Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement From the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Mortality and Timing of Withdrawal of Life-Sustaining Therapies After Out-of-Hospital Cardiac Arrest: Two-Center Retrospective Pediatric Cohort Study.

OBJECTIVES: Pediatric out-of-hospital cardiac arrest (OHCA) is associated with substantial morbidity and mortality. Limited data exist to guide timing and method of neurologic prognostication after pediatric OHCA, making counseling on withdrawal of life-sustaining therapies (WLSTs) challenging. This study investigates the timing and mode of death after pediatric OHCA and factors associated with mortality. Additionally, this study explores delayed recovery after comatose examination on day 3 postarrest. DESIGN: This is a retrospective, observational study based on data collected from hospital databases and chart reviews. SETTING: Data collection occurred in two pediatric academic hospitals between January 1, 2016, and December 31, 2020. PATIENTS: Patients were identified from available databases and electronic medical record queries for the International Classification of Diseases , 10th Edition (ICD-10) code I46.9 (Cardiac Arrest). Patient inclusion criteria included age range greater than or equal to 48 hours to less than 18 years, OHCA within 24 hours of admission, greater than or equal to 1 min of cardiopulmonary resuscitation, and return-of-spontaneous circulation for greater than or equal to 20 min. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-five children (65% male) with a median age of 3 years (interquartile range 0.6-11.8) met inclusion criteria. Overall, 63 of 135 patients (47%) died before hospital discharge, including 34 of 63 patients (54%) after WLST. Among these, 20 of 34 patients underwent WLST less than or equal to 3 days postarrest, including 10 of 34 patients who underwent WLST within 1 day. WLST occurred because of poor perceived neurologic prognosis in all cases, although 7 of 34 also had poor perceived systemic prognosis. Delayed neurologic recovery from coma on day 3 postarrest was observed in 7 of 72 children (10%) who ultimately survived to discharge. CONCLUSIONS: In our two centers between 2016 and 2020, more than half the deaths after pediatric OHCA occurred after WLST, and a majority of WLST occurred within 3 days postarrest. Additional research is warranted to determine optimal timing and predictors of neurologic prognosis after pediatric OHCA to better inform families during goals of care discussions.

Early Burst Suppression Similarity Association with Structural Brain Injury Severity on MRI After Cardiac Arrest.

BACKGROUND: Identical bursts on electroencephalography (EEG) are considered a specific predictor of poor outcomes in cardiac arrest, but its relationship with structural brain injury severity on magnetic resonance imaging (MRI) is not known. METHODS: This was a retrospective analysis of clinical, EEG, and MRI data from adult comatose patients after cardiac arrest. Burst similarity in first 72 h from the time of return of spontaneous circulation were calculated using dynamic time-warping (DTW) for bursts of equal (i.e., 500 ms) and varying (i.e., 100-500 ms) lengths and cross-correlation for bursts of equal lengths. Structural brain injury severity was measured using whole brain mean apparent diffusion coefficient (ADC) on MRI. Pearson's correlation coefficients were calculated between mean burst similarity across consecutive 12-24-h time blocks and mean whole brain ADC values. Good outcome was defined as Cerebral Performance Category of 1-2 (i.e., independence for activities of daily living) at the time of hospital discharge. RESULTS: Of 113 patients with cardiac arrest, 45 patients had burst suppression (mean cardiac arrest to MRI time 4.3 days). Three study participants with burst suppression had a good outcome. Burst similarity calculated using DTW with bursts of varying lengths was correlated with mean ADC value in the first 36 h after cardiac arrest: Pearson's r: 0-12 h: - 0.69 (p = 0.039), 12-24 h: - 0.54 (p = 0.002), 24-36 h: - 0.41 (p = 0.049). Burst similarity measured with bursts of equal lengths was not associated with mean ADC value with cross-correlation or DTW, except for DTW at 60-72 h (- 0.96, p = 0.04). CONCLUSIONS: Burst similarity on EEG after cardiac arrest may be associated with acute brain injury severity on MRI. This association was time dependent when measured using DTW.

Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement from the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

The International Cardiac Arrest Research Consortium Electroencephalography Database.

