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Background and Purpose: Perihematomal edema (PHE) represents the secondary brain injury after intracerebral hemorrhage (ICH). However, neurobiological characteristics of post-ICH parenchymal injury other than PHE volume have not been fully characterized. Using intravoxel incoherent motion imaging (IVIM), we explored the clinical correlates of PHE diffusion and (micro)perfusion metrics in subacute ICH., Materials and Methods: In 41 consecutive patients scanned 1-to-7 days after supratentorial ICH, we determined the mean diffusion (D), pseudo-diffusion (D*), and perfusion fraction (F) within manually segmented PHE. Using univariable and multivariable statistics, we evaluated the relationship of these IVIM metrics with 3-month outcome based on the modified Rankin Scale (mRS)., Results: In our cohort, the average (± standard deviation) age of patients was 68.6±15.6 years, median (interquartile) baseline National Institute of Health Stroke Scale (NIHSS) was 7 (3-13), 11 (27 %) patients had poor outcomes (mRS>3), and 4 (10 %) deceased during the follow-up period. In univariable analyses, admission NIHSS (p < 0.001), ICH volume (p = 0.019), ICH+PHE volume (p = 0.016), and average F of the PHE (p = 0.005) had significant correlation with 3-month mRS. In multivariable model, the admission NIHSS (p = 0.006) and average F perfusion fraction of the PHE (p = 0.003) were predictors of 3-month mRS., Conclusion: The IVIM perfusion fraction (F) maps represent the blood flow within microvasculature. Our pilot study shows that higher PHE microperfusion in subacute ICH is associated with worse outcomes. Once validated in larger cohorts, IVIM metrics may provide insight into neurobiology of post-ICH secondary brain injury and identify at-risk patients who may benefit from neuroprotective therapy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Seyedmehdi Payabvash reports a relationship with National Institutes of Health that includes: funding grants. Seyedmehdi Payabvash reports a relationship with Doris Duke Charitable Foundation that includes: funding grants. Seyedmehdi Payabvash reports a relationship with Foundation of the American Society of Neuroradiology that includes: funding grants. Emily J Gilmore reports a relationship with National Institutes of Health that includes: funding grants. Emily J Gilmore reports a relationship with UCB that includes: consulting or advisory. Emily J Gilmore reports a relationship with Intracranial Bioanalytics that includes: non-financial support. Guido J. Falcone reports a relationship with National Institutes of Health that includes: funding grants. Guido J. Falcone reports a relationship with Neurocritical Care Society that includes: funding grants. Guido J. Falcone reports a relationship with Yale Pepper Scholar Award that includes: funding grants. Guido J. Falcone reports a relationship with American Heart Association that includes: funding grants. Kevin N. Sheth reports a relationship with National Institutes of Health that includes: funding grants. Kevin N. Sheth reports a relationship with American Heart Association that includes: funding grants. Kevin N. Sheth reports a relationship with Hyperfine Research Inc that includes: funding grants. Adam de Havenon reports a relationship with National Institutes of Health that includes: funding grants. Adam de Havenon reports a relationship with American Academy of Neurology that includes: funding grants. Adam de Havenon reports a relationship with Novo Nordisk that includes: consulting or advisory. Adam de Havenon reports a relationship with Integra that includes: consulting or advisory. Adam de Havenon reports a relationship with Titin KM that includes: equity or stocks. Adam de Havenon reports a relationship with UpToDate that includes: paid expert testimony., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: Topographic patterns of brain injury in neonates can help with differentiation and prognostic categorization of hypoxic ischemic encephalopathy (HIE). In this study, we quantitatively and objectively characterized the location of hypoxic ischemic lesions in term neonates with varying severity of HIE., Methods: We analyzed term neonates (born ≥37 postmenstrual gestational weeks) with MRI diffusion-weighted imaging (DWI) and diagnoses of HIE. Neonates' HIE was categorized into mild, moderate, and severe. The hypoxic ischemic lesions were segmented on DWI series with attention to T1- and T2-weighted images and then co-registered onto standard brain space to generate summation maps for each severity category. Applying voxel-wise general linear models, we also identified cerebral regions more likely to infarct with increasing severity of HIE, after correction for lesion volume and time-to-scan as covariates., Results: We included 33 neonates: 20 with mild, eight with moderate, and five with severe HIE. Infarct volumes (p = .00052) and Appearance, Pulse, Grimace, Activity, and Respiration scores at 1 minute (p = .032) differed between HIE severity categories. Hypoxic ischemic lesions in neonates with mild and moderate HIE were predominant in subcortical and deep white matter along the border zones of arterial supply territories, while severe HIE also involved basal ganglia, hippocampus, and thalamus. In voxel-wise analysis, higher severity of HIE was associated with the presence of lesions in hippocampus, thalamus, and lentiform nucleus., Conclusions: In term neonates, mild/moderate HIE is associated with infarctions of arterial territory watershed zones, whereas severe HIE distinctively involves basal ganglia, thalami, and hippocampi., (© 2022 American Society of Neuroimaging.)

