Search

Background: Although larger hematoma volume is associated with worse outcome after intracerebral hemorrhage (ICH), the association between perihematomal edema (PHE) volume and outcome remains uncertain, as does the impact of sex on PHE and outcome. Here we aimed to determine whether larger PHE volume is associated with worse outcome and whether PHE volume trajectories differ by sex., Methods: We conducted a post hoc analysis of the Factor VIIa for Acute Hemorrhagic Stroke Treatment (FAST) trial, which randomized patients with ICH to receive recombinant activated factor VIIa or placebo. Computerized planimetry calculated PHE and ICH volumes on serial computed tomography (CT) scans (at baseline [within 3 h of onset], at 24 h, and at 72 h). Generalized estimating equations examined interactions between sex, CT time points, and FAST treatment arm on PHE and ICH volumes. Mixed and multivariable logistic models examined associations between sex, PHE, and outcomes., Results: A total of 781 patients with supratentorial ICH (mean age 65 years) were included. Compared to women (n = 296), men (n = 485) had similar median ICH (14.9 vs. 13.6 mL, p = 0.053) and PHE volumes (11.1 vs. 10.5 mL, p = 0.56) at baseline but larger ICH and PHE volumes at 24 h (19.0 vs. 14.0 mL, p < 0.001; 22.2 vs. 15.7 mL, p < 0.001) and 72 h (16.0 vs. 11.8 mL, p < 0.001; 28.7 vs. 19.9 mL, p < 0.001). Men had higher absolute early PHE expansion (p < 0.001) and more hematoma expansion (growth ≥ 33% or 6 mL at 24 h, 33% vs. 22%, p < 0.001). An interaction between sex and CT time points on PHE volume (p < 0.001), but not on ICH volume, confirmed a steeper PHE trajectory in men. PHE expansion (per 5 mL, odds radio 1.19, 95% confidence interval 1.10-1.28), but not sex, was associated with poor outcome., Conclusions: Early PHE expansion and trajectory in men were significantly higher. PHE expansion was associated with poor outcomes independent of sex. Mechanisms leading to sex differences in PHE trajectories merit further investigation., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Delirium occurs frequently in patients with stroke and neurocritical illness but is often underrecognized. We developed a novel delirium screening tool designed specifically for neurocritical care patients called the fluctuating mental status evaluation (FMSE) and aimed to test its usability and accuracy in a representative cohort of patients with intracerebral hemorrhage (ICH)., Methods: We performed a single-center prospective study in a pilot cohort of patients with ICH who had daily delirium assessments throughout their admission. Reference-standard expert ratings were performed each afternoon using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and were derived from bedside assessments and clinical data from the preceding 24 h. Paired FMSE assessments were performed by patients' clinical nurses after receiving brief one-on-one training from research staff. Nursing assessments were aggregated over 24-h periods (including day and night shifts), and accuracy of the FMSE was analyzed in patients who were not comatose to determine optimal scoring thresholds., Results: We enrolled 40 patients with ICH (mean age 71.1 ± 12.2, 55% male, median National Institutes of Health Stroke Scale score 16.5 [interquartile range 12-20]), of whom 85% (n = 34) experienced delirium during their hospitalization. Of 308 total coma-free days with paired assessments, 208 (68%) were rated by experts as days with delirium. Compared with expert ratings, FMSE scores ≥ 1 had 86% sensitivity and 73% specificity on a per-day basis, whereas FMSE scores ≥ 2 had 68% sensitivity and 82% specificity. Accuracy remained high in patients with aphasia (FMSE scores ≥ 1: 83% sensitivity, 77% specificity; FMSE scores ≥ 2: 68% sensitivity, 85% specificity) and decreased arousal (FMSE scores ≥ 1: 80% sensitivity, 100% specificity; FMSE scores ≥ 2: 73% sensitivity, 100% specificity)., Conclusions: In this pilot study, the FMSE achieved a high sensitivity and specificity in detecting delirium. Follow-up validation studies in a larger more diverse cohort of neurocritical care patients will use score cutoffs of ≥ 1 as "possible" delirium and ≥ 2 as "probable" delirium., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Although coma is commonly encountered in critical care, worldwide variability exists in diagnosis and management practices. We aimed to assess variability in coma definitions, etiologies, treatment strategies, and attitudes toward prognosis., Methods: As part of the Neurocritical Care Society Curing Coma Campaign, between September 2020 and January 2021, we conducted an anonymous, international, cross-sectional global survey of health care professionals caring for patients with coma and disorders of consciousness in the acute, subacute, or chronic setting. Survey responses were solicited by sequential emails distributed by international neuroscience societies and social media. Fleiss κ values were calculated to assess agreement among respondents., Results: The survey was completed by 258 health care professionals from 41 countries. Respondents predominantly were physicians (n = 213, 83%), were from the United States (n = 141, 55%), and represented academic centers (n = 231, 90%). Among eight predefined items, respondents identified the following cardinal features, in various combinations, that must be present to define coma: absence of wakefulness (81%, κ = 0.764); Glasgow Coma Score (GCS) ≤ 8 (64%, κ = 0.588); failure to respond purposefully to visual, verbal, or tactile stimuli (60%, κ = 0.552); and inability to follow commands (58%, κ = 0.529). Reported etiologies of coma encountered included medically induced coma (24%), traumatic brain injury (24%), intracerebral hemorrhage (21%), and cardiac arrest/hypoxic-ischemic encephalopathy (11%). The most common clinical assessment tools used for coma included the GCS (94%) and neurological examination (78%). Sixty-six percent of respondents routinely performed sedation interruption, in the absence of contraindications, for clinical coma assessments in the intensive care unit. Advanced neurological assessment techniques in comatose patients included quantitative electroencephalography (EEG)/connectivity analysis (16%), functional magnetic resonance imaging (7%), single-photon emission computerized tomography (6%), positron emission tomography (4%), invasive EEG (4%), and cerebral microdialysis (4%). The most commonly used neurostimulants included amantadine (51%), modafinil (37%), and methylphenidate (28%). The leading determinants for prognostication included etiology of coma, neurological examination findings, and neuroimaging. Fewer than 20% of respondents reported routine follow-up of coma survivors after hospital discharge; however, 86% indicated interest in future research initiatives that include postdischarge outcomes at six (85%) and 12 months (65%)., Conclusions: There is wide heterogeneity among health care professionals regarding the clinical definition of coma and limited routine use of advanced coma assessment techniques in acute care settings. Coma management practices vary across sites, and mechanisms for coordinated and sustained follow-up after acute treatment are inconsistent. There is an urgent need for the development of evidence-based guidelines and a collaborative, coordinated approach to advance both the science and the practice of coma management globally., (© 2022. The Author(s).)

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.