OBJECTIVES: To develop the International Cardiac Arrest Research (I-CARE), a harmonized multicenter clinical and electroencephalography database for acute hypoxic-ischemic brain injury research involving patients with cardiac arrest. DESIGN: Multicenter cohort, partly prospective and partly retrospective. SETTING: Seven academic or teaching hospitals from the United States and Europe. PATIENTS: Individuals 16 years old or older who were comatose after return of spontaneous circulation following a cardiac arrest who had continuous electroencephalography monitoring were included. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Clinical and electroencephalography data were harmonized and stored in a common Waveform Database-compatible format. Automated spike frequency, background continuity, and artifact detection on electroencephalography were calculated with 10-second resolution and summarized hourly. Neurologic outcome was determined at 3-6 months using the best Cerebral Performance Category (CPC) scale. This database includes clinical data and 56,676 hours (3.9 terabytes) of continuous electroencephalography data for 1,020 patients. Most patients died ( n = 603, 59%), 48 (5%) had severe neurologic disability (CPC 3 or 4), and 369 (36%) had good functional recovery (CPC 1-2). There is significant variability in mean electroencephalography recording duration depending on the neurologic outcome (range, 53-102 hr for CPC 1 and CPC 4, respectively). Epileptiform activity averaging 1 Hz or more in frequency for at least 1 hour was seen in 258 patients (25%) (19% for CPC 1-2 and 29% for CPC 3-5). Burst suppression was observed for at least 1 hour in 207 (56%) and 635 (97%) patients with CPC 1-2 and CPC 3-5, respectively. CONCLUSIONS: The I-CARE consortium electroencephalography database provides a comprehensive real-world clinical and electroencephalography dataset for neurophysiology research of comatose patients after cardiac arrest. This dataset covers the spectrum of abnormal electroencephalography patterns after cardiac arrest, including epileptiform patterns and those in the ictal-interictal continuum.

Practice Standards for the Use of Multimodality Neuromonitoring: A Delphi Consensus Process.

OBJECTIVES: To address areas in which there is no consensus for the technologies, effort, and training necessary to integrate and interpret information from multimodality neuromonitoring (MNM). DESIGN: A three-round Delphi consensus process. SETTING: Electronic surveys and virtual meeting. SUBJECTS: Participants with broad MNM expertise from adult and pediatric intensive care backgrounds. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two rounds of surveys were completed followed by a virtual meeting to resolve areas without consensus and a final survey to conclude the Delphi process. With 35 participants consensus was achieved on 49% statements concerning MNM. Neurologic impairment and the potential for MNM to guide management were important clinical considerations. Experts reached consensus for the use of MNM-both invasive and noninvasive-for patients in coma with traumatic brain injury, aneurysmal subarachnoid hemorrhage, and intracranial hemorrhage. There was consensus that effort to integrate and interpret MNM requires time independent of daily clinical duties, along with specific skills and expertise. Consensus was reached that training and educational platforms are necessary to develop this expertise and to provide clinical correlation. CONCLUSIONS: We provide expert consensus in the clinical considerations, minimum necessary technologies, implementation, and training/education to provide practice standards for the use of MNM to individualize clinical care.

Post-cardiac arrest Sedation Promotes Electroencephalographic Slow-wave Activity and Improves Survival in a Mouse Model of Cardiac Arrest.

BACKGROUND: Patients resuscitated from cardiac arrest are routinely sedated during targeted temperature management, while the effects of sedation on cerebral physiology and outcomes after cardiac arrest remain to be determined. The authors hypothesized that sedation would improve survival and neurologic outcomes in mice after cardiac arrest. METHODS: Adult C57BL/6J mice of both sexes were subjected to potassium chloride-induced cardiac arrest and cardiopulmonary resuscitation. Starting at the return of spontaneous circulation or at 60 min after return of spontaneous circulation, mice received intravenous infusion of propofol at 40 mg · kg-1 · h-1, dexmedetomidine at 1 µg · kg-1 · h-1, or normal saline for 2 h. Body temperature was lowered and maintained at 33°C during sedation. Cerebral blood flow was measured for 4 h postresuscitation. Telemetric electroencephalogram (EEG) was recorded in freely moving mice from 3 days before up to 7 days after cardiac arrest. RESULTS: Sedation with propofol or dexmedetomidine starting at return of spontaneous circulation improved survival in hypothermia-treated mice (propofol [13 of 16, 81%] vs. no sedation [4 of 16, 25%], P = 0.008; dexmedetomidine [14 of 16, 88%] vs. no sedation [4 of 16, 25%], P = 0.002). Mice receiving no sedation exhibited cerebral hyperemia immediately after resuscitation and EEG power remained less than 30% of the baseline in the first 6 h postresuscitation. Administration of propofol or dexmedetomidine starting at return of spontaneous circulation attenuated cerebral hyperemia and increased EEG slow oscillation power during and early after sedation (40 to 80% of the baseline). In contrast, delayed sedation failed to improve outcomes, without attenuating cerebral hyperemia and inducing slow-wave activity. CONCLUSIONS: Early administration of sedation with propofol or dexmedetomidine improved survival and neurologic outcomes in mice resuscitated from cardiac arrest and treated with hypothermia. The beneficial effects of sedation were accompanied by attenuation of the cerebral hyperemic response and enhancement of electroencephalographic slow-wave activity.