Importance: Clinical text reports from head computed tomography (CT) represent rich, incompletely utilized information regarding acute brain injuries and neurologic outcomes. CT reports are unstructured; thus, extracting information at scale requires automated natural language processing (NLP). However, designing new NLP algorithms for each individual injury category is an unwieldy proposition. An NLP tool that summarizes all injuries in head CT reports would facilitate exploration of large data sets for clinical significance of neuroradiological findings., Objective: To automatically extract acute brain pathological data and their features from head CT reports., Design, Setting, and Participants: This diagnostic study developed a 2-part named entity recognition (NER) NLP model to extract and summarize data on acute brain injuries from head CT reports. The model, termed BrainNERD, extracts and summarizes detailed brain injury information for research applications. Model development included building and comparing 2 NER models using a custom dictionary of terms, including lesion type, location, size, and age, then designing a rule-based decoder using NER outputs to evaluate for the presence or absence of injury subtypes. BrainNERD was evaluated against independent test data sets of manually classified reports, including 2 external validation sets. The model was trained on head CT reports from 1152 patients generated by neuroradiologists at the Yale Acute Brain Injury Biorepository. External validation was conducted using reports from 2 outside institutions. Analyses were conducted from May 2020 to December 2021., Main Outcomes and Measures: Performance of the BrainNERD model was evaluated using precision, recall, and F1 scores based on manually labeled independent test data sets., Results: A total of 1152 patients (mean [SD] age, 67.6 [16.1] years; 586 [52%] men), were included in the training set. NER training using transformer architecture and bidirectional encoder representations from transformers was significantly faster than spaCy. For all metrics, the 10-fold cross-validation performance was 93% to 99%. The final test performance metrics for the NER test data set were 98.82% (95% CI, 98.37%-98.93%) for precision, 98.81% (95% CI, 98.46%-99.06%) for recall, and 98.81% (95% CI, 98.40%-98.94%) for the F score. The expert review comparison metrics were 99.06% (95% CI, 97.89%-99.13%) for precision, 98.10% (95% CI, 97.93%-98.77%) for recall, and 98.57% (95% CI, 97.78%-99.10%) for the F score. The decoder test set metrics were 96.06% (95% CI, 95.01%-97.16%) for precision, 96.42% (95% CI, 94.50%-97.87%) for recall, and 96.18% (95% CI, 95.151%-97.16%) for the F score. Performance in external institution report validation including 1053 head CR reports was greater than 96%., Conclusions and Relevance: These findings suggest that the BrainNERD model accurately extracted acute brain injury terms and their properties from head CT text reports. This freely available new tool could advance clinical research by integrating information in easily gathered head CT reports to expand knowledge of acute brain injury radiographic phenotypes.

