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The standard-of-care for postoperative care following elective craniotomy has historically been ICU admission. However, recent literature interrogating complications and interventions during this postoperative ICU stay suggests that all patients may not require this level of care. Thus, hospitals began implementing non-ICU postoperative care pathways for elective craniotomy. This systematic review aims to summarize and evaluate the existing literature regarding outcomes and costs for patients receiving non-ICU care after elective craniotomy.A systematic review of the PubMed database was performed following PRISMA guidelines from database inception to August 2021.Included studies were published in peer-reviewed journals, in English, and described outcomes for patients undergoing elective craniotomies without postoperative ICU care.Data regarding study design, patient characteristics, and postoperative care pathways were extracted independently by two authors. Quality and risk of bias were evaluated using the Oxford Centre for Evidence-Based Medicine Levels of Evidence tool and Risk Of Bias In Non-Randomized Studies-of Interventions tool, respectively.In total, 1,131 unique articles were identified through the database search, with 27 meeting inclusion criteria. Included articles were published from 2001 to 2021 and included non-ICU inpatient care and same-day discharge pathways. Overall, the studies demonstrated that postoperative non-ICU care for elective craniotomies led to length of stay reduction ranging from 6 hours to 4 days and notable cost reductions. Across 13 studies, 53 of the 2,469 patients (2.1%) intended for postoperative management in a non-ICU setting required subsequent care escalation.Overall, these studies suggest that non-ICU care pathways for appropriately selected postcraniotomy patients may represent a meaningful opportunity to improve care value. However, included studies varied greatly in patient selection, postoperative care protocol, and outcomes reporting. Standardization and multi-institutional collaboration are needed to draw definitive conclusions regarding non-ICU postoperative care for elective craniotomy.

AIM: The “2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage” replaces the 2012 “Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage.” The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage. METHODS: A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. STRUCTURE: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients’ and their families’ and caregivers’ interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

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.

Cerebral autoregulation (CA) prevents brain injury by maintaining a relatively constant cerebral blood flow despite fluctuations in cerebral perfusion pressure. This process is disrupted consequent to various neurologic pathologic processes, which may result in worsening neurologic outcomes. Herein, we aim to highlight evidence describing CA changes and the impact of CA monitoring in patients with cerebrovascular disease, including ischemic stroke, intracerebral hemorrhage (ICH), and aneurysmal subarachnoid hemorrhage (aSAH). The study was preformed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. English language publications were identified through a systematic literature conducted in Ovid Medline, PubMed, and Embase databases. The search spanned the dates of each database's inception through January 2021. We selected case-control studies, cohort observational studies, and randomized clinical trials for adult patients (≥ 18 years) who were monitored with continuous metrics using transcranial Doppler, near-infrared spectroscopy, and intracranial pressure monitors. Of 2799 records screened, 48 studies met the inclusion criteria. There were 23 studies on ischemic stroke, 18 studies on aSAH, 5 studies on ICH, and 2 studies on systemic hypertension. CA impairment was reported after ischemic stroke but generally improved after tissue plasminogen activator administration and successful mechanical thrombectomy. Persistent impairment in CA was associated with hemorrhagic transformation, malignant cerebral edema, and need for hemicraniectomy. Studies that investigated large ICHs described bilateral CA impairment up to 12 days from the ictus, especially in the presence of small vessel disease. In aSAH, impairment of CA was associated with angiographic vasospasm, delayed cerebral ischemia, and poor functional outcomes at 6 months. This systematic review highlights the available evidence for CA disruption during cerebrovascular diseases and its possible association with long-term neurological outcome. CA may be disrupted even before acute stroke in patients with untreated chronic hypertension. Monitoring CA may help in establishing individualized management targets in patients with cerebrovascular disease.