Neurocritical Care Performance Measures Derived from Electronic Health Record Data are Feasible and Reveal Site-Specific Variation: A CHoRUS Pilot Project.

BACKGROUND: We evaluated the feasibility and discriminability of recently proposed Clinical Performance Measures for Neurocritical Care (Neurocritical Care Society) and Quality Indicators for Traumatic Brain Injury (Collaborative European NeuroTrauma Effectiveness Research in TBI; CENTER-TBI) extracted from electronic health record (EHR) flowsheet data. METHODS: At three centers within the Collaborative Hospital Repository Uniting Standards (CHoRUS) for Equitable AI consortium, we examined consecutive neurocritical care admissions exceeding 24 h (03/2015-02/2020) and evaluated the feasibility, discriminability, and site-specific variation of five clinical performance measures and quality indicators: (1) intracranial pressure (ICP) monitoring (ICPM) within 24 h when indicated, (2) ICPM latency when initiated within 24 h, (3) frequency of nurse-documented neurologic assessments, (4) intermittent pneumatic compression device (IPCd) initiation within 24 h, and (5) latency to IPCd application. We additionally explored associations between delayed IPCd initiation and codes for venous thromboembolism documented using the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) system. Median (interquartile range) statistics are reported. Kruskal-Wallis tests were measured for differences across centers, and Dunn statistics were reported for between-center differences. RESULTS: A total of 14,985 admissions met inclusion criteria. ICPM was documented in 1514 (10.1%), neurologic assessments in 14,635 (91.1%), and IPCd application in 14,175 (88.5%). ICPM began within 24 h for 1267 (83.7%), with site-specific latency differences among sites 1-3, respectively, (0.54 h [2.82], 0.58 h [1.68], and 2.36 h [4.60]; p < 0.001). The frequency of nurse-documented neurologic assessments also varied by site (17.4 per day [5.97], 8.4 per day [3.12], and 15.3 per day [8.34]; p < 0.001) and diurnally (6.90 per day during daytime hours vs. 5.67 per day at night, p < 0.001). IPCds were applied within 24 h for 12,863 (90.7%) patients meeting clinical eligibility (excluding those with EHR documentation of limiting injuries, actively documented as ambulating, or refusing prophylaxis). In-hospital venous thromboembolism varied by site (1.23%, 1.55%, and 5.18%; p < 0.001) and was associated with increased IPCd latency (overall, 1.02 h [10.4] vs. 0.97 h [5.98], p = 0.479; site 1, 2.25 h [10.27] vs. 1.82 h [7.39], p = 0.713; site 2, 1.38 h [5.90] vs. 0.80 h [0.53], p = 0.216; site 3, 0.40 h [16.3] vs. 0.35 h [11.5], p = 0.036). CONCLUSIONS: Electronic health record-derived reporting of neurocritical care performance measures is feasible and demonstrates site-specific variation. Future efforts should examine whether performance or documentation drives these measures, what outcomes are associated with performance, and whether EHR-derived measures of performance measures and quality indicators are modifiable.

Proceedings from the Neurotherapeutics Symposium on Neurological Emergencies: Shaping the Future of Neurocritical Care.

