Cognitive Motor Dissociation: Gap Analysis and Future Directions.

BACKGROUND: Patients with disorders of consciousness who are behaviorally unresponsive may demonstrate volitional brain responses to motor imagery or motor commands detectable on functional magnetic resonance imaging or electroencephalography. This state of cognitive motor dissociation (CMD) may have prognostic significance. METHODS: The Neurocritical Care Society's Curing Coma Campaign identified an international group of experts who convened in a series of monthly online meetings between September 2021 and April 2023 to examine the science of CMD and identify key knowledge gaps and unmet needs. RESULTS: The group identified major knowledge gaps in CMD research: (1) lack of information about patient experiences and caregiver accounts of CMD, (2) limited epidemiological data on CMD, (3) uncertainty about underlying mechanisms of CMD, (4) methodological variability that limits testing of CMD as a biomarker for prognostication and treatment trials, (5) educational gaps for health care personnel about the incidence and potential prognostic relevance of CMD, and (6) challenges related to identification of patients with CMD who may be able to communicate using brain-computer interfaces. CONCLUSIONS: To improve the management of patients with disorders of consciousness, research efforts should address these mechanistic, epidemiological, bioengineering, and educational gaps to enable large-scale implementation of CMD assessment in clinical practice.

Resting-State EEG Signature of Early Consciousness Recovery in Comatose Patients with Traumatic Brain Injury.

BACKGROUND: Resting-state electroencephalography (rsEEG) is usually obtained to assess seizures in comatose patients with traumatic brain injury (TBI). We aim to investigate rsEEG measures and their prediction of early recovery of consciousness in patients with TBI. METHODS: This is a retrospective study of comatose patients with TBI who were admitted to a trauma center (October 2013 to January 2022). Demographics, basic clinical data, imaging characteristics, and EEGs were collected. We calculated the following using 10-min rsEEGs: power spectral density, permutation entropy (complexity measure), weighted symbolic mutual information (wSMI, global information sharing measure), Kolmogorov complexity (Kolcom, complexity measure), and heart-evoked potentials (the averaged EEG signal relative to the corresponding QRS complex on electrocardiography). We evaluated the prediction of consciousness recovery before hospital discharge using clinical, imaging, and rsEEG data via a support vector machine. RESULTS: We studied 113 of 134 (84%) patients with rsEEGs. A total of 73 (65%) patients recovered consciousness before discharge. Patients who recovered consciousness were younger (40 vs. 50 years, p = 0.01). Patients who recovered also had higher Kolcom (U = 1688, p = 0.01), increased beta power (U = 1,652 p = 0.003) with higher variability across channels (U = 1534, p = 0.034) and epochs (U = 1711, p = 0.004), lower delta power (U = 981, p = 0.04), and higher connectivity across time and channels as measured by wSMI in the theta band (U = 1636, p = 0.026; U = 1639, p = 0.024) than those who did not recover. The area under the receiver operating characteristic curve for rsEEG was higher than that for clinical data (using age, motor response, pupil reactivity) and higher than that for the Marshall computed tomography classification (0.69 vs. 0.66 vs. 0.56, respectively; p < 0.001). CONCLUSIONS: We describe the rsEEG signature in recovery of consciousness prior to discharge in comatose patients with TBI. rsEEG measures performed modestly better than the clinical and imaging data in predicting recovery.

Impact of Time to Treatment on Endovascular Thrombectomy Outcomes in the Early Versus Late Treatment Time Windows.

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows. METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and categorized into early window treated (OTP ≤6 hours) and late window treated (OTP >6 and ≤24 hours). Association between OTP and favorable discharge outcomes (independent ambulation, discharge home and to acute rehabilitation facility) as well as symptomatic intracerebral hemorrhage and in-hospital mortality were examined using multilevel-multivariable analysis with generalized estimating equations. RESULTS: Among 8002 EVT patients (50.9% women; median age [±SD], 71.5 [±14.5] years; 61.7% White, 17.5% Black, and 21% Hispanic), 34.2% were treated in the late time window. Among all EVT patients, 32.4% were discharged home, 23.5% to rehabilitation facility, 33.7% ambulated independently at discharge, 5.1% had symptomatic intracerebral hemorrhage, and 9.2% died. As compared with the early window, treatment in the late window was associated with lower odds of independent ambulation (odds ratio [OR], 0.78 [0.67-0.90]) and discharge home (OR, 0.71 [0.63-0.80]). For every 60-minute increase in OTP, the odds of independent ambulation reduced by 8% (OR, 0.92 [0.87-0.97]; P<0.001) and 1% (OR, 0.99 [0.97-1.02]; P=0.5) and the odds of discharged home reduced by 10% (OR, 0.90 [0.87-0.93]; P<0.001) and 2% (OR, 0.98 [0.97-1.00]; P=0.11) in the early and late windows, respectively. CONCLUSIONS: In routine practice, just over one-third of EVT-treated patients independently ambulate at discharge and only half are discharged to home/rehabilitation facility. Increased time from symptom onset to treatment is significantly associated with lower chance of independent ambulation and ability to be discharged home after EVT in the early time window.