Background: Assessment of brain injury severity is critically important after survival from cardiac arrest (CA). Recent advances in low-field MRI technology have permitted the acquisition of clinically useful bedside brain imaging. Our objective was to deploy a novel approach for evaluating brain injury after CA in critically ill patients at high risk for adverse neurological outcome., Methods: This retrospective, single center study involved review of all consecutive portable MRIs performed as part of clinical care for CA patients between September 2020 and January 2022. Portable MR images were retrospectively reviewed by a blinded board-certified neuroradiologist (S.P.). Fluid-inversion recovery (FLAIR) signal intensities were measured in select regions of interest., Results: We performed 22 low-field MRI examinations in 19 patients resuscitated from CA (68.4% male, mean [standard deviation] age, 51.8 [13.1] years). Twelve patients (63.2%) had findings consistent with HIBI on conventional neuroimaging radiology report. Low-field MRI detected findings consistent with HIBI in all of these patients. Low-field MRI was acquired at a median (interquartile range) of 78 (40-136) hours post-arrest. Quantitatively, we measured FLAIR signal intensity in three regions of interest, which were higher amongst patients with confirmed HIBI. Low-field MRI was completed in all patients without disruption of intensive care unit equipment monitoring and no safety events occurred., Conclusion: In a critically ill CA population in whom MR imaging is often not feasible, low-field MRI can be deployed at the bedside to identify HIBI. Low-field MRI provides an opportunity to evaluate the time-dependent nature of MRI findings in CA survivors., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Rachel Beekman reports no disclosures. Anna Crawford reports no disclosures. Mercy H. Mazurek reports no disclosures. Anjali M. Prabhat reports no disclosures. Isha R. Chavva reports no disclosures. Nethra Parasuram reports no disclosures. Noah Kim reports no disclosures. Dr. Jennifer A. Kim reports no disclosures. Dr. Nils Petersen reports no disclosures. Dr. Adam de Havenon reports no disclosures. Dr. Akhil Khosla reports no disclosures. Dr. Shyoko Honiden reports no disclosures. Dr. P. Elliott Miller reports no disclosures. Dr. Charles Wira reports no disclosures. Dr. James Daley reports no disclosures. Dr. Seyedmehdi Payabvash reports no disclosures. Dr. David M. Greer reports no disclosures. Dr. Emily J. Gilmore reports no disclosures. Dr. W. Taylor Kimberly receives grants from the NIH and AHA to support his work with portable MRI. Dr. Kevin N. Sheth receives support from the Collaborative Science Award (American Heart Association), National Institutes of Health Supplement Grant (U01NS106513-S1), and Hyperfine Research, Inc. research grant for his work with portable MRI., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Sulfonylurea receptor 1 (SUR1) is a member of the adenosine triphosphate (ATP)-binding cassette (ABC) protein superfamily, encoded by Abcc8, and is recognized as a key mediator of central nervous system (CNS) cellular swelling via the transient receptor potential melastatin 4 (TRPM4) channel. Discovered approximately 20 years ago, this channel is normally absent in the CNS but is transcriptionally upregulated after CNS injury. A comprehensive review on the pathophysiology and role of SUR1 in the CNS was published in 2012. Since then, the breadth and depth of understanding of the involvement of this channel in secondary injury has undergone exponential growth: SUR1-TRPM4 inhibition has been shown to decrease cerebral edema and hemorrhage progression in multiple preclinical models as well as in early clinical studies across a range of CNS diseases including ischemic stroke, traumatic brain injury, cardiac arrest, subarachnoid hemorrhage, spinal cord injury, intracerebral hemorrhage, multiple sclerosis, encephalitis, neuromalignancies, pain, liver failure, status epilepticus, retinopathies and HIV-associated neurocognitive disorder. Given these substantial developments, combined with the timeliness of ongoing clinical trials of SUR1 inhibition, now, another decade later, we review advances pertaining to SUR1-TRPM4 pathobiology in this spectrum of CNS disease-providing an overview of the journey from patch-clamp experiments to phase III trials.

