Acute brain injury increases pulmonary capillary permeability via sympathetic activation-mediated high fluid shear stress and destruction of the endothelial glycocalyx layer.

Neurogenic pulmonary edema secondary to acute brain injury (ABI) is a common and fatal disease condition. However, the pathophysiology of brain-lung interactions is incompletely understood. This study aims to investigate whether sympathetic activation-mediated high fluid shear stress after ABI would damage pulmonary endothelial glycocalyx thus leading to increased pulmonary capillary permeability. The tricuspid annular plane systolic excursion (TAPSE) was detected in a rat model of controlled cortical impact (CCI) and CCI + transection of the cervical sympathetic trunk (TCST). Changes in pulmonary capillary permeability were assessed by analyzing the Evans blue, measuring the dry/wet weight ratio of the lungs and altering protein levels in the bronchoalveolar lavage fluid (BALF). The parallel-plate flow chamber system was used to simulate the fluid shear stress in vitro. Western blotting and immunofluorescence staining were used to determine the expression levels of hyaluronan-binding protein (CEMIP), syndecan-1 and tight junction proteins (TJPs, including claudin-5 and occludin). TCST could restrain cardiac overdrive and sympathetic activation in a rat model of CCI. Compared to the CCI group, the CCI + TCST group showed a reduction of CEMPI (which degrades hyaluronic acid), along with an increase of syndecan-1 and TJPs. CCI + TCST group presented decreasing pulmonary capillary permeability. In vitro, high shear stress (HSS) increased the expression of CEMIP and reduced syndecan-1 and TJPs, which was coordinated with the results in vivo. Our findings show that sympathetic activation-mediated high fluid shear stress after ABI would damage pulmonary endothelial glycocalyx thus leading to increased pulmonary capillary permeability.

A Dynamic Balance between Neuronal Death and Clearance in an in Vitro Model of Acute Brain Injury.

In in vitro models of acute brain injury, neuronal death may overwhelm the capacity for microglial phagocytosis, creating a queue of dying neurons awaiting clearance. Neurons undergoing programmed cell death are in this queue, and are the most visible and frequently quantified measure of neuronal death after injury. However, the size of this queue should be equally sensitive to changes in neuronal death and the rate of phagocytosis. Using rodent organotypic hippocampal slice cultures as a model of acute perinatal brain injury, serial imaging demonstrated that the capacity for microglial phagocytosis of dying neurons was overwhelmed for 2 weeks. Altering phagocytosis rates (e.g., by changing the number of microglia) dramatically changed the number of visibly dying neurons. Similar effects were generated when the visibility of dying neurons was altered by changing the membrane permeability for stains that label dying neurons. Canonically neuroprotective interventions, such as seizure blockade, and neurotoxic maneuvers, such as perinatal ethanol exposure, were mediated by effects on microglial activity and the membrane permeability of neurons undergoing programmed cell death. These canonically neuroprotective and neurotoxic interventions had either no or opposing effects on healthy surviving neurons identified by the ongoing expression of transgenic fluorescent proteins.SIGNIFICANCE STATEMENT In in vitro models of acute brain injury, microglial phagocytosis is overwhelmed by the number of dying cells. Under these conditions, the assumptions on which assays for neuroprotective and neurotoxic effects are based are no longer valid. Thus, longitudinal assays of healthy cells, such as serial assessment of the fluorescence emission of transgenically expressed proteins, provide more accurate estimates of cell death than do single-time point anatomic or biochemical assays of the number of dying neurons. More accurate estimates of death rates in vitro will increase the translatability of preclinical studies of neuroprotection and neurotoxicity.

Combined depth and scalp electroencephalographic monitoring in acute brain injury: Yield and prognostic value.