Determinants and Temporal Trends of Dual Antiplatelet Therapy After Mild Noncardioembolic Stroke.

BACKGROUND: Short-term dual antiplatelet therapy (DAPT) reduces early stroke recurrence after mild noncardioembolic ischemic stroke (NCIS). We aim to evaluate temporal trends and determinants of DAPT prescription after mild NCIS in the Florida Stroke Registry, a statewide registry across Get With The Guidelines-Stroke participating hospitals. METHODS: In this cross-sectional analysis of a cohort study, we included patients with mild NCIS (National Institutes of Health Stroke Scale score ≤3) who were potentially eligible for DAPT across 168 Florida Stroke Registry participating hospitals between January 2010 and September 2022. Using antiplatelet prescription as the dependent variable (DAPT versus single antiplatelet therapy), we fit logistic regression models adjusted for patient-related factors, hospital-related factors, clinical presentation, vascular risk factors, and ischemic stroke subtype, to obtain adjusted odds ratios (aORs) with 95% CIs. RESULTS: From 283 264 Florida Stroke Registry ischemic stroke patients during the study period, 109 655 NCIS were considered eligible. Among these, 37 058 patients with National Institutes of Health Stroke Scale score >3 were excluded, resulting in a sample of 72 597 mild NCIS (mean age 68±14 years; female 47.3%). Overall, 24 693 (34.0%) patients with mild NCIS were discharged on DAPT and 47 904 (66.0%) on single antiplatelet therapy. DAPT prescription increased from 25.7% in 2010 to 52.8% in 2022 (ß/year 2.5% [95% CI, 1.5%-3.4%]). Factors associated with DAPT prescription were premorbid antiplatelet therapy (aOR, 4.66 [95% CI, 2.20-9.88]), large-artery atherosclerosis (aOR, 1.68 [95% CI, 1.43-1.97]), diabetes (aOR, 1.29 [95% CI, 1.13-1.47]), and hyperlipidemia (aOR, 1.24 [95% CI, 1.10-1.39]), whereas female sex (aOR, 0.83 [95% CI, 0.75-0.93]), being non-Hispanic Black patients (compared with non-Hispanic White patients; aOR, 0.78 [95% CI, 0.68-0.90]), admission to a Thrombectomy-capable Stroke Center (compared with Comprehensive Stroke Center; aOR, 0.78 [95% CI, 0.66-0.92]), time-to-presentation 1 to 7 days from last seen well (compared with <24 h; aOR, 0.86 [95% CI, 0.76-0.96]), and small-vessel disease stroke (aOR, 0.81 [95% CI, 0.72-0.94]) were associated with not receiving DAPT at discharge. CONCLUSIONS: Despite a temporal trend increase in DAPT prescription after mild NCIS, we found substantial underutilization of evidence-based DAPT associated with significant disparities in stroke care.

Nationally Certified Stroke Centers Outperform Self-Attested Stroke Centers in the Florida Stroke Registry.