Background: We evaluated the effect of persistent hyperglycemia on outcomes in 1000 patients with intracerebral hemorrhage enrolled within 4.5 hours of symptom onset. Methods: We defined moderate and severe hyperglycemia based on serum glucose levels ≥140 mg/dL— Results: In the multivariate analysis, both moderate (odds ratio, 1.8 [95% CI, 1.1–2.8]) and severe (odds ratio, 1.8 [95% CI, 1.2–2.7]) hyperglycemia were associated with higher 90-day death or disability after adjusting for Glasgow Coma Scale score, hematoma volume, presence or absence of intraventricular hemorrhage, hyperlipidemia, cigarette smoking, and hypertension (no interaction between hyperglycemia and preexisting diabetes, P =0.996). Among the patients without preexisting diabetes, both moderate (odds ratio, 1.8 [95% CI, 1.0–3.2]) and severe (odds ratio, 2.0 [95% CI, 1.1–3.7]) hyperglycemia were associated with 90-day death or disability after adjusting for above mentioned potential confounders. Among the patients with preexisting diabetes, moderate and severe hyperglycemia were not associated with 90-day death or disability. Conclusions: Persistent hyperglycemia, either moderate or severe, increased the risk of death or disability in nondiabetic patients with intracerebral hemorrhage. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01176565.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of stroke frequently affecting young to middle-aged adults, with an unmet need to improve outcome. This special report focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress, arriving at a Delphi-based global consensus regarding the pathophysiological role of extracellular hemoglobin and research priorities for clinical translation of hemoglobin-scavenging therapeutics. After aneurysmal subarachnoid hemorrhage, erythrocyte lysis generates cell-free hemoglobin in the cerebrospinal fluid, which is a strong determinant of secondary brain injury and long-term clinical outcome. Haptoglobin is the body’s first-line defense against cell-free hemoglobin by binding it irreversibly, preventing translocation of hemoglobin into the brain parenchyma and nitric oxide-sensitive functional compartments of cerebral arteries. In mouse and sheep models, intraventricular administration of haptoglobin reversed hemoglobin-induced clinical, histological, and biochemical features of human aneurysmal subarachnoid hemorrhage. Clinical translation of this strategy imposes unique challenges set by the novel mode of action and the anticipated need for intrathecal drug administration, necessitating early input from stakeholders. Practising clinicians (n=72) and scientific experts (n=28) from 5 continents participated in the Delphi study. Inflammation, microvascular spasm, initial intracranial pressure increase, and disruption of nitric oxide signaling were deemed the most important pathophysiological pathways determining outcome. Cell-free hemoglobin was thought to play an important role mostly in pathways related to iron toxicity, oxidative stress, nitric oxide, and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field was ready for an early phase trial. The highest research priorities were related to confirming haptoglobin’s anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics, and outcome measure selection. These results highlight the need for early phase trials of intracranial haptoglobin for aneurysmal subarachnoid hemorrhage, and the value of early input from clinical disciplines on a global scale during the early stages of clinical translation.

Introduction: Cerebral infarction from delayed cerebral ischemia (DCI) is a leading cause of poor neurological outcome after aneurysmal subarachnoid hemorrhage (aSAH). We performed an international clinical practice survey to identify monitoring and management strategies for cerebral vasospasm associated with DCI in aSAH patients requiring intensive care unit admission. Methods: The survey questionnaire was available on the European Society of Intensive Care Medicine (May 2021-June 2022) and Neurocritical Care Society (April - June 2022) websites following endorsement by these societies. Results: There were 292 respondents from 240 centers in 38 countries. In conscious aSAH patients or those able to tolerate an interruption of sedation, neurological examination was the most frequently used diagnostic modality to detect delayed neurological deficits related to DCI caused by cerebral vasospasm (278 respondents, 95.2%), while in unconscious patients transcranial Doppler/cerebral ultrasound was most frequently used modality (200, 68.5%). Computed tomography angiography was mostly used to confirm the presence of vasospasm as a cause of DCI. Nimodipine was administered for DCI prophylaxis by the majority of the respondents (257, 88%), mostly by an enteral route (206, 71.3%). If there was a significant reduction in arterial blood pressure after nimodipine administration, a vasopressor was added and nimodipine dosage unchanged (131, 45.6%) or reduced (122, 42.5%). Induced hypertension was used by 244 (85%) respondents as first-line management of DCI related to vasospasm; 168 (59.6%) respondents used an intra-arterial procedure as second-line therapy. Conclusions: This survey demonstrated variability in monitoring and management strategies for DCI related to vasospasm after aSAH. These findings may be helpful in promoting educational programs and future research.