BACKGROUND AND PURPOSE: Depth electroencephalography (dEEG) is an emerging neuromonitoring technology in acute brain injury (ABI). We aimed to explore the concordances between electrophysiological activities on dEEG and on scalp EEG (scEEG) in ABI patients. METHODS: Consecutive ABI patients who received dEEG monitoring between 2018 and 2022 were included. Background, sporadic epileptiform discharges, rhythmic and periodic patterns (RPPs), electrographic seizures, brief potentially ictal rhythmic discharges, ictal-interictal continuum (IIC) patterns, and hourly RPP burden on dEEG and scEEG were compared. RESULTS: Sixty-one ABI patients with a median dEEG monitoring duration of 114 h were included. dEEG significantly showed less continuous background (75% vs. 90%, p = 0.03), higher background amplitude (p < 0.001), more frequent rhythmic spike-and-waves (16% vs. 3%, p = 0.03), more IIC patterns (39% vs. 21%, p = 0.03), and greater hourly RPP burden (2430 vs. 1090 s/h, p = 0.01), when compared to scEEG. Among five patients with seizures on scEEG, one patient had concomitant seizures on dEEG, one had periodic discharges (not concomitant) on dEEG, and three had no RPPs on dEEG. Features and temporal occurrence of electrophysiological activities observed on dEEG and scEEG are not strongly associated. Patients with seizures and IIC patterns on dEEG seemed to have a higher rate of poor outcomes at discharge than patients without these patterns on dEEG (42% vs. 25%, p = 0.37). CONCLUSIONS: dEEG can detect abnormal electrophysiological activities that may not be seen on scEEG and can be used as a complement in the neuromonitoring of ABI patients.

Point-of-Care Bedside Brain Magnetic Resonance Imaging Is Safe in Extracorporeal Membrane Oxygenation Patients With Swan Ganz Catheters: A Phantom Experiment and Single Center Experience.

INTRODUCTION: More than 1.2 million pulmonary artery catheters (PACs) are used in cardiac patients per annum within the United States. However, it is contraindicated in traditional 1.5 and 3T magnetic resonance imaging (MRI) scans. We aimed to test preclinical and clinical safety of using this imaging modality given the potential utility of needing it in the clinical setting. METHODS: We conducted two phantom experiments to ensure that the electromagnetic field power deposition associated with bare and jacketed PACs was safe and within the acceptable limit established by the Food and Drug Administration. The primary end points were the safety and feasibility of performing Point-of-Care (POC) MRI without imaging-related adverse events. We performed a preclinical computational electromagnetic simulation and evaluated these findings in nine patients with PACs on veno-arterial extracorporeal membrane oxygenation. RESULTS: The phantom experiments showed that the baseline point specific absorption rate through the head averaged 0.4 W/kg. In both the bare and jacketed catheters, the highest net specific absorption rates were at the neck entry point and tip but were negligible and unlikely to cause any heat-related tissue or catheter damage. In nine patients (median age 66, interquartile range 42-72 y) with veno-arterial extracorporeal membrane oxygenation due to cardiogenic shock and PACs placed for close hemodynamic monitoring, POC MRI was safe and feasible with good diagnostic imaging quality. CONCLUSIONS: Adult ECMO patients with PACs can safely undergo point-of-care low-field (64 mT) brain MRI within a reasonable timeframe in an intensive care unit setting to assess for acute brain injury that might otherwise be missed with conventional head computed tomography.

Multimodal prediction of residual consciousness in the intensive care unit: the CONNECT-ME study.

