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This proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.

Transcranial Doppler ultrasonography (TCD) is a portable, bedside, noninvasive diagnostic tool used for the real-time assessment of cerebral hemodynamics. Despite the evident utility of TCD and the ability of this technique to function as a stethoscope to the brain, its use has been limited to specialized centers because of the dearth of technical and clinical expertise required to acquire and interpret the cerebrovascular parameters. Additionally, the conventional pragmatic episodic TCD monitoring protocols lack dynamic real-time feedback to guide time-critical clinical interventions. Fortunately, with the recent advent of automated robotic TCD technology in conjunction with the automated software for TCD data processing, we now have the technology to automatically acquire TCD data and obtain clinically relevant information in real-time. By obviating the need for highly trained clinical personnel, this technology shows great promise toward a future of widespread noninvasive monitoring to guide clinical care in patients with acute brain injury.Here, we describe a proposal for a prospective observational multicenter clinical trial to evaluate the safety and feasibility of prolonged automated robotic TCD monitoring in patients with severe acute traumatic brain injury (TBI). We will enroll patients with severe non-penetrating TBI with concomitant invasive multimodal monitoring including, intracranial pressure, brain tissue oxygenation, and brain temperature monitoring as part of standard of care in centers with varying degrees of TCD availability and experience. Additionally, we propose to evaluate the correlation of pertinent TCD-based cerebral autoregulation indices such as the critical closing pressure, and the pressure reactivity index with the brain tissue oxygenation values obtained invasively.The overarching goal of this study is to establish safety and feasibility of prolonged automated TCD monitoring for patients with TBI in the intensive care unit and identify clinically meaningful and pragmatic noninvasive targets for future interventions.

Considering the COVID-19 pandemic where concomitant occurrence of ARDS and severe acute brain injury (sABI) has increasingly coemerged, we synthesize existing data regarding the simultaneous management of both conditions. Our aim is to provide readers with fundamental principles and concepts for the management of sABI and ARDS, and highlight challenges and conflicts encountered while managing concurrent disease. Up to 40% of patients with sABI can develop ARDS. Although there are trials and guidelines to support the mainstays of treatment for ARDS and sABI independently, guidance on concomitant management is limited. Treatment strategies aimed at managing severe ARDS may at times conflict with the management of sABI. In this narrative review, we discuss the physiological basis and risks involved during simultaneous management of ARDS and sABI, summarize evidence for treatment decisions, and demonstrate these principles using hypothetical case scenarios. Use of invasive or noninvasive monitoring to assess brain and lung physiology may facilitate goal-directed treatment strategies with the potential to improve outcome. Understanding the pathophysiology and key treatment concepts for comanagement of these conditions is critical to optimizing care in this high-acuity patient population.

The original article has been updated to correct Row 2 of Table 4 “04-Jul” to “4–7”. in press

Background Guillain–Barré syndrome (GBS) often carries a favorable prognosis. Of adult patients with GBS, 10–30% require mechanical ventilation during the acute phase of the disease. After the acute phase, the focus shifts to restoration of motor strength, ambulation, and neurological function, with variable speed and degree of recovery. The objective of these guidelines is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling adult patients with GBS and/or their surrogates. Methods A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Time frame/Setting (PICOTS) question was framed as follows: “When counseling patients or surrogates of critically ill patients with Guillain–Barré syndrome, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of [outcome, with time frame of assessment]?” Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. Results Eight candidate clinical variables and six prediction models were selected. A total of 45 articles met our eligibility criteria to guide recommendations. We recommend bulbar weakness (the degree of motor weakness at disease nadir) and the Erasmus GBS Respiratory Insufficiency Score as moderately reliable for prediction of the need for mechanical ventilation. The Erasmus GBS Outcome Score (EGOS) and modified EGOS were identified as moderately reliable predictors of independent ambulation at 3 months and beyond. Good practice recommendations include consideration of both acute and recovery phases of the disease during prognostication, discussion of the possible need for mechanical ventilation and enteral nutrition during counseling, and consideration of the complete clinical condition as opposed to a single variable during prognostication. Conclusions These guidelines provide recommendations on the reliability of predictors of the need for mechanical ventilation, poor functional outcome, and independent ambulation following GBS in the context of counseling patients and/or surrogates and suggest broad principles of neuroprognostication. Few predictors were considered moderately reliable based on the available body of evidence, and higher quality data are needed.

Background Among cardiac arrest survivors, about half remain comatose 72 h following return of spontaneous circulation (ROSC). Prognostication of poor neurological outcome in this population may result in withdrawal of life-sustaining therapy and death. The objective of this article is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling surrogates of comatose cardiac arrest survivors. Methods A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, which included clinical variables and prediction models, were selected based on clinical relevance and the presence of an appropriate body of evidence. The Population, Intervention, Comparator, Outcome, Timing, Setting (PICOTS) question was framed as follows: “When counseling surrogates of comatose adult survivors of cardiac arrest, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of poor functional outcome assessed at 3 months or later?” Additional full-text screening criteria were used to exclude small and lower-quality studies. Following construction of the evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. Results Eleven candidate clinical variables and three prediction models were selected based on clinical relevance and the presence of an appropriate body of literature. A total of 72 articles met our eligibility criteria to guide recommendations. Good practice recommendations include waiting 72 h following ROSC/rewarming prior to neuroprognostication, avoiding sedation or other confounders, the use of multimodal assessment, and an extended period of observation for awakening in patients with an indeterminate prognosis, if consistent with goals of care. The bilateral absence of pupillary light response > 72 h from ROSC and the bilateral absence of N20 response on somatosensory evoked potential testing were identified as reliable predictors. Computed tomography or magnetic resonance imaging of the brain > 48 h from ROSC and electroencephalography > 72 h from ROSC were identified as moderately reliable predictors. Conclusions These guidelines provide recommendations on the reliability of predictors of poor outcome in the context of counseling surrogates of comatose survivors of cardiac arrest and suggest broad principles of neuroprognostication. Few predictors were considered reliable or moderately reliable based on the available body of evidence.

