Association Between EEG Patterns and Serum Neurofilament Light After Cardiac Arrest: A Post Hoc Analysis of the TTM Trial.

BACKGROUND AND OBJECTIVES: EEG is widely used for prediction of neurologic outcome after cardiac arrest. To better understand the relationship between EEG and neuronal injury, we explored the association between EEG and neurofilament light (NfL) as a marker of neuroaxonal injury, evaluated whether highly malignant EEG patterns are reflected by high NfL levels, and explored the association of EEG backgrounds and EEG discharges with NfL. METHODS: We performed a post hoc analysis of the Target Temperature Management After Out-of-Hospital Cardiac Arrest trial. Routine EEGs were prospectively performed after the temperature intervention ≥36 hours postarrest. Patients who awoke or died prior to 36 hours postarrest were excluded. EEG experts blinded to clinical information classified EEG background, amount of discharges, and highly malignant EEG patterns according to the standardized American Clinical Neurophysiology Society terminology. Prospectively collected serum samples were analyzed for NfL after trial completion. The highest available concentration at 48 or 72 hours postarrest was used. RESULTS: A total of 262/939 patients with EEG and NfL data were included. Patients with highly malignant EEG patterns had 2.9 times higher NfL levels than patients with malignant patterns and NfL levels were 13 times higher in patients with malignant patterns than those with benign patterns (95% CI 1.4-6.1 and 6.5-26.2, respectively; effect size 0.47; p < 0.001). Both background and the amount of discharges were independently strongly associated with NfL levels (p < 0.001). The EEG background had a stronger association with NfL levels than EEG discharges (R2 = 0.30 and R2 = 0.10, respectively). NfL levels in patients with a continuous background were lower than for any other background (95% CI for discontinuous, burst-suppression, and suppression, respectively: 2.26-18.06, 3.91-41.71, and 5.74-41.74; effect size 0.30; p < 0.001 for all). NfL levels did not differ between suppression and burst suppression. Superimposed discharges were only associated with higher NfL levels if the EEG background was continuous. DISCUSSION: Benign, malignant, and highly malignant EEG patterns reflect the extent of brain injury as measured by NfL in serum. The extent of brain injury is more strongly related to the EEG background than superimposed discharges. Combining EEG and NfL may be useful to better identify patients misclassified by single methods. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT01020916.

Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest.

PURPOSE: The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered "indeterminate". We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines. METHODS: Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1-2) at 6 months. RESULTS: Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2-98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87-95% of patients). Normal S100B and NSE predicted good outcome with NPV 76-82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as "indeterminate outcome" by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome. CONCLUSION: Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy.

Reduced EEG montage has a high accuracy in the post cardiac arrest setting.

OBJECTIVE: To study if comatose cardiac arrest patients can be assessed with a reduced number of EEG electrodes. METHODS: 110 routine EEGs from 67 consecutive patients, including both hypothermic and normothermic EEGs were retrospectively assessed by three blinded EEG-experts using two different electrode montages. A standard 19-electrode-montage was compared to the reduced version of the same EEGs, down-sampled to six electrodes (F3, T3, P3, F4, T4, P4). We used intra-rater and inter-observer statistics to assess the reliability of the reduced montage for background features and discharges. RESULTS: The reduced montage had almost perfect performance for background continuity (κ 0.80-0.88), including identification of highly malignant backgrounds (burst-suppression/suppression) (κ 0.85-0.94) and benign backgrounds (continuous/nearly continuous) (κ 0.85-0.91). We found substantial performance for identifying rhythmic/periodic discharges (κ 0.79-0.86). The reduced montage had high accuracy for assessment of both highly malignant (sensitivity 91-95%, specificity 94-99%) and benign (sensitivity 89-98%, specificity 91-96%) backgrounds, and periodic/rhythmic patterns (sensitivity 79-100%, specificity 89-99%), compared to the full montage. The inter-observer variability was not increased by the reduced montage. CONCLUSION: Reduced EEG had high performance for classifying important background and discharge patterns in this post cardiac arrest cohort. SIGNIFICANCE: Our results support the use of reduced EEG-montage for monitoring comatose cardiac arrest patients.

Performance of a guideline-recommended algorithm for prognostication of poor neurological outcome after cardiac arrest.