BACKGROUND: The Florida Stroke Act, signed into law in 2004, set criteria for Comprehensive Stroke Centers (CSC). For a set time period, Florida hospitals were permitted to either receive national certification (NC) or could self-attest (SA) as fulfilling CSC criteria. The aim of this project was to evaluate the quality of ischemic stroke care in NC versus SA stroke centers in Florida, using well-known, guideline-driven ischemic stroke outcome metrics. METHODS: A total of 37 CSCs (74% of Florida CSCs) in the Florida Stroke Registry from January 2013 through December 2018 were analyzed, including 19 SA CSCs and 18 NC (13 CSCs and 5 Thrombectomy-Capable Stroke Center). Hospital- and patient-level characteristics and stroke metrics were evaluated, adjusting for demographics, medical comorbidities, and stroke severity. RESULTS: A total of 78 424 acute ischemic stroke cases, 36 089 from SA CSCs and 42 335 from NC CSC/Thrombectomy-Capable Stroke Centers were analyzed. NC centers had older patients (73 [61-83] versus 71 [60-81]; P<0.001) with more severe strokes (median National Institutes of Health Stroke Scale score of 5 versus 4; P<0.001). NC had higher intravenous tissue-type plasminogen activator utilization (15% versus 13%; P<0.001), endovascular treatment (10% versus 7%; P<0.001) and faster median door-to-computed tomography (23 minutes [11-73] versus 31 [12-78]; P<0.001), door-to-needle (37 minutes [26-50] versus 45 [34-58]; P<0.001) and door-to-puncture times (77 minutes [50-113] versus 93 [62-140]; P<0.001). In adjusted analysis, patients arriving to NC hospitals by 3 hours were more likely to get intravenous tissue-type plasminogen activator in the 3- to 4.5-hour window (adjusted odds ratio, 1.87 [95% CI, 1.30-2.68]; P=0.001) and more likely to be treated with intravenous tissue-type plasminogen activator within 45 minutes (adjusted odds ratio, 1.61 [95% CI, 1.04-2.50]; P=0.04) compared with SA CSCs. CONCLUSIONS: Among Florida-Stroke Registry CSCs, acute ischemic stroke performance and treatment measures at NC centers are superior to SA CSCs. These findings have implications for stroke systems of care in Florida and support legislation updates requiring NC and removal of SA claims.

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.

Quantitative epileptiform burden and electroencephalography background features predict post-traumatic epilepsy.

BACKGROUND: Post-traumatic epilepsy (PTE) is a severe complication of traumatic brain injury (TBI). Electroencephalography aids early post-traumatic seizure diagnosis, but its optimal utility for PTE prediction remains unknown. We aim to evaluate the contribution of quantitative electroencephalograms to predict first-year PTE (PTE1). METHODS: We performed a multicentre, retrospective case-control study of patients with TBI. 63 PTE1 patients were matched with 63 non-PTE1 patients by admission Glasgow Coma Scale score, age and sex. We evaluated the association of quantitative electroencephalography features with PTE1 using logistic regressions and examined their predictive value relative to TBI mechanism and CT abnormalities. RESULTS: In the matched cohort (n=126), greater epileptiform burden, suppression burden and beta variability were associated with 4.6 times higher PTE1 risk based on multivariable logistic regression analysis (area under the receiver operating characteristic curve, AUC (95% CI) 0.69 (0.60 to 0.78)). Among 116 (92%) patients with available CT reports, adding quantitative electroencephalography features to a combined mechanism and CT model improved performance (AUC (95% CI), 0.71 (0.61 to 0.80) vs 0.61 (0.51 to 0.72)). CONCLUSIONS: Epileptiform and spectral characteristics enhance covariates identified on TBI admission and CT abnormalities in PTE1 prediction. Future trials should incorporate quantitative electroencephalography features to validate this enhancement of PTE risk stratification models.

Posttraumatic Stress Symptoms Among COVID-19 Survivors After Hospitalization.

OBJECTIVE: Limited data are available on posttraumatic stress symptoms (PTSS) among COVID-19 survivors. This study aimed to contribute to this knowledge base. METHODS: PTSS among COVID-19 survivors who had been hospitalized were investigated. Patients were identified as COVID-19 positive at hospital admission. COVID-19 survivors were surveyed with the Posttraumatic Stress Disorder Checklist (PCL-5) between March and October 2020 at 5- and 12-month postdischarge follow-up points. RESULTS: Of 411 patients, 331 (81%) survived to hospital discharge. Of these survivors, 83 (25%) completed the PCL-5 at the 5-month follow-up. Of those patients, 12 (14%) screened positive for PTSS. At the 12-month follow-up, four of eight patients remained PTSS positive. Mean age of follow-up participants was 62±15 years; 47% were women, 65% were White, and 63% were Hispanic. PTSS-positive patients were predominantly non-White (67% vs. 30%, p=0.02), and although the differences were not statistically significant, these patients tended to be younger (56 vs. 63 years, p=0.08) and have shorter intensive care unit stays (2.0 vs. 12.5 days, p=0.06). PTSS-positive and PTSS-negative groups did not differ significantly in prehospitalization neurological diagnoses (11% vs. 8%), psychiatric diagnoses (17% vs. 21%), and intensive care admission status (25% vs. 25%). More patients in the PTSS-positive group had returned to the emergency department (50% vs. 14%, p<0.01) and reported fatigue at follow-up (100% vs. 42%, p<0.001). In the multivariate logistic regression model, non-White race (OR=11, 95% CI=2-91) and returning to the emergency department (OR=19, 95% CI=3-252) were associated with PTSS-positive status. CONCLUSION: PTSS were twice as common among hospitalized COVID-19 survivors than among those in the general population.

