Hemorrhage Brain Injury Research Articles

Soluble Urokinase-Type Plasminogen Activator Receptor and Inflammatory Biomarker Response with Prognostic Significance after Acute Neuronal Injury - a Prospective Cohort Study.

Aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI) are severe conditions impacting individuals and society. Identifying reliable prognostic biomarkers for predicting survival or recovery remains a challenge. Soluble urokinase type plasminogen activator receptor (suPAR) has gained attention as a potential prognostic biomarker in acute sepsis. This study evaluates suPAR and related neuroinflammatory biomarkers in serum for brain injury prognosis. This prospective study included 31 aSAH, 30 IS, 13 TBI, and three healthy controls (n = 77). Serum samples were collected on average 5.9days post-injury, analyzing suPAR, IL-1β, cyclophilin A, and TNFα levels using ELISA. Outcomes were assessed 90days post-injury with the modified Rankin Scale (mRS), categorized as favorable (mRS 0-2) or unfavorable (mRS 3-6). Statistical analyses included 2-tailed t-tests, Pearson's correlations, and machine learning linear discriminant analysis (LDA) for biomarker combinations. Elevated suPAR levels were found in brain injury patients compared to controls (p = 0.017). Increased suPAR correlated with unfavorable outcomes (p = 0.0018) and showed prognostic value (AUC = 0.66, p = 0.03). IL-1β levels were higher in the unfavorable group (p = 0.0015). LDA combinatory analysis resulted a fair prognostic accuracy with canonical equation = 0.775[suPAR] + 0.667[IL1-β] (AUC = 0.77, OR 0.296, sensitivity 93.1%, specificity 53.1%, p = 0.0007). No correlation was found between suPAR and CRP or infection status. Elevated suPAR levels in acute brain injury patients were associated with poorer outcomes, highlighting suPAR's potential as a prognostic biomarker across different brain injury types. Combining IL-1β with suPAR improved prognostic accuracy, supporting a multimodal biomarker approach for predicting outcomes.

Plasma treatment is associated with decreased brain lesion and resuscitation requirements after traumatic brain injury in a swine model of prolonged damage-control resuscitation

BACKGROUND Hemorrhage and traumatic brain injury (TBI) are the leading causes of death in trauma. Future military conflicts are likely to be in austere environments, where prolonged damage-control resuscitation (p-DCR) may be required for 72 hours before evacuation. Previous studies showed that early administration of fresh frozen plasma (FFP) during p-DCR can significantly decrease the volume of resuscitation required in models of hemorrhagic shock and also provide neuroprotection after TBI. In the current study, we hypothesized that the addition of FFP to p-DCR would decrease the resuscitation requirements and improve neurological outcomes in a large animal model of combined hemorrhagic shock and TBI. METHODS Yorkshire swine (40–45 kg; n = 10) were subjected to TBI (controlled cortical impact) and 40% blood volume hemorrhage. After 2 hours of shock, they were randomized to either: (1) p-DCR–normal saline or (2) p-DCR–FFP (250 mL). Prolonged damage-control resuscitation targeted a systolic blood pressure of 90% of baseline, in line with Tactical Combat Casualty Care principles. At 72 hours, animals were transfused 1 U of packed red blood cells, simulating evacuation to higher echelons of care. Brain lesion size, physiologic parameters, resuscitation fluid requirements, and neurological severity score were used to compare the clinical outcomes. RESULTS The p-DCR–FFP group required significantly less total volume (4,540.0 ± 151.7 mL vs. 974.0 ± 167.0 mL, p < 0.01) of resuscitation to maintain the target systolic blood pressure. Fresh frozen plasma–treated animals had significantly reduced brain lesion size (4,517.0 ± 180.0 mm3 vs. 2,477.0 ± 1,191.0 mm3, p < 0.01) and showed significantly decreased functional neurologic impairment. CONCLUSION In this exploratory study, treatment with FFP decreased resuscitation requirements, reduced brain lesion size, and improved neurological outcomes when added to prolonged DCR in a porcine model of combined hemorrhagic shock and TBI.

Energy Expenditure in Critically Ill Patients with Aneurysmal Subarachnoid Hemorrhage, Intracerebral Hemorrhage, and Traumatic Brain Injury-A Prospective Observational Study.