Effective treatment options for patients with life-threatening neurological disorders are limited. To address this unmet need, high-impact translational research is essential for the advancement and development of novel therapeutic approaches in neurocritical care. "The Neurotherapeutics Symposium 2019-Neurological Emergencies" conference, held in Rochester, New York, in June 2019, was designed to accelerate translation of neurocritical care research via transdisciplinary team science and diversity enhancement. Diversity excellence in the neuroscience workforce brings innovative and creative perspectives, and team science broadens the scientific approach by incorporating views from multiple stakeholders. Both are essential components needed to address complex scientific questions. Under represented minorities and women were involved in the organization of the conference and accounted for 30-40% of speakers, moderators, and attendees. Participants represented a diverse group of stakeholders committed to translational research. Topics discussed at the conference included acute ischemic and hemorrhagic strokes, neurogenic respiratory dysregulation, seizures and status epilepticus, brain telemetry, neuroprognostication, disorders of consciousness, and multimodal monitoring. In these proceedings, we summarize the topics covered at the conference and suggest the groundwork for future high-yield research in neurologic emergencies.

Quantitative Electroencephalogram Trends Predict Recovery in Hypoxic-Ischemic Encephalopathy.

OBJECTIVES: Electroencephalogram features predict neurologic recovery following cardiac arrest. Recent work has shown that prognostic implications of some key electroencephalogram features change over time. We explore whether time dependence exists for an expanded selection of quantitative electroencephalogram features and whether accounting for this time dependence enables better prognostic predictions. DESIGN: Retrospective. SETTING: ICUs at four academic medical centers in the United States. PATIENTS: Comatose patients with acute hypoxic-ischemic encephalopathy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 12,397 hours of electroencephalogram from 438 subjects. From the electroencephalogram, we extracted 52 features that quantify signal complexity, category, and connectivity. We modeled associations between dichotomized neurologic outcome (good vs poor) and quantitative electroencephalogram features in 12-hour intervals using sequential logistic regression with Elastic Net regularization. We compared a predictive model using time-varying features to a model using time-invariant features and to models based on two prior published approaches. Models were evaluated for their ability to predict binary outcomes using area under the receiver operator curve, model calibration (how closely the predicted probability of good outcomes matches the observed proportion of good outcomes), and sensitivity at several common specificity thresholds of interest. A model using time-dependent features outperformed (area under the receiver operator curve, 0.83 ± 0.08) one trained with time-invariant features (0.79 ± 0.07; p < 0.05) and a random forest approach (0.74 ± 0.13; p < 0.05). The time-sensitive model was also the best-calibrated. CONCLUSIONS: The statistical association between quantitative electroencephalogram features and neurologic outcome changed over time, and accounting for these changes improved prognostication performance.

Estimating the False Positive Rate of Absent Somatosensory Evoked Potentials in Cardiac Arrest Prognostication.

OBJECTIVES: Absence of somatosensory evoked potentials is considered a nearly perfect predictor of poor outcome after cardiac arrest. However, reports of good outcomes despite absent somatosensory evoked potentials and high rates of withdrawal of life-sustaining therapies have raised concerns that estimates of the prognostic value of absent somatosensory evoked potentials may be biased by self-fulfilling prophecies. We aimed to develop an unbiased estimate of the false positive rate of absent somatosensory evoked potentials as a predictor of poor outcome after cardiac arrest. DATA SOURCES: PubMed. STUDY SELECTION: We selected 35 studies in cardiac arrest prognostication that reported somatosensory evoked potentials. DATA EXTRACTION: In each study, we identified rates of withdrawal of life-sustaining therapies and good outcomes despite absent somatosensory evoked potentials. We appraised studies for potential biases using the Quality in Prognosis Studies tool. Using these data, we developed a statistical model to estimate the false positive rate of absent somatosensory evoked potentials adjusted for withdrawal of life-sustaining therapies rate. DATA SYNTHESIS: Two-thousand one-hundred thirty-three subjects underwent somatosensory evoked potential testing. Five-hundred ninety-four had absent somatosensory evoked potentials; of these, 14 had good functional outcomes. The rate of withdrawal of life-sustaining therapies for subjects with absent somatosensory evoked potential could be estimated in 14 of the 35 studies (mean 80%, median 100%). The false positive rate for absent somatosensory evoked potential in predicting poor neurologic outcome, adjusted for a withdrawal of life-sustaining therapies rate of 80%, is 7.7% (95% CI, 4-13%). CONCLUSIONS: Absent cortical somatosensory evoked potentials do not infallibly predict poor outcome in patients with coma following cardiac arrest. The chances of survival in subjects with absent somatosensory evoked potentials, though low, may be substantially higher than generally believed.

Small RNA signatures of acute ischemic stroke in L1CAM positive extracellular vesicles.