In recent years, the volume of digitalized web-based information utilizing modern computer-based technology for data storage, processing, and analysis has grown rapidly. Humans can process a limited number of variables at any given time. Thus, the deluge of clinically useful information in the intensive care unit environment remains untapped. Innovations in machine learning technology with the development of deep neural networks and efficient, cost-effective data archival systems have provided the infrastructure to apply artificial intelligence on big data for determination of clinical events and outcomes. Here, we introduce a few computer-based technologies that have been tested across these domains.

Coma and disorders of consciousness (DoC) are highly prevalent and constitute a burden for patients, families, and society worldwide. As part of the Curing Coma Campaign, the Neurocritical Care Society partnered with the National Institutes of Health to organize a symposium bringing together experts from all over the world to develop research targets for DoC. The conference was structured along six domains: (1) defining endotype/phenotypes, (2) biomarkers, (3) proof-of-concept clinical trials, (4) neuroprognostication, (5) long-term recovery, and (6) large datasets. This proceedings paper presents actionable research targets based on the presentations and discussions that occurred at the conference. We summarize the background, main research gaps, overall goals, the panel discussion of the approach, limitations and challenges, and deliverables that were identified. Supplementary Information The online version contains supplementary material available at 10.1007/s12028-021-01260-x.

Several recent studies across the field of medicine have indicated gender disparity in the reception of prestigious awards and research grants, placing women in medicine at a distinct disadvantage. Gender disparity has been observed in neurology, critical care medicine and within various professional societies. In this study, we have examined the longitudinal trends of gender parity in awards and grants within the Neurocritical Care Society (NCS). A retrospective analysis was conducted of all available data longitudinally from 2004, when NCS first granted awards through 2019. We used self-identified gender in the membership roster to record gender for each individual. For individuals without recorded gender, we used a previously validated double verification method using a systematic web-based search. We collected data on six awards distributed by the NCS and divided these awards into two main categories: (1) scientific category: (a) Christine Wijman Young Investigator Award; (b) Best Scientific Abstract Award; (c) Fellowship Grant; (d) INCLINE Grant; and (2) non-scientific category: (a) Travel Grant; and (b) Presidential Citation. Available data were analyzed to evaluate longitudinal trends in awards using descriptive statistics and simple or multiple linear regression analyses, as appropriate. A total of 445 awards were granted between the years 2004 and 2019. Thirty-six awards were in the scientific category, while 409 awards were in the non-scientific category. Only 8% of women received NCS awards in the scientific awards category, whereas 44% of women received an award in the non-scientific category. Most notable in the scientific category are the Best Scientific Abstract Award and the Fellowship Grant, in which no woman has ever received an award to date, compared to 18 men between both awards. In contrast, women are well represented in the non-scientific awards category with an average of 5% increase per year in the number of women awardees. Our data reveal gender disparity, mainly for scientific or research awards. Prompt evaluation of the cause and further actions to address gender disparity in NCS grants and recognition awards is needed to establish gender equity in this area.

Recovery from coma or disordered consciousness is a central issue in patients with acute brain injuries such as stroke, trauma, cardiac arrest, and brain infections. Yet, major gaps remain in the scientific underpinnings of coma and this has led to inaccuracy in prognostication and limited interventions for coma recovery. Even so, recent studies have begun to elucidate mechanisms of consciousness early and prolonged after acute brain injury and some pilot interventions have begun to be tested. The importance and scope of this led in 2019 to the development of the Curing Coma Campaign, an initiative of the Neurocritical Care Society designed to provide a platform for scientific collaboration across the patient care continuum and to empower a community for purposes of research, education, implementation science, and advocacy. Seen as a “grand challenge,” the Curing Coma Campaign has developed an infrastructure of scientific working groups and operational modules, along with a 10-year roadmap.

Several studies in critical care and neurology demonstrate women under-representation in professional societies; representation trends within the Neurocritical Care Society (NCS) are unknown. We examined longitudinal gender parity trends in membership and leadership within NCS. A retrospective study of NCS membership and leadership rosters was conducted. To determine gender, self-reported binary gender was extracted. For individuals without recorded gender, a systematic Web-based search to identify usage of gender-specific pronouns in publicly available biographies was performed. According to previously published methods, available photographs were utilized to record presumed gender identification in the absence of available pronoun descriptors. We analyzed available data longitudinally from 2002 to 2019 and performed descriptive statistical and linear regression analyses. In overall membership, the proportion of women members demonstrated an average 11% increase between 2005 and 2018 (95% confidence interval (CI) − 8.1 to 30.1, p = 0.08). The proportion of women Board of Directors (BOD) members increased significantly over time to 50% in 2019. There was an increase in women Officers from 0% in the first 3 years (2002–2004) to 40% in 2019, with two women Presidents out of 17 from 2002 to 2019. For available Executive Committee rosters, there was a statistically significant nearly 3% increase per year (95% CI 1.5–4; p = 0.0007) in the proportion of women members. Rosters for Committee members and chairpersons were also incomplete, but in an analysis of the available data, there was a statistically significant increase of 5% per year analyzed (95% CI 0.5–9.7; p = 0.04) in the proportion of women Committee members. We also found a statistically significant 4.3% increase per year analyzed (95% CI 2.4–6.1; p = 0.003) in the proportion of women Committee chairpersons. This is the first study of longitudinal gender parity trends within neurocritical care. We report that from 2002 to 2019, the NCS has undergone a significant increase in women representation in general membership, committee membership, and leadership positions.

