predictor were calculated. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed. Ninety-four studies (30,200 patients) were included. Bilaterally absent pupillary or corneal reflexes after day 4 from ROSC, high blood values of neuron-specific enolase from 24 h after ROSC, absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) or unequivocal seizures on electroencephalogram (EEG) from the day of ROSC, EEG background suppression or burst-suppression from 24 h after ROSC, diffuse cerebral oedema on brain CT from 2 h after ROSC, or reduced diffusion on brain MRI at 2-5 days after ROSC had 0% FPR for poor outcome in most studies. Risk of bias assessed using the QUIPS tool was high for all predictors. In comatose resuscitated patients, clinical, biochemical, neurophysiological, and radiological tests have a potential to predict poor neurological outcome with no false-positive predictions within the first week after CA. Guidelines should consider the methodological concerns and limited sensitivity for individual modalities. (PROSPERO CRD42019141169)

Standardized EEG interpretation accurately predicts prognosis after cardiac arrest.

OBJECTIVE: To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. METHODS: In this cohort study, 4 EEG specialists, blinded to outcome, evaluated prospectively recorded EEGs in the Target Temperature Management trial (TTM trial) that randomized patients to 33°C vs 36°C. Routine EEG was performed in patients still comatose after rewarming. EEGs were classified into highly malignant (suppression, suppression with periodic discharges, burst-suppression), malignant (periodic or rhythmic patterns, pathological or nonreactive background), and benign EEG (absence of malignant features). Poor outcome was defined as best Cerebral Performance Category score 3-5 until 180 days. RESULTS: Eight TTM sites randomized 202 patients. EEGs were recorded in 103 patients at a median 77 hours after cardiac arrest; 37% had a highly malignant EEG and all had a poor outcome (specificity 100%, sensitivity 50%). Any malignant EEG feature had a low specificity to predict poor prognosis (48%) but if 2 malignant EEG features were present specificity increased to 96% (p &lt; 0.001). Specificity and sensitivity were not significantly affected by targeted temperature or sedation. A benign EEG was found in 1% of the patients with a poor outcome. CONCLUSIONS: Highly malignant EEG after rewarming reliably predicted poor outcome in half of patients without false predictions. An isolated finding of a single malignant feature did not predict poor outcome whereas a benign EEG was highly predictive of a good outcome

Stratifying comatose postanoxic patients for somatosensory evoked potentials using routine EEG

Introduction: Multimodal neurological prognostication is recommended for comatose patients after cardiac arrest. The absence of cortical N20-potentials in a somatosensory evoked potential (SSEP) examination reliably predicts poor outcome, but presence of N20-potentials have limited prognostic value. A benign routine electroencephalogram (EEG) may identify patients with a favourable prognosis who are likely to have present N20-potentials. Objective: To investigate whether a routine EEG can identify patients where SSEP is unnecessary to perform. Methods: In a multi-centre trial, comatose patients after cardiac arrest were randomised to a controlled temperature of 33 °C or 36 °C. A routine EEG was protocolised and SSEP performed at the clinicians’ discretion, both during normothermic conditions. EEGs were categorised into benign, malignant or highly malignant based on standardised terminology. A benign EEG was defined as a continuous normal-voltage background without abundant discharges. The N20-potentials were reported as absent (bilaterally) or present (bilaterally or unilaterally). Results: Both EEG and SSEP were performed in 161 patients. EEG was performed before SSEP in 60%. A benign EEG was seen in 29 patients and 100% (CI 88–100%) had present N20-potentials. For the 69 patients with a malignant EEG and the 63 patients with a highly malignant EEG, 67% (CI 55–77%) and 44% (CI 33–57%) had present N20-potentials, respectively. Conclusions: All patients with a benign EEG had present N20-potentials, suggesting that SSEP may be omitted in these patients to save resources. SSEP is useful in patients with a malignant or highly malignant EEG since these patterns are associated with both present and absent N20-potentials

Stimulus-induced EEG-patterns and outcome after cardiac arrest

Objective: EEG is commonly used to predict prognosis in post anoxic coma. We investigated if stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) add prognostic information after cardiac arrest. Methods: In the multicenter Targeted Temperature Management trial, routine-EEGs were prospectively recorded after rewarming (≥36 h). Presence and subtype of SIRPIDs and main EEG-pattern (benign, malignant, highly malignant) were retrospectively reported according to a standardised classification. Patients were followed up after 180 days. Poor outcome was defined as severe neurological disability or death (Cerebral Performance Category 3–5). Results: Of 142 patients, 71% had poor outcome and 14% had SIRPIDs. There was no significant difference in outcome between patients with and without SIRPIDs, even when subgrouped according to underlying main EEG-pattern. Comparing subtypes of SIRPIDs, 82% of patients with stimulus-induced periodic discharges had poor outcome compared to 44% of patients with stimulus-induced rhythmic delta activity, but the difference was not significant. Conclusions: In EEGs performed ≥36 h after cardiac arrest, SIRPIDs cannot be used to reliably predict poor outcome. Whether certain subtypes of SIRPIDs indicate worse prognosis needs further investigation. Significance: Categorising the main EEG-pattern has important prognostic implications, but assessment of late appearing SIRPIDs does not seem to add prognostic information

Highly malignant routine EEG predicts poor prognosis after cardiac arrest in the Target Temperature Management trial

Introduction: Routine EEG is widely used and accessible for post arrest neuroprognostication. Recent studies, using standardised EEG terminology, have proposed highly malignant EEG patterns with promising predictive ability. Objectives: To validate the performance of standardised routine EEG patterns to predict neurological outcome after cardiac arrest. Methods: In the prospective multicenter Target Temperature Management trial, comatose cardiac arrest patients were randomised to different temperature levels (950 patients, 36 sites). According to the prospective protocol a routine EEG was performed in patients who remained comatose after the 36 h temperature control intervention. EEGs were retrospectively reviewed blinded to outcome using the standardised American Clinical Neurophysiology Society terminology. Highly malignant, malignant and benign EEG patterns were correlated to poor and good outcome, defined by best achieved Cerebral Performance Category up to 180 days. Results: At 20 sites 207 patients had a routine EEG performed at median 76 h after cardiac arrest. Highly malignant patterns (suppression or burst-suppression with or without discharges) had a high specificity for poor outcome (98%, CI 92–100), but with limited sensitivity (31%, CI 24–39). Our false positive patient had a burst-suppression pattern during ongoing sedation. A benign EEG, i.e. continuous normal-voltage background without malignant features, identified patients with good outcome with 77% (CI 66–86) sensitivity and 80% (CI 73–86) specificity. Conclusion: Highly malignant routine EEG after targeted temperature management is a strong predictor of poor outcome. A benign EEG is an important indicator of a good outcome for patients remaining in coma