Functional MRI (fMRI) and EEG may reveal residual consciousness in patients with disorders of consciousness (DoC), as reflected by a rapidly expanding literature on chronic DoC. However, acute DoC is rarely investigated, although identifying residual consciousness is key to clinical decision-making in the intensive care unit (ICU). Therefore, the objective of the prospective, observational, tertiary centre cohort, diagnostic phase IIb study 'Consciousness in neurocritical care cohort study using EEG and fMRI' (CONNECT-ME, NCT02644265) was to assess the accuracy of fMRI and EEG to identify residual consciousness in acute DoC in the ICU. Between April 2016 and November 2020, 87 acute DoC patients with traumatic or non-traumatic brain injury were examined with repeated clinical assessments, fMRI and EEG. Resting-state EEG and EEG with external stimulations were evaluated by visual analysis, spectral band analysis and a Support Vector Machine (SVM) consciousness classifier. In addition, within- and between-network resting-state connectivity for canonical resting-state fMRI networks was assessed. Next, we used EEG and fMRI data at study enrolment in two different machine-learning algorithms (Random Forest and SVM with a linear kernel) to distinguish patients in a minimally conscious state or better (≥MCS) from those in coma or unresponsive wakefulness state (≤UWS) at time of study enrolment and at ICU discharge (or before death). Prediction performances were assessed with area under the curve (AUC). Of 87 DoC patients (mean age, 50.0 ± 18 years, 43% female), 51 (59%) were ≤UWS and 36 (41%) were ≥ MCS at study enrolment. Thirty-one (36%) patients died in the ICU, including 28 who had life-sustaining therapy withdrawn. EEG and fMRI predicted consciousness levels at study enrolment and ICU discharge, with maximum AUCs of 0.79 (95% CI 0.77-0.80) and 0.71 (95% CI 0.77-0.80), respectively. Models based on combined EEG and fMRI features predicted consciousness levels at study enrolment and ICU discharge with maximum AUCs of 0.78 (95% CI 0.71-0.86) and 0.83 (95% CI 0.75-0.89), respectively, with improved positive predictive value and sensitivity. Overall, both machine-learning algorithms (SVM and Random Forest) performed equally well. In conclusion, we suggest that acute DoC prediction models in the ICU be based on a combination of fMRI and EEG features, regardless of the machine-learning algorithm used.

"NeuroVanguard": a contemporary strategy in neuromonitoring for severe adult brain injury patients.

Severe acute brain injuries, stemming from trauma, ischemia or hemorrhage, remain a significant global healthcare concern due to their association with high morbidity and mortality rates. Accurate assessment of secondary brain injuries severity is pivotal for tailor adequate therapies in such patients. Together with neurological examination and brain imaging, monitoring of systemic secondary brain injuries is relatively straightforward and should be implemented in all patients, according to local resources. Cerebral secondary injuries involve factors like brain compliance loss, tissue hypoxia, seizures, metabolic disturbances and neuroinflammation. In this viewpoint, we have considered the combination of specific noninvasive and invasive monitoring tools to better understand the mechanisms behind the occurrence of these events and enhance treatment customization, such as intracranial pressure monitoring, brain oxygenation assessment and metabolic monitoring. These tools enable precise intervention, contributing to improved care quality for severe brain injury patients. The future entails more sophisticated technologies, necessitating knowledge, interdisciplinary collaboration and resource allocation, with a focus on patient-centered care and rigorous validation through clinical trials.

Prevalence and Neurological Outcomes of Comatose Patients With Extracorporeal Membrane Oxygenation.

OBJECTIVES: To investigate prevalence, risk factors, and in-hospital outcomes of comatose extracorporeal membrane oxygenation (ECMO) patients. DESIGN: Retrospective observational. SETTING: Tertiary academic hospital. PARTICIPANTS: Adults received venoarterial (VA) or venovenous (VV) ECMO support between November 2017 and April 022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined 24-hour off sedation as no sedative infusion (except dexmedetomidine) or paralytics administration over a continuous 24-hour period while on ECMO. Off-sedation coma (comaoff) was defined as a Glasgow Coma Scale score of ≤8 after achieving 24-hour off sedation. On-sedation coma (comaon) was defined as a Glasgow Coma Scale score of ≤8 during the entire ECMO course without off sedation for 24 hours. Neurological outcomes were assessed at discharge using the modified Rankin scale (good, 0-3; poor, 4-6). We included 230 patients (VA-ECMO 143, 65% male); 24-hour off sedation was achieved in 32.2% VA-ECMO and 26.4% VV-ECMO patients. Among all patients off sedation for 24 hours (n = 69), 56.5% VA-ECMO and 52.2% VV-ECMO patients experienced comaoff. Among those unable to be sedation free for 24 hours (n = 161), 50.5% VA-ECMO and 17.2% VV-ECMO had comaon. Comaoff was associated with poor outcomes (p < 0.05) in VA-ECMO and VV-ECMO groups, whereas comaon only impacted the VA-ECMO group outcomes. In a multivariable analysis, requirement of renal replacement therapy was an independent risk factor for comaoff after adjusting for ECMO configuration, after adjusting for ECMO configuration, acute brain injury, pre-ECMO partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, pH, and bicarbonate level (worst value within 24 hours before cannulation). CONCLUSIONS: Comaoff was common and associated with poor outcomes at discharge. Requirement of renal replacement therapy was an independent risk factor.