Background and aims Nicardipine has strong, rapidly acting antihypertensive activity. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine after onset of intracerebral hemorrhage on clinical outcomes were determined. Methods A systematic review and individual participant data analysis of articles before 1 October 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving hyperacute intracerebral hemorrhage adults treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale were eligible. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4–6, and hematoma expansion, defined as an increase ≥6 mL from baseline to 24-h computed tomography. Summary of review Three studies met the eligibility criteria. For 1265 patients enrolled (age 62.6 ± 13.0 years, 484 women), death or disability occurred in 38.2% and hematoma expansion occurred in 17.4%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio (aOR) 1.12, 95% confidence interval (CI) 1.00–1.26 per 10 mmHg) and hematoma expansion (1.16, 1.02–1.32). Mean hourly systolic blood pressure from 1 h to any timepoint during the initial 24 h was positively associated with death or disability. Later achievement of systolic blood pressure to ≤140 mmHg increased the risk of death or disability (aOR 1.02, 95% CI 1.00–1.05 per hour). Conclusions Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h in hyperacute intracerebral hemorrhage was associated with lower risks of hematoma expansion and 90-day death or disability without increasing serious adverse events.

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.

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.

Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality despite advances in management. We evaluated the prognostic significance of a qualitative score using brain magnetic resonance imaging (MRI) features obtained early after aSAH. Patients with aSAH were enrolled in a prospective observational cohort and underwent brain MRI during their acute hospitalization. MRIs were rated using a scoring system that considers the anatomical location of signal intensity changes on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences. The relationship between MRI scores and functional outcome defined by modified Rankin scale (mRS) at 6 months was evaluated in uni- and multivariable models. The cohort included 45 aSAH patients (median World Federation of Neurologic Surgeons (IQR) 2 (1–4)) who underwent brain MRI a mean (SD) of 9.0 ± 8.0 days after aSAH. At 6 months after aSAH, 26 patients had achieved a favorable outcome (mRS ≤ 2) while 15 had an unfavorable outcome (mRS > 2). Deep gray nuclei (DGN) score (p = 0.016), cortex + DGN score (p = 0.015), FLAIR score (p = 0.016), DWI score (p = 0.0045), and overall score (p = 0.0081) were significantly lower in patients with favorable outcome compared to those with unfavorable outcome. However, MRI scores were not independent predictors of outcome in multivariable models adjusting for admission Hunt and Hess, Glasgow Coma Scale, or World Federation of Neurologic Surgeons scales. In this pilot study, a qualitative scoring system using anatomically defined MRI FLAIR and DWI signal abnormalities identified in the acute phase of aSAH was linked to 6-month functional outcome. However, these scores did not add prognostic value to established indices of neurological severity.

The coronavirus disease 2019 pandemic may require rationing of various medical resources if demand exceeds supply. Theoretical frameworks for resource allocation have provided much needed ethical guidance, but hospitals still need to address objective practicalities and legal vetting to operationalize scarce resource allocation schemata. To develop operational scarce resource allocation processes for public health catastrophes, including the coronavirus disease 2019 pandemic, five health systems in Maryland formed a consortium-with diverse expertise and representation-representing more than half of all hospitals in the state. Our efforts built on a prior statewide community engagement process that determined the values and moral reference points of citizens and health-care professionals regarding the allocation of ventilators during a public health catastrophe. Through a partnership of health systems, we developed a scarce resource allocation framework informed by citizens' values and by general expert consensus. Allocation schema for mechanical ventilators, ICU resources, blood components, novel therapeutics, extracorporeal membrane oxygenation, and renal replacement therapies were developed. Creating operational algorithms for each resource posed unique challenges; each resource's varying nature and underlying data on benefit prevented any single algorithm from being universally applicable. The development of scarce resource allocation processes must be iterative, legally vetted, and tested. We offer our processes to assist other regions that may be faced with the challenge of rationing health-care resources during public health catastrophes.