Background: 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., Methods: 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., Results: 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 < 20 mmHg, worse outcomes were observed for SBP reduction = 40-60 mmHg (adjusted-OR = 1.940, 95% CI 1.129-3.353, P = 0.017) and > 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 (< 7.42 mL) and medium-size (≥ 7.42 and < 30.47 mL) hematomas. Furthermore, while the likelihood of good outcome was low in those with large hematomas (≥ 30.47 mL), smaller SBP reduction was associated with decreasing probability of severe outcome (mRS 5-6)., Conclusion: Our analyses suggest that in the first 6 h SBP reduction is significantly associated with the in-hospital outcome that varies with initial hematoma volume, and early SBP reduction > 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-à-vis hematoma volume should be considered.

Background: Rapid diagnosis and proper management of intracerebral hemorrhage (ICH) play a crucial role in the outcome. Prediction of the outcome with a high degree of accuracy based on admission data including imaging information can potentially influence clinical decision-making practice., Methods: We conducted a retrospective multicenter study of consecutive ICH patients admitted between 2012-2017. Medical history, admission data, and initial head computed tomography (CT) scan were collected. CT scans were semiautomatically segmented for hematoma volume, hematoma density histograms, and sphericity index (SI). Discharge unfavorable outcomes were defined as death or severe disability (modified Rankin Scores 4-6). We compared (1) hematoma volume alone; (2) multiparameter imaging data including hematoma volume, location, density heterogeneity, SI, and midline shift; and (3) multiparameter imaging data with clinical information available on admission for ICH outcome prediction. Multivariate analysis and predictive modeling were used to determine the significance of hematoma characteristics on the outcome., Results: We included 430 subjects in this analysis. Models using automated hematoma segmentation showed incremental predictive accuracies for in-hospital mortality using hematoma volume only: area under the curve (AUC): 0.85 [0.76-0.93], multiparameter imaging data (hematoma volume, location, CT density, SI, and midline shift): AUC: 0.91 [0.86-0.97], and multiparameter imaging data plus clinical information on admission (Glasgow Coma Scale (GCS) score and age): AUC: 0.94 [0.89-0.99]. Similarly, severe disability predictive accuracy varied from AUC: 0.84 [0.76-0.93] for volume-only model to AUC: 0.88 [0.80-0.95] for imaging data models and AUC: 0.92 [0.86-0.98] for imaging plus clinical predictors., Conclusions: Multiparameter models combining imaging and admission clinical data show high accuracy for predicting discharge unfavorable outcome after ICH.

Introduction: The Common Data Elements (CDEs) initiative is a National Institute of Health/National Institute of Neurological Disorders and Stroke (NINDS) effort to standardize naming, definitions, data coding, and data collection for observational studies and clinical trials in major neurological disorders. A working group of experts was established to provide recommendations for Unruptured Aneurysms and Aneurysmal Subarachnoid Hemorrhage (SAH) CDEs., Methods: This paper summarizes the recommendations of the Hospital Course and Acute Therapies after SAH working group. Consensus recommendations were developed by assessment of previously published CDEs for traumatic brain injury, stroke, and epilepsy. Unruptured aneurysm- and SAH-specific CDEs were also developed. CDEs were categorized into "core", "supplemental-highly recommended", "supplemental" and "exploratory"., Results: We identified and developed CDEs for Hospital Course and Acute Therapies after SAH, which included: surgical and procedure interventions; rescue therapy for delayed cerebral ischemia (DCI); neurological complications (i.e. DCI; hydrocephalus; rebleeding; seizures); intensive care unit therapies; prior and concomitant medications; electroencephalography; invasive brain monitoring; medical complications (cardiac dysfunction; pulmonary edema); palliative comfort care and end of life issues; discharge status. The CDEs can be found at the NINDS Web site that provides standardized naming, and definitions for each element, and also case report form templates, based on the CDEs., Conclusion: Most of the recommended Hospital Course and Acute Therapies CDEs have been newly developed. Adherence to these recommendations should facilitate data collection and data sharing in SAH research, which could improve the comparison of results across observational studies, clinical trials, and meta-analyses of individual patient data.

Objectives: The goal for this project was to develop a comprehensive set of common data elements (CDEs), data definitions, case report forms and guidelines for use in unruptured intracranial aneurysm (UIA) and subarachnoid hemorrhage (SAH) clinical research, as part of a new joint effort between the National Institute of Neurological Disorders and Stroke (NINDS) and the National Library of Medicine of the US National Institutes of Health. These UIA and SAH CDEs will join several other neurological disease-specific CDEs that have already been developed and are available for use by research investigators., Methods: A Working Group (WG) divided into eight sub-groups and a Steering Committee comprised of international UIA and SAH experts reviewed existing NINDS CDEs and instruments, created new elements when needed and provided recommendations for UIA and SAH clinical research. The recommendations were compiled, internally reviewed by the entire UIA and SAH WG and posted online for 6 weeks for external public comments. The UIA and SAH WG and the NINDS CDE team reviewed the final version before posting the SAH Version 1.0 CDE recommendations., Results: The NINDS UIA and SAH CDEs and supporting documents are publicly available on the NINDS CDE ( https://www.commondataelements.ninds.nih.gov/#page=Default ) and NIH Repository ( https://cde.nlm.nih.gov/home ) websites. The recommendations are organized into domains including Participant Characteristics and Outcomes and Endpoints., Conclusion: Dissemination and widespread use of CDEs can facilitate UIA and SAH clinical research and clinical trial design, data sharing, and analyses of observational retrospective and prospective data. It is vital to maintain an international and multidisciplinary collaboration to ensure that these CDEs are implemented and updated when new information becomes available.

Introduction: Clinical seizures and status epilepticus are frequent complications of encephalitis, can lead to depressed level of consciousness, and are associated with poor outcome. We sought to determine the frequency, risk factors, and clinical impact of electrographic seizures detected with continuing electroencephalography (cEEG) in patients with encephalitis and altered level of consciousness., Methods: We retrospectively identified all patients with presumed or definite viral or autoimmune encephalitis who underwent cEEG monitoring at Henry Ford Hospital from January 2012 to October 2017. Clinical data and cEEG monitoring reports were abstracted and recorded. The primary outcome was electrographic seizures detected by cEEG., Results: Of 1,735 patients who underwent a minimum of 12 h of cEEG monitoring, we identified 54 with a verified discharge diagnosis of encephalitis. Twenty-two of these patients (41%) had electrographic seizures on cEEG. Compared with encephalitis patients without seizures, electrographic seizures were associated with lower serum sodium levels (137 ± 5 vs 141 ± 7, P = 0.027) and more often were on antiepileptic therapy (100% vs 78%, P = 0.033) on the first day of monitoring. Seizures were also associated with a higher frequency of cortical imaging abnormalities (68% vs 28%, P = 0.005), lateralized periodic discharges (LPDs; 50% vs 16%, P = 0.014), delta background frequency (81% vs 45%, P = 0.010), low or suppressed voltage (96% vs 62%, P = 0.005), and focal slowing (86% vs 47%, P = 0.004). There was no association between electrographic seizures and clinical outcome at discharge., Conclusion: Electrographic seizures occur in approximately 40% of patients with acute encephalitis. Low serum sodium, cortical imaging abnormalities, and on cEEG LPDs and background abnormalities are associated factors. The lack of association with short-term outcome suggests that with aggressive treatment, the clinical impact of electrographic seizures in encephalitis can be minimized.