Ventriculostomy-associated infection (VAI) in patients with acute brain injury-a retrospective study.

BACKGROUND: Ventriculostomy-associated infection (VAI) is common after external ventricular drains (EVD) insertion but is difficult to diagnose in patients with acute brain injury. Previously, we proposed a set of criteria for ruling out VAI in traumatic brain injury. This study aimed to validate these criteria. For exploratory purposes, we sought to develop and validate a score for VAI risk assessment in patients with different types of severe acute brain injury. METHODS: This retrospective cohort study included adults with acute brain injury who received an EVD and in whom CSF samples were taken over a period of 57 months. As standard non-coated bolt-connected EVDs were used. The predictive performance of biomarkers was analyzed as defined previously. A multivariable regression model was performed with five variables. RESULTS: A total of 683 patients with acute brain injury underwent EVD placement and had 1272 CSF samples; 92 (13.5%) patients were categorized as culture-positive VAI, 130 (19%) as culture-negative VAI, and 461 (67.5%) as no VAI. A low CSF WBC/RBC ratio (< 0.037), high CSF/plasma glucose ratio (> 0.6), and low CSF protein (< 0.5g/L) showed a positive predictive value of 0.09 (95%CI, 0.05-0.13). In the multivariable logistic regression model, days to sample (OR 1.09; 95%CI, 1.03-1.16) and CSF WBC/RBC ratio (OR 34.86; 95%CI, 3.94-683.15) were found to predict VAI. CONCLUSION: In patients with acute brain injury and an EVD, our proposed combined cut-off for ruling out VAI performed satisfactorily. Days to sample and CSF WBC/RBC ratio were found independent predictors for VAI in the multivariable logistic regression model.

Delirium in Neurocritical Care: Uncovering Undisclosed Psychotropic Substance and Medication Use and Stress Exposure by Hair Analysis.

OBJECTIVE: In intensive care, delirium is frequent, prolongs the stay, increases health care costs, and worsens patient outcome. Several substances and medications as well as stress can impact the risk of delirium; however, assessment of previous exposure to psychotropic agents and stress by self-reports or third-party information is not always reliable. Hair analysis can be used to objectively assess medication and substance use (including chronic alcohol consumption), and allows for the determination of stress-related long-term changes in steroid hormones and endocannabinoids. METHODS: Consecutive adult patients with acute brain injury admitted to the neurocritical care unit were included. Delirium was diagnosed using the Confusion Assessment Method for the Intensive Care Unit. Liquid chromatography coupled with tandem mass spectrometry was used to investigate psychoactive substances and medications, ethyl glucuronide, steroid hormones, and endocannabinoids in hair samples. Univariable and multivariable analyses were used to reveal any associations with the occurrence of delirium. RESULTS: Of 50 consecutive patients, 21 (42%) were diagnosed with delirium. Detection of antipsychotics or antidepressants in hair was more frequent in patients with delirium (antidepressants: 43% vs. 14%, p = 0.040; antipsychotics: 29% vs. 0%, p = 0.021). These patients also displayed higher ethyl glucuronide levels (p = 0.049). Anandamide (AEA) concentrations were higher in patients with delirium (p = 0.005), whereas oleoylethanolamide (p = 0.045) and palmitoylethanolamide (PEA) (p = 0.017) concentrations were lower in patients with delirium. Backward stepwise logistic regression analysis revealed antidepressants and AEA/PEA to be independent relevant predictors of delirium. CONCLUSIONS: Hair analysis provides crucial and otherwise unattainable information regarding chronic stress and the use of psychotropic substances and medications. Undisclosed antidepressant/antipsychotic use or intense chronic alcohol consumption is susceptible to treatment (continuation of medication or provision of low-dose benzodiazepines in case of alcohol). Chronic stress can be evaluated using stress markers and endocannabinoids in hair, potentially allowing for personalized delirium risk stratification and preventive measures.