Energy expenditure (EE) in patients with aneurysmal subarachnoid hemorrhage (SAH) may differ from other intracranial pathologies, such as intracerebral hemorrhage (ICH) or traumatic brain injury (TBI), due to an activation of the sympathetic nervous system. Indirect calorimetry (IC) is recommended, but is not always available. We study EE, catabolism, and metabolic stress in patients with SAH, TBI, ICH, and sepsis as controls. A prospective observational study was conducted in the intensive care units of the University Medical Center Hamburg-Eppendorf, Germany. IC was used to measure EE on days 2-3, 5-7, and 10-15 post-admission. Urinary catecholamines, metabolites, and urine urea were also measured. Statistical analysis included t-tests, Chi-square tests, and generalized mixed models. We included 110 patients-43 SAH patients (13 with the surgical securing of the aneurysm and 30 with coil embolization of the aneurysm), 22 TBI patients, 23 ICH patients, and 22 controls. The generalized linear mixed model analysis for groups and timepoints including age, height, and weight as covariates revealed a significantly lower EE at timepoint 1 for ICH versus SAH-interventional (p = 0.003) and versus the control (p = 0.004), as well as at timepoint 2 for ICH versus SAH-interventional (p = 0.002) and versus SAH-surgical (p = 0.013) with a lower EE in ICH patients. No significant differences between groups were found for EE at the other timepoints, or concerning urine urea and measurements of catecholamines in urine. In patients with SAH, ICH, and TBI, no meaningful differences in EE were detected compared to septic critically ill patients, except for a lower EE in ICH patients in the early phase.

Clinical Use of Bedside Portable Ultra-Low-Field Brain Magnetic Resonance Imaging in Patients on Extracorporeal Membrane Oxygenation: Results From the Multicenter SAFE MRI ECMO Study.

Early detection of acute brain injury (ABI) at the bedside is critical in improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to examine the safety of ultra-low-field (ULF; 0.064-T) portable magnetic resonance imaging (pMRI) in patients undergoing ECMO and to investigate the ABI frequency and types with ULF-pMRI. This was a multicenter prospective observational study (SAFE MRI ECMO study [Assessing the Safety and Feasibility of Bedside Portable Low-Field Brain Magnetic Resonance Imaging in Patients on ECMO]; NCT05469139) from 2 tertiary centers (Johns Hopkins, Baltimore, MD and University of Texas-Houston) with specially trained intensive care units. Primary outcomes were safety of ULF-pMRI during ECMO support, defined as completion of ULF-pMRI without significant adverse events. Of 53 eligible patients, 3 were not scanned because of a large head size that did not fit within the head coil. ULF-pMRI was performed in 50 patients (median age, 58 years; 52% male), with 34 patients (68%) on venoarterial ECMO and 16 patients (32%) on venovenous ECMO. Of 34 patients on venoarterial ECMO, 11 (22%) were centrally cannulated and 23 (46%) were peripherally cannulated. In venovenous ECMO, 9 (18%) had single-lumen cannulation and 7 (14%) had double-lumen cannulation. Of 50 patients, adverse events occurred in 3 patients (6%), with 2 minor adverse events (ECMO suction event; transient low ECMO flow) and one serious adverse event (intra-aortic balloon pump malfunction attributable to electrocardiographic artifacts). All images demonstrated discernible intracranial pathologies with good quality. ABI was observed in 22 patients (44%). Ischemic stroke (36%) was the most common type of ABI, followed by intracranial hemorrhage (6%) and hypoxic-ischemic brain injury (4%). Of 18 patients (36%) with both ULF-pMRI and head computed tomography within 24 hours, ABI was observed in 9 patients with a total of 10 events (8 ischemic, 2 hemorrhagic events). Of the 8 ischemic events, pMRI observed all 8, and head computed tomography observed only 4 events. For intracranial hemorrhage, pMRI observed only 1 of them, and head computed tomography observed both (2 events). Our study demonstrates that ULF-pMRI can be performed in patients on ECMO across different ECMO cannulation strategies in specially trained intensive care units. The incidence of ABI was high, seen in 44% of ULF-pMRI studies. ULF-pMRI imaging appears to be more sensitive to ABI, particularly ischemic stroke, compared with head computed tomography.