Background: Nimodipine is the only drug approved in the treatment of aneurysmal subarachnoid hemorrhage (aSAH) in many countries. EG-1962, a product developed using the Precisa™ platform, is an extended-release microparticle formulation of nimodipine that can be administered intraventricularly or intracisternally. It was developed to test the hypothesis that delivering higher concentrations of extended-release nimodipine directly to the cerebrospinal fluid would provide superior efficacy compared to systemic administration., Results: A Phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation study determined the maximum tolerated dose and supported the safety and tolerability of EG-1962 in patients with aSAH. EG-1962, 600 mg, was selected for a pivotal, Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group efficacy, and safety study comparing it to standard of care oral nimodipine in adults with aSAH. Key inclusion criteria are patients with a ruptured saccular aneurysm repaired by clipping or coiling, World Federation of Neurological Surgeons grade 2-4, and modified Fisher score of > 1. Patients must have an external ventricular drain as part of standard of care. Patients are randomized to receive intraventricular investigational product (EG-1962 or NaCl solution) and an oral placebo or oral nimodipine in the approved dose regimen (active control) within 48 h of aSAH. The primary objective is to determine the efficacy of EG-1962 compared to oral nimodipine., Conclusions: The primary endpoint is the proportion of subjects with favorable outcome (6-8) on the Extended Glasgow Outcome Scale assessed 90 days after aSAH. The secondary endpoint is the proportion of subjects with favorable outcome on the Montreal Cognitive Assessment 90 days after aSAH. Data on safety, rescue therapy, delayed cerebral infarction, and health economics will be collected. Trail registration NCT02790632.

External ventricular drains (EVD) are essential in the early management of hydrocephalus and elevated intracranial pressure after subarachnoid hemorrhage (SAH). Once in place, management of the EVD is thought to influence long-term patient outcomes, rates of ventriculitis, incidence of delayed cerebral ischemia, need for a ventriculoperitoneal shunt, and intensive care unit (ICU) and hospital length of stay. The available evidence supports adopting early clamp trials and intermittent cerebrospinal fluid (CSF) drainage. However, a recent survey demonstrated that most neurological ICUs employ the opposite approach of continuously open EVDs and gradual weaning. In this article, we review the literature and arguments for and against the different EVD approaches. We conclude that an early clamp trial and intermittent CSF drainage can be safe and result in fewer EVD complications and shorter length of stay. Given the discrepancy between the available evidence and current practice, more studies on the optimal management of EVDs are warranted with the greatest need for multicenter prospective studies.

Background: Anemia adversely affects cerebral oxygenation and metabolism after subarachnoid hemorrhage (SAH) and is also associated with poor outcome. There is limited evidence to support the use of packed red blood cell (PRBC) transfusion to optimize brain homeostasis after SAH. The aim of this study was to investigate the effect of transfusion on cerebral oxygenation and metabolism in patients with SAH., Methods: This was a prospective observational study in a neurological intensive care unit of a university hospital. Nineteen transfusions were studied in 15 consecutive patients with SAH that underwent multimodality monitoring (intracranial pressure, brain tissue oxygen, and cerebral microdialysis). Data were collected at baseline and for 12 h after transfusion. The relationship between hemoglobin (Hb) change and lactate/pyruvate ratio (LPR) orbrain tissue oxygen (PbtO2) was tested using univariate and multivariable analyses., Results: PRBC transfusion was administered on the median post-bleed day 8. The average Hb concentration at baseline was 8.1 g/dL and increased by 2.2 g/dL after transfusion. PbtO2 increased between hours 2 and 4 post-transfusion and this increase was maintained until hour 10. LPR did not change significantly during the 12-h monitoring period. After adjusting for SpO2, cerebral perfusion pressure, and LPR, the change in Hb concentration was independently and positively associated with a change in PbtO2 (adjusted b estimate = 1.39 [95% confidence interval 0.09-2.69]; P = 0.04). No relationship between the change in Hb concentration and LPR was found., Conclusions: PRBC transfusion resulted in PbtO2 improvement without a clear effect on cerebral metabolism prior to SAH.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. EG-1962 is a sustained-release microparticle formulation of nimodipine that has shown preclinical efficacy when administered intraventricularly or intracisternally to dogs with SAH, without evidence of toxicity at doses in the anticipated therapeutic range. Thus, we propose to administer EG-1962 to humans in order to assess safety and tolerability and determine a dose to investigate efficacy in subsequent clinical studies., Methods: We describe a Phase 1/2a multicenter, controlled, randomized, open-label, dose escalation study to determine the maximum tolerated dose (MTD) and assess the safety and tolerability of EG-1962 in patients with aSAH. The study will comprise two parts: a dose escalation period (Part 1) to determine the MTD of EG-1962 and a treatment period (Part 2) to assess the safety and tolerability of the selected dose of EG-1962. Patients with a ruptured saccular aneurysm treated by neurosurgical clipping or endovascular coiling will be considered for enrollment. Patients will be randomized to receive either EG-1962 (study drug: nimodipine microparticles) or oral nimodipine in the approved dose regimen (active control) within 60 h of aSAH., Results: Primary objectives are to determine the MTD and the safety and tolerability of the selected dose of intraventricular EG-1962 as compared to enteral nimodipine. The secondary objective is to determine release and distribution by measuring plasma and CSF concentrations of nimodipine. Exploratory objectives are to determine the incidence of delayed cerebral infarction on computed tomography, clinical features of delayed cerebral ischemia, angiographic vasospasm, and incidence of rescue therapy and clinical outcome. Clinical outcome will be determined at 90 days after aSAH using the extended Glasgow outcome scale, modified Rankin scale, Montreal cognitive assessment, telephone interview of cognitive status, and Barthel index., Conclusion: Here, we describe a Phase 1/2a multicenter, controlled, randomized, open-label, dose escalation study to determine the MTD and assess the safety and tolerability of EG-1962 in patients with aSAH.