Background: Patients with a severe acute brain injury admitted to the intensive care unit often have a poor neurological prognosis. In these situations, a clinician is responsible for conducting a goals-of-care conversation with the patient's surrogate decision makers. The diversity in thought and background of surrogate decision makers can present challenges during these conversations. For this reason, our study aimed to identify predictive characteristics of US surrogate decision makers' favoring life-sustaining treatment (LST) over comfort measures only for patients with severe acute brain injury., Methods: We analyzed data from a cross-sectional survey study that had recruited 1588 subjects from an online probability-based US population sample. Seven hundred and ninety-two subjects had randomly received a hypothetical scenario regarding a relative intubated with severe acute brain injury with a prognosis of severe disability but with the potential to regain some consciousness. Seven hundred and ninety-six subjects had been randomized to a similar scenario in which the relative was projected to remain vegetative. For each scenario, we conducted univariate analyses and binary logistic regressions to determine predictors of LST selection among available respondent characteristics., Results: 15.0% of subjects selected LST for the severe disability scenario compared to 11.4% for the vegetative state scenario (p = 0.07), with those selecting LST in both groups expressing less decisional certainty. For the severe disability scenario, independent predictors of LST included having less than a high school education (adjusted OR = 2.87, 95% CI = 1.23-6.76), concern regarding prognostic accuracy (7.64, 3.61-16.15), and concern regarding the cost of care (4.07, 1.80-9.18). For the vegetative scenario, predictors included the youngest age group (30-44 years, 3.33, 1.02-10.86), male gender (3.26, 1.75-6.06), English as a second language (2.94, 1.09-7.89), Evangelical Protestant (3.72, 1.28-10.84) and Catholic (4.01, 1.72-9.36) affiliations, and low income (< $25 K)., Conclusion: Several demographic and decisional characteristics of US surrogate decision makers predict LST selection for patients with severe brain injury with varying degrees of poor prognosis. Surrogates concerned about the cost of medical care may nevertheless be inclined to select LST, albeit with high levels of decisional uncertainty, for patients projected to have severe disabilities., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Purpose of Review: Acute brain injury (ABI) is a broad category of pathologies, including traumatic brain injury, and is commonly complicated by seizures. Electroencephalogram (EEG) studies are used to detect seizures or other epileptiform patterns. This review seeks to clarify EEG findings relevant to ABI, explore practical barriers limiting EEG implementation, discuss strategies to leverage EEG monitoring in various clinical settings, and suggest an approach to utilize EEG for triage., Recent Findings: Current literature suggests there is an increased morbidity and mortality risk associated with seizures or patterns on the ictal-interictal continuum (IIC) due to ABI. Further, increased use of EEG is associated with better clinical outcomes. However, there are many logistical barriers to successful EEG implementation that prohibit its ubiquitous use. Solutions to these limitations include the use of rapid EEG systems, non-expert EEG analysis, machine learning algorithms, and the incorporation of EEG data into prognostic models.

Objective: To determine whether groups of surrogates for patients with severe acute brain injury (SABI) with poor prognosis can be identified based on their prioritization of goals-of-care (GOC) decisional concerns, an online survey of 1,588 adults recruited via a probability-based panel representative of the US population was conducted., Methods: Participants acted as a surrogate for a GOC decision for a hypothetical patient with SABI and were randomized to 1 of 2 prognostic scenarios: the patient likely being left with a range of severe functional disability (SD) or remaining in a vegetative state (VS). Participants prioritized a list of 12 decisional concerns via best-worst scaling. Latent class analysis (LCA) was used to discover decisional groups., Results: The completion rate was 44.6%; data weighting was conducted to mitigate nonresponse bias. For 792 SD respondents, LCA revealed 4 groups. All groups shared concerns regarding respecting patient wishes and minimizing suffering. The 4 groups were otherwise distinguished by unique concerns that their members highlighted: an older adult remaining severely disabled (34.4%), family consensus (26.4%), doubt regarding prognostic accuracy (20.7%), and cost of long-term care (18.6%). For the 796 VS respondents, LCA revealed 5 groups. Four of the 5 groups had similar concern profiles to the 4 SD groups. The largest (29.0%) expressed the most prognostic doubt. An additional group (15.8%) prioritized religious concerns., Conclusions: Although surrogate decision makers for patients with SABI are concerned with respecting patient wishes and minimizing suffering, certain groups highly prioritize other specific decisional factors. These data can help inform future interventions for supporting decision makers., (© 2020 American Academy of Neurology.)