Intracranial Pressure Variability Associates with 3-Month Outcomes in Spontaneous Intracerebral Hemorrhage: A Retrospective Analysis of 597 Patients

Background and ObjectiveSpontaneous intracerebral hemorrhage (ICH) is a devastating type of stroke but most favorable treatments to improve patients’ neurological outcomes are not clear. Invasive intracranial pressure (ICP) monitoring is a common treatment of ICH, but whether ICH patients could benefit from ICP monitoring is controversial. ICP variability (IPV) has been shown to correlate with poor outcomes in patients with subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI), but this association has not been clearly elucidated in ICH patients. We hypothesized that 72 hour-IPV from time of ICP probe implantation is associated with outcomes in ICH patients. MethodsA retrospective chart review analysis of adult ICH patients, who received ICP monitoring at Huashan Hospital Fudan University between Jan. 2008 and Jan. 2023, was performed. We included ICH patients within 6 hours of signs or symptoms onset. Outcomes of ICH patients were assessed using 3-month mRS, and were dichotomized into poor (mRS 4 to 6) and good (mRS 0 to 3) outcome group. ICPs were recorded from the implantation of invasive ICP probe until it was removed. ICP was analyzed in the acute period, from 0 to 72 hours after ICP implantation. IPV was analyzed by SD (Standard deviation), CV (Coefficient of variation) and SV (Successive variation) of ICP. ResultsWe analyzed 597 patients’ charts. The 1st ICP assessment, immediately after ICP implantation, at median 117 minutes (interquartile range, 82-231 minutes) after admission was mean 20.5±7.8 mmHg. The 2nd ICP assessment, on NICU arrival after operation, was mean 14.6±8.3 mmHg. Poor outcomes occurred in 213 patients (35.68%). In univariate analysis, univariate quintile analysis or multivariate analysis, ICPSD, ICPCV and ICPSV were associated with poor outcomes. ConclusionsIPV during the first 72 hours after ICP implantation in patients with ICH was independently associated with poor functional outcome at 3-month. Stabilization of IPV during hyperacute and acute period maybe a potential therapeutic target to improve functional outcomes of these patients.

High frequency oscillations may improve somatosensory evoked potential detection of good outcomes in disorders of consciousness secondary to acute neurologic injury

BackgroundSomatosensory evoked potentials (SEPs) are highly specific predictors of poor prognosis in hypoxic-ischemic coma when cortical responses (N20s) are absent. However, bilateral N20 presence is nonspecific for good outcomes. High-frequency oscillations (HFOs) in the SEP waveform predict neurologic recovery in animals, but clinical applications are poorly understood. We sought to develop a clinical measure of HFOs to potentially improve detection of good outcomes in coma. Materials and MethodsWe collected SEP waveform data from all comatose inpatients (GCS<=8) who underwent neurologic prognostication from 2020 to 2022 at Johns Hopkins Hospital. We developed a novel measure − HFO evoked to spontaneous ratios (HFO-ESRs) – and applied this to those patients with bilaterally present N20s using both standard univariate classification and cubic kernal vector machine (SVM) models to predict the last documented in-hospital Glasgow Coma Scale (GCS) prior to discharge or death. ResultsOf 58 total patients, 34 (58.6%) had bilaterally present N20s. Of these, 14 had final GCS>=9, and 20 had final GCS<=8. Mean age was 52 (+/− 17) years, 20.1% female. Etiologies of coma were primarily global hypoxic-ischemic brain injury (79.4%), intracranial hemorrhage (11.8%), and traumatic brain injury (2.9%). In univariate classification, the addition of averaged HFO-ESRs to bilaterally present N20s predicted final GCS>=9 with 68% specificity. The SVM model further improved specificity to 85%. ConclusionsIn this pilot investigation, we developed a novel clinical measure of SEP HFOs. Incorporation of this measure may improve the specificity of the SEP to predict in-hospital GCS outcomes in coma, but requires further validation in specific neurologic injuries and with longitudinal outcomes.

Noninvasive Monitoring of Changes in Cerebral Hemodynamics During Prolonged Field Care for Hemorrhagic Shock and Hypoxia-Induced Injuries With Portable Diffuse Optical Sensors.