Background: Mechanical ventilation is frequently performed in patients with ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). In this study, we used statewide administrative claims data to examine the rates of use, associated conditions, and in-hospital mortality rates for mechanically ventilated stroke patients., Methods: We used statewide administrative claims data from three states and ICD-9-CM codes to identify patients admitted with stroke and those who received mechanical ventilation and tracheostomy. Descriptive statistics and exact 95 % confidence intervals were used to report rates of mechanical ventilation, tracheostomy, and in-hospital mortality. Logistic regression analysis was performed to identify conditions associated with mechanical ventilation based on previously described risk factors., Results: 798,255 hospital admissions for stroke were identified. 12.5 % of these patients underwent mechanical ventilation. This rate varied by stroke type: 7.9 % for IS, 29.9 % for ICH, and 38.5 % for SAH. Increased age was associated with a decreased risk of receiving mechanical ventilation (RR per decade, 0.91). Of stroke patients who underwent mechanical ventilation, 16.3 % received a tracheostomy. Mechanical ventilation was more likely to occur in association with status epilepticus (RR, 5.1), pneumonia (RR, 4.9), sepsis (RR, 3.6), and hydrocephalus (RR, 3.3). In-hospital mortality rate for mechanically ventilated stroke patients was 52.7 % (46.8 % for IS, 61.0 % for ICH, and 54.6 % for SAH)., Conclusions: In this large population-based sample, over half of mechanically ventilated stroke patients died in the hospital despite the fact that younger patients were more likely to receive mechanical ventilation. Future studies are indicated to elucidate mechanical ventilation strategies to optimize long-term outcomes after severe stroke.

Background: It is common for patients who die from subarachnoid hemorrhage to have a focus on comfort measures at the end of life. The potential role of ethnicity in end-of-life decisions after brain injury has not been extensively studied., Methods: Patients with subarachnoid hemorrhage were prospectively followed in an observational database. Demographic information including ethnicity was collected from medical records and self-reported by patients or their family. Significant in-hospital events including do-not-resuscitate orders, comfort measures only orders (CMO; care withheld or withdrawn), and mortality were recorded prospectively., Results: 1255 patients were included in our analysis: 650 (52 %) were White, 387 (31 %) Hispanic, and 218 (17 %) Black. Mortality was similar between the groups. CMO was more commonly observed in Whites (14 %) compared to either Blacks (10 %) or Hispanics (9 %) (p = 0.04). In a multivariate analysis controlling for age and Hunt-Hess grade, Hispanics were less likely to have CMO than Whites (OR, 0.6; 95 %CI, 0.4-0.9; p = 0.02). Of the 229 patients who died, 77 % of Whites had CMO compared to 54 % of Blacks and 49 % of Hispanics (p < 0.01). In a multivariate analysis, Blacks (OR, 0.3; 95 %CI, 0.2-0.7; p < 0.01) and Hispanics (OR, 0.3; 95 %CI, 0.2-0.6; p < 0.01) were less likely to die with CMO orders than Whites., Conclusion: After subarachnoid hemorrhage, Blacks and Hispanics are less likely to die with CMO orders than Whites. Further research to confirm and investigate the causes of these ethnic differences should be performed.

Large hemispheric infarction (LHI), also known as malignant middle cerebral infarction, is a devastating disease associated with significant disability and mortality. Clinicians and family members are often faced with a paucity of high quality clinical data as they attempt to determine the most appropriate course of treatment for patients with LHI, and current stroke guidelines do not provide a detailed approach regarding the day-to-day management of these complicated patients. To address this need, the Neurocritical Care Society organized an international multidisciplinary consensus conference on the critical care management of LHI. Experts from neurocritical care, neurosurgery, neurology, interventional neuroradiology, and neuroanesthesiology from Europe and North America were recruited based on their publications and expertise. The panel devised a series of clinical questions related to LHI, and assessed the quality of data related to these questions using the Grading of Recommendation Assessment, Development and Evaluation guideline system. They then developed recommendations (denoted as strong or weak) based on the quality of the evidence, as well as the balance of benefits and harms of the studied interventions, the values and preferences of patients, and resource considerations.

Background: In subarachnoid hemorrhage (SAH), brain injury visible within 48 h of onset may impact on admission neurological disability and 3-month functional outcome. With volumetric MRI, we measured the volume of brain injury visible after SAH, and assessed the association with admission clinical grade and 3-month functional outcome., Methods: Retrospective cohort study conducted in the Neurocritical Care Division, Columbia University Medical Center, New York, USA. On brain MRI acquired within 48 h of SAH-onset and before aneurysm-securing (n = 27), two blinded readers measured DWI and FLAIR-lesion volumes using semi-automated, computer segmentation software., Results: Compared to post-resuscitation Hunt-Hess grade 1-3 (70 %), high-grade patients (30 %) had higher lesion volumes on DWI (34 ml [IQR: 0-64] vs. 2 ml [IQR: 0.5-7], P = 0.02) and on FLAIR (81 ml [IQR: 24-127] vs. 3 ml [IQR: 0-27], P = 0.02). On DWI, each 10 ml increase in lesion volume was associated with a 101 %-increase in the odds of presenting with 1 grade more in the Hunt-Hess scale (aOR 2.01, 95 % CI 1.10-3.68, P = 0.02), but was not significantly associated with 3-month outcome. On FLAIR, each 10 ml increase in lesion volume was associated with 34 % higher odds of a 1-point increase on the Hunt-Hess scale (aOR 1.34, 95 % CI 1.06-1.68, P = 0.01) and 139 % higher odds of a 1-point increase on the 3-month mRS (aOR 2.39, 95 % CI 1.13-5.07, P = 0.02)., Conclusion: The volume of brain injury visible on DWI and FLAIR within 48 h after SAH is proportional to neurological impairment on admission. Moreover, FLAIR-imaging implicates chronic brain injury-predating SAH-as potentially relevant cause of poor functional outcome.

Background: We sought to determine whether therapeutic temperature modulation (TTM) to treat fever after intracerebral hemorrhage (ICH) is associated with improved hospital complications and discharge outcomes., Methods: We performed a retrospective case-control study of patients admitted with spontaneous ICH having two consecutive fevers ≥38.3 °C despite acetaminophen administration. Cases were enrolled from a prospective database of patients receiving TTM from 2006 to 2010. All cases received TTM for fever control with goal temperature of 37 °C with a shiver-control protocol. Controls were matched in severity by ICH score and retrospectively obtained from 2001 to 2004, before routine use of TTM for ICH. Primary outcome was discharge-modified Rankin score., Results: Forty patients were enrolled in each group. Median admission ICH Score, ICH volume, and GCS were similar. TTM was initiated with a median of 3 days after ICH onset and for a median duration of 7 days. Mean daily T max was significantly higher in the control group over the first 12 days (38.1 vs. 38.7 °C, p ≤ 0.001). The TTM group had more days of IV sedation (median 8 vs. 1, p < 0.001) and mechanical ventilation (18 vs. 9, p = 0.003), and more frequently underwent tracheostomy (55 vs. 23 %, p = 0.005). Mean NICU length of stay was longer for TTM patients (15 vs. 11 days, p = 0.007). There was no difference in discharge outcomes between the two groups (overall mortality 33 %, moderate or severe disability 67 %)., Conclusions: Therapeutic normothermia is associated with increased duration of sedation, mechanical ventilation, and NICU stay, but is not clearly associated with improved discharge outcome.