PURPOSE: To assess the performance of a 4-step algorithm for neurological prognostication after cardiac arrest recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM). METHODS: Retrospective descriptive analysis with data from the Target Temperature Management (TTM) Trial. Associations between predicted and actual neurological outcome were investigated for each step of the algorithm with results from clinical neurological examinations, neuroradiology (CT or MRI), neurophysiology (EEG and SSEP) and serum neuron-specific enolase. Patients examined with Glasgow Coma Scale Motor Score (GCS-M) on day 4 (72-96 h) post-arrest and available 6-month outcome were included. Poor outcome was defined as Cerebral Performance Category 3-5. Variations of the ERC/ESICM algorithm were explored within the same cohort. RESULTS: The ERC/ESICM algorithm identified poor outcome patients with 38.7% sensitivity (95% CI 33.1-44.7) and 100% specificity (95% CI 98.8-100) in a cohort of 585 patients. An alternative cut-off for serum neuron-specific enolase, an alternative EEG-classification and variations of the GCS-M had minor effects on the sensitivity without causing false positive predictions. The highest overall sensitivity, 42.5% (95% CI 36.7-48.5), was achieved when prognosticating patients irrespective of GCS-M score, with 100% specificity (95% CI 98.8-100) remaining. CONCLUSION: The ERC/ESICM algorithm and all exploratory multimodal variations thereof investigated in this study predicted poor outcome without false positive predictions and with sensitivities 34.6-42.5%. Our results should be validated prospectively, preferably in patients where withdrawal of life-sustaining therapy is uncommon to exclude any confounding from self-fulfilling prophecies.

Bedside interpretation of simplified continuous EEG after cardiac arrest.

BACKGROUND: Continuous EEG-monitoring (cEEG) in the ICU is recommended to assess prognosis and detect seizures after cardiac arrest but implementation is often limited by the lack of EEG-technicians and experts. The aim of the study was to assess ICU physicians ability to perform preliminary interpretations of a simplified cEEG in the post cardiac arrest setting. METHODS: Five ICU physicians received training in interpretation of simplified cEEG - total training duration 1 day. The ICU physicians then interpreted 71 simplified cEEG recordings from 37 comatose survivors of cardiac arrest. The cEEG included amplitude-integrated EEG trends and two channels with original EEG-signals. Basic EEG background patterns and presence of epileptiform discharges or seizure activity were assessed on 5-grade rank-ordered scales based on standardized EEG terminology. An EEG-expert was used as reference. RESULTS: There was substantial agreement (κ 0.69) for EEG background patterns and moderate agreement (κ 0.43) for epileptiform discharges between ICU physicians and the EEG-expert. Sensitivity for detecting seizure activity by ICU physicians was limited (50%), but with high specificity (87%). CONCLUSIONS: After cardiac arrest, preliminary bedside interpretations of simplified cEEGs by trained ICU physicians may allow earlier detection of clinically relevant cEEG changes, prompting changes in patient management as well as additional evaluation by an EEG-expert. This strategy requires awareness of limitations of both the simplified electrode montage and the cEEG interpretations performed by ICU physicians. cEEG evaluation by an expert should not be delayed.

Swedish consensus reached on recording, interpretation and reporting of neonatal continuous simplified electroencephalography that is supported by amplitude-integrated trend analysis.

Continuous monitoring of electroencephalography (EEG), with a focus on amplitude-integrated EEG (aEEG), has been used in neonatal intensive care for decades. A number of systems have been suggested for describing and quantifying aEEG patterns. Extensive full-montage EEG monitoring is used in specialised intensive care units. The American Clinical Neurophysiology Society published recommendations for defining and reporting EEG findings in critically ill adults and infants. Swedish neonatologists and clinical neurophysiologists collaborated to optimise simplified neonatal continuous aEEG and EEG recordings based on these American documents. CONCLUSION: This paper describes the Swedish consensus document produced by those meetings.

Electroencephalographic characteristics of status epilepticus after cardiac arrest.

OBJECTIVE: To describe the electrophysiological characteristics and pathophysiological significance of electrographic status epilepticus (ESE) after cardiac arrest and specifically compare patients with unequivocal ESE to patients with rhythmic or periodic borderline patterns defined as possible ESE. METHODS: Retrospective cohort study of consecutive patients treated with targeted temperature management and monitored with simplified continuous EEG. Patients with ESE were identified and electrographically characterised until 72h after ESE start using the standardised terminology of the American Clinical Neurophysiology Society. RESULTS: ESE occurred in 41 of 127 patients and 22 fulfilled the criteria for unequivocal ESE, which typically appeared early and transiently. Three of the four survivors had unequivocal ESE, starting after rewarming from a continuous background. There were no differences between the groups of unequivocal ESE and possible ESE regarding outcome, neuron-specific enolase levels or prevalence of reported clinical convulsions. CONCLUSION: ESE is common after cardiac arrest. The distinction between unequivocal and possible ESE patterns was not reflected by differences in clinical features or survival. SIGNIFICANCE: A favourable outcome is seen infrequently in patients with ESE, regardless of using strict or liberal ESE definitions.