Achieving simultaneous cerebral blood flow (CBF) and oxygenation measures, specifically for point-of-care injury monitoring in prolonged field care, requires the implementation of appropriate methodologies and advanced medical device design, development, and evaluation. The near-infrared spectroscopy (NIRS) method measures the absorbance of light whose attenuation is related to cerebral blood volume and oxygenation. By contrast, diffuse correlation spectroscopy (DCS) allows continuous noninvasive monitoring of microvascular blood flow by directly measuring the degree of light scattering because of red blood cell (RBC) movement in tissue capillaries. Hence, this study utilizes these two optical approaches (DCS-NIRS) to obtain a more complete hemodynamic monitoring by providing cerebral microvascular blood flow, hemoglobin oxygenation and deoxygenation in hemorrhage, and hypoxia-induced injuries. Piglet models of hemorrhage and hypoxia-induced brain injury were used with DCS and NIRS sensors placed over the preorbital to temporal skull regions. To induce hemorrhagic shock, up to 70% of the animal's total blood volume was withdrawn through graded hemorrhage serially via a syringe from a femoral artery cannula in 10 mL/kg aliquots over 1 minute every 10 minutes. A second group of animals was subjected to hypoxia for ∼1 hour through graded hypoxia by serial titration from normoxic fraction inspired oxygen of 21% to hypoxic fraction inspired oxygen of 6%. A subset of animals served as sham-controls undergoing anesthesia, instrumentation, and ventilation as the injury groups, yet experiencing no blood loss or hypoxia. We first investigated the relationship between hemorrhagic shock and no shock by using measured biomarkers, including blood flow index from DCS associated with CBF and oxygenated (HbO) and de-oxygenated hemoglobin from NIRS. The statistical analysis revealed a significant difference between no shock and hemorrhagic shock (P < .01). The HbO decreased with each blood loss as expected, yet the de-oxygenated hemoglobin was slightly changed. During hypoxia-induced global hypoxic-ischemic injury tests, the CBF results from graded hypoxia were consistent with the response previously measured during hemorrhagic shock. Moreover, HbO decreased when the animal was hypoxic, as expected. A statistical analysis was also conducted to compare the results with those of the sham controls. There is a consistency in blood flow measures in both injury mechanisms (hemorrhagic shock and hypoxia), which is significant as the new prototype system provides similar measures and trends for each brain injury type, suggesting that the optical system can be used in response to different injury mechanisms. Notably, the results support the idea that this optical system can probe the hemodynamic status of local cerebral cortical tissue and provide insight into the underlying changes of cerebral tissue perfusion at the microvascular level. These measurement capabilities can improve shock identification and monitoring of medical management of injuries, particularly hemorrhagic shock, in prolonged field care.

The silent information regulator 1 agonist SRT1720 reduces experimental intracerebral hemorrhagic brain injury by regulating the blood-brain barrier integrity.

Intracerebral hemorrhage (ICH) is a significant public health matter that has no effective treatment. ICH-induced destruction of the blood-brain barrier (BBB) leads to neurological deterioration. Astrocytic sonic hedgehog (SHH) alleviates brain injury by maintaining the integrity of the BBB after ICH. Silent information regulator 1 (SIRT1) is neuroprotective in several central nervous system diseases via BBB regulation. It is also a possible influential factor of the SHH signaling pathway. Nevertheless, the role of SIRT1 on BBB and the underlying pathological process associated with the SHH signaling pathway after ICH remain unclear. We established an intracerebral hemorrhagic mouse model by collagenase injection. SRT1720 (a selective agonist of SIRT1) was used to evaluate the effect of SIRT1 on BBB integrity after ICH. SIRT1 expression was reduced in the mouse brain after ICH. SRT1720 attenuated neurobehavioral impairments and brain edema of ICH mouse. After ICH induction, SRT1720 improved BBB integrity and tight junction expressions in the mouse brain. The SHH signaling pathway-related factors smoothened and glioma-associated oncogene homolog-1 were increased with the intervention of SRT1720, while cyclopamine (a specific inhibitor of the SHH signaling pathway) reversed these effects. These findings suggest that SIRT1 protects from ICH by altering BBB permeability and tight junction expression levels. This process is associated with the SHH signaling pathway, suggesting that SIRT1 may be a potential therapeutic target for ICH.