ObjectiveTo determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive patients and recorded new neurologic disorders and hospital outcomes.MethodsWe conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders.ResultsOf 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all p < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17–1.62, p < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63–0.85, p < 0.001).ConclusionsNeurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

Background and Purpose The computed tomography angiographic (CTA) spot sign has been shown to predict hematoma expansion in patients with intracranial hemorrhage (ICH), but the significance of the spot sign density (SSD) and the spot sign ratio (SSR) has not yet been explored. Methods Using the institutional Neurocritical care and Stroke registry, we retrospectively reviewed patients with ICH from January-2013 to June-2017. We selected patients who had baseline CT-head (CTH), CTA with positive-spot sign within 6 hours of last known well and at least one follow-up CTH within 24 hours. Baseline demographics and variables known to affect hematoma-volume were collected. Hematoma-volumes and SSR were calculated using computer-assisted 3D-volumetric measurement and the average of the surrounding hematoma density divided by the SSD, respectively. The 2-sample t test and the area-under-the-curve (receiver operating characteristic) were used to detect the association between hematoma expansion and outcome at discharge. Results A total of 320 patients were reviewed; 22 met the inclusion criteria. Significant hematoma expansion (volume expansion ≥12.5 cc or ≥33% compared to baseline) was noted in 14 (64%) subjects. SSD was significantly higher in subjects with hematoma expansion (216 ± 66) than those without (155 ± 52, P = .036). With a cut-off SSD of ≥150 HU, we had sensitivity of 86% and specificity of 75%. For SSR, lower ratios suggested a trend toward hematoma expansion, although it was not statistically significant (P = .12). There was no significant correlation between SSD or SSR and modified ranking scale at discharge and after 3-6 months. Conclusion SSD might be a good predictor of hematoma growth. Although SSR showed a trend toward expansion, results were not statistically significant.

The purpose of this paper is to provide an overview of the utility and indications of sonography in the Neuro ICU, with focus on recent studies and advances. Emerging data continue to shed light on the benefit of critical care sonography with neurovascular ultrasound being of particular interest in the Neuro ICU. Recent development of safe and feasible robotic TCDs holds promise in allowing continuous bedside monitoring of cerebrovascular hemodynamics, especially in conjunction with the use of automated software such as ICM+. Although newer and feasible methods for non-invasive measures of intracranial fluid and hemodynamics are rapidly emerging, use of neurovascular ultrasound remains limited due to lack of clinical and technical expertise. Recently published consensus statement on the recommended skills and competence level required to perform brain ultrasonography in the critical care setting may serve as a helpful framework to guide further training and protocol development. Utilization of systemic sonography has grown as a diagnostic and procedural aid in the critical care setting, while the rising body of literature continues to demonstrate the value of routine use of neurovascular ultrasound. Standardization of protocols and training paradigms could promote integration of this valuable tool in guiding management of brain injury patients.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic continues to affect millions globally, with increasing reports of COVID-19 neurological manifestations but limited data on their population prevalence and outcome. This is the first report from two international consortia studies aimed to determine the neurological phenotypes, prevalence, and outcomes among hospitalized COVID-19 patients. Methods: The Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) is a multi-center cohort study enrolling consecutive hospitalized COVID-19 patients to determine type, prevalence, and outcomes of COVID-19 neurological manifestations. The European Academy of Neurology (EAN) Neuro-COVID Registry (ENERGY) is a global registry to capture COVID-19 neurological manifestations and outcomes. Using harmonized data elements across two consortia, this is the first report describing 3744 subjects from 28 centers, representing 13 countries and 4 continents. Findings: Data are presented from three separate cohorts: the GCS-NeuroCOVID “ALL COVID” cohort (n=3055), which includes consecutive hospitalized COVID-19 patients with and without neurological manifestations, the GCS-NeuroCOVID “COVID NEURO” cohort (n=475), consisting of consecutive hospitalized COVID-19 patients with confirmed neurological manifestations, and the ENERGY cohort (n=214), which includes COVID-19 patients with a neurological consultation. Across cohorts, neurological manifestations are present in up to 80% of hospitalized COVID-19 patients. The most common self-reported neurological symptoms included headache (38%) and anosmia/ageusia (28%). The most common neurological signs/syndrome are acute encephalopathy (50%), coma (17%), and stroke (3%) while meningitis/encephalitis are rare (0.1%). Pre-existing neurological disorders is associated with higher risk for developing new neurological signs/syndromes with COVID-19, which in-hospital mortality after adjusting for age, sex, race, and ethnicity. Interpretation: Neurological manifestations are prevalent across hospitalized COVID-19 patients in two large global consortia representing North America, Europe, Asia and Africa. Having neurological manifestations with COVID-19 is associated with higher in-hospital mortality. Subsequent studies are needed to determine potential pathophysiologic mechanisms and long-term outcomes of COVID-19 neurologic manifestations. Funding Statement: National Center for Advancing Translational Sciences (NCATS) UL1 TR001857 (Chou); National Institutes of Neurological Disorders and Stroke (NINDS) R21NS113037 (Chou). Declaration of Interests: Chou S H-Y declares no interests. Beghi E declares no interests. Helbok R declares no interests. Moro E declares no interests. Sampson J declares no interests. Altamirano V declares no interests. Mainali S declares no interests Basetti C declares no interests. Suarez J declares no interests. McNett M declares no interests. Ethics Approval Statement: The central coordinating center (University of Pittsburgh) established ethics approval for a multicenter study, confirmed local ethics approval and executed data use agreements with each participating site.

