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Importance: Traumatic brain injury (TBI) is associated with persistent functional and cognitive deficits, which may be susceptible to secondary insults. The implications of exposure to surgery and anesthesia after TBI warrant investigation, given that surgery has been associated with neurocognitive disorders., Objective: To examine whether exposure to extracranial (EC) surgery and anesthesia is related to worse functional and cognitive outcomes after TBI., Design, Setting, and Participants: This study was a retrospective, secondary analysis of data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective cohort study that assessed longitudinal outcomes of participants enrolled at 18 level I US trauma centers between February 1, 2014, and August 31, 2018. Participants were 17 years or older, presented within 24 hours of trauma, were admitted to an inpatient unit from the emergency department, had known Glasgow Coma Scale (GCS) and head computed tomography (CT) status, and did not undergo cranial surgery. This analysis was conducted between January 2, 2020, and August 8, 2023., Exposure: Participants who underwent EC surgery during the index admission were compared with participants with no surgery in groups with a peripheral orthopedic injury or a TBI and were classified as having uncomplicated mild TBI (GCS score of 13-15 and negative CT results [CT- mTBI]), complicated mild TBI (GCS score of 13-15 and positive CT results [CT+ mTBI]), or moderate to severe TBI (GCS score of 3-12 [m/sTBI])., Main Outcomes and Measures: The primary outcomes were functional limitations quantified by the Glasgow Outcome Scale-Extended for all injuries (GOSE-ALL) and brain injury (GOSE-TBI) and neurocognitive