L1CAM-positive extracellular vesicles (L1EV) are an emerging biomarker that may better reflect ongoing neuronal damage than other blood-based biomarkers. The physiological roles and regulation of L1EVs and their small RNA cargoes following stroke is unknown. We sought to characterize L1EV small RNAs following stroke and assess L1EV RNA signatures for diagnosing stroke using weighted gene co-expression network analysis and random forest (RF) machine learning algorithms. Interestingly, small RNA sequencing of plasma L1EVs from patients with stroke and control patients (n = 28) identified micro(mi)RNAs known to be enriched in the brain. Weighted gene co-expression network analysis (WGCNA) revealed small RNA transcript modules correlated to diagnosis, initial NIH stroke scale, and age. L1EV RNA signatures associated with the diagnosis of AIS were derived from WGCNA and RF classification. These small RNA signatures demonstrated a high degree of accuracy in the diagnosis of AIS with an area under the curve (AUC) of the signatures ranging from 0.833 to 0.932. Further work is necessary to understand the role of small RNA L1EV cargoes in the response to brain injury, however, this study supports the utility of L1EV small RNA signatures as a biomarker of stroke.

Increased task-relevant fMRI responsiveness in comatose cardiac arrest patients is associated with improved neurologic outcomes.

Early prediction of the recovery of consciousness in comatose cardiac arrest patients remains challenging. We prospectively studied task-relevant fMRI responses in 19 comatose cardiac arrest patients and five healthy controls to assess the fMRI's utility for neuroprognostication. Tasks involved instrumental music listening, forward and backward language listening, and motor imagery. Task-specific reference images were created from group-level fMRI responses from the healthy controls. Dice scores measured the overlap of individual subject-level fMRI responses with the reference images. Task-relevant responsiveness index (Rindex) was calculated as the maximum Dice score across the four tasks. Correlation analyses showed that increased Dice scores were significantly associated with arousal recovery (P < 0.05) and emergence from the minimally conscious state (EMCS) by one year (P < 0.001) for all tasks except motor imagery. Greater Rindex was significantly correlated with improved arousal recovery (P = 0.002) and consciousness (P = 0.001). For patients who survived to discharge (n = 6), the Rindex's sensitivity was 75% for predicting EMCS (n = 4). Task-based fMRI holds promise for detecting covert consciousness in comatose cardiac arrest patients, but further studies are needed to confirm these findings. Caution is necessary when interpreting the absence of task-relevant fMRI responses as a surrogate for inevitable poor neurological prognosis.

Impact of telemedicine implementation in thrombolytic use for acute ischemic stroke: the University of Pittsburgh Medical Center telestroke network experience.

BACKGROUND: Intravenous thrombolysis is the only therapy for acute ischemic stroke that is approved by the US Food and Drug Association. The use of telemedicine in stroke makes it possible to bring the expertise of academic stroke centers to underserved areas, potentially increasing the quality of stroke care. METHODS: All consecutive admissions for stroke were reviewed for 1 year before telemedicine implementation and for variable periods thereafter. A retrospective review identified 2588 admissions for acute stroke between March 2005 and December 2008 at 12 hospitals participating in a telestroke network, including 919 patients before telemedicine was available and 1669 patients after telemedicine was available. The primary outcome measure was the rate of intravenous tissue plasminogen activator (IV tPA) use before and after telemedicine implementation. RESULTS: One hundred thirty-nine patients received IV tPA in both study phases, with 26 (2.8%) patients treated before starting telemedicine and 113 (6.8%) after starting telemedicine (P < .001). Incorrect treatment decisions occurred 7 times (0.39%), with 2 (0.2%) pretelemedicine and 5 (0.3%) posttelemedicine (P = .70). Arrivals within 3 hours from symptom onset were more frequent in the posttelemedicine compared to the pretelemedicine phases (55 [6%] vs 159 [9.5%]; P = .002). Among the patients treated with IV tPA, symptomatic intracranial hemorrhage occurred in 2 patients (1 [10.7%] pretelemedicine vs 1 [1.8%] posttelemedicine; P = .34). CONCLUSIONS: Telestroke implementation was associated with an increased rate of thrombolytic use in remote hospitals within the telemedicine network.

A quantitative EEG index for the recognition of arterial ischemic stroke in children.