Background: Zinc impairs replication of RNA viruses such as SARS-CoV-1, and may be effective against SARS-CoV-2. However, to achieve adequate intracellular zinc levels, administration with an ionophore, which increases intracellular zinc levels, may be necessary. We evaluated the impact of zinc with an ionophore (Zn+ionophore) on COVID-19 in-hospital mortality rates. Methods: A multicenter cohort study was conducted of 3,473 adult hospitalized patients with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) positive SARS-CoV-2 infection admitted to four New York City hospitals between March 10 through May 20, 2020. Exclusion criteria were: death or discharge within 24h, comfort-care status, clinical trial enrollment, treatment with an IL-6 inhibitor or remdesivir. Patients who received Zn+ionophore were compared to patients who did not using multivariable time-dependent cox proportional hazards models for time to in-hospital death adjusting for confounders including age, sex, race, BMI, diabetes, week of admission, hospital location, sequential organ failure assessment (SOFA) score, intubation, acute renal failure, neurological events, treatment with corticosteroids, azithromycin or lopinavir/ritonavir and the propensity score of receiving Zn+ionophore. A sensitivity analysis was performed using a propensity score-matched cohort of patients who did or did not receive Zn+ionophore matched by age, sex and ventilator status. Results: Among 3,473 patients (median age 64, 1947 [56%] male, 522 [15%] ventilated, 545[16%] died), 1,006 (29%) received Zn+ionophore. Zn+ionophore was associated with a 24% reduced risk of in-hospital mortality (12% of those who received Zn+ionophore died versus 17% who did not; adjusted Hazard Ratio [aHR] 0.76, 95% CI 0.60–0.96, P=0.023). More patients who received Zn+ionophore were discharged home (72% Zn+ionophore vs 67% no Zn+ionophore, P=0.003) Neither Zn nor the ionophore alone were associated with decreased mortality rates. Propensity score-matched sensitivity analysis (N=1356) validated these results (Zn+ionophore aHR for mortality 0.63, 95%CI 0.44–0.91, P=0.015). There were no significant interactions for Zn+ionophore with other COVID-19 specific medications. Conclusions: Zinc with an ionophore was associated with increased rates of discharge home and a 24% reduced risk of in-hospital mortality among COVID-19 patients, while neither zinc alone nor the ionophore alone reduced mortality. Further randomized trials are warranted., Summery In this study of 3,473 hospitalized COVID-19 patients, treatment with zinc and an ionophore was associated with a 24% reduced risk of in-hospital mortality in multivariable Cox regression analysis. A sensitivity analysis in a propensity score-matched cohort supported this finding.

Since its original report in January 2020, the coronavirus disease 2019 (COVID-19) due to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly become one of the deadliest global pandemics. Early reports indicate possible neurological manifestations associated with COVID-19, with symptoms ranging from mild to severe, highly variable prevalence rates, and uncertainty regarding causal or coincidental occurrence of symptoms. As neurological involvement of any systemic disease is frequently associated with adverse effects on morbidity and mortality, obtaining accurate and consistent global data on the extent to which COVID-19 may impact the nervous system is urgently needed. To address this need, investigators from the Neurocritical Care Society launched the Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID). The GCS-NeuroCOVID consortium rapidly implemented a Tier 1, pragmatic study to establish phenotypes and prevalence of neurological manifestations of COVID-19. A key component of this global collaboration is development and application of common data elements (CDEs) and definitions to facilitate rigorous and systematic data collection across resource settings. Integration of these elements is critical to reduce heterogeneity of data and allow for future high-quality meta-analyses. The GCS-NeuroCOVID consortium specifically designed these elements to be feasible for clinician investigators during a global pandemic when healthcare systems are likely overwhelmed and resources for research may be limited. Elements include pediatric components and translated versions to facilitate collaboration and data capture in Latin America, one of the epicenters of this global outbreak. In this manuscript, we share the specific data elements, definitions, and rationale for the adult and pediatric CDEs for Tier 1 of the GCS-NeuroCOVID consortium, as well as the translated versions adapted for use in Latin America. Global efforts are underway to further harmonize CDEs with other large consortia studying neurological and general aspects of COVID-19 infections. Ultimately, the GCS-NeuroCOVID consortium network provides a critical infrastructure to systematically capture data in current and future unanticipated disasters and disease outbreaks.

Several recent studies across the field of medicine have indicated gender disparity in the reception of prestigious awards and research grants, placing women in medicine at a distinct disadvantage. Gender disparity has been observed in neurology, critical care medicine and within various professional societies. In this study, we have examined the longitudinal trends of gender parity in awards and grants within the Neurocritical Care Society (NCS).A retrospective analysis was conducted of all available data longitudinally from 2004, when NCS first granted awards through 2019. We used self-identified gender in the membership roster to record gender for each individual. For individuals without recorded gender, we used a previously validated double verification method using a systematic web-based search. We collected data on six awards distributed by the NCS and divided these awards into two main categories: (1) scientific category: (a) Christine Wijman Young Investigator Award; (b) Best Scientific Abstract Award; (c) Fellowship Grant; (d) INCLINE Grant; and (2) non-scientific category: (a) Travel Grant; and (b) Presidential Citation. Available data were analyzed to evaluate longitudinal trends in awards using descriptive statistics and simple or multiple linear regression analyses, as appropriate.A total of 445 awards were granted between the years 2004 and 2019. Thirty-six awards were in the scientific category, while 409 awards were in the non-scientific category. Only 8% of women received NCS awards in the scientific awards category, whereas 44% of women received an award in the non-scientific category. Most notable in the scientific category are the Best Scientific Abstract Award and the Fellowship Grant, in which no woman has ever received an award to date, compared to 18 men between both awards. In contrast, women are well represented in the non-scientific awards category with an average of 5% increase per year in the number of women awardees.Our data reveal gender disparity, mainly for scientific or research awards. Prompt evaluation of the cause and further actions to address gender disparity in NCS grants and recognition awards is needed to establish gender equity in this area.