Neurophysiologic Features Reflecting Brain Injury During Pediatric ECMO Support.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides lifesaving support to critically ill patients who experience refractory cardiopulmonary failure but carries a high risk for acute brain injury. We aimed to identify characteristics reflecting acute brain injury in children requiring ECMO support. METHODS: This is a prospective observational study from 2019 to 2022 of pediatric ECMO patients undergoing neuromonitoring, including continuous electroencephalography, cerebral oximetry, and transcranial Doppler ultrasound (TCD). The primary outcome was acute brain injury. Clinical and neuromonitoring characteristics were collected. Multivariate logistic regression was implemented to model odds ratios (ORs) and identify the combined characteristics that best discriminate risk of acute brain injury using the area under the receiver operating characteristic curve. RESULTS: Seventy-five pediatric patients requiring ECMO support were enrolled in this study, and 62 underwent neuroimaging or autopsy evaluations. Of these 62 patients, 19 experienced acute brain injury (30.6%), including seven (36.8%) with arterial ischemic stroke, four (21.1%) with hemorrhagic stroke, seven with hypoxic-ischemic brain injury (36.8%), and one (5.3%) with both arterial ischemic stroke and hypoxic-ischemic brain injury. A univariate analysis demonstrated acute brain injury to be associated with maximum hourly seizure burden (p = 0.021), electroencephalographic suppression percentage (p = 0.022), increased interhemispheric differences in electroencephalographic total power (p = 0.023) and amplitude (p = 0.017), and increased differences in TCD Thrombolysis in Brain Ischemia (TIBI) scores between bilateral middle cerebral arteries (p = 0.023). Best subset model selection identified increased seizure burden (OR = 2.07, partial R2 = 0.48, p = 0.013), increased quantitative electroencephalographic interhemispheric amplitude differences (OR = 2.41, partial R2 = 0.48, p = 0.013), and increased interhemispheric TCD TIBI score differences (OR = 4.66, partial R2 = 0.49, p = 0.006) to be independently associated with acute brain injury (area under the receiver operating characteristic curve = 0.92). CONCLUSIONS: Increased seizure burden and increased interhemispheric differences in both quantitative electroencephalographic amplitude and TCD MCA TIBI scores are independently associated with acute brain injury in children undergoing ECMO support.

Cognitive Motor Dissociation: Gap Analysis and Future Directions.

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

Evaluating the Impact of Point-of-Care Electroencephalography on Length of Stay in the Intensive Care Unit: Subanalysis of the SAFER-EEG Trial.