Preexisting Depression and Ambulatory Status After Stroke: Florida-Puerto Rico Collaboration to Reduce Stroke Disparities.

OBJECTIVE: Stroke is a global public health burden, and therefore it is critical to identify modifiable risk factors to reduce stroke incidence and improve outcomes. Depression is such a risk factor; however, the association between preexisting depression and stroke outcomes, such as independent ambulation, is not well studied, especially among racial-ethnic minority groups. To address this gap in the literature, effects of preexisting depression on ambulatory status at hospital discharge after stroke were evaluated among individuals participating in the racially and ethnically diverse Florida-Puerto Rico Collaboration to Reduce Stroke Disparities project. METHODS: Data were analyzed from a total of 42,031 ischemic stroke patients, who were independently ambulatory prior to their stroke, after discharge from 84 hospitals between 2014 and 2017. Preexisting depression was confirmed by medical history or antidepressant medication use. Multilevel multivariate logistic regression analyses were used to assess the association of preexisting depression with independent ambulation at hospital discharge. Effects of sex and race-ethnicity on this association were examined. RESULTS: Of 42,031 participants (mean±SD age=70.4±14.2 years; 48% were female; race-ethnicity: 16% Black, 12% Hispanic living in Florida, and 7% Hispanic living in Puerto Rico), 6,379 (15%) had preexisting depression. Compared with participants without depression, those with preexisting depression were older, were more likely to be female and non-Hispanic White, and had a greater burden of vascular risk factors or comorbid conditions. Independent ambulation at hospital discharge was less frequent among women, Black participants, and individuals with vascular risk factors or comorbid conditions. In multivariate models, preexisting depression decreased the likelihood of independent ambulation at discharge (odds ratio=0.88, 95% CI=0.81, 0.97). No interactions were found between preexisting depression and race-ethnicity or sex. CONCLUSIONS: Preexisting depression was independently associated with dependent ambulation at hospital discharge after stroke, regardless of sex and race-ethnicity. Treating depression may contribute to primary stroke prevention and could improve ambulatory status at discharge.

Evaluating salvage electroconvulsive therapy for the treatment of prolonged super refractory status epilepticus: A case series.

BACKGROUND AND OBJECTIVES: Clinicians have treated super refractory status epilepticus (SRSE) with electroconvulsive therapy (ECT); however, data supporting the practice are scant and lack rigorous evaluation of continuous electroencephalogram (cEEG) changes related to therapy. This study aims to describe a series of patients with SRSE treated at our institution with ECT and characterize cEEG changes using a blinded review process. METHODS: We performed a single-center retrospective study of consecutive patients admitted for SRSE and treated with ECT from January 2014 to December 2022. Our primary outcome was the resolution of SRSE. Secondary outcomes included changes in ictal-interictal EEG patterns, anesthetic burden, treatment-associated adverse events, and changes in clinical examination. cEEG was reviewed pre- and post-ECT by blinded epileptologists. RESULTS: Ten patients underwent treatment with ECT across 11 admissions (8 female, median age 57 years). At the time of ECT initiation, nine patients had ongoing SRSE while two had highly ictal patterns and persistent encephalopathy following anesthetic wean, consistent with late-stage SRSE. Super-refractory status epilepticus resolution occurred with a median time to cessation of 4 days (interquartile range [IQR]: 3-9 days) following ECT initiation. Background continuity improved in five patients and periodic discharge frequency decreased in six. There was a decrease in anesthetic use following the completion of ECT and an improvement in neurological exams. There were no associated adverse events. DISCUSSION: In our cohort, ECT was associated with improvement of ictal-interictal patterns on EEG, and resolution of SRSE, and was not associated with serious adverse events. Further controlled studies are needed.