Background: We sought to determine if monitoring heart rate variability (HRV) would enable preclinical detection of secondary complications after subarachnoid hemorrhage (SAH)., Methods: We studied 236 SAH patients admitted within the first 48 h of bleed onset, discharged after SAH day 5, and had continuous electrocardiogram records available. The diagnosis and date of onset of infections and DCI events were prospectively adjudicated and documented by the clinical team. Continuous ECG was collected at 240 Hz using a high-resolution data acquisition system. The Tompkins-Hamilton algorithm was used to identify R-R intervals excluding ectopic and abnormal beats. Time, frequency, and regularity domain calculations of HRV were generated over the first 48 h of ICU admission and 24 h prior to the onset of each patient's first complication, or SAH day 6 for control patients. Clinical prediction rules to identify infection and DCI events were developed using bootstrap aggregation and cost-sensitive meta-classifiers., Results: The combined infection and DCI model predicted events 24 h prior to clinical onset with high sensitivity (87 %) and moderate specificity (66 %), and was more sensitive than models that predicted either infection or DCI. Models including clinical and HRV variables together substantially improved diagnostic accuracy (AUC 0.83) compared to models with only HRV variables (AUC 0.61)., Conclusions: Changes in HRV after SAH reflect both delayed ischemic and infectious complications. Incorporation of concurrent disease severity measures substantially improves prediction compared to using HRV alone. Further research is needed to refine and prospectively evaluate real-time bedside HRV monitoring after SAH.

Introduction: Sympathetic nervous system hyperactivity is common after subarachnoid hemorrhage (SAH). We sought to determine whether uncontrolled prolonged heart rate elevation is a risk factor for adverse cardiopulmonary events and poor outcome after SAH., Methods: We prospectively studied 447 SAH patients between March 2006 and April 2012. Prior studies define prolonged elevated heart rate (PEHR) as heart rate >95 beats/min for >12 h. Major adverse cardiopulmonary events were documented according to the predefined criteria. Global outcome at 3 months was assessed with the modified Rankin Scale (mRS)., Results: 175 (39 %) patients experienced PEHR. Nonwhite race/ethnicity, admission Hunt-Hess grade ≥4, elevated APACHE-2 physiological subscore, and modified Fisher score were significant admission predictors of PEHR, whereas documented pre-hospital beta-blocker use was protective. After controlling for admission Hunt-Hess grade, Cox regression using time-lagged covariates revealed that PEHR onset in the previous 48 h was associated with an increased hazard for delayed cerebral ischemia, myocardial injury, and pulmonary edema. PEHR was associated with 3-month poor outcome (mRS 4-6) after controlling for known predictors., Conclusions: PEHR is associated with major adverse cardiopulmonary events and poor outcome after SAH. Further study is warranted to determine if early sympatholytic therapy targeted at sustained heart rate control can improve outcome after SAH.

Background: The objective of this study was to investigate the relationship between cardiac index (CI) response to a fluid challenge and changes in brain tissue oxygen pressure (PbtO(2)) in patients with subarachnoid hemorrhage (SAH)., Methods: Prospective observational study was conducted in a neurological intensive care unit of a university hospital. Fifty-seven fluid challenges were administered to ten consecutive comatose SAH patients that underwent multimodality monitoring of CI, intracranial pressure (ICP), and PbtO(2), according to a standardized fluid management protocol., Results: The relationship between CI and PbtO(2) was analyzed with logistic regression utilizing generalized estimating equations. Of the 57 fluid boluses analyzed, 27 (47 %) resulted in a ≥ 10 % increase in CI. Median absolute (+5.8 vs. +1.3 mmHg) and percent (20.7 vs. 3.5 %) changes in PbtO(2) were greater in CI responders than in non-responders within 30 min after the end of the fluid bolus infusion. In a multivariable model, a CI response was independently associated with PbtO(2) response (adjusted odds ratio 21.5, 95 % CI 1.4-324, P = 0.03) after adjusting for mean arterial pressure change and end-tidal CO(2). Stroke volume variation showed a good ability to predict CI and PbtO(2) response with areas under the ROC curve of 0.86 and 0.81 with the best cut-off values of 9 % for both responses., Conclusion: Bolus fluid resuscitation resulting in augmentation of CI can improve cerebral oxygenation after SAH.

Background: The brain is dependent on glucose to meet its energy demands. We sought to evaluate the potential importance of impaired glucose transport by assessing the relationship between brain/serum glucose ratios, cerebral metabolic distress, and mortality after severe brain injury., Methods: We studied 46 consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring. Continuous insulin infusion was used to maintain target serum glucose levels of 80-120 mg/dL (4.4-6.7 mmol/L). General linear models of logistic function utilizing generalized estimating equations were used to relate predictors of cerebral metabolic distress (defined as a lactate/pyruvate ratio [LPR] ≥ 40) and mortality., Results: A total of 5,187 neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133 mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and baseline Glasgow Coma Scale score (P < 0.0001), brain/serum glucose ratios below the median of 0.12 were independently associated with an increased risk of metabolic distress (adjusted OR = 1.4 [1.2-1.7], P < 0.001). Low brain/serum glucose ratios were also independently associated with in-hospital mortality (adjusted OR = 6.7 [1.2-38.9], P < 0.03) in addition to Glasgow Coma Scale scores (P = 0.029)., Conclusions: Reduced brain/serum glucose ratios, consistent with impaired glucose transport across the blood brain barrier, are associated with cerebral metabolic distress and increased mortality after severe brain injury.

Background: Intracerebral hemorrhage (ICH) causes 15 % of strokes annually in the United States., Methods: Using the National Hospital Discharge Survey, we studied the disposition and mortality trends of ICH admissions from 1979 to 2008. Cases were identified using the International Classification of Disease, 9th Revision, Clinical-Modification code 431., Results: There was an annualized increase in the admission rate of ICH from about an average of 24,000 cases (12.9 per 100,000 persons per year) during the first epoch to 40,600 cases (17.0 per 100,000 persons per year) during the second epoch. Thereafter, the annual admission rate after ICH remained stable with about 63,000 cases (21 per 100,000 persons per year) during the last epoch. Nonwhites experienced higher growth rates than whites, and the risk of ICH was higher across all age subgroups, in men than women, and nonwhites compared with whites. In-hospital mortality after ICH fell significantly from 45 % (95 % CI, 31-59 %) during the first epoch (1979-1983) to 34 % (95 % CI, 20-38 %) during the second epoch (1984-1988) (p = 0.03) but did not change significantly after that. Groups with higher in-hospital mortality were whites, women, and persons older than 65 years, black women younger than 45 years, and middle-aged black men. Average days of care for ICH hospitalizations decreased significantly., Conclusion: Though the ICH admission rate increased and the in-hospital mortality decreased during the first epochs of the study, these have not significantly changed over the last two decades. ICH remains the most severe form of stroke with limited options to improve survival. More research targeting novel therapies to improve outcomes after ICH is desperately needed.