Background: Civilian penetrating traumatic brain injury (pTBI) is a serious public health problem in the United States, but predictors of outcome remain largely understudied. We previously developed the Survival After Acute Civilian Penetrating Brain Injuries (SPIN) score, a logistic, regression-based risk stratification scale for estimating in-hospital and 6-mo survival after civilian pTBI with excellent discrimination (area under the receiver operating curve [AUC-ROC = 0.96]) and calibration, but it has not been validated., Objective: To validate the SPIN score in a multicenter cohort., Methods: We identified pTBI patients from 3 United States level-1 trauma centers. The SPIN score variables (motor Glasgow Coma Scale [mGCS], sex, admission pupillary reactivity, self-inflicted pTBI, transfer status, injury severity score, and admission international normalized ratio [INR]) were retrospectively collected from local trauma registries and chart review. Using the original SPIN score multivariable logistic regression model, AUC-ROC analysis and Hosmer-Lemeshow goodness of fit testing were performed to determine discrimination and calibration., Results: Of 362 pTBI patients available for analysis, 105 patients were lacking INR, leaving 257 patients for the full SPIN model validation. Discrimination (AUC-ROC = 0.88) and calibration (Hosmer-Lemeshow goodness of fit, P value = .58) were excellent. In a post hoc sensitivity analysis, we removed INR from the SPIN model to include all 362 patients (SPINNo-INR), still resulting in very good discrimination (AUC-ROC = 0.82), but reduced calibration (Hosmer-Lemeshow goodness of fit, P value = .04)., Conclusion: This multicenter pTBI study confirmed that the full SPIN score predicts survival after civilian pTBI with excellent discrimination and calibration. Admission INR significantly adds to the prediction model discrimination and should be routinely measured in pTBI patients., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Neurosurgeons increasingly use decompressive craniectomy (DC) in neurocritical care. In this review, the authors summarize the topic of DC for the neurointensivist. Following a brief overview of the procedure, the major indications for the procedure are described. This includes a review of the literature regarding well-established indications, such as infarction and traumatic brain injury, as well as lesser known indications, including intracerebral hemorrhage, ruptured cerebrovascular malformations, sinus thrombosis, and infection. Complications unique to DC, specifically syndrome of the trephined, hygroma, and hydrocephalus, also are reviewed with a discussion of their management, both in the immediate and the postoperative period., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To identify predictors associated with survival in civilian penetrating traumatic brain injury (pTBI) utilizing a contemporary, large, diverse 2-center cohort, and to develop a parsimonious survival prediction score for pTBI., Methods: Our cohort comprised 413 pTBI patients retrospectively identified from the local trauma registries at 2 US level 1 trauma centers, of which one was predominantly urban and the other predominantly rural. Predictors of in-hospital and 6-month survival identified in univariate and multivariable logistic regression were used to develop the simple Surviving Penetrating Injury to the Brain (SPIN) score., Results: The mean age was 33 ± 16 years and patients were predominantly male (87%). Survival at hospital discharge as well as 6 months post pTBI was 42.4%. Higher motor Glasgow Coma Scale subscore, pupillary reactivity, lack of self-inflicted injury, transfer from other hospital, female sex, lower Injury Severity Score, and lower international normalized ratio were independently associated with survival (all p < 0.001; model area under the curve 0.962). Important radiologic factors associated with survival were also identified but their addition to the full multivariable would have resulted in model overfitting without much gain in the area under the curve., Conclusions: The SPIN score, a logistic regression-based clinical risk stratification scale estimating survival after pTBI, was developed in this large, diverse 2-center cohort. While this preliminary clinical survival prediction tool does not include radiologic factors, it may support clinical decision-making after civilian pTBI if external validation confirms the probability estimates., (© 2016 American Academy of Neurology.)