Common Data Elements for Disorders of Consciousness: Recommendations from the Electrophysiology Working Group.

BACKGROUND: Electroencephalography (EEG) has long been recognized as an important tool in the investigation of disorders of consciousness (DoC). From inspection of the raw EEG to the implementation of quantitative EEG, and more recently in the use of perturbed EEG, it is paramount to providing accurate diagnostic and prognostic information in the care of patients with DoC. However, a nomenclature for variables that establishes a convention for naming, defining, and structuring data for clinical research variables currently is lacking. As such, the Neurocritical Care Society's Curing Coma Campaign convened nine working groups composed of experts in the field to construct common data elements (CDEs) to provide recommendations for DoC, with the main goal of facilitating data collection and standardization of reporting. This article summarizes the recommendations of the electrophysiology DoC working group. METHODS: After assessing previously published pertinent CDEs, we developed new CDEs and categorized them into "disease core," "basic," "supplemental," and "exploratory." Key EEG design elements, defined as concepts that pertained to a methodological parameter relevant to the acquisition, processing, or analysis of data, were also included but were not classified as CDEs. RESULTS: After identifying existing pertinent CDEs and developing novel CDEs for electrophysiology in DoC, variables were organized into a framework based on the two primary categories of resting state EEG and perturbed EEG. Using this categorical framework, two case report forms were generated by the working group. CONCLUSIONS: Adherence to the recommendations outlined by the electrophysiology working group in the resting state EEG and perturbed EEG case report forms will facilitate data collection and sharing in DoC research on an international level. In turn, this will allow for more informed and reliable comparison of results across studies, facilitating further advancement in the realm of DoC research.

Big data and predictive analytics in neurocritical care.

PURPOSE OF REVIEW: To describe predictive data and workflow in the intensive care unit when managing neurologically ill patients. RECENT FINDINGS: In the era of Big Data in medicine, intensive critical care units are data-rich environments. Neurocritical care adds another layer of data with advanced multimodal monitoring to prevent secondary brain injury from ischemia, tissue hypoxia, and a cascade of ongoing metabolic events. A step closer toward personalized medicine is the application of multimodal monitoring of cerebral hemodynamics, bran oxygenation, brain metabolism, and electrophysiologic indices, all of which have complex and dynamic interactions. These data are acquired and visualized using different tools and monitors facing multiple challenges toward the goal of the optimal decision support system. In this review, we highlight some of the predictive data used to diagnose, treat, and prognosticate the neurologically ill patients. We describe information management in neurocritical care units including data acquisition, wrangling, analysis, and visualization.

Quantitative EEG-Based Seizure Estimation in Super-Refractory Status Epilepticus.

BACKGROUND: The objective of this study was to evaluate the accuracy of seizure burden in patients with super-refractory status epilepticus (SRSE) by using quantitative electroencephalography (qEEG). METHODS: EEG recordings from 69 patients with SRSE (2009-2019) were reviewed and annotated for seizures by three groups of reviewers: two board-certified neurophysiologists using only raw EEG (gold standard), two neurocritical care providers with substantial experience in qEEG analysis (qEEG experts), and two inexperienced qEEG readers (qEEG novices) using only a qEEG trend panel. RESULTS: Raw EEG experts identified 35 (51%) patients with seizures, accounting for 2950 seizures (3,126 min). qEEG experts had a sensitivity of 93%, a specificity of 61%, a false positive rate of 6.5 per day, and good agreement (κ = 0.64) between both qEEG experts. qEEG novices had a sensitivity of 98.5%, a specificity of 13%, a false positive rate of 15 per day, and fair agreement (κ = 0.4) between both qEEG novices. Seizure burden was not different between the qEEG experts and the gold standard (3,257 vs. 3,126 min), whereas qEEG novices reported higher burden (6066 vs. 3126 min). CONCLUSIONS: Both qEEG experts and novices had a high sensitivity but a low specificity for seizure detection in patients with SRSE. qEEG could be a useful tool for qEEG experts to estimate seizure burden in patients with SRSE.

Predicting Shunt Dependency from the Effect of Cerebrospinal Fluid Drainage on Ventricular Size.