Background: Altered cerebral vasomotor reactivity leading to vasospasm can be seen both in patients with primary headache disorders (PHD) and in patients with subarachnoid hemorrhage (SAH). The pathogenesis of vasospasm in post-SAH patients and in headache disorder sufferers may be related. To address this hypothesis, we analyzed a large cohort of SAH patients to determine whether a diagnosis of PHD predisposes to vasospasm, delayed cerebral ischemia, or worsened clinical outcome., Methods: Prospectively collected data from patients enrolled in the SAH Outcomes Project between 1996 and 2006 were analyzed. Patients were segregated based on whether they had a diagnosis of PHD or not and were subsequently compared for differences in clinical and radiographic outcome., Results: A total of 921 SAH patients were analyzed, 265 of which had a diagnosis of PHD. In total, symptomatic vasospasm was seen in 17%, while angiographic vasospasm was seen in 28%. Vasospasm rates were similar among patients with a PHD and in those without a PHD (p > 0.05). However, on multivariate analysis new ischemic infarcts were more common in patients with a PHD as compared to patients without a PHD (p = 0.015). Functional outcomes at 3 months were similar among PHD and non-PHD patients (p > 0.05)., Conclusion: A history of PHD is associated with an increased rate of ischemic infarcts during admission for SAH. Increased rates of vasospasm within small cerebral blood vessels may be implicated. Further studies are warranted to more closely link the mechanisms of vasospasm in PHD and SAH patients.

Background: Fever and hematoma growth are known to be independent predictors of poor outcome after intracerebral hemorrhage (ICH). We sought to assess the distribution of temperature at different stages in relation to hematoma growth and functional outcome at 90 days in a cohort of ICH patients., Methods: Data of patients registered in the Virtual International Stroke Trials Archive--ICH were analyzed. Temperatures at baseline, 24, 48, 72, and 168 h were assessed in relation to the hematoma growth and functional outcome at 90 days. We calculated the daily linear variation of each subject's temperature by subtracting 37 °C from the maximal daily recorded temperature (delta-temperature). We used logistic regression and mixed-effects models to identify factors associated with hematoma growth, poor outcome, and temperature elevation after ICH., Results: 303 patients were included in the analysis. The average age was 66 ± 12 years, 200 (66 %) were males, median admission NIHSS was 13 [Interquartile range (IQR), 9-18), median GCS was 15 (IQR, 14-15). Hematoma growth occurred in 22 % and poor functional outcome at 90-days occurred in 41 % of the patients. Cumulative delta-temperature at 72 h was associated with hematoma growth; age, ICH score, hematoma growth, and cumulative delta-temperature at 168 h were associated with poor outcome at 90 days. Factors associated with fever in mixed-models were day after onset of ICH, hypertension, base hematoma volume, intraventricular-hemorrhage, pneumonia, and hematoma growth., Conclusions: There is a temporal and independent association between fever and hematoma growth. Fever after ICH is associated with poor outcome at 90 days. Future research is needed to study the mechanisms of this phenomenon and if early protocols of temperature modulation would be associated with improved outcomes after ICH.

Background: Nicardipine and labetalol are two commonly used antihypertensives for treating elevated blood pressures in the setting of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). There are no studies comparing these two agents as continuous infusions., Methods: A retrospective chart review was conducted of patients admitted between November 2009 and January 2011 with ICH and SAH to compare effectiveness and safety between both agents. Percent time spent at goal was set as the primary outcome. The secondary outcomes included blood pressure variability, time to goal, incidence of bradycardia, tachycardia, and hypotension., Results: A total of 81 patients were available for analysis, 10 initiated on labetalol (LAB), 57 on nicardipine (NIC), and 14 required the combination of these agents (COMB) to reach goal. We found no difference between NIC, LAB, and the COMB groups in the median percent time at goal [88 % (61-98); 93 % (51-99); 66 % (25-95), (p = NS)]. Median percentage of blood pressure variability, hypotension, and bradycardia were also comparable between groups, however, more tachycardia was observed in the COMB group versus both LAB and NIC groups (45 vs. 0 vs. 3 %; p < 0.001). Mean time to goal SBP in 24 patients who had BP readings available at 1st h of initiation was 32 ± 34 min in the NIC group and 53 ± 42 min in the LAB group (p = 0.03)., Conclusions: Both agents appear equally effective and safe for blood pressure control in SAH and ICH during the initial admission hours. A prospective study is needed to validate these findings.

Background: Periodic epileptiform discharges (PEDs) are a frequent finding in comatose patients undergoing continuous EEG (cEEG) monitoring, but their clinical significance is unclear. PET and SPECT studies indicate that PEDs can be associated with focal hypermetabolism and hyperemia, suggesting that in some cases this pattern may be ictal and potentially harmful. We hypothesized that frequent PED activity in comatose patients is associated with reduced likelihood of recovery of consciousness., Methods: We identified all comatose patients treated in the Columbia neuro-ICU between June 2008 and August 2009 who underwent ten or more consecutive days of video cEEG monitoring (N = 67), and classified them into three groups: those with (1) prolonged PEDs (five or more consecutive days), (2) intermittent PEDs (at least one but fewer than five consecutive days), and (3) no PEDs. Outcome at discharge was assessed by the Glasgow Outcome Scale and classified as dead (GOS 1), vegetative (GOS 2), and command-following (GOS 3-5)., Results: Mean age was 56 years, mean admission Glasgow Coma Scale score was seven, and the median duration of cEEG monitoring was 18 (range 10-111) days. The most common diagnoses were hypoxic-ischemic encephalopathy (18%), subarachnoid hemorrhage (16%), epilepsy (15%), encephalitis (15%), metabolic encephalopathy (13%), and intracerebral hemorrhage (12%). 37% of patients (N = 25) had prolonged PEDs, 31% (N = 21) had intermittent PEDs, and 31% (N = 21) had no PEDs. Prolonged PEDs were associated with the presence of SIRPIDS (P = 0.009), electrographic seizures (P = 0.019), and number of AEDs administered (P < 0.0001). However, the presence of intermittent or prolonged PED activity had no impact on mortality (31% overall) or recovery of consciousness (command-following) at the time of discharge (36% overall)., Conclusion: Persistent spontaneous PED activity in comatose patients is associated with SIRPIDs and electrographic seizures, but has no impact on the likelihood of survival or recovery of consciousness.

