Near-infrared spectroscopy (NIRS) may provide a noninvasive way to monitor cerebral oxygenation in patients with traumatic brain injury, therein allowing for timely intervention aimed at reversing regional brain tissue hypoxia. We conducted a systematic review of NIRS-based oximetry measurements and their association with (A) patient functional outcome (B) other neurophysiological parameters. We searched MEDLINE, EMBASE, SCOPUS, BIOSIS, GlobalHealth and Cochrane Databases from inception to December 2018 and relevant conference proceedings published over the last 5 years. A total of 42 studies meeting our inclusion criteria were found (37 prospective observational, 5 retrospective designs). Seven studies reporting on the association between NIRS-based cerebral oxygenated hemoglobin measurements, mortality, modified Rankin Scale, Glasgow Outcome Scale, or Extended Glasgow Outcome Scale were identified. Forty-two studies exploring associations with neurophysiological parameters were included. Notwithstanding significant gaps in the currently available literature, our analysis suggests a link between NIRS-detected cerebral hypoxia during the acute phase of traumatic brain injury and poor functional outcome. NIRS measurements appear to reflect changes in intracranial pressure, invasively monitored brain tissue oxygen tension and various cerebrovascular reactivity indices although low quality contradicting data exist. More importantly, our review highlights the need for more prospective work before routine integration of NIRS-based techniques into multimodality monitoring regimen.

An increasing number of elderly patients are being affected by traumatic brain injury (TBI) and a significant proportion are on pre-hospital antithrombotic therapy for cardio- or cerebrovascular indications. We have quantified the impact of antiplatelet/anticoagulant (APAC) agents on radiological lesion progression in acute TBI, using a novel, semi-automated approach to volumetric lesion measurement, and explored the impact of use on clinical outcomes in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We used a 1:1 propensity-matched cohort design, matching controls to APAC users based on demographics, baseline clinical status, pre-injury comorbidities, and injury severity. Subjects were selected from a pool of patients enrolled in CENTER-TBI with computed tomography (CT) scan at admission and repeated within 7 days of injury. We calculated absolute changes in volume of intraparenchymal, extra-axial, intraventricular, and total intracranial hemorrhage (ICH) between scans, and compared volume of hemorrhagic progression, proportion of patients with significant degree of progression (>25% of initial volume), proportion with new ICH on follow-up CT, as well as clinical course and outcomes. A total of 316 patients were included (158 APAC users; 158 controls). The mean volume of progression was significantly higher in the APAC group for extra-axial (3.1 vs. 1.3 mL, p = 0.01), but not intraparenchymal (3.8 vs. 4.6 mL, p = 0.65), intraventricular (0.2 vs. 0.0 mL, p = 0.79), or total intracranial hemorrhage (ICH; 7.0 vs. 6.0 mL, p = 0.08). More patients had significant hemorrhage growth (54.1 vs. 37.0%, p = 0.003) and delayed ICH (4 of 18 vs. none; p = 0.04) in the APAC group compared with controls, but this was not associated with differences in length of stay (LOS), rates of neurosurgical intervention, mortality or Glasgow Outcome Scale Extended (GOS-E) score at 6 months. Pre-injury use of antithrombotic agents was associated with greater expansion of extra-axial lesions, higher rates of significant hemorrhagic progression, and higher risk of delayed traumatic ICH, but this was not associated with worse clinical course or functional outcomes.

Background: Blunt cerebrovascular injuries (BCVIs) may occur following trauma and lead to ischemic stroke if untreated. Antithrombotic therapy decreases this risk, however, the optimal agent has yet to be determined in this population. Aim of this study was to compare the risk-benefit profile of antiplatelet (AP) versus anticoagulant (AC) therapy in rates of ischemic stroke and hemorrhagic complications in BCVI patients. Methods: We performed a retrospective review of BCVI patients at our tertiary care Trauma hospital from 2010-2015, and a systematic review and meta-analysis of the literature. The OVID Medline, Embase, Web of Science, and Cochrane Library databases were searched from inception to September 16, 2019. References of included publications were searched manually for other relevant papers. The search was limited to articles in humans, in patients >= 18 years of age, and English. Studies that reported treatment-stratified clinical outcomes following AP or AC treatment in BCVI patients were included. Exclusion criteria included case reports, case series with n<5, review articles, conference abstracts, animal studies, and non-peer reviewed publications. Data was extracted from each study independently by two reviewers, including study design, country of origin, sex and age of patients, injury severity score, Biffl grade, type of treatment, ischemic stroke rate and hemorrhage rate. Pooled estimates using odds-ratio were combined using a random-effects model using a Mantel-Hanzel weighting. The main outcome of interest was ischemic stroke rate due to BCVI and the secondary outcome was hemorrhage rate based on AC or AP treatment. Results: In total, there were 2044 BCVI patients, as reported in the 22 studies in combination with our institutional data. The stroke rate was not significantly different between the two treatment groups (OR 1.27, 95% CI 0.40-3.99); however, the hemorrhage rate was decreased in AP versus AC treated groups (OR 0.38, 95% CI 0.15-1.00). Conclusions: Based on this meta-analysis, both AC and AP seem similarly effective in preventing ischemic stroke, but AP is better tolerated in the trauma population. This suggests that antiplatelet therapy may be preferred, but this should be further assessed with prospective randomized trials. Type of study Review Article Level of evidence II