Several studies in critical care and neurology demonstrate women under-representation in professional societies; representation trends within the Neurocritical Care Society (NCS) are unknown. We examined longitudinal gender parity trends in membership and leadership within NCS.A retrospective study of NCS membership and leadership rosters was conducted. To determine gender, self-reported binary gender was extracted. For individuals without recorded gender, a systematic Web-based search to identify usage of gender-specific pronouns in publicly available biographies was performed. According to previously published methods, available photographs were utilized to record presumed gender identification in the absence of available pronoun descriptors. We analyzed available data longitudinally from 2002 to 2019 and performed descriptive statistical and linear regression analyses.In overall membership, the proportion of women members demonstrated an average 11% increase between 2005 and 2018 (95% confidence interval (CI) - 8.1 to 30.1, p = 0.08). The proportion of women Board of Directors (BOD) members increased significantly over time to 50% in 2019. There was an increase in women Officers from 0% in the first 3 years (2002-2004) to 40% in 2019, with two women Presidents out of 17 from 2002 to 2019. For available Executive Committee rosters, there was a statistically significant nearly 3% increase per year (95% CI 1.5-4; p = 0.0007) in the proportion of women members. Rosters for Committee members and chairpersons were also incomplete, but in an analysis of the available data, there was a statistically significant increase of 5% per year analyzed (95% CI 0.5-9.7; p = 0.04) in the proportion of women Committee members. We also found a statistically significant 4.3% increase per year analyzed (95% CI 2.4-6.1; p = 0.003) in the proportion of women Committee chairpersons.This is the first study of longitudinal gender parity trends within neurocritical care. We report that from 2002 to 2019, the NCS has undergone a significant increase in women representation in general membership, committee membership, and leadership positions.

Background As the COVID-19 pandemic developed, reports of neurological dysfunctions spanning the central and peripheral nervous systems have emerged. The spectrum of acute neurological dysfunctions may implicate direct viral invasion, para-infectious complications, neurological manifestations of systemic diseases, or co-incident neurological dysfunction in the context of high SARS-CoV-2 prevalence. A rapid and pragmatic approach to understanding the prevalence, phenotypes, pathophysiology and prognostic implications of COVID-19 neurological syndromes is urgently needed. Methods The Global Consortium to Study Neurological dysfunction in COVID-19 (GCS-NeuroCOVID), endorsed by the Neurocritical Care Society (NCS), was rapidly established to address this need in a tiered approach. Tier-1 consists of focused, pragmatic, low-cost, observational common data element (CDE) collection, which can be launched immediately at many sites in the first phase of this pandemic and is designed for expedited ethical board review with waiver-of-consent. Tier 2 consists of prospective functional and cognitive outcomes assessments with more detailed clinical, laboratory and radiographic data collection that would require informed consent. Tier 3 overlays Tiers 1 and 2 with experimental molecular, electrophysiology, pathology and imaging studies with longitudinal outcomes assessment and would require centers with specific resources. A multicenter pediatrics core has developed and launched a parallel study focusing on patients ages

Introduction: Vizient clinical database-resource manager (CDB/RM) is an alliance of Academic Medical Centers and their affiliated hospital that collects data to enhance patient care by aligning cost, quality and market performance. The observed-to-expected mortality (O/E) is a risk-adjusted measure of a hospital’s mortality and is based upon documentation of specific variables associated with mortality. Methods: Our comprehensive stroke program participates in Vizient CDB/RM. We defined observed mortality as the rate of patient deaths in the hospital each month. Expected mortality is calculated as the sum of all individually calculated risks with conditions that affect severity, for discharges each month. The O/E ratio is calculated by dividing observed mortality by the expected mortality. An O/E ratio score higher than 1.0 means the hospital’s mortality is higher than expected. Results: We identified the most common discharge diagnosis-related group (DRG) codes for ischemic stroke used by our neurovascular service in 2018. We used the Academic Medical Center Hospital: Risk Modeling Summary for 2016 to determine the model group that was relevant for our population. We chose Model group 23 as the highest yield, as that model covers nearly half our volume based upon our frequently used DRG codes. The team used a shared mortality risk factor standard template to improve documentation practices. The Quality Intervention (QI) plan was implemented July 22, 2019 using an interdisciplinary approach. Clinical teams were educated on specific documentation of variables associated with in-hospital mortality. Vizient CDB/RM data on stroke mortality will be reviewed in September 2019 to determine the effect of the QI on mortality O/E ratio for our ischemic stroke population. Conclusions: Our comprehensive stroke program implemented a clinical documentation improvement QI plan to improve Vizient CDB/RM Risk Adjusted Mortality for our ischemic stroke population. We expect that improving appropriate documentation will assist coding specialist to capture the severity of cases, which should improve the mortality O/E ratio.