BACKGROUND: Prolonged external ventricular drainage (EVD) in patients with subarachnoid hemorrhage (SAH) leads to morbidity, whereas early removal can have untoward effects related to recurrent hydrocephalus. A metric to help determine the optimal time for EVD removal or ventriculoperitoneal shunt (VPS) placement would be beneficial in preventing the prolonged, unnecessary use of EVD. This study aimed to identify whether dynamics of cerebrospinal fluid (CSF) biometrics can temporally predict VPS dependency after SAH. METHODS: This was a retrospective analysis of a prospective, single-center, observational study of patients with aneurysmal SAH who required EVD placement for hydrocephalus. Patients were divided into VPS-dependent (VPS+) and non-VPS dependent groups. We measured the bicaudate index (BCI) on all available computed tomography scans and calculated the change over time (ΔBCI). We analyzed the relationship of ΔBCI with CSF output by using Pearson's correlation. A k-nearest neighbor model of the relationship between ΔBCI and CSF output was computed to classify VPS. RESULTS: Fifty-eight patients met inclusion criteria. CSF output was significantly higher in the VPS+ group in the 7 days post EVD placement. There was a negative correlation between delta BCI and CSF output in the VPS+ group (negative delta BCI means ventricles become smaller) and a positive correlation in the VPS- group starting from days four to six after EVD placement (p < 0.05). A weighted k-nearest neighbor model for classification had a sensitivity of 0.75, a specificity of 0.70, and an area under the receiver operating characteristic curve of 0.80. CONCLUSIONS: The correlation of ΔBCI and CSF output is a reliable intraindividual biometric for VPS dependency after SAH as early as days four to six after EVD placement. Our machine learning model leverages this relationship between ΔBCI and cumulative CSF output to predict VPS dependency. Early knowledge of VPS dependency could be studied to reduce EVD duration in many centers (intensive care unit length of stay).

Withdrawal of Life-Sustaining Treatment Mediates Mortality in Patients With Intracerebral Hemorrhage With Impaired Consciousness.

BACKGROUND AND PURPOSE: Impaired level of consciousness (LOC) on presentation at hospital admission in patients with intracerebral hemorrhage (ICH) may affect outcomes and the decision to withhold or withdraw life-sustaining treatment (WOLST). METHODS: Patients with ICH were included across 121 Florida hospitals participating in the Florida Stroke Registry from 2010 to 2019. We studied the effect of LOC on presentation on in-hospital mortality (primary outcome), WOLST, ambulation status on discharge, hospital length of stay, and discharge disposition. RESULTS: Among 37 613 cases with ICH (mean age 71, 46% women, 61% White, 20% Black, 15% Hispanic), 12 272 (33%) had impaired LOC at onset. Compared with cases with preserved LOC, patients with impaired LOC were older (72 versus 70 years), more women (49% versus 45%), more likely to have aphasia (38% versus 16%), had greater ICH score (3 versus 1), greater risk of WOLST (41% versus 18%), and had an increased in-hospital mortality (32% versus 12%). In the multivariable-logistic regression with generalized estimating equations accounting for basic demographics, comorbidities, ICH severity, hospital size and teaching status, impaired LOC was associated with greater mortality (odds ratio, 3.7 [95% CI, 3.1-4.3], P<0.0001) and less likely discharged home or to rehab (odds ratio, 0.3 [95% CI, 0.3-0.4], P<0.0001). WOLST significantly mediated the effect of impaired LOC on mortality (mediation effect, 190 [95% CI, 152-229], P<0.0001). Early WOLST (<2 days) occurred among 51% of patients. A reduction in early WOLST was observed in patients with impaired LOC after the 2015 American Heart Association/American Stroke Association ICH guidelines recommending aggressive treatment and against early do-not-resuscitate. CONCLUSIONS: In this large multicenter stroke registry, a third of ICH cases presented with impaired LOC. Impaired LOC was associated with greater in-hospital mortality and worse disposition at discharge, largely influenced by early decision to withhold or WOLST.