OBJECTIVE: To describe and assess performance of the Correlate Of Injury to the Nervous system (COIN) index, a quantitative electroencephalography (EEG) metric designed to identify areas of cerebral dysfunction concerning for stroke. METHODS: Case-control study comparing continuous EEG data from children with acute ischemic stroke to children without stroke, with or without encephalopathy. COIN is calculated continuously and compares EEG power between cerebral hemispheres. Stroke relative infarct volume (RIV) was calculated from quantitative neuroimaging analysis. Significance was determined using a two-sample t-test. Sensitivity, specificity, and accuracy were measured using logistic regression. RESULTS: Average COIN values were -34.7 in the stroke cohort compared to -9.5 in controls without encephalopathy (p = 0.003) and -10.5 in controls with encephalopathy (p = 0.006). The optimal COIN cutoff to discriminate stroke from controls was -15 in non-encephalopathic and -18 in encephalopathic controls with >92% accuracy in strokes with RIV > 5%. A COIN cutoff of -20 allowed discrimination between strokes with <5% and >5% RIV (p = 0.027). CONCLUSIONS: We demonstrate that COIN can identify children with acute ischemic stroke. SIGNIFICANCE: COIN may be a valuable tool for stroke identification in children. Additional studies are needed to determine utility as a monitoring technique for children at risk for stroke.

The International Cardiac Arrest Research (I-CARE) Consortium Electroencephalography Database.

Objective: To develop a harmonized multicenter clinical and electroencephalography (EEG) database for acute hypoxic-ischemic brain injury research involving patients with cardiac arrest. Design: Multicenter cohort, partly prospective and partly retrospective. Setting: Seven academic or teaching hospitals from the U.S. and Europe. Patients: Individuals aged 16 or older who were comatose after return of spontaneous circulation following a cardiac arrest who had continuous EEG monitoring were included. Interventions: not applicable. Measurements and Main Results: Clinical and EEG data were harmonized and stored in a common Waveform Database (WFDB)-compatible format. Automated spike frequency, background continuity, and artifact detection on EEG were calculated with 10 second resolution and summarized hourly. Neurological outcome was determined at 3-6 months using the best Cerebral Performance Category (CPC) scale. This database includes clinical and 56,676 hours (3.9 TB) of continuous EEG data for 1,020 patients. Most patients died (N=603, 59%), 48 (5%) had severe neurological disability (CPC 3 or 4), and 369 (36%) had good functional recovery (CPC 1-2). There is significant variability in mean EEG recording duration depending on the neurological outcome (range 53-102h for CPC 1 and CPC 4, respectively). Epileptiform activity averaging 1 Hz or more in frequency for at least one hour was seen in 258 (25%) patients (19% for CPC 1-2 and 29% for CPC 3-5). Burst suppression was observed for at least one hour in 207 (56%) and 635 (97%) patients with CPC 1-2 and CPC 3-5, respectively. Conclusions: The International Cardiac Arrest Research (I-CARE) consortium database provides a comprehensive real-world clinical and EEG dataset for neurophysiology research of comatose patients after cardiac arrest. This dataset covers the spectrum of abnormal EEG patterns after cardiac arrest, including epileptiform patterns and those in the ictal-interictal continuum.

Neurophysiology State Dynamics Underlying Acute Neurologic Recovery After Cardiac Arrest.

BACKGROUND AND OBJECTIVES: Epileptiform activity and burst suppression are neurophysiology signatures reflective of severe brain injury after cardiac arrest. We aimed to delineate the evolution of coma neurophysiology feature ensembles associated with recovery from coma after cardiac arrest. METHODS: Adults in acute coma after cardiac arrest were included in a retrospective database involving 7 hospitals. The combination of 3 quantitative EEG features (burst suppression ratio [BSup], spike frequency [SpF], and Shannon entropy [En]) was used to define 5 distinct neurophysiology states: epileptiform high entropy (EHE: SpF ≥4 per minute and En ≥5); epileptiform low entropy (ELE: SpF ≥4 per minute and <5 En); nonepileptiform high entropy (NEHE: SpF <4 per minute and ≥5 En); nonepileptiform low entropy (NELE: SpF <4 per minute and <5 En), and burst suppression (BSup ≥50% and SpF <4 per minute). State transitions were measured at consecutive 6-hour blocks between 6 and 84 hours after return of spontaneous circulation. Good neurologic outcome was defined as best cerebral performance category 1-2 at 3-6 months. RESULTS: One thousand thirty-eight individuals were included (50,224 hours of EEG), and 373 (36%) had good outcome. Individuals with EHE state had a 29% rate of good outcome, while those with ELE had 11%. Transitions out of an EHE or BSup state to an NEHE state were associated with good outcome (45% and 20%, respectively). No individuals with ELE state lasting >15 hours had good recovery. DISCUSSION: Transition to high entropy states is associated with an increased likelihood of good outcome despite preceding epileptiform or burst suppression states. High entropy may reflect mechanisms of resilience to hypoxic-ischemic brain injury.