MULTIMODAL NEUROMONITORING IN DIFFERENT NEUROCRITICAL CONDITIONS – FIRST EXPERIENCES IN SINGLE NEUROCRITICAL CARE CENTRE

The study explores the use of multimodal neuromonitoring in a neurocritical care center, focusing on patients with acute brain injuries. The monitoring involves various sensors to track intracranial pressure (ICP), partial brain tissue oxygenation (PbO2), cerebral perfusion pressure (CPP), and more. The research, conducted at the Lithuanian University of Health Sciences, covers a small sample size (13 patients), mainly dealing with subarachnoid hemorrhage and traumatic brain injury cases. Results indicate challenges, such as episodes of intracranial hypertension and cerebral hypoxia, despite adherence to treatment protocols. The study faces limitations due to manual data registration, leading to potential inaccuracies. The outcomes reveal a mortality rate of 23.1%, with the majority experiencing unfavorable results. In conclusion, the study underscores the significance of multimodal monitoring but highlights the need for larger sample sizes, improved data recording methods, and emphasizes the complexity and challenges in managing neurocritical conditions.

Dual roles of microglia in the pathological injury and repair of hemorrhagic cerebrovascular diseases

Microglia are one of the most important immune cells in the central nervous system, which mainly play an immune surveillance role under normal conditions to maintain central nervous system homeostasis. In the early stages of hemorrhagic brain injury, microglia are activated to the classical phenotype (M1 type). At this time, microglia can promote the inflammatory response by secreting inflammatory cytokines and reactive oxygen species, thereby disrupting the blood–brain barrier. Consequently, this leads to neuronal cell necrosis, aggravates brain edema, and triggers secondary brain injury. However, in the later stages of hemorrhagic brain injury, microglia can switch from the M1 phenotype to the alternative activating M2 phenotype. This transition allows them to participate in the repair process of the nervous system after a brain hemorrhage. They achieve this by phagocytosing tissue debris, secreting anti-inflammatory cytokines, and releasing growth factors to suppress the overacting inflammatory response and promote angiogenesis. Therefore, this paper presents an account of cerebral hemorrhage and subarachnoid hemorrhage, with a primary focus on exploring the role of microglia in hemorrhagic cerebrovascular disease. The aim is to provide new perspectives for basic and clinical translational research in hemorrhagic cerebrovascular disease.

Examining Transcriptomic Alterations in Rat Models of Intracerebral Hemorrhage and Severe Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. This study investigates transcriptomic alterations in rodent models of ICH and severe ICH to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to ICH and severe ICH rats. We employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the molecular pathways involved. We identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, ICH, and severe ICH groups in the upregulated genes group, and 1196 common genes in the downregulated genes, respectively. A volcano plot comparing these groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.

Ultrasonic cerebrospinal fluid clearance improves outcomes in hemorrhagic brain injury models.

Impaired clearance of the byproducts of aging and neurologic disease from the brain exacerbates disease progression and severity. We have developed a noninvasive, low intensity transcranial focused ultrasound protocol that facilitates the removal of pathogenic substances from the cerebrospinal fluid (CSF) and the brain interstitium. This protocol clears neurofilament light chain (NfL) - an aging byproduct - in aged mice and clears red blood cells (RBCs) from the central nervous system in two mouse models of hemorrhagic brain injury. Cleared RBCs accumulate in the cervical lymph nodes from both the CSF and interstitial compartments, indicating clearance through meningeal lymphatics. Treating these hemorrhagic brain injury models with this ultrasound protocol reduced neuroinflammatory and neurocytotoxic profiles, improved behavioral outcomes, decreased morbidity and, importantly, increased survival. RBC clearance efficacy was blocked by mechanosensitive channel antagonism and was effective when applied in anesthetized subjects, indicating a mechanosensitive channel mediated mechanism that does not depend on sensory stimulation or a specific neural activity pattern. Notably, this protocol qualifies for an FDA non-significant risk designation given its low intensity, making it readily clinically translatable. Overall, our results demonstrate that this low-intensity transcranial focused ultrasound protocol clears hemorrhage and other harmful substances from the brain via the meningeal lymphatic system, potentially offering a novel therapeutic tool for varied neurologic disorders.