Background: Nimodipine is the only medication shown to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH). Preliminary theories regarding the mechanism by which it prevents vasospasm have been challenged. The acute physiologic and metabolic effects of oral Nimodipine have not been examined in patients with poor-grade SAH., Methods: This is an observational study performed in 16 poor-grade SAH patients undergoing multimodality monitoring who received oral Nimodipine as part of routine clinical care. A total of 663 doses of Nimodipine were observed. Changes in physiologic measurements including MAP, CPP, ICP, P(bt)O(2), and CBF were examined., Results: Administration of oral Nimodipine was associated with a 1.33 mmHg decrease in MAP (P < 0.001) and a 1.22 mmHg decrease in CPP (P < 0.001). When administration of Nimodipine was associated with MAP decreases, P(bt)O(2) (1.03 mmHg; P < 0.001) and CBF (0.39 ml/100 g/min; P = 0.002) also decreased., Conclusions: Despite CPP targeted therapy with vasopressor medication, oral Nimodipine was associated with a decrease in MAP and CPP. When Nimodipine administration was associated with a decrease in MAP, there were concomitant drops in P(bt)O(2) and CBF. These findings suggest that MAP support after oral Nimodipine may be important to maintain adequate CBF in patients with poor-grade subarachnoid hemorrhage.

Background: Intracerebral hemorrhage (ICH) is the deadliest and most disabling form of stroke. Little is known about the causes of persistent neurological impairment among ICH survivors., Methods: Factor seven for acute hemorrhagic stroke (FAST) was a randomized, multicenter, double-blind, placebo-controlled trial conducted at 122 sites in 22 countries. Neurological impairment was evaluated according to the NIHSS in all patients at hospital admission, and at days 1, 2, 3, 15 and day 90 after ICH onset. Multivariate stepwise logistic regression was applied to identify predictors of neurological impairment 90 days after hospital admission., Results: A total of 821 patients were enrolled; 638 survivors were evaluated with the NIHSS at day 90. Mean NIHSS score at admission was 13.2 (SD 6.6), decreasing to 9.6 (SD 7.7) at day 15 and 5.1 (SD 5.5) at day 90. Twenty-five percent of patients had severe neurological impairment (NIHSS ≥ 15) at baseline compared to 6% of those alive at day 90. Neurological worsening within the first 72 h (defined as worsening of GCS of two or more points or increase in NIHSS score ≥ 4) predicted greater neurological impairment at day 90 in all models. A decrease of <10% in systolic blood pressure (SBP) within the first 24 h was significantly associated with less severe neurologic impairment compared to more severe reductions., Conclusion: Neurological deterioration within 24 h of ICH onset is a powerful determinant of persistent neurological impairment. Careful reduction of the SBP by 1–10% in the first 24 h may lower the risk.

Background: Neurological patients have lower mortality and better outcomes when cared for in specialized neurointensive care units than in general ICUs. However, little is known about how the process of care differs between these types of units., Methods: The Greater New York Hospital Association conducted a city-wide 24-h ICU prevalence survey on March 15th, 2007. Data was collected on all patients admitted to 143 ICUs in 69 different hospitals., Results: Of 1,906 ICU patients surveyed, 231 had a primary neurological diagnosis. Of these, 52 (22%) were admitted to one of 9 neuro-ICU's in NY and 179 (78%) to a medical or surgical ICU. Neurological patients in neuro-ICUs were more likely to have been transferred from an outside hospital (37% vs. 11%, P < 0.0001). Hemorrhagic stroke was more frequent in neuro-ICUs (46% vs. 16%, P < 0.0001), whereas traumatic brain injury (2% vs. 24%, P < 0.0001) and ischemic stroke (0% vs. 19%, P = 0.001) were less common. Despite a lower rate of mechanical ventilation (39% vs. 50%, P = 0.15), ICU length of stay was longer in neuro-ICU patients (≥10 days, 40% vs. 17%, P < 0.0001). More neuro-ICU patients had undergone tracheostomy (35% vs. 15%, P = 0.04), invasive hemodynamic monitoring (40% vs. 20%, P = 0.002), and invasive intracranial pressure monitoring (29% vs. 9%, P < 0.001) than patients cared for in general ICUs. Intravenous sedation was less prevalent in neuro-ICUs (12% vs. 30%, P = 0.009) and more patients were receiving nutritional support compared to general ICUs (67% vs. 39%, P < 0.001)., Conclusions: Neurological patients cared for in specialty neuro-ICUs underwent more invasive intracranial and hemodynamic monitoring, tracheostomy, and nutritional support, and received less IV sedation than patients in general ICUs. These differences in care may explain previously observed disparities in outcome between neurocritical care and general ICUs.

Background and Methods: We report the case of a young woman with delayed cerebral infarction and intracranial hypertension following subarachnoid hemorrhage requiring hemicraniectomy, who underwent multimodality neuromonitoring of the contralateral hemisphere before and after craniectomy., Results: Intracranial hypertension was preceded by signs of ischemia and impaired brain metabolism diagnosed through cerebral microdialysis and PbtO2 monitoring, as well as a decrease in cerebral perfusion pressure (CPP) to <40 mmHg despite increasing vasopressor requirements. We describe how a comprehensive multimodality neuromonitoring approach was utilized to inform the decision to perform an early decompressive hemicraniectomy. Post-operatively, CPP and intracranial pressure (ICP) normalized, and the patient was weaned off all pressors within hours. The modified Rankin score at 3 and 12 months was 5., Conclusions: Delayed rescue hemicraniectomy can be life-saving after poor grade SAH. The role of multimodality brain monitoring for determining the optimal timing of hemicraniectomy deserves further study.

Background: As the practice of aggressive temperature control has become more commonplace, new clinical problems are arising, of which shivering is the most common. Treatment for shivering while avoiding the negative consequences of many anti-shivering therapies is often difficult. We have developed a stepwise protocol that emphasizes use of the least sedating regimen to achieve adequate shiver control., Methods: All patients treated with temperature modulating devices in the neurological intensive care unit were prospectively entered into a database. Baseline demographic information, daily temperature goals, best daily GCS, and type and cumulative dose of anti-shivering agents were recorded., Results: We collected 213 patients who underwent 1388 patient days of temperature modulation. Eighty-nine patients underwent hypothermia and 124 patients underwent induced normothermia. In 18% of patients and 33% of the total patient days only none-sedating baseline interventions were needed. The first agent used was most commonly dexmeditomidine at 50% of the time, followed by an opiate and increased doses of propofol. Younger patients, men, and decreased BSA were factors associated with increased number of anti-shivering interventions., Conclusions: A significant proportion of patients undergoing temperature modulation can be effectively treated for shivering without over-sedation and paralysis. Patients at higher risk for needing more interventions are younger men with decreased BSA.