OBJECTIVES:Stroke is commonly reported in patients receiving venovenous extracorporeal membrane oxygenation, but risk factors are not well described. We sought to determine preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors for both ischemic and hemorrhagic strokes in patients with venovenous extracorporeal membrane oxygenation support.DESIGN:Retrospective analysis.SETTING:Data reported to the Extracorporeal Life Support Organization by 366 extracorporeal membrane oxygenation centers from 2013 to 2019.PATIENTS:Patients older than 18 years supported with a single run of venovenous extracorporeal membrane oxygenation.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Of 15,872 venovenous extracorporeal membrane oxygenation patients, 812 (5.1%) had at least one type of acute brain injury, defined as ischemic stroke, hemorrhagic stroke, or brain death. Overall, 215 (1.4%) experienced ischemic stroke and 484 (3.1%) experienced hemorrhagic stroke. Overall inhospital mortality was 36%, but rates were higher in those with ischemic or hemorrhagic stroke (68% and 73%, respectively). In multivariable analysis, preextracorporeal membrane oxygenation pH (adjusted odds ratio = 0.10; 95% CI, 0.03-0.35; p < 0.001), hemolysis (adjusted odds ratio = 2.27; 95% CI, 1.22-4.24; p = 0.010), gastrointestinal hemorrhage (adjusted odds ratio = 2.01; 95% CI 1.12-3.59; p = 0.019), and disseminated intravascular coagulation (adjusted odds ratio = 3.61; 95% CI, 1.51-8.66; p = 0.004) were independently associated with ischemic stroke. Pre-extracorporeal membrane oxygenation pH (adjusted odds ratio = 0.28; 95% CI, 0.12-0.65; p = 0.003), preextracorporeal membrane oxygenation Po-2 (adjusted odds ratio = 0.96; 95% CI, 0.93-0.99; p = 0.021), gastrointestinal hemorrhage (adjusted odds ratio = 1.70; 95% CI, 1.15-2.51; p = 0.008), and renal replacement therapy (adjusted odds ratio=1.57; 95% CI, 1.22-2.02; p < 0.001) were independently associated with hemorrhagic stroke.CONCLUSIONS:Among venovenous extracorporeal membrane oxygenation patients in the Extracorporeal Life Support Organization registry, approximately 5% had acute brain injury. Mortality rates increased two-fold when ischemic or hemorrhagic strokes occurred. Risk factors such as lower pH and hypoxemia during the pericannulation period and markers of coagulation disturbances were associated with acute brain injury. Further research on understanding preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors and the timing of acute brain injury is necessary to develop appropriate prevention and management strategies.

Improving neurosurgical quality metrics necessitates the analysis of patient safety indicator (PSI) 04, a measure of failure to rescue (FTR).To demonstrate that PSI 04 is not an appropriate measure for capturing FTR within neurosurgery.We conducted a single-center retrospective cohort study. Patients from January 1, 2017 to June 1, 2021, who sustained a PSI 04-attributed complication (pneumonia, deep vein thrombosis/pulmonary embolism, sepsis, shock/cardiac arrest, or gastrointestinal hemorrhage/acute ulcer), underwent a neurosurgical procedure, had inpatient mortality, and were identified using patient safety indicator 04 (PSI 04) tracking algorithm. The primary outcome was whether the attributed PSI 04 designation was the primary driver of mortality.We identified 67 patients who met the PSI 04 criteria (median age, 61 years; female sex, 43.4%). Nearly 20% of patients met the PSI complication criteria before admission. Patients who underwent emergent bedside procedures were more likely to present with a poor Glasgow Coma Scale (P = .016), more likely to be intubated before admission (P = .016), and less likely to have mortality due to a PSI 04-related complication (P = .002). PSI 04-related complications were identified as the cause of death in only 43.2% of cases. Procedures occurring in the interventional radiology suite (odds ratio, 23.2; 95% CI, 3.5-229.3; P = .003) or the operating room (odds ratio, 6.2; 95% CI, 1.25-39.5; P = .03) were more likely to have mortality because of a PSI 04-related complication compared with bedside procedures.In total, 65.7% of patients were inappropriately flagged as meeting PSI 04 criteria. PSI 04 currently identifies patients with complications unrelated to operating room procedures. Improvement in patient safety within neurosurgery necessitates the development of a subspecialty specific measure to capture FTR.

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 Management of stroke patients in the acute setting is a high-stakes task with several challenges including the need for rapid assessment and treatment, maintenance of high-performing team dynamics, management of cognitive load affecting providers, and factors impacting team communication. Crisis resource management (CRM) provides a framework to tackle these challenges and is well established in other resuscitative disciplines. The current Coronavirus Disease 2019 (COVID-19) pandemic has exposed a potential quality gap in emergency preparedness and the ability to adapt to emergency scenarios in real time. Methods Available resources in the literature in other disciplines and expert consensus were used to identify key elements of CRM as they apply to acute stroke management. Results We outline essential ingredients of CRM as a means to mitigate nontechnical challenges providers face during acute stroke care. These strategies include situational awareness, triage and prioritization, mitigation of cognitive load, team member role clarity, communication, and debriefing. Incorporation of CRM along with simulation is an established tool in other resuscitative disciplines and can be incorporated into acute stroke care. Conclusions As stroke care processes evolve during these trying times, the importance of consistent, safe, and efficacious care facilitated by CRM principles offers a unique avenue to alleviate human factors and support high-performing teams.