Ac2-26 activated the AKT1/GSK3β pathway to reduce cerebral neurons pyroptosis and improve cerebral function in rats after cardiopulmonary bypass

BackgroundCardiopulmonary bypass (CPB) results in brain injury, which is primarily caused by inflammation. Ac2-26 protects against ischemic or hemorrhage brain injury. The present study was to explore the effect and mechanism of Ac2-26 on brain injury in CPB rats.MethodsForty-eight rats were randomized into sham, CPB, Ac, Ac/AKT1, Ac/GSK3βi and Ac/AKT1/GSK3βa groups. Rats in sham group only received anesthesia and in the other groups received standard CPB surgery. Rats in the sham and CPB groups received saline, and rats in the Ac, Ac/AKT1, Ac/GSK3βi and Ac/AKT1/GSK3βa groups received Ac2-26 immediately after CPB. Rats in the Ac/AKT1, Ac/GSK3βi and Ac/AKT1/GSK3βa groups were injected with shRNA, inhibitor and agonist of GSK3β respectively. The neurological function score, brain edema and histological score were evaluated. The neuronal survival and hippocampal pyroptosis were assessed. The cytokines, activity of NF-κB, S100 calcium-binding protein β(S100β) and neuron-specific enolase (NSE), and oxidative were tested. The NLRP3, cleaved-caspase-1 and cleaved-gadermin D (GSDMD) in the brain were also detected.ResultsCompared to the sham group, all indicators were aggravated in rats that underwent CPB. Compared to the CPB group, Ac2-26 significantly improved neurological scores and brain edema and ameliorated pathological injury. Ac2-26 reduced the local and systemic inflammation, oxidative stress response and promoted neuronal survival. Ac2-26 reduced hippocampal pyroptosis and decreased pyroptotic proteins in brain tissue. The protection of Ac2-26 was notably lessened by shRNA and inhibitor of GSK3β. The agonist of GSK3β recovered the protection of Ac2-26 in presence of shRNA.ConclusionsAc2-26 significantly improved neurological function, reduced brain injury via regulating inflammation, oxidative stress response and pyroptosis after CPB. The protective effect of Ac2-26 primarily depended on AKT1/ GSK3β pathway.

Injuries in Fatalities of Dismounted Blast: Identification of Four Mechanisms of Head and Spine Injury.

Blast is the most common injury mechanism in conflicts of this century due to the widespread use of explosives, confirmed by recent conflicts such as in Ukraine. Data from conflicts in the last century such as Northern Ireland, the Falklands, and Vietnam up to the present day show that between 16% and 21% of personnel suffered a traumatic brain injury. Typical features of fatal brain injury to those outside of a vehicle (hereafter referred to as dismounted) due to blast include the presence of hemorrhagic brain injury alongside skull fractures rather than isolated penetrating injuries more typical of traditional ballistic head injuries. The heterogeneity of dismounted blast has meant that analysis from databases is limited and therefore a detailed look at the radiological aspects of injury is needed to understand the mechanism and pathology of dismounted blast brain injury. The aim of this study was to identify the head and spinal injuries in fatalities due to dismounted blast. All UK military fatalities from dismounted blast who suffered a head injury from 2007-2013 in the Iraq and Afghanistan conflicts were identified retrospectively. Postmortem computerized tomography images (CTPMs) were interrogated for injuries to the head, neck, and spine. All injuries were documented and classified using a radiology brain injury classification (BIC) tool. Chi-squared (χ2) and Fisher's exact tests were used to investigate correlations between injuries, along with odds ratios for determining the direction of correlation. The correlations were clustered. There were 71 fatalities from dismounted blast with an associated head injury with a CTPM or initial CT available for analysis. The results showed the heterogeneity of injury from dismounted blast but also some potential identifiable injury constellations. These were: intracranial haemorrhage, intracranial deep haemorrhage, spinal injury, and facial injury. These identified injury patterns can now be investigated to consider injury mechanisms and so develop mitigation strategies or clinical treatments. Level of Evidence: Observational. Study type: cohort observational.

The Optimal pressure reactivity index range is disease-specific: A comparison between aneurysmal subarachnoid hemorrhage and traumatic brain injury