Outcome following postanoxic status epilepticus in patients with targeted temperature management after cardiac arrest.

BACKGROUND: Postanoxic electrographic status epilepticus (ESE) is considered a predictor of poor outcome in resuscitated patients after cardiac arrest (CA). Observational data suggest that a subgroup of patients may have a good outcome. This study aimed to describe the prevalence of ESE and potential clinical and electrographic prognostic markers. METHODS: In this retrospective single study, we analyzed consecutive patients who suffered from CA, and who received temperature management and were monitored with simplified continuous EEG (cEEG) during a five-year period. The patients' charts and cEEG data were initially screened to identify patients with clinical seizures or ESE. The cEEG diagnosis of ESE was retrospectively reanalyzed according to strict criteria by a neurophysiologist blinded to patient outcome. The EEG background patterns prior to the onset of ESE, duration of ESE, presence of clinical seizures, and use of antiepileptic drugs were analyzed. The results of somatosensory-evoked potentials (SSEPs) and neuron-specific enolase (NSE) at 48 h after CA were described in all patients with ESE. Antiepileptic treatment strategies were not protocolized. Outcome was evaluated using the Cerebral Performance Category (CPC) scale at 6 months, and good outcome was defined as CPC 1-2. RESULTS: Of 127 patients, 41 (32%) developed ESE. Twenty-five patients had a discontinuous EEG background prior to ESE, and all died without regaining consciousness. Sixteen patients developed a continuous EEG background prior to the start of ESE, four of whom survived, three with CPC 1-2 and one with CPC 3 at 6 months. Among survivors, ESE developed at a median of 46 h after CA. All had preserved N20 peaks on SSEP and NSE values of 18-37 µg/l. CONCLUSION: Electrographic status epilepticus is common among comatose patients after cardiac arrest, with few survivors. A combination of a continuous EEG background prior to ESE, preserved N20 peaks on SSEPs, and low or moderately elevated NSE levels may indicate a good outcome. This article is part of a Special Issue entitled "Status Epilepticus".

Exploratory study of EEG burst characteristics in preterm infants.

In this paper, we study machine learning techniques and features of electroencephalography activity bursts for predicting outcome in extremely preterm infants. It was previously shown that the distribution of interburst interval durations predicts clinical outcome, but in previous work the information within the bursts has been neglected. In this paper, we perform exploratory analysis of feature extraction of burst characteristics and use machine learning techniques to show that such features could be used for outcome prediction. The results are promising, but further verification in larger datasets is needed to obtain conclusive results.

Pre-surgical epilepsy evaluation using 3T MRI. Do surface coils provide additional information?

PURPOSE: To assess if 3T MRI can be further improved by adding surface coil imaging, in the context of detection and characterization of cerebral lesions in patients with drug-resistant epilepsy. METHODS: Twenty five patients with drug-resistant epilepsy undergoing evaluation for epilepsy surgery were examined with high resolution 3T MRI. The patients were MRI-negative (n = 15), or had unclear findings (n = 10), on previous MRI at 1.0-1.5T. Surface coils were applied over the suspected epileptogenic zone after imaging in the head coil. In MRI-negative patients, placement of the coils was defined by semiological analysis, extracranial video-EEG, and, in selected cases, subtraction ictal SPECT co-registered with MRI and PET. Coil placement was re-analyzed and graded, based on the degree of convergence between different investigational modalities. RESULTS: Surface coil MRI allowed visualization of the cortical lesions with somewhat better demarcation and detail, but did not contribute to detection of previously undiagnosed lesions and did not provide additional information regarding type of lesion. Possible epileptogenic lesions were detected on 3T MRI in 12 patients. No abnormalities were found in the remaining 13 patients. 3T MRI provided new or additional information about the cortex, compared with reports from previous 1.0-1.5T MRI in 5 patients (20%). CONCLUSION: 3T MRI with high resolution is valuable for lesion detection, especially MCD, in patients with drug-resistant epilepsy. We question the additional contribution from supplementary surface coil imaging at 3T MRI.