Early systolic blood pressure (SBP) reduction is believed to improve outcome after spontaneous intracerebral hemorrhage (ICH), but there has been a limited assessment of SBP trajectories in individual patients. We aimed to determine the prognostic significance of SBP trajectories in ICH. We collected routine data on spontaneous ICH patients from two healthcare systems over 10 years. Unsupervised functional principal components analysis (FPCA) was used to characterize SBP trajectories over first 24 h and their relationship to the primary outcome of unfavorable shift on modified Rankin scale (mRS) at hospital discharge, categorized as an ordinal trichotomous variable (mRS 0–2, 3–4, and 5–6 defined as good, poor, and severe, respectively). Ordinal logistic regression models adjusted for baseline SBP and ICH volume were used to determine the prognostic significance of SBP trajectories. The 757 patients included in the study were 65 ± 23 years old, 56% were men, with a median (IQR) Glasgow come scale of 14 (8). FPCA revealed that mean SBP over 24 h and SBP reduction within the first 6 h accounted for 76.8% of the variation in SBP trajectories. An increase in SBP reduction (per 10 mmHg) was significantly associated with unfavorable outcomes defined as mRS > 2 (adjusted-OR = 1.134; 95% CI 1.044–1.233, P = 0.003). Compared with SBP reduction 60 mmHg, (adjusted-OR = 1.965, 95% CI 1.011, 3.846, P = 0.047). Furthermore, the association of SBP reduction and outcome varied according to initial hematoma volume. Smaller SBP reduction was associated with good outcome (mRS 0–2) in small ( 40 mmHg may be harmful in ICH patients. For early SBP reduction to have an effective therapeutic effect, both target levels and optimum SBP reduction goals vis-a-vis hematoma volume should be considered.

Patients, clinicians, and hospitals have undergone monumental changes during the coronavirus disease 2019 (COVID-19) pandemic. This crisis has forced us to consider the obligations that we neurologists have to our individual patients as well as the greater community. By returning to our fundamental understanding of these duties, we can ensure that we are providing the most ethically appropriate contingency and crisis care possible. We recommend specific adaptations to both the inpatient and outpatient settings, as well as changes to medical and trainee education. Furthermore, we explore the daunting but potentially necessary implementation of scare resource allocation protocols. As the pandemic evolves, we will need to adapt continuously to these rapidly changing circumstances and consider both national and regional standards and variation.

Background and Purpose— EG-1962 is a sustained release formulation of nimodipine administered via external ventricular drain in patients with aneurysmal subarachnoid hemorrhage. A randomized, open-label, phase 1/2a, dose-escalation study provided impetus for this study to evaluate efficacy and safety of a single intraventricular 600 mg dose of EG-1962 to patients with aneurysmal subarachnoid hemorrhage, compared with standard of care oral nimodipine. Methods— Subjects were World Federation of Neurological Surgeons grades 2–4, modified Fisher grades 2–4 and had an external ventricular drain inserted as part of standard of care. The primary end point was the proportion of subjects with favorable outcome at day 90 after aneurysmal subarachnoid hemorrhage (extended Glasgow outcome scale 6–8). The proportion of subjects with favorable outcome at day 90 on the Montreal cognitive assessment, as well as the incidence of delayed cerebral ischemia and infarction, use of rescue therapy and safety were evaluated. Results— The study was halted by the independent data monitoring board after planned interim analysis of 210 subjects (289 randomized) with day 90 outcome found the study was unlikely to achieve its primary end point. After day 90 follow-up of all subjects, the proportion with favorable outcome on the extended Glasgow outcome scale was 45% (65/144) in the EG-1962 and 42% (62/145) in the placebo group (risk ratio, 1.01 [95% CI, 0.83–1.22], P =0.95). Consistent with its mechanism of action, EG-1962 significantly reduced vasospasm (50% [69/138] EG-1962 versus 63% [91/144], P =0.025) and hypotension (7% [9/138] versus 10% [14/144]). Analysis of prespecified subject strata suggested potential efficacy in World Federation of Neurological Surgeons 3–4 subjects (46% [32/69] EG-1962 versus 32% [24/75] placebo, odds ratio, 1.22 [95% CI, 0.94–1.58], P =0.13). No safety concerns were identified that halted the study or that preclude further development. Conclusions— There was no significant increase in favorable outcome for EG-1962 compared with standard of care in the overall study population. The safety profile was acceptable. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02790632.