PurposeImpaired cerebral pressure autoregulation is common and detrimental after acute brain injuries. Based on the prevalence of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage (aSAH) patients compared to traumatic brain injury (TBI), we hypothesized that the type of autoregulatory disturbance and the optimal PRx range may differ between these two conditions. The aim of this study was to determine the optimal PRx ranges in relation to functional outcome following aSAH and TBI, respectively.MethodsIn this observational study, 487 aSAH patients and 413 TBI patients, treated in the neurointensive care, Uppsala, Sweden, between 2008 and 2018, were included. The percentage of good monitoring time (%GMT) of PRx was calculated within 8 intervals covering the range from -1.0 to + 1.0, and analyzed in relation to favorable outcome (GOS-E 5 to 8).ResultsIn multiple logistic regressions, a higher %GMTs of PRx in the intervals -1.0 to -0.5 and + 0.75 to + 1.0 were independently associated with a lower rate of favorable outcome in the aSAH cohort. In a similar analysis in the TBI cohort, only positive PRx in the interval + 0.75 to + 1.0 was independently associated with a lower rate of favorable outcome.ConclusionExtreme PRx values in both directions were unfavorable in aSAH, possibly as high PRx could indicate proximal vasospasm with exhausted distal vasodilatory reserve, while very negative PRx could reflect myogenic hyperreactivity with suppressed cerebral blood flow. Only elevated PRx was unfavorable in TBI, possibly as pressure passive vessels may be a more predominant pathomechanism in this disease.

Research priorities in tranexamic acid after trauma: Secondary analysis of the National Trauma Research Action Plan.

Tranexamic acid (TXA) is an antifibrinolytic drug that is used in traumatic hemorrhage and traumatic brain injury. Although TXA is considered relatively safe and inexpensive and is widely available, data regarding its mechanisms, optimal dosing, and timing, as well as relative risks and benefits for different patient populations, are inconsistent. In this study, we aim to identify and summarize consensus research questions related to TXA across all National Trauma Research Action Plan (NTRAP) Delphi expert panels to identify priorities for future research on TXA in trauma. A secondary analysis was performed using consensus-based research priorities collected by 11 NTRAP topic panels using a Delphi methodology. The database of questions was queried for the keywords "tranexamic" and "TXA." The identified questions were sorted by subject matter and summarized. Seven panels included a total of 73 TXA-related questions. Forty-six questions reached consensus. The most addressed topic was outcomes (discussed in 64% of questions) followed by indications (49%) and specific patient populations (38%). Because of overlap across panels, questions were summarized and sorted by topic resulting in 21 priority research questions. Seventy-three total questions and 46 questions reaching consensus were identified by NTRAP panelists. The key topics identified in these questions should be prioritized in future funded research on TXA in trauma. Prognostic and Epidemiological; Level V.

The Impact of SARS-CoV-2 Infection on the Length of Stay in the Neuro-ICU:A Prospective Multicenter Cohort Study in Eight Neuro-ICU, China Between February and April 2023.

The SARS-CoV-2 infection cases are increasing rapidly in neuro-intensive care units (neuro-ICUs) at the beginning of 2023 in China. We aimed to characterize the prevalence, risk factors, and prognosis of critically ill patients treated in neuro-ICUs. In the prospective, multicenter, observational registry study, critically ill patients with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI) admitted to eight Chinese neuro-ICUs between Feb 16, 2023, to Apr 30, 2023 were enrolled for the study. Mortality and ICU stay day were used as the primary outcomes. 131 patients were finally included and analyzed (mean age 60.36 years [SD 13.81], 64.12% male, 39.69% SARS-CoV-2 infected). The mortality is higher in the SARS-CoV-2 infection group without statistical signification (7.69% vs 5.06%, p>0.05). The length of stay (LOS) in neuro-ICUs was significantly longer among the SARS-CoV-2 infection patients (7(1-12) vs 4(1-8), p<0.01), with increased viral pneumonia occurrence (58.54% vs 7.32%, p<0.01). SARS-CoV-2 infection, surgery, and low GCS scores were independent risk factors for prolonged LOS, and respiratory/renal failure were independent risk factors for death. Based on the present neuro-ICU cohort, SARS-CoV-2 infection was a significant risk for the prolonged LOS of neuro-critically ill patients. Registered with Chictr.org.cn (ChiCTR2300068355) at 16 February 2023, Prospective registration. https://www.chictr.org.cn/showproj.html?proj=188252.

Terson Syndrome: what an ophthalmologist should know?