Correction: Expert-augmented automated machine learning optimizes hemodynamic predictors of spinal cord injury outcome.

[This corrects the article DOI: 10.1371/journal.pone.0265254.].

Geometric and Morphologic Features of Ruptured Intracranial Aneurysms Associated with Methamphetamine Use.

BACKGROUND: Methamphetamine (MA) use is associated with poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). MA exerts both hemodynamic and inflammatory effects, but whether these manifest with altered intracranial aneurysm (IA) remodeling is unknown. The objective of this study was to compare IA geometric and morphologic features in patients with and without MA detected on urine toxicology (Utox) at presentation. METHODS: We retrospectively reviewed 160 consecutive patients with SAH and Utox at time of admission. Geometric-morphologic IA characteristics were assessed by blinded neuroradiologists. Studied features were maximum sac diameter, location, size, ellipsoid volume, aspect ratio, size ratio, volume: neck ratio, dome: neck ratio, bottleneck factor, morphology (saccular, fusiform/dissecting, blister, mycotic), and presence of bleb, vasculopathy, or additional unruptured IA. RESULTS: Of 139/160 patients with aSAH, 23/139 (16.5%) were Utox MA+. There was no difference in aneurysm subtype frequency, presence of bleb, vasculopathy, or presence of an additional (unruptured) aneurysm with a trend toward posterior circulation location and higher Hunt and Hess grade (P = 0.09 for both) in the MA+ group. Maximum IA sac diameter, ellipsoid volume, dome-neck ratio, and size ratio were similar between groups. Only the aspect ratio (AR) differed between groups (MA+ = 2.20 vs. MA- = 1.74, P = 0.02). The AR remained a significant predictor of Utox MA+ in a multiple logistic regression analysis (odds ratio 1.87, 95% confidence interval 1.06-3.39). CONCLUSIONS: Active use of methamphetamine is independently associated with larger AR in patients with ruptured IA. This may indicate hazardous remodeling due to hemodynamic and/or inflammatory changes.

High incidence of epileptiform activity in adults undergoing extracorporeal membrane oxygenation.

OBJECTIVE: The prevalence of seizures and other types of epileptiform brain activity in patients undergoing extracorporeal membrane oxygenation (ECMO) is unknown. We aimed to estimate the prevalence of seizures and ictal-interictal continuum patterns in patients undergoing electroencephalography (EEG) during ECMO. METHODS: Retrospective review of a prospective ECMO registry from 2011-2018 in a university-affiliated academic hospital. Adult subjects who had decreased level of consciousness and underwent EEG monitoring for seizure screening were included. EEG classification followed the American Clinical Neurophysiology Society criteria. Poor neurological outcome was defined as a Cerebral Performance Category of 3-5 at hospital discharge. RESULTS: Three hundred and ninety-five subjects had ECMO, and one hundred and thirteen (28.6%) had EEG monitoring. Ninety-two (23.3%) subjects had EEG performed during ECMO and were included in the study (average EEG duration 54 h). Veno-arterial ECMO was the most common cannulation strategy (83%) and 26 (28%) subjects had extracorporeal cardiopulmonary resuscitation. Fifty-eight subjects (63%) had epileptiform activity or ictal-interictal continuum patterns on EEG, including three (3%) subjects with nonconvulsive status epilepticus, 33 (36%) generalized periodic discharges, and 4 (5%) lateralized periodic discharges. Comparison between subjects with or without epileptiform activity showed comparable in-hospital mortality (57% vs. 47%, p = 0.38) and poor neurological outcome (and 56% and 36%, p = 0.23). Twenty-seven subjects (33%) had acute neuroimaging abnormalities (stroke N = 21). CONCLUSIONS: Seizures and ictal-interictal continuum patterns are commonly observed in patients managed with ECMO. Further studies are needed to evaluate whether epileptiform activity is an actionable target for interventions. SIGNIFICANCE: Epileptiform and ictal-interictal continuum abnormalities are frequently observed in patients supported with ECMO undergoing EEG monitoring.