Optimal neurologic monitoring methods have not been characterized for patients on extracorporeal membrane oxygenation (ECMO). We assessed the feasibility of noninvasive multimodal neuromonitoring (NMN) to prognosticate outcome. In this prospective observational study, neurologic examinations, transcranial Doppler (TCD), electroencephalography (EEG), and somatosensory evoked potentials (SSEPs) were performed at prespecified intervals. Outcome at discharge was defined as favorable when modified Rankin Scale (mRS) 0-3; unfavorable when mRS >3. Of 20 patients (median age 60 years), 17 had TCDs, 13 had EEGs, and seven had SSEPs. With NMN, 17 (85%) were found to have neurologic complications. Fourteen (70%) had unfavorable outcomes. The unfavorable outcome was associated with absent EEG reactivity, coma, central cannulation, higher transfusion requirement, and higher Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores. Seven patients had both SSEPs and EEGs and exhibited intact N20 responses despite poor outcomes. Four of these seven showed absent EEG reactivity despite intact N20. Eighteen thromboembolic events were observed, 14 of which had positive microembolic signals (MESs) in TCD. All 10 patients with arterial-sided thrombotic events had positive MES. NMN caused no adverse effects. NMN during ECMO is feasible and found high neurologic complication rate. EEG and TCD showed potential for prognostication of neurologic outcome.

The Neurocritical Care Society and the Society of Critical Care Medicine have worked together to create a perspective regarding the Standards of Neurologic Critical Care Units (Moheet et al. in Neurocrit Care 29:145-160, 2018). The most neurologically ill or injured patients warrant the highest standard of care available; this supports the need for defining and establishing specialized neurological critical care units. Rather than interpreting the Standards as being exclusionary, it is most appropriate to embrace them in the setting of team-based care. Since there are many more patients than there are highly specialized beds, collaborative care and appropriate transfer agreements are essential in promoting excellent patient outcomes. This viewpoint addresses areas of clarification and emphasizes the need for collegiality and partnership in delivering the best specialty critical care to our patients.

Background Decompressive craniectomy is a lifesaving treatment for intractable intracranial hypertension. For patients who survive, a second surgery for cranial reconstruction (cranioplasty) is required. The effect of cranioplasty on intracranial pressure (ICP) is unknown. Objective To integrate the recently Food and Drug Administration-approved, fully implantable, noninvasive ICP sensor within a customized cranial implant (CCI) for postoperative monitoring in patients at high risk for intracranial hypertension. Methods A 16-yr-old female presented for cranioplasty 4-mo after decompressive hemicraniectomy for craniocerebral gunshot wound. Given the persistent transcranial herniation with concomitant subdural hygroma, there was concern for intracranial hypertension following cranioplasty. Thus, cranial reconstruction was performed utilizing a CCI with an integrated wireless ICP sensor, and noninvasive postoperative monitoring was performed. Results Intermittent ICP measurements were obtained twice daily using a wireless, handheld monitor. The ICP ranged from 2 to 10 mmHg in the supine position and from -5 to 4 mmHg in the sitting position. Interestingly, an average of 7 mmHg difference was consistently noted between the sitting and supine measurements. Conclusion This first-in-human experience demonstrates several notable findings, including (1) newfound safety and efficacy of integrating a wireless ICP sensor within a CCI for perioperative neuromonitoring; (2) proven restoration of normal ICP postcranioplasty despite severe preoperative transcranial herniation; and (3) proven restoration of postural ICP adaptations following cranioplasty. To the best of our knowledge, this is the first case demonstrating these intriguing findings with the potential to fundamentally alter the paradigm of cranial reconstruction.