Dynamic Detection of Delayed Cerebral Ischemia: A Study in 3 Centers.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage negatively impacts long-term recovery but is often detected too late to prevent damage. We aim to develop hourly risk scores using routinely collected clinical data to detect DCI. METHODS: A DCI classification model was trained using vital sign measurements (heart rate, blood pressure, respiratory rate, and oxygen saturation) and demographics routinely collected for clinical care. Twenty-two time-varying physiological measures were computed including mean, SD, and cross-correlation of heart rate time series with each of the other vitals. Classification was achieved using an ensemble approach with L2-regularized logistic regression, random forest, and support vector machines models. Classifier performance was determined by area under the receiver operating characteristic curves and confusion matrices. Hourly DCI risk scores were generated as the posterior probability at time t using the Ensemble classifier on cohorts recruited at 2 external institutions (n=38 and 40). RESULTS: Three hundred ten patients were included in the training model (median, 54 years old [interquartile range, 45-65]; 80.2% women, 28.4% Hunt and Hess scale 4-5, 38.7% Modified Fisher Scale 3-4); 101 (33%) developed DCI with a median onset day 6 (interquartile range, 5-8). Classification accuracy before DCI onset was 0.83 (interquartile range, 0.76-0.83) area under the receiver operating characteristic curve. Risk scores applied to external institution datasets correctly predicted 64% and 91% of DCI events as early as 12 hours before clinical detection, with 2.7 and 1.6 true alerts for every false alert. CONCLUSIONS: An hourly risk score for DCI derived from routine vital signs may have the potential to alert clinicians to DCI, which could reduce neurological injury.

Prone Position Ventilation in Neurologically Ill Patients: A Systematic Review and Proposed Protocol.

OBJECTIVES: Prone positioning has been shown to be a beneficial adjunctive supportive measure for patients who develop acute respiratory distress syndrome. Studies have excluded patients with reduced intracranial compliance, whereby patients with concomitant neurologic diagnoses and acute respiratory distress syndrome have no defined treatment algorithm or recommendations for management. In this study, we aim to determine the safety and feasibility of prone positioning in the neurologically ill patients. DESIGN AND SETTING: A systematic review of the literature, performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses 2009 guidelines, yielded 10 articles for analysis. Using consensus from these articles, in combination with review of multi-institutional proning protocols for patients with nonneurologic conditions, a proning protocol for patients with intracranial pathology and concomitant acute respiratory distress syndrome was developed. MEASUREMENTS AND MAIN RESULTS: Among 10 studies included in the final analysis, we found that prone positioning is safe and feasible in the neurologically ill patients with acute respiratory distress syndrome. Increased intracranial pressure and compromised cerebral perfusion pressure may occur with prone positioning. We propose a prone positioning protocol for the neurologically ill patients who require frequent neurologic examinations and intracranial monitoring. CONCLUSIONS: Although elevations in intracranial pressure and reductions in cerebral perfusion pressure do occur during proning, they may not occur to a degree that would warrant exclusion of prone ventilation as a treatment modality for patients with acute respiratory distress syndrome and concomitant neurologic diagnoses. In cases where intracranial pressure, cerebral perfusion pressure, and brain tissue oxygenation can be monitored, prone position ventilation should be considered a safe and viable therapy.

Use of Clustering to Investigate Changes in Intracranial Pressure Waveform Morphology in Patients with Ventriculitis.

OBJECTIVE: This study aimed to examine whether changes in intracranial pressure (ICP) waveform morphologies can be used as a biomarker for early detection of ventriculitis. METHODS: Consecutive patients (N = 1653) were prospectively enrolled in a hemorrhage outcomes study from 2006 to 2018. Of these, 435 patients (26%) required external ventricular drains (EVDs) and 76 (17.5% of those with EVDs) had ventriculitis treated with antibiotics. Nineteen patients (25% of those with ventriculitis) showed culture-positive cerebrospinal fluid (CSF) and were included in the present analysis. CSF was routinely cultured three times per week and additionally if infection was suspected. EVDs were left open for drainage, with ICP assessed hourly by clamping. Using wavelet analysis, we extracted uninterrupted segments of ICP waveforms. We extracted dominant pulses from continuous high-resolution data, using morphological clustering analysis of intracranial pressure (MOCAIP). Then we applied k-means clustering, using the dynamic time warping distance to obtain morphologically similar groupings. Finally, metaclusters and further-split clusters (when equipoise existed) were categorized for broad comparison by clinician consensus. RESULTS: We extracted 275,911 dominant pulses from 459.9 h of EVD data. Of these, 112,898 pulses (40.9%) occurred before culture positivity, 41,300 pulses (15.0%) occurred during culture positivity, and 121,713 pulses (44.1%) occurred after it. K-means identified 20 clusters, which were further grouped into metaclusters: tri-/biphasic, single-peak, and artifactual waveforms. Prior to ventriculitis, 61.8% of dominant pulses were tri-/biphasic; this percentage reduced to 22.6% during ventriculitis and 28.4% after it (p < 0.0001). One day before the first positive cultures were collected, the distribution of metaclusters changed to include more single-peak and artifactual ICP waveforms (p < 0.0001). CONCLUSION: The distribution of ICP waveform morphology changes significantly prior to clinical diagnosis of ventriculitis and may be a potential biomarker.