This study investigates the potential clinical utility in the emergency department (ED) of an index of brain electrical activity to identify intracranial hematomas. The relationship between this index and depth, size, and type of hematoma was explored. Ten minutes of brain electrical activity was recorded from a limited montage in 38 adult patients with traumatic hematomas (CT scan positive) and 38 mild head injured controls (CT scan negative) in the ED. The volume of blood and distance from recording electrodes were measured by blinded independent experts. Brain electrical activity data were submitted to a classification algorithm independently developed traumatic brain injury (TBI) index to identify the probability of a CT+traumatic event. There was no significant relationship between the TBI-Index and type of hematoma, or distance of the bleed from recording sites. A significant correlation was found between TBI-Index and blood volume. The sensitivity to hematomas was 100%, positive predictive value was 74.5%, and positive likelihood ratio was 2.92. The TBI-Index, derived from brain electrical activity, demonstrates high accuracy for identification of traumatic hematomas. Further, this was not influenced by distance of the bleed from the recording electrodes, blood volume, or type of hematoma. Distance and volume limitations noted with other methods, (such as that based on near-infrared spectroscopy) were not found, thus suggesting the TBI-Index to be a potentially important adjunct to acute assessment of head injury. Because of the life-threatening risk of undetected hematomas (false negatives), specificity was permitted to be lower, 66%, in exchange for extremely high sensitivity.

Objective: Detecting and treating elevated intracranial pressure (ICP) is a cornerstone of management in patients with severe traumatic brain injury. The aim of this study was to determine the association between area under the curve measurement of elevated ICP and clinical outcome., Methods: Single center observational study using prospectively collected data at a University hospital, level one-trauma center. Sixty prospective patients with severe traumatic brain injury were prospectively enrolled over a 2-year period. Intracranial pressure measurements were captured using a real-time automated, high resolution vital signs data recording system. Mortality and functional outcome were assessed at 30 days, 3 and 6 months using Extended Glasgow Outcome Scale., Results: Increasing elevated intracranial pressure time dose was associated with mortality (OR 1.08; 95 % confidence interval [CI], 1.01-1.15, p = 0.03) and poor functional outcome at 3 (OR 1.04; CI 1.00-1.07, p = 0.03) and 6 months (1.04; CI 1.01-1.08, p = 0.02). However, there was no association between episodic ICP data and outcome., Conclusions: These results suggest that pressure time dose measurement of intracranial pressure may be used to predict outcome in severe traumatic brain injury and may be a candidate biomarker in this disease.

Purpose of Review: Hyperadrenergic activity leading to autonomic dysfunction after acute brain injury is an underrecognized, yet important source of complications following a variety of neurologic injuries. Autonomic dysfunction may prolong ICU stay and increase healthcare costs driven by extensive diagnostic workups and/or ensuing complications. In this review article, we intend to illustrate commonalities between various hyperadrenergic states in acquired brain injury. Specifically, this review will focus on autonomic dysfunction in two common conditions in the neurocritical care unit, traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH)., Recent Findings: Elevated levels of catecholamines have been well documented in SAH and to a lesser extent in paroxysmal sympathetic hyperactivity, hinting at the underlying increased sympathetic tone in both disease states. The resultant hyperadrenergic state may manifest with vital sign alterations, or end-organ dysfunction such as heart failure. Neuroimaging and limited clinical data have elucidated some information regarding underlying mechanisms, but the gaps in understanding have thus far limited prospective clinical trials. A multitude of therapeutic options to reduce adrenergic tone have been employed with varying degrees of success., Summary: The pathophysiology of autonomic dysfunction is incompletely understood and treatment options are few. However, recognizing hyperadrenergic commonality in disparate neurologic disease may facilitate novel inquiries into lesion localization and therapeutics. It is possible that adrenergic blockade may diminish or abrogate end-organ dysfunction in TBI and SAH.