Introduction: Presence of functional leptomeningeal collaterals has been found to be one of the key determinants of good outcomes. We evaluated the effects of certain environmental and physical factors in cerebral collateral circulation. Methods: After IRB approval, data was collected from prospective institutional Neurocritical Care and Stroke Registry. Stroke patients presenting with acute anterior circulation large vessel occlusion between May 2013 and August 2018 were included. Collaterals were graded based on CT-Angiogram and CT-Perfusion images obtained on presentation, by a blinded Neuroradiologist as good (grade 3-4) and poor (grades 0-2). Ohio air pollution data (2013-2018) were obtained from the US EPA and summarized as a single mean concentration by monitor. Strokes were geocoded and linked with the closest monitor. Odds of good (vs. poor) collateral grade were compared using BMI (linear), smoking status, antiplatelet medication use, and mean PM 2.5 concentration (cubic). Sensitivity analyses assessed additional adjustment by sex and change in NIHSS (admission to discharge). Results: A total of 73 strokes were analyzed with 48% male, mean BMI of 30.4 (SD=7.2), and 22% with good collateral grade. For each kg/m 2 greater BMI, the odds of having good collaterals (vs. poor) were 11% higher (OR: 1.11; 95%CI:1.01-1.22; p =0.029). Higher PM 2.5 concentrations were suggestive of lower odds of good collaterals ( p =0.124). Antiplatelet medication use (OR: 2.10; 95%CI:0.59-7.45) and smoking status (OR: 1.35; 95%CI:0.73-13.9) were not associated with the odds of having good collateral grade. After controlling for change in NIHSS and sex, higher BMI remained associated with good collateral grade (fig.1). Conclusions: Higher BMI was independently associated with higher odds of good collateral grade; this association needs to be explored in larger population taking other factors like age and medical comorbidities into account.

The use of weight loss drugs and dietary supplements is common, but safety profiles for these drugs are largely unknown. Reports of toxicity have been published, and the use of these agents should be considered in clinical differential diagnoses. We report the case of a patient with toxic leukoencephalopathy and hyponatremia associated with oral consumption of a thermogenic dietary supplement and essential oils. A 30-year-old woman presented after 2 days of headache, blurred vision, photophobia, vomiting, and hand spasms. She was taking a thermogenic dietary supplement daily for 6 months as well as a number of essential oils. Examination revealed mild right sided ataxia and diffuse hyperreflexia. Neuroimaging demonstrated bilaterally symmetric T2 hyperintensities of the corpus callosum and periventricular white matter. Approximately 18 h after admission she became unresponsive with brief extensor posturing and urinary incontinence. She partially recovered, but 1 h later became unresponsive with dilated nonreactive pupils and extensor posturing (central herniation syndrome). She was intubated, hyperventilated, and given hyperosmotic therapy. Emergent imaging showed diffuse cerebral edema. Intracranial pressure was elevated but normalized with treatment; she regained consciousness the following day. She was extubated one day later and discharged on hospital day 5. She was seen 2 months later with no further symptoms and a normal neurologic examination. The pathophysiology of this patient’s hyponatremia and toxic leukoencephalopathy is unknown. However, physicians must be aware of the association between thermogenic dietary supplements and toxic leukoencephalopathy. Vigilance for life-threatening complications including hyponatremia and cerebral edema is critical.

Acute stroke care requires rapid assessment and intervention. Replacing traditional sequential algorithms in stroke care with parallel processing using telestroke consultation could be useful in the management of acute stroke patients. The purpose of this study was to assess the feasibility of a nurse-driven acute stroke protocol using a parallel processing model.This is a prospective, nonrandomized, feasibility study of a quality improvement initiative. Stroke team members had a 1-month training phase, and then the protocol was implemented for 6 months and data were collected on a "run-sheet." The primary outcome of this study was to determine if a nurse-driven acute stroke protocol is feasible and assists in decreasing door to needle (intravenous tissue plasminogen activator [IV-tPA]) times.Of the 153 stroke patients seen during the protocol implementation phase, 57 were designated as "level 1" (symptom onset4.5 hours) strokes requiring acute stroke management. Among these strokes, 78% were nurse-driven, and 75% of the telestroke encounters were also nurse-driven. The average door to computerized tomography time was significantly reduced in nurse-driven codes (38.9 minutes versus 24.4 minutes; P .04).The use of a nurse-driven protocol is feasible and effective. When used in conjunction with a telestroke specialist, it may be of value in improving patient outcomes by decreasing the time for door to decision for IV-tPA.