Failure of cerebral autoregulation has been linked to unfavourable outcome after traumatic brain injury. Preliminary evidence from a retrospective single-center analysis suggest that autoregulatory dysfunction may be associated with traumatic lesion expansion, particularly for pericontusional edema. The goal of this study was to explore these associations using prospective multi-center data from the Collaborative European Neurotrauma Effectiveness Research in TBI and to further assess the relationship between autoregulatory failure, lesion progression and patient outcome. 88 subjects from the CENTER-TBI High Resolution ICU cohort were included. All patients had an admission computed tomography (CT) scan and early repeat scan available and high-frequency neurophysiological recordings covering the between-scan interval. Using a novel, semi-automated approach at lesion segmentation, we calculated absolute changes in volume of contusion core, pericontusional edema and extra-axial hemorrhage between the imaging studies. We then evaluated associations between cerebrovascular reactivity metrics and radiological lesion progression using mixed regression. Analyses were adjusted for baseline covariates and non-neurophysiological factors associated with lesion growth using multivariate methods. Impairment in cerebrovascular reactivity was significantly associated with progression of pericontusional edema, and to a lesser degree, intraparenchymal hemorrhage. In contrast, there were no significant associations with extra-axial hemorrhage. The strongest relationships were observed between RAC-based metrics and edema formation. PAx showed weaker, but consistent associations with contusion growth. Cerebrovascular reactivity metrics remained strongly associated with lesion progression after taking into account contributions from non-neurophysiological factors and mean CPP. Total hemorrhagic core and edema volumes on repeat CT were significantly larger in patients who were deceased at 6 months, and the amount of edema was greater in patients with an unfavourable outcome (GOSE 1-4). Our study suggests associations between autoregulatory failure, traumatic edema progression and poor outcome. This is in keeping with findings from a single-center retrospective analysis, providing multi-center prospective data to support those results.

There is an increasing number of trauma patients presenting on pre-injury antiplatelet (AP) agents attributable to an aging population and expanding cardio- or cerebrovascular indications for antithrombotic therapy. The effects of different AP regimens on outcomes after traumatic brain injury (TBI) have yet to be elucidated, despite the implications on patient/family counseling and the potential need for better reversal strategies. The goal of this systematic review and meta-analysis was to assess the impact of different pre-injury AP regimens on outcomes after TBI. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the OVID Medline, Embase, BIOSIS, Scopus, and Cochrane databases were searched from inception to February 2022 using a combination of terms pertaining to TBI and use of AP agents. Baseline demographics and study characteristics as well as outcome data pertaining to intracerebral hematoma (ICH) progression, need for neurosurgical intervention, hospital length of stay, mortality, and functional outcome were extracted. Pooled odds ratios (ORs) and mean differences comparing groups were calculated using random-effects models. Thirteen observational studies, totaling 1244 patients receiving single AP therapy with acetylsalicylic acid or clopidogrel, 413 patients on dual AP therapy, and 3027 non-AP users were included. No randomized controlled trials were identified. There were significant associations between dual AP use and ICH progression (OR, 2.81; 95% confidence interval [CI], 1.19–6.61; I ² , 85%; p = 0.02) and need for neurosurgical intervention post-TBI (OR, 1.61; 95% CI, 1.15–2.28; I ² , 15%; p = 0.006) compared to non-users, but not between single AP therapy and non-users. There were no associations between AP use and hospital length of stay or mortality after trauma. Pre-injury dual AP use, but not single AP use, is associated with higher rates of ICH progression and neurosurgical intervention post-TBI. However, the overall quality of studies was low, and this association should be further investigated in larger studies.

Background: Failure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI. Methods: We conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses. Results: We observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status. Conclusions: Our preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.