Background: Poor clinical condition is the most important predictor of neurological outcome and mortality after subarachnoid hemorrhage (SAH). Rupture of an intracranial aneurysm was shown to be associated with acute ischemic brain injury in poor grade patients in autopsy studies and small magnetic resonance imaging series., Methods: We performed diffusion-weighted magnetic resonance imaging (DWI) within 96 h of onset in 21 SAH patients with Hunt-Hess grade 4 or 5 enrolled in the Columbia University SAH Outcomes Project between July 2004 and February 2007. We analyzed demographic, radiological, clinical data, and 3 months outcome., Results: Of the 21 patients 13 were Hunt-Hess grade 5, and eight were grade 4. Eighteen patients (86%) displayed bilateral and symmetric abnormalities on DWI, but not on computed tomography (CT). Involved regions included both anterior cerebral artery territories (16 patients), and less often the thalamus and basal ganglia (4 patients), middle (6 patients) or posterior cerebral artery territories (2 patients), or cerebellum (2 patients). At 1-year, 15 patients were dead (life support had been withdrawn in 6), 2 were moderately to severely disabled (modified Rankin Scale [mRS] = 4-5), and 4 had moderate-to-no disability (mRS = 1-3)., Conclusions: Admission DWI demonstrates multifocal areas of acute ischemic injury in poor grade SAH patients. These ischemic lesions may be related to transient intracranial circulatory arrest, acute vasoconstriction, microcirculatory disturbances, or decreased cerebral perfusion from neurogenic cardiac dysfunction. Ischemic brain injury in poor grade SAH may be a feasible target for acute resuscitation strategies.

Background: Silent infarction is common in poor-grade subarachnoid hemorrhage (SAH) patients and associated with poor outcome. Invasive neuromonitoring devices may detect changes in cerebral metabolism and oxygenation., Methods: From a consecutive series of 32 poor-grade SAH patients we identified all CT-scans obtained during multimodal neuromonitoring and analyzed microdialysis parameters and brain tissue oxygen tension (PbtO2) preceding CT-scanning., Results: Eighteen percent of the reviewed head-CTs (12/67) revealed new infarcts. Of the eight infarcts in the vascular territory of the neuromonitoring, seven were clinically silent. Neuromonitoring changes preceding radiological evidence of infarction included lactate-pyruvate-ratio elevation and brain glucose decreases when compared to those with distant or no ischemia (P ≤ 0.03, respectively). PbtO2 was lower, but this did not reach statistical significance., Conclusions: These data suggest that there may be distinct changes in brain metabolism and oxygenation associated with the development of silent infarction within the monitored vascular territory in poor-grade SAH patients. Larger prospective studies are needed to determine whether treatment triggered by neuromonitoring data has an impact on outcome.

Background: We evaluated the safety of nicotine replacement therapy (NRT) in active smokers with acute (aneurysmal) subarachnoid hemorrhage (SAH)., Methods: A retrospective observational cohort study was conducted in a prospectively collected database including all SAH patients admitted to an 18-bed neuro-ICU between January 1, 2001 and October 1, 2007. Univariate and multivariable models were constructed, employing stepwise logistic regression. The primary endpoint was 3-month mortality. Delayed cerebral ischemia (DCI) due to vasospasm, angiographic and TCD evidence of vasospasm, and delirium were secondary endpoints., Results: Active cigarette smokers admitted with SAH included 128 that received NRT and 106 that did not. Patients were well-matched for age, admission Hunt-Hess Grade, radiographic findings, and APACHE II scores, but those who received NRT were more likely to be heavy smokers (>10 cigarettes daily), diabetic, heavy alcohol users, and to have cerebral edema on admission. NRT was associated in multivariate analysis with a lower risk of death at 3 months (OR 0.12, 95% CI 0.04-0.37, P < 0.001). There were no differences in the frequency of DCI and most other medical complications, but delirium (19 vs. 9%, P = 0.006) and seizures (9 vs. 2%, P = 0.024) were more common in patients who received NRT., Conclusions: Despite vasoactive properties, administration of NRT among active smokers with acute SAH appeared to be safe, with similar rates of vasospasm and DCI, and a slightly higher rate of seizures. The association of NRT with lower mortality could be due to chance, to uncontrolled factors, or to a neuroprotective effect of nicotine in active smokers hospitalized with SAH, and should be tested prospectively.

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is a frequent but unpredictable complication associated with poor outcome. Current vasospasm therapies are suboptimal; new therapies are needed. Clazosentan, an endothelin receptor antagonist, has shown promise in phase 2 studies, and two randomized, double-blind, placebo-controlled phase 3 trials (CONSCIOUS-2 and CONSCIOUS-3) are underway to further investigate its impact on vasospasm-related outcome after aSAH. Here, we describe the design of these studies, which was challenging with respect to defining endpoints and standardizing endpoint interpretation and patient care. Main inclusion criteria are: age 18-75 years; SAH due to ruptured saccular aneurysm secured by surgical clipping (CONSCIOUS-2) or endovascular coiling (CONSCIOUS-3); substantial subarachnoid clot; and World Federation of Neurosurgical Societies grades I-IV prior to aneurysm-securing procedure. In CONSCIOUS-2, patients are randomized 2:1 to clazosentan (5 mg/h) or placebo. In CONSCIOUS-3, patients are randomized 1:1:1 to clazosentan 5, 15 mg/h, or placebo. Treatment is initiated within 56 h of aSAH and continued until 14 days after aSAH. Primary endpoint is a composite of mortality and vasospasm-related morbidity within 6 weeks of aSAH (all-cause mortality, vasospasm-related new cerebral infarction, vasospasm-related delayed ischemic neurological deficit, neurological signs or symptoms in the presence of angiographic vasospasm leading to rescue therapy initiation). Main secondary endpoint is extended Glasgow Outcome Scale at week 12. A critical events committee assesses all data centrally to ensure consistency in interpretation, and patient management guidelines are used to standardize care. Results are expected at the end of 2010 and 2011 for CONSCIOUS-2 and CONSCIOUS-3, respectively.

Background: To study the feasibility of utilizing intracortical electroencephalography (ICE) including quantitative EEG (qEEG) analysis for the detection of vasospasm in five consecutive poor-grade SAH patients., Methods: Intracortical electroencephalography (ICE) was obtained via a single miniature parenchymal 8-contact depth electrode placed at the bedside. Quantitative EEG parameters, calculated on surface EEG and ICE, included alpha/delta ratio (ADR), mean amplitude, suppression percent, and total power. Percent changes between averaged values over 4-6 h of baseline EEG and EEG prior to angiography were calculated. The entire continuous qEEG recording for each patient was then reviewed to determine optimal automated alarm criteria., Results: ICE ADR was the most accurate for predicting angiographic vasospasm (5/5). ICE ADR decreased between baseline and follow-up by 42% (from 0.56 ± 0.07 to 0.32 ± 0.03) for those with vasospasm (N = 3) compared to 17% (0.62 ± 0.06 to 0.51 ± 0.03) for those without (N = 2). A sustained decrease in the ICE ADR from baseline (>25% for ≥ 4 h) occurred in all three patients with angiographically confirmed vasospasm and not in the two without; this decline occurred 1-3 days prior to angiographic confirmation., Conclusions: Intracortical EEG is promising for detecting ischemia from vasospasm in poor-grade SAH patients, may be superior to scalp EEG, and allow automated detection, particularly using the ADR. Larger studies are needed to better define the effectiveness of this approach.