Key Points Question What are the incidence of and outcomes associated with neurologic manifestations in patients with COVID-19? Findings In this cohort study of 3744 patients in 2 large consortia, neurological manifestations were found in approximately 80% of patients hospitalized with COVID-19; the most common self-reported symptoms included headache (37%) and anosmia or ageusia (26%), whereas the most common neurological signs and/or syndromes were acute encephalopathy (49%), coma (17%), and stroke (6%). Presence of clinically captured neurologic signs and/or syndromes was associated with increased risk of in-hospital death. Meaning These findings suggest that neurological manifestations are prevalent among patients hospitalized with COVID-19 and are associated with higher in-hospital mortality., This cohort study investigates the neurological phenotypes, incidence, and outcomes among adults hospitalized with COVID-19., Importance The COVID-19 pandemic continues to affect millions of people globally, with increasing reports of neurological manifestations but limited data on their incidence and associations with outcome. Objective To determine the neurological phenotypes, incidence, and outcomes among adults hospitalized with COVID-19. Design, Setting, and Participants This cohort study included patients with clinically diagnosed or laboratory-confirmed COVID-19 at 28 centers, representing 13 countries and 4 continents. The study was performed by the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) from March 1 to September 30, 2020, and the European Academy of Neurology (EAN) Neuro-COVID Registry (ENERGY) from March to October 2020. Three cohorts were included: (1) the GCS-NeuroCOVID all COVID-19 cohort (n = 3055), which included consecutive hospitalized patients with COVID-19 with and without neurological manifestations; (2) the GCS-NeuroCOVID COVID-19 neurological cohort (n = 475), which comprised consecutive patients hospitalized with COVID-19 who had confirmed neurological manifestations; and (3) the ENERGY cohort (n = 214), which included patients with COVID-19 who received formal neurological consultation. Exposures Clinically diagnosed or laboratory-confirmed COVID-19. Main Outcomes and Measures Neurological phenotypes were classified as self-reported symptoms or neurological signs and/or syndromes assessed by clinical evaluation. Composite incidence was reported for groups with at least 1 neurological manifestation. The main outcome measure was in-hospital mortality. Results Of the 3055 patients in the all COVID-19 cohort, 1742 (57%) were men, and the mean age was 59.9 years (95% CI, 59.3-60.6 years). Of the 475 patients in the COVID-19 neurological cohort, 262 (55%) were men, and the mean age was 62.6 years (95% CI, 61.1-64.1 years). Of the 214 patients in the ENERGY cohort, 133 (62%) were men, and the mean age was 67 years (95% CI, 52-78 years). A total of 3083 of 3743 patients (82%) across cohorts had any neurological manifestation (self-reported neurological symptoms and/or clinically captured neurological sign and/or syndrome). The most common self-reported symptoms included headache (1385 of 3732 patients [37%]) and anosmia or ageusia (977 of 3700 patients [26%]). The most prevalent neurological signs and/or syndromes were acute encephalopathy (1845 of 3740 patients [49%]), coma (649 of 3737 patients [17%]), and stroke (222 of 3737 patients [6%]), while meningitis and/or encephalitis were rare (19 of 3741 patients [0.5%]). Presence of clinically captured neurologic signs and/or syndromes was associated with increased risk of in-hospital death (adjusted odds ratio [aOR], 5.99; 95% CI, 4.33-8.28) after adjusting for study site, age, sex, race, and ethnicity. Presence of preexisting neurological disorders (aOR, 2.23; 95% CI, 1.80-2.75) was associated with increased risk of developing neurological signs and/or syndromes with COVID-19. Conclusions and Relevance In this multicohort study, neurological manifestations were prevalent among patients hospitalized with COVID-19 and were associated with higher in-hospital mortality. Preexisting neurological disorders were associated with increased risk of developing neurological signs and/or syndromes in COVID-19.

BackgroundAcute ischemic stroke (AIS) due to emergent large-vessel occlusion (ELVO) has a poor prognosis.ObjectiveTo examine the hypothesis that a better collateral score on pretreatment CT angiography (CTA) would correlate with a smaller final infarct volume and a more favorable clinical outcome after endovascular therapy (EVT).MethodsA retrospective chart review of the University of Tennessee AIS database from February 2011 to February 2013 was conducted. All patients with CTA-proven LVO treated with EVT were included. Recanalization after EVT was defined by Thrombolysis in Cerebral Infarction (TICI) score ≥2. Favorable outcome was assessed as a modified Rankin Score ≤3.ResultsFifty patients with ELVO were studied. The mean National Institutes of Health Stroke Scale score was 17 (2–27) and 38 of the patients (76%) received intravenous tissue plasminogen activator. The recanalization rate for EVT was 86.6%. Good clinical outcome was achieved in 32% of patients. Univariate predictors of good outcome included good collateral scores (CS) on presenting CTA (p=0.043) and successful recanalization (p=0.02). Multivariate analysis confirmed both good CS (p=0.024) and successful recanalization (p=0.009) as predictors of favorable outcome. Applying results of the multivariate analysis to our cohort we were able to determine the likelihood of good clinical outcome as well as predictors of smaller final infarct volume after successful recanalization.ConclusionsGood CS predict smaller infarct volumes and better clinical outcome in patients recanalized with EVT. These data support the use of this technique in selecting patients for EVT. Poor CS should be considered as an exclusion criterion for EVT as patients with poor CS have poor clinical outcomes despite recanalization.

Background: Use of tissue plasminogen activator (TPA) during pregnancy is controversial given potential risks of placental and fetal complications. Since knowledge on this topic is limited, we assessed rates of TPA use during pregnancy and the associated patient characteristics and outcomes in a population-based sample of patients. Methods: We used administrative claims data on all discharges from nonfederal emergency departments and acute care hospitals in California, Florida, and New York between 2005 and 2012. Pregnancy was defined as the 40 weeks prior to delivery or abortive outcome. Using a validated ICD-9-CM diagnosis code algorithm, we identified cases of ischemic stroke, as well as cases of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) since these may represent hemorrhagic transformation of an infarct. We included only the first recorded stroke to focus on incident cases. TPA use was identified by ICD-9-CM procedure code 99.10, which has been validated as 98% specific in this population. Comparisons between groups were made using Fisher’s exact test and t-test or rank-sum test as appropriate. Results: Among 428,564 women with stroke, 599 cases occurred during pregnancy. The rate of TPA use for stroke was significantly lower during pregnancy (1.2%; 95% CI, 0.4-2.4%) than otherwise (3.5%; 95% CI, 3.4-3.6%; P = 0.001). Among pregnant stroke patients, we found few notable differences in the baseline characteristics of the 7 who received TPA versus the 592 who did not: those receiving TPA had higher rates of heart failure (28.6% versus 2.2%; P = 0.01) and pneumonia (14.3% versus 1.2%; P = 0.09) and lower rates of of pre-eclampsia (0.0% versus 29.1%; P = 0.09). There were no notable differences between pregnant stroke patients who did or did not receive TPA in terms of length of hospital stay, discharge disposition, and in-hospital mortality rate. However, we noted a significantly higher rate of abortive pregnancy outcomes during stroke hospitalization in those who received TPA than those who did not (28.6% versus 4.6%; P = 0.04). Conclusion: We found a significantly higher rate of abortive pregnancy outcomes in patients who received TPA. This suggests the need for caution and further research regarding TPA use for stroke in pregnancy.