Background: Management strategies after severe traumatic brain injury (TBI) target prevention and treatment of intracranial hypertension (ICH) and cerebral hypoperfusion (CH). We have previously established that continuous automated recordings of vital signs (VS) are more highly correlated with outcome than manual end-hour recordings. One potential benefit of automated vital sign data capture is the ability to detect brief episodes of ICH and CH. The purpose of this study was to establish whether a relationship exists between brief episodes of ICH and CH and outcome after severe TBI., Materials: Patients at the R Adams Cowley Shock Trauma Center were prospectively enrolled over a 2-year period. Inclusion criteria were as follows: age >14 years, admission within the first 6 hours after injury, Glasgow Coma Scale score <9 on admission, and placement of a clinically indicated ICP monitor. From high-resolution automated VS data recording system, we calculated the 5-minute means of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Brain Trauma Index (BTI = CPP/ICP). Patients were stratified by mortality and 6-month Extended Glasgow Outcome Score (GOSE)., Results: Sixty subjects were enrolled with a mean admission Glasgow Coma Scale score of 6.4 ± 3.1, a mean Head Abbreviated Injury Severity Scale score of 4.2 ± 0.7, and a mean Marshall CT score of 2.5 ± 0.9. Significant differences in the mean number of brief episodes of CPP <50 and BTI <2 in patients with a GOSE 1-4 versus GOSE 5-8 (9.4 vs. 4.7, p = 0.02 and 9.3 vs. 4.9, p = 0.03) were found. There were significantly more mean brief episodes per day of ICP >30 (0.52 vs. 0.29, p = 0.02), CPP <50 (0.65 vs. 0.28, p < 0.001), CPP <60 (1.09 vs. 0.7, p = 0.03), BTI <2 (0.66 vs. 0.31, p = 0.002), and BTI <3 (1.1 vs. 0.64, p = 0.01) in those patients with GOSE 1-4. Number of brief episodes of CPP <50, CPP <60, BTI <2, and BTI <3 all demonstrated high predictive power for unfavorable functional outcome (area under the curve = 0.65-0.75, p < 0.05)., Conclusions: This study demonstrates that the number of brief 5-minute episodes of ICH and CH is predictive of poor outcome after severe TBI. This finding has important implications for management paradigms which are currently targeted to treatment rather than prevention of ICH and CH. This study demonstrates that these brief episodes may play a significant role in outcome after severe TBI.

Cerebral edema and contusion expansion are major determinants of morbidity and mortality after TBI. Current treatment options are reactive, suboptimal and associated with significant side effects. First discovered in models of focal cerebral ischemia, there is increasing evidence that the sulfonylurea receptor 1 (SUR1)-Transient receptor potential melastatin 4 (TRPM4) channel plays a key role in these critical secondary injury processes after TBI. Targeted SUR1-TRPM4 channel inhibition with glibenclamide has been shown to reduce edema and progression of hemorrhage, particularly in preclinical models of contusional TBI. Results from small clinical trials evaluating glibenclamide in TBI have been encouraging. A Phase-2 study evaluating the safety and efficacy of intravenous glibenclamide (BIIB093) in brain contusion is actively enrolling subjects. In this comprehensive narrative review, we summarize the molecular basis of SUR1-TRPM4 related pathology and discuss TBI-specific expression patterns, biomarker potential, genetic variation, preclinical experiments, and clinical studies evaluating the utility of treatment with glibenclamide in this disease.

Abstract: Objective: Intracerebral hemorrhage carries a high mortality and survivors are frequently left with significant disability. Immunological mechanisms may play an important role in hemorrhage‐induced brain injury, however, research linking these mechanisms with clinical outcome remains limited. We aim to identify serum inflammatory mediators that are associated with outcome after intracerebral hemorrhage in order to translate data from experimental models to a patient cohort and identify potential targets worthy of reverse translation. Methods: A prospective cohort study at two comprehensive stroke centers enrolled patients with spontaneous intracerebral hemorrhage. Peripheral blood was collected at 6, 24, and 72 h from onset. Functional outcome was assessed at 90 days using the modified Rankin Scale (mRS). Serum inflammatory mediators were measured using multiplex ELISA. Multivariable modeling identified serum biomarkers independently associated with functional outcome at 90 days. Results: 115 patients completed the study. At 6 h after onset, patients with elevated CCL2 had worse mRS score at day 90 (OR 4.07, 95% CI 1.27–13.10, P = 0.02) after adjusting for age, gender, ICH volume, IVH, infratentorial location and NIHSS score. At 24 and 72 h after onset, elevation in CXCL10 was independently associated with worse 90 days mRS score (24 h: OR 8.08, 95% CI 2.69–24.30, P < 0.001; 72 h: OR 3.89, 95% CI 1.12–13.49, P = 0.03). Interpretation: Acute and subacute elevations in specific immune factors are associated with poor outcome, highlighting potential pathways that may contribute to ongoing brain injury in patients with intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