BACKGROUND: Electroencephalography (EEG) is needed to diagnose nonconvulsive seizures. Prolonged nonconvulsive seizures are associated with neuronal injuries and deleterious clinical outcomes. However, it is uncertain whether the rapid identification of these seizures using point-of-care EEG (POC-EEG) can have a positive impact on clinical outcomes. METHODS: In a retrospective subanalysis of the recently completed multicenter Seizure Assessment and Forecasting with Efficient Rapid-EEG (SAFER-EEG) trial, we compared intensive care unit (ICU) length of stay (LOS), unfavorable functional outcome (modified Rankin Scale score ≥ 4), and time to EEG between adult patients receiving a US Food and Drug Administration-cleared POC-EEG (Ceribell, Inc.) and those receiving conventional EEG (conv-EEG). Patient records from January 2018 to June 2022 at three different academic centers were reviewed, focusing on EEG timing and clinical outcomes. Propensity score matching was applied using key clinical covariates to control for confounders. Medians and interquartile ranges (IQRs) were calculated for descriptive statistics. Nonparametric tests (Mann-Whitney U-test) were used for the continuous variables, and the χ2 test was used for the proportions. RESULTS: A total of 283 ICU patients (62 conv-EEG, 221 POC-EEG) were included. The two populations were matched using demographic and clinical characteristics. We found that the ICU LOS was significantly shorter in the POC-EEG cohort compared to the conv-EEG cohort (3.9 [IQR 1.9-8.8] vs. 8.0 [IQR 3.0-16.0] days, p = 0.003). Moreover, modified Rankin Scale functional outcomes were also different between the two EEG cohorts (p = 0.047). CONCLUSIONS: This study reveals a significant association between early POC-EEG detection of nonconvulsive seizures and decreased ICU LOS. The POC-EEG differed from conv-EEG, demonstrating better functional outcomes compared with the latter in a matched analysis. These findings corroborate previous research advocating the benefit of early diagnosis of nonconvulsive seizure. The causal relationship between the type of EEG and metrics of interest, such as ICU LOS and functional/clinical outcomes, needs to be confirmed in future prospective randomized studies.

Ten good reasons to consider gastrointestinal function after acute brain injury.

The brain-gut axis represents a bidirectional communication linking brain function with the gastrointestinal (GI) system. This interaction comprises a top-down communication from the brain to the gut, and a bottom-up communication from the gut to the brain, including neural, endocrine, immune, and humoral signaling. Acute brain injury (ABI) can lead to systemic complications including GI dysfunction. Techniques for monitoring GI function are currently few, neglected, and many under investigation. The use of ultrasound could provide a measure of gastric emptying, bowel peristalsis, bowel diameter, bowel wall thickness and tissue perfusion. Despite novel biomarkers represent a limitation in clinical practice, intra-abdominal pressure (IAP) is easy-to-use and measurable at bedside. Increased IAP can be both cause and consequence of GI dysfunction, and it can influence cerebral perfusion pressure and intracranial pressure via physiological mechanisms. Here, we address ten good reasons to consider GI function in patients with ABI, highlighting the importance of its assessment in neurocritical care.

Predicting short-term outcomes in brain-injured patients: a comprehensive approach with transcranial Doppler and intracranial compliance assessment.

Neurocritical patients frequently exhibit abnormalities in cerebral hemodynamics (CH) and/or intracranial compliance (ICC), all of which significantly impact their clinical outcomes. Transcranial Doppler (TCD) and the cranial micro-deformation sensor (B4C) are valuable techniques for assessing CH and ICC, respectively. However, there is a scarcity of data regarding the predictive value of these techniques in determining patient outcomes. We prospectively included neurocritical patients undergoing intracranial pressure (ICP) monitoring within the first 5 days of hospital admission for TCD and B4C assessments. Comprehensive clinical data were collected alongside parameters obtained from TCD (including the estimated ICP [eICP] and estimated cerebral perfusion pressure [eCPP]) and B4C (measured as the P2/P1 ratio). These parameters were evaluated individually as well as in combination. The short-term outcomes (STO) of interest were the therapy intensity levels (TIL) for ICP management recommended by the Seattle International Brain Injury Consensus Conference, as TIL 0 (STO 1), TIL 1-3 (STO 2) and death (STO 3), at the seventh day after last data collection. The dataset was randomly separated in test and training samples, area under the curve (AUC) was used to represent the noninvasive techniques ability on the STO prediction and association with ICP. A total of 98 patients were included, with 67% having experienced severe traumatic brain injury and 15% subarachnoid hemorrhage, whilst the remaining patients had ischemic or hemorrhagic stroke. ICP, P2/P1, and eCPP demonstrated the highest ability to predict early mortality (p = 0.02, p = 0.02, and p = 0.006, respectively). P2/P1 was the only parameter significant for the prediction of STO 1 (p = 0.03). Combining B4C and TCD parameters, the highest AUC was 0.85 to predict death (STO 3), using P2/P1 + eCPP, whereas AUC was 0.72 to identify ICP > 20 mmHg using P2/P1 + eICP. The combined noninvasive neuromonitoring approach using eCPP and P2/P1 ratio demonstrated improved performance in predicting outcomes during the early phase after acute brain injury. The correlation with intracranial hypertension was moderate, by means of eICP and P2/P1 ratio. These results support the need for interpretation of this information in the ICU and warrant further investigations for the definition of therapy strategies using ancillary tests.