Structure and Outcomes of Educational Programs for Training Non-electroencephalographers in Performing and Screening Adult EEG: A Systematic Review.

OBJECTIVE: To qualitatively and quantitatively summarize curricula, teaching methods, and effectiveness of educational programs for training bedside care providers (non-experts) in the performance and screening of adult electroencephalography (EEG) for nonconvulsive seizures and other patterns. METHODS: PRISMA methodological standards were followed. MEDLINE, EMBASE, Cochrane, CINAHL, WOS, Scopus, and MedEdPORTAL databases were searched from inception until February 26, 2020 with no restrictions. Abstract and full-text review was completed in duplicate. Studies were included if they were original research; involved non-experts performing, troubleshooting, or screening adult EEG; and provided qualitative descriptions of curricula and teaching methods and/or quantitative assessment of non-experts (vs gold standard EEG performance by neurodiagnostic technologists or interpretation by neurophysiologists). Data were extracted in duplicate. A content analysis and a meta-narrative review were performed. RESULTS: Of 2430 abstracts, 35 studies were included. Sensitivity and specificity of seizure identification varied from 38 to 100% and 65 to 100% for raw EEG; 40 to 93% and 38 to 95% for quantitative EEG, and 95 to 100% and 65 to 85% for sonified EEG, respectively. Non-expert performance of EEG resulted in statistically significant reduced delay (86 min, p < 0.0001; 196 min, p < 0.0001; 667 min, p < 0.005) in EEG completion and changes in management in approximately 40% of patients. Non-experts who were trained included physicians, nurses, neurodiagnostic technicians, and medical students. Numerous teaching methods were utilized and often combined, with instructional and hands-on training being most common. CONCLUSIONS: Several different bedside providers can be educated to perform and screen adult EEG, particularly for the purpose of diagnosing nonconvulsive seizures. While further rigorous research is warranted, this review demonstrates several potential bridges by which EEG may be integrated into the care of critically ill patients.

Electrocerebral Signature of Cardiac Death.

BACKGROUND: Electroencephalography (EEG) findings following cardiovascular collapse in death are uncertain. We aimed to characterize EEG changes immediately preceding and following cardiac death. METHODS: We retrospectively analyzed EEGs of patients who died from cardiac arrest while undergoing standard EEG monitoring in an intensive care unit. Patients with brain death preceding cardiac death were excluded. Three events during fatal cardiovascular failure were investigated: (1) last recorded QRS complex on electrocardiogram (QRS0), (2) cessation of cerebral blood flow (CBF0) estimated as the time that blood pressure and heart rate dropped below set thresholds, and (3) electrocerebral silence on EEG (EEG0). We evaluated EEG spectral power, coherence, and permutation entropy at these time points. RESULTS: Among 19 patients who died while undergoing EEG monitoring, seven (37%) had a comfort-measures-only status and 18 (95%) had a do-not-resuscitate status in place at the time of death. EEG0 occurred at the time of QRS0 in five patients and after QRS0 in two patients (cohort median - 2.0, interquartile range - 8.0 to 0.0), whereas EEG0 was seen at the time of CBF0 in six patients and following CBF0 in 11 patients (cohort median 2.0 min, interquartile range - 1.5 to 6.0). After CBF0, full-spectrum log power (p < 0.001) and coherence (p < 0.001) decreased on EEG, whereas delta (p = 0.007) and theta (p < 0.001) permutation entropy increased. CONCLUSIONS: Rarely may patients have transient electrocerebral activity following the last recorded QRS (less than 5 min) and estimated cessation of cerebral blood flow. These results may have implications for discussions around cardiopulmonary resuscitation and organ donation.