Introduction. Noncontrast head CT (NCCT) is the standard radiologic test for patients presenting with acute stroke. Early ischemic changes (EIC) are often overlooked on initial NCCT. We determine the sensitivity and specificity of improved EIC detection by a standardized method of image evaluation (Stroke Windows). Methods. We performed a retrospective chart review to identify patients with acute ischemic stroke who had NCCT at presentation. EIC was defined by the presence of hyperdense MCA/basilar artery sign; sulcal effacement; basal ganglia/subcortical hypodensity; and loss of cortical gray-white differentiation. NCCT was reviewed with standard window settings and with specialized Stroke Windows. Results. Fifty patients (42% females, 58% males) with a mean NIHSS of 13.4 were identified. EIC was detected in 9 patients with standard windows, while EIC was detected using Stroke Windows in 35 patients (18% versus 70%; P<0.0001). Hyperdense MCA sign was the most commonly reported EIC; it was better detected with Stroke Windows (14% and 36%; P<0.0198). Detection of the remaining EIC also improved with Stroke Windows (6% and 46%; P<0.0001). Conclusions. Detection of EIC has important implications in diagnosis and treatment of acute ischemic stroke. Utilization of Stroke Windows significantly improved detection of EIC.

INTRODUCTION: Non-contrast head CT (NCCT) is the standard radiologic test performed in the emergency department (ED) for patients presenting with symptoms of acute stroke. Early ischemic changes (EIC) in NCCT are often missed by ED physicians and on-call radiologists. We assessed the hypothesis that detection of EIC can be improved by a standardized method of image evaluation. METHODS: Retrospective chart review was performed of the University of Tennessee Health Science Center prospective database of acute ischemic stroke from January - July 2012. Patients treated with IV TPA who had NCCT as the initial neuroimaging exam were identified and additional baseline characteristics were noted. EIC was defined as findings consistent with: 1) Hyperdense MCA/basilar artery sign 2) Sulcal effacement 3) Basal ganglia/subcortical hypodensity and 4) Loss of cortical gray-white differentiation. Initial NCCT was reviewed by a blinded neurology resident (except presenting complaints). First, images were reviewed with standard window settings of center and width level of 40 and 100 Hounsfield units (HU). Then, all images were interpreted with ”stroke windows” of center 35 and width of 30 HU. This was compared with the radiologists’ final report. Final interpretations based on "stroke windows" were compared with follow up imaging studies to assess accuracy. Fisher’s exact test was used for statistical analysis. RESULTS: NCCTs of 50 patients (42% females) with an average age 75.4 years and mean NIHSS of 13.4 were reviewed. The mean time to CT from symptom onset was 97.7 minutes. Out of 50 patients, radiologists detected EIC in 9 patients while authors detected EIC in 35 patients (18% vs. 70% with 100% accuracy; p < 0.0001). Hyperdense MCA sign although most commonly reported by radiologists, was better appreciated with "stroke windows" (14% and 56%; p CONCLUSIONS: EIC although common in acute ischemic stroke are often missed by the interpreting radiologists. We conclude that the rates of detection can be significantly improved with standardized “Stroke Windows”. This has important implications in regards to rapid diagnosis and treatment of acute ischemic stroke.

Free floating thrombus of the carotid artery (FFT) is defined as n elongated thrombus attached to the arterial wall with circumerential blood flow at its distal most aspect, with cyclical motion elating to cardiac cycles. FFT is a rare condition and the actual ncidence is not known. It is more frequently reported in men than omen, with a ratio of nearly 2:1. The internal carotid artery is he most commonly affected (75%), with atherosclerosis being the ost common associated pathology [1]. The guidelines for treatment of FFT are not clear due to the rarty of this condition and the lack of comparative studies between edical management (anticoagulation and/or antiplatelet) and urgical management (stenting, carotid endarterectomy or carotid ypass surgery). Anecdotal evidence supports early initiation f intravenous unfractionated heparin (IV-UFH) to prevent troke recurrence in certain situations including acquired or nherited hypercoagulable states, extracranial cervicocephalic rterial dissection, and intraluminal arterial thrombus [2]. Urgent ndarterectomy or endovascular embolectomy has both been eported as successful treatments for this condition [1,3].

Introduction Estimates indicate that West Nile virus infects approximately one and a half million people in the United States of America. Up to 1% may develop West Nile virus neuroinvasive disease, in which infected patients develop any combination of meningitis, encephalitis, or acute paralysis. Case presentation A 56-year-old African-American man presented to our hospital with headache, restlessness, fever, myalgias, decreased appetite, and progressive confusion. A cerebrospinal fluid examination showed mild leukocytosis and an elevated protein level. Testing for routine infections was negative. Brain T2-weighted magnetic resonance imaging scans showed marked enlargement of caudate nuclei and increased intensity within the basal ganglia and thalami. A West Nile virus titer was positive, and serial brain magnetic resonance imaging scans showed resolving abnormalities that paralleled his neurological examination. Conclusion This report is unusual as it portrays the natural history and long-term consequences of West Nile virus meningoencephalitis diagnosed on the basis of serial brain images.