We sought to review the role that cerebral edema plays in neurologic outcome following cardiac arrest, to understand whether cerebral edema might be an appropriate therapeutic target for neuroprotection in patients who survive cardiopulmonary resuscitation. Articles indexed in PubMed and written in English. Following cardiac arrest, cerebral edema is a cardinal feature of brain injury and is a powerful prognosticator of neurologic outcome. Like other conditions characterized by cerebral ischemia/reperfusion, neuroprotection after cardiac arrest has proven to be difficult to achieve. Neuroprotection after cardiac arrest generally has focused on protecting neurons, not the microvascular endothelium or blood-brain barrier. Limited preclinical data suggest that strategies to reduce cerebral edema may improve neurologic outcome. Ongoing research will be necessary to determine whether targeting cerebral edema will improve patient outcomes after cardiac arrest. [ABSTRACT FROM AUTHOR]

Background: Stroke can result in varying degrees of respiratory failure. Some patients require tracheostomy in order to facilitate weaning from mechanical ventilation, long-term airway protection, or a combination of the two. Little is known about the rate and predictors of this outcome in patients with severe stroke. We aim to determine the rate of tracheostomy after severe ischemic stroke. Methods: Using the Nationwide Inpatient Sample database from 2007 to 2009, patients hospitalized with ischemic stroke were identified based on validated International Classification of Diseases, 9th revision, Clinical Modification codes. Next, patients with stroke were stratified based on whether they were treated with or without decompressive craniectomy, and the rate of tracheostomy for each group was determined. A logistic regression analysis was used to identify predictors of tracheostomy after decompressive craniectomy. Survey weights were used to obtain nationally representative estimates. Results: In 1,550,000 patients discharged with ischemic stroke nationwide, the rate of tracheostomy was 1.3% (95% confidence interval [CI], 1.2-1.4%), with a 1.3% (95% CI, 1.1-1.4%) rate in patients without decompressive craniectomy and a 33% (95% CI, 26-39%) rate in the surgical treatment group. Logistic regression analysis identified pneumonia as being significantly associated with tracheostomy after decompressive craniectomy (odds ratio, 3.95; 95% CI, 1.95-6.91). Conclusions: Tracheostomy is common after decompressive craniectomy and is strongly associated with the development of pneumonia. Given its impact on patient function and potentially modifiable associated factors, tracheostomy may warrant further study as an important patient-centered outcome among patients with stroke. [Copyright &y& Elsevier]

Osmotic agents play a vital role in the reduction of elevated intracranial pressure and treatment of cerebral edema in Neurologic critical care. Both mannitol and hypertonic saline reduce cerebral edema in many clinical syndromes, yet there is controversy over agent selection, timing, and dosing regimens. Despite the lack of randomized, controlled trials, our knowledge base on the appropriate clinical use of osmotic agents continues to expand. This review will summarize the evidence for the use of mannitol and hypertonic saline in a variety of disease states causing cerebral edema, as well as outlining monitoring and safety considerations. [ABSTRACT FROM AUTHOR]

Perihaematomal oedema (PHO) is an important pathophysiological marker of secondary injury in intracerebral haemorrhage (ICH). In this Review, we describe a novel method to conceptualize PHO formation within the framework of Starling's principle of movement of fluid across a capillary wall. We consider progression of PHO through three stages, characterized by ionic oedema (stage 1) and progressive vasogenic oedema (stages 2 and 3). In this context, possible modifiers of PHO volume and their value in identifying patients who would benefit from therapies that target secondary injury are discussed; the practicalities of using neuroimaging to measure PHO volume are also considered. We examine whether PHO can be used as a predictor of neurological outcome following ICH, and we provide an overview of emerging therapies. Our discussion emphasizes that PHO has clinical relevance both as a therapeutic target, owing to its augmentation of the mass effect of a haemorrhage, and as a surrogate marker for novel interventions that target secondary injury. [ABSTRACT FROM AUTHOR]