Delirium and Its Associations with Critical Care Utilizations and Outcomes at the Time of Hospital Discharge in Patients with Acute Brain Injury.

Background and Objectives: We analyzed delirium testing, delirium prevalence, critical care associations outcomes at the time of hospital discharge in patients with acute brain injury (ABI) due to acute ischemic stroke (AIS), non-traumatic subarachnoid hemorrhage (SAH), non-traumatic intraparenchymal hemorrhage (IPH), and traumatic brain injury (TBI) admitted to an intensive care unit. Materials and Methods: We examined the frequency of assessment for delirium using the Confusion Assessment Method for the intensive care unit. We assessed delirium testing frequency, associated factors, positive test outcomes, and their correlations with clinical care, including nonpharmacological interventions and pain, agitation, and distress management. Results: Amongst 11,322 patients with ABI, delirium was tested in 8220 (726%). Compared to patients 18-44 years of age, patients 65-79 years (aOR 0.79 [0.69, 0.90]), and those 80 years and older (aOR 0.58 [0.50, 0.68]) were less likely to undergo delirium testing. Compared to English-speaking patients, non-English-speaking patients (aOR 0.73 [0.64, 0.84]) were less likely to undergo delirium testing. Amongst 8220, 2217 (27.2%) tested positive for delirium. For every day in the ICU, the odds of testing positive for delirium increased by 1.11 [0.10, 0.12]. Delirium was highest in those 80 years and older (aOR 3.18 [2.59, 3.90]). Delirium was associated with critical care resource utilization and with significant odds of mortality (aOR 7.26 [6.07, 8.70] at the time of hospital discharge. Conclusions: In conclusion, we find that seven out of ten patients in the neurocritical care unit are tested for delirium, and approximately two out of every five patients test positive for delirium. We demonstrate disparities in delirium testing by age and preferred language, identified high-risk subgroups, and the association between delirium, critical care resource use, complications, discharge GCS, and disposition. Prioritizing equitable testing and diagnosis, especially for elderly and non-English-speaking patients, is crucial for delivering quality care to this vulnerable group.

Paroxysmal Sympathetic Hyperactivity after Traumatic Brain Injury: Current Understanding and Therapeutic Options.

How to cite this article: Nasa P, Majeed NA, Juneja D. Paroxysmal Sympathetic Hyperactivity after Traumatic Brain Injury: Current Understanding and Therapeutic Options. Indian J Crit Care Med 2024;28(2):97-99.

A subset of OPCs do not express Olig2 during development which can be increased in the adult by brain injuries and complex motor learning.