Based on the relationship between hyperchloremia and mortality in critically ill patients, we investigated the effect of early hyperchloremia on 90-day outcomes in acute ischemic stroke patients.Acute ischemic stroke patients recruited within 5 h of symptom onset were analyzed. Hyperchloremia (defined as 110 mmol/L or greater) at either baseline, or 24, or 48 h after randomization was identified and classified as one occurrence or two or more occurrences. Logistic regression analyses were performed to determine the effects of hyperchloremia on: favorable outcomes (defined by a National Institutes of Health Stroke Scale and/or modified Rankin scale scores of 0-1) at 90-day, death or disability at 90-day, and death within 90-day after accounting for potential confounders.Among the total of 1275 patients, one and two or more occurrence of hyperchloremia within 48 h were seen in 191 patients and 108 patients, respectively. Compared with patients without hyperchloremia, patients with two or more occurrences of hyperchloremia at significantly higher odds of lack of favorable outcomes (odds ratio 3.0, 95% confidence interval 1.8-5.1) and death or disability (odds ratio 2.6, 95% confidence interval 1.6-4.1) at 90-day after adjustment for age, National Institutes of Health Stroke Scale score strata (6-9, 10-19, ≥ 20), study intervention, initial SBP, and intra-arterial treatment.The independent association between sustained hyperchloremia and lack of favorable outcomes at 90-day suggest that avoidance of hyperchloremia may reduce the rate of lack of favorable outcomes and death or disability in patients with acute ischemic stroke.

Objective: The aim of this study was to better define the shape of association between the degree (“magnitude”) of early (Methods: Association of the continuous magnitude of SBP reduction described using cubic splines and an ordinal measure of the functional outcome on the modified Rankin scale (mRS) scores at 90 days were analyzed in generalized linear mixed models. Models were adjusted for achieved (mean) and variability (standard deviation, SD) of SBP between 1 and 24 h, various baseline covariates, and trial as a random effect. Results: Among 3796 patients (mean age 63.1 (SD = 13.0) years; female 37.4%), with a mean magnitude ( 70 mmHg. Similar J-shape associations were evident across various time epochs across 24 h and consistent according to baseline hematoma volume and SBP and history of hypertension. Interpretation: A moderate degree of rapid SBP lowering is associated with improved functional outcome after ICH, but large SBP reductions over 1 h (e.g. from > 200 to target

Antiseizure medications (ASDs) are a class of medications used to prevent and treat seizures in a wide range of disease states. Clinicians encounter many different disease states and syndromes associated with seizures, and the role of ASDs in these settings can vary. This chapter contains information on several topics including; the current management of status epilepticus (SE) and the different ASDs and strategies used in its management; recommendations and evidence regarding ASDs in the prevention of seizures in aneurysmal subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), traumatic brain injury (TBI), hypoxic–ischemic injury (HII), and postoperative patients. This chapter first outlines some key questions in the management of SE, and seizures. The laboratory evidence section contains an overview of different ASDs and the clinical Evidence section provides information on each key question. The consensus statement section provides a summary of recommendations.

Background: Intracranial pressure (ICP) monitoring and its management in aneurysmal subarachnoid hemorrhage (aSAH) is variable worldwide. The present study aimed to explore the practice of ICP monitoring, its variability across countries, and the association with 6-month outcomes in aSAH. Methods: This was a preplanned subanalysis of SYNAPSE-ICU, a multicenter, international, prospective, observational cohort study focused on patients diagnosed with aSAH. We evaluated the variability in ICP monitoring across countries through a logistic regression model adjusted for case-mix and considered countries as a random effect. The association between ICP probe insertion and 6-month mortality and a poor neurological outcome, defined as an Glasgow Outcome Score Extended ≤ 4, was assessed by using a propensity score approach. Results: A total of 423 patients with aSAH from 92 centers across 32 countries were included in this analysis. ICP monitoring was used in 295 (69.7%) patients. Significant between-country variability in ICP insertion was observed, with an incidence ranging between 4.7% and 79.9% (median odd ratio 3.04). The median duration of ICP monitoring was 12 days (first quartile [Q1] through third quartile [Q3] range 8–18), with an overall daily median ICP value of 14 mm Hg (Q1–Q3 10–19) and a median maximum value of 21 mm Hg (Q1–Q3 16–30). Patients monitored with ICP received more aggressive therapy treatments compared with non-monitored patients (therapy intensity level, TIL, score 10.33 [standard deviation 3.61] vs. 6.3 [standard deviation 4.19], p < 0.001). In more severe patients, ICP monitoring was significantly associated with better 6-month outcome (poor neurological outcome: odds ratio 0.14, 95% confidence interval 0.02–0.53, p = 0.0113; mortality: hazard ratio 0.25, 95% confidence interval 0.13–0.49, p < 0.0001). However, no significant effect was observed in patients with both reactive pupils. Conclusions: Our cohort demonstrated high variability in ICP insertion practice among countries. A more aggressive treatment approach was applied in ICP-monitored patients. In patients with severe aSAH, ICP monitoring might reduce unfavorable outcomes and mortality at 6 months.