Abstract&#x0D; Introduction : Terson syndrome is the occurrence of any intraocular hemorrhage in patients with intracranial hemorrhage or traumatic brain injury. In this article we present a case of patient with Terson Syndrome after craniotomy.&#x0D; Case Illustration : Forty-six yo female patient consulted from neurosurgery department with chief complain of blurry vision in both eyes since 1 day before. Pain or red eyes were denied. There was no history of visual field defect. She had history of breast cancer and she underwent craniotomy four days before because of her brain metastases. Her Glasgow Coma Scale was 15. In ophthalmology examination, her visual acuity is 6/6 with correction in both eyes with good ocular motility. RAPD was positive in her left eye, and posterior segment showed bilateral optic disc edema with intrapapillary and peripapillary hemorrhage. Humphrey examination revealed enlargement of blind spot in the right eye. Brain CT Scan demonstrated hemorrhagic lesion with pneumoencephal within post operative defect area in right parietal lobe. Laboratory examination showed normal fibrinogen and thrombocyte aggregation with elevation of d-dimer. After two weeks observation, visual acuity still 6/6 in both eyes with decreasing intrapapillary and peripapillary hemorrhage.&#x0D; Discussion : The exact pathophysiology of Terson Syndrome is still unknown. Even though, it has association with high intracranial pressure. Patient with Terson Syndrome will develop 5 times higher mortality rate compare to subarachnoid hemorrhage without Terson Syndrome.&#x0D; Conclusion : Terson Syndrome needs to be recognized early since it will bring significant prognostic effect and cause permanent vision loss if left untreated

Terson Syndrome: A Rare, Treatable Visual Loss After Subarachnoid and Intraventricular Hemorrhage

Abstract&#x0D; Introduction : Intracranial pathologies commonly affect vision through optic neuropathy. However, visual loss could be due to vitreous hemorrhage as in Terson syndrome. This report warns us rare cases of visual loss after intracranial hemorrhage that requires totally different management than more commonly found optic neuropathies.&#x0D; Case Illustration : Female, 46 years old, had a severe headache and decreased consciousness two days later. CT angiography revealed wide subarachnoid hemorrhage and intraventricular hemorrhage causing hydrocephalus. She received emergency lumbar drainage followed by digital subtraction angiography and flow diverter device. Postoperative she regained consciousness, CT scan showed reduced ventricular size without residual hemorrhage, yet visual acuity of left eye reduced to hand movement and did not improve until one month later. Ophthalmologic examination showed vitreous hemorrhage of the left eye. Right eye was normal. Vitrectomy was planned to clear the vitreous hemorrhage.&#x0D; Discussion : Terson syndrome is intraocular hemorrhage associated with subarachnoid hemorrhage, cerebral hemorrhage, or traumatic brain injury. The proposed mechanisms were transmission of subarachnoid blood to the optic nerve sheath and rapid effusion of cerebrospinal fluid into the optic nerve sheath due to sudden increase of intracranial pressure. It compresses central retinal vein, causing vascular rupture. The manifestations could be vitreous, subhyaloid, subretinal, or intraretinal hemorrhage. Visual prognosis is good in those resolved spontaneously or receiving vitrectomy in nonresolving cases.&#x0D; Conclusion : Visual loss from intracranial hemorrhage or trauma could be caused by intraocular hemorrhage. It deserved different management than optic neuropathies. Prompt recognition should improve the management and the prognosis of rare cases such as Terson syndrome.

Amantadine as an Aid to Extubation in Severe Acute Brain Injury: A Case Series.

For a subset of patients with severe acute brain injury (SABI) undergoing invasive mechanical ventilation, the primary barrier to successful extubation is depressed mental status. Amantadine is a neurostimulant that has been demonstrated to increase arousal and improve functional outcomes in patients with SABI. In this case series, we describe 5 patients with SABI and invasive mechanical ventilation who received amantadine as an agent to improve mental status to allow extubation. The primary barrier to extubation for all patients was depressed mental status. Median age was 77 (range 32 to 82). Primary diagnoses were ischemic stroke (n = 1), subdural hemorrhage (n = 2), intracerebral hemorrhage (n = 1), and traumatic brain injury (n = 1). Median Glasgow Coma Score was 7T prior to administration of amantadine and 10T on the day after amantadine was initiated, with improvements in eye-opening and motor response. Four patients displayed improvement in arousal and attention and were successfully extubated 1 to 4days after initiation of amantadine (median 2days). The fifth patient only displayed marginal improvement in mental status after starting amantadine, but was ultimately able to be extubated 7days later. Amantadine may improve the likelihood of or reduce the time to successful extubation in patients with SABI.