Oligodendrocyte precursor cells (OPCs) are uniformly distributed in the mammalian brain; however, their function is rather heterogeneous in respect to their origin, location, receptor/channel expression and age. The basic helix-loop-helix transcription factor Olig2 is expressed in all OPCs as a pivotal determinant of their differentiation. Here, we identified a subset (2%-26%) of OPCs lacking Olig2 in various brain regions including cortex, corpus callosum, CA1 and dentate gyrus. These Olig2 negative (Olig2neg ) OPCs were enriched in the juvenile brain and decreased subsequently with age, being rarely detectable in the adult brain. However, the loss of this population was not due to apoptosis or microglia-dependent phagocytosis. Unlike Olig2pos OPCs, these subset cells were rarely labeled for the mitotic marker Ki67. And, accordingly, BrdU was incorporated only by a three-day long-term labeling but not by a 2-hour short pulse, suggesting these cells do not proliferate any more but were derived from proliferating OPCs. The Olig2neg OPCs exhibited a less complex morphology than Olig2pos ones. Olig2neg OPCs preferentially remain in a precursor stage rather than differentiating into highly branched oligodendrocytes. Changing the adjacent brain environment, for example, by acute injuries or by complex motor learning tasks, stimulated the transition of Olig2pos OPCs to Olig2neg cells in the adult. Taken together, our results demonstrate that OPCs transiently suppress Olig2 upon changes of the brain activity.

Contribution of intracranial pressure to human dynamic cerebral autoregulation after acute brain injury.

Cerebral perfusion pressure (CPP) is normally expressed by the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP) but comparison of the separate contributions of MAP and ICP to human cerebral blood flow autoregulation has not been reported. In patients with acute brain injury (ABI), internal jugular vein compression (IJVC) was performed for 60 s. Dynamic cerebral autoregulation (dCA) was assessed in recordings of middle cerebral artery blood velocity (MCAv, transcranial Doppler), and invasive measurements of MAP and ICP. Patients were separated according to injury severity as having whole/undamaged skull, large fractures, or craniotomies, or following decompressive craniectomy. Glasgow coma score was not different for the three groups. IJVC induced changes in MCAv, MAP, ICP, and CPP in all three groups. The MCAv response to step changes in MAP and ICP expressed the dCA response to these two inputs and was quantified with the autoregulation index (ARI). In 85 patients, ARI was lower for the ICP input as compared with the MAP input (2.25 ± 2.46 vs. 3.39 ± 2.28; P < 0.0001), and particularly depressed in the decompressive craniectomy (DC) group (n = 24, 0.35 ± 0.62 vs. 2.21 ± 1.96; P < 0.0005). In patients with ABI, the dCA response to changes in ICP is less efficient than corresponding responses to MAP changes. These results should be taken into consideration in studies aimed to optimize dCA by manipulation of CPP in neurocritical patients.

The intracranial compartmental syndrome: a proposed model for acute brain injury monitoring and management.

For decades, one of the main targets in the management of severe acute brain injury (ABI) has been intracranial hypertension (IH) control. However, the determination of IH has suffered variations in its thresholds over time without clear evidence for it. Meanwhile, progress in the understanding of intracranial content (brain, blood and cerebrospinal fluid) dynamics and recent development in monitoring techniques suggest that targeting intracranial compliance (ICC) could be a more reliable approach rather than guiding actions by predetermined intracranial pressure values. It is known that ICC impairment forecasts IH, as intracranial volume may rapidly increase inside the skull, a closed bony box with derisory expansibility. Therefore, an intracranial compartmental syndrome (ICCS) can occur with deleterious brain effects, precipitating a reduction in brain perfusion, thereby inducing brain ischemia. The present perspective review aims to discuss the ICCS concept and suggest an integrative model for the combination of modern invasive and noninvasive techniques for IH and ICC assessment. The theory and logic suggest that the combination of multiple ancillary methods may enhance ICC impairment prediction, pointing proactive actions and improving patient outcomes.

Respiratory challenges and ventilatory management in different types of acute brain-injured patients.

Acute brain injury (ABI) covers various clinical entities that may require invasive mechanical ventilation (MV) in the intensive care unit (ICU). The goal of MV, which is to protect the lung and the brain from further injury, may be difficult to achieve in the most severe forms of lung or brain injury. This narrative review aims to address the respiratory issues and ventilator management, specific to ABI patients in the ICU.