On the basis of increased mortality associated with hyperchloremia among critically ill patients, we investigated the effect of occurrence of early hyperchloremia on death or disability at 90 days in patients with intracerebral hemorrhage (ICH).We analyzed the data from Antihypertensive Treatment of Cerebral Hemorrhage 2 trial, which recruited patients with spontaneous ICH within 4.5 h of symptom onset. Patients with increased serum chloride levels (110 mmol/L or greater) at either baseline or 24, 48, or 72 h after randomization were identified. We further graded hyperchloremia into one occurrence or two or more occurrences within the first 72 h. Two logistic regression analyses were performed to determine the effects of hyperchloremia on (1) death within 90 days and (2) death or disability at 90 days after adjustment for potential confounders.Among the total of 1,000 patients analyzed, hyperchloremia within 72 h was seen in 114 patients with one occurrence and in 154 patients with two or more occurrences. Patients with one occurrence of hyperchloremia (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.1-5.5) and those with two or more occurrences (OR 2.6, 95% CI 1.3-5.0) had significantly higher odds of death within 90 days after adjustment for age, race and ethnicity, National Institutes of Health Stroke Scale score strata, hematoma volume, presence or absence of intraventricular hemorrhage, cigarette smoking, previous stroke, and maximum hourly dose of nicardipine. Patients with two or more occurrences of hyperchloremia (OR 3.4, 95% CI 2.1-5.6) had significantly higher odds of death or disability at 90 days compared with patients without hyperchloremia after adjustment for the abovementioned potential confounders.The independent association between hyperchloremia and death or disability at 90 days suggests that avoidance of hyperchloremia may reduce the observed death or disability in patients with ICH.ClinicalTrials.gov: NCT01176565.

Transcranial Doppler (TCD)/transcranial color-coded duplex sonography (TCCS) is a common tool and has become a fundamental element of the armament in the diagnostic research of neurocritical care and stroke units. The role of TCD/TCCS in acute ischemic stroke is primarily in the detection of middle cerebral artery occlusion, its reperfusion and re-occlusion, monitoring of microembolic signals, and documentation and follow-up of cerebral arterial stenosis. In those patients treated with thrombectomy, TCD can be used at the beginning of the evaluation of the patient with acute ischemic stroke to document the initial findings and once treatment has been received, intermittent evaluation is continued to examine the changes in flow velocity of the affected vessels.

The majority of neurological disorders exist in low- and middle-income countries, but these nations have the fewest neurologists and neurological training opportunities worldwide. The objective of this study was to assess the effectiveness, relevance, and feasibility of a five-day neurocritical care course delivered online to African healthcare workers and to understand participants' prior neurological and neurocritical care training experiences. We offered the Neurocritical Care Society's Emergency Neurological Life Support (ENLS) course covering 14 neurocritical conditions via Zoom to 403 African healthcare workers over a 4-day period. An additional day was devoted to management of neurological emergencies in resource-limited settings. Participants completed pre- and post-course surveys to assess the effectiveness, relevance, and feasibility of the overall course to their settings. 318 participants (46% female; 56% residents; 24% neurologists; 9.0 ± 6.7 years practicing medicine) from 11 African countries completed the pre-course self-assessment, and 232 completed the post-course self-assessment. 97% reported prior experience caring for patients with neurological emergencies but only 35% reported prior neurology training and 9% prior neurocritical care training. Pre-course and post-course comfort levels showed statistically significant improvements (p 0.001) across all fourteen neurocritical topics. 95% of participants found the course relevant to their current practice setting, 94% agreed the Zoom online platform was easy to use, and 93% reported it facilitated their learning. Suggestions for course improvement included addition of non-critical neurological conditions and inclusion of locally available diagnostics and treatment modalities. Study results suggest virtual platforms may offer a way to improve neurology training in areas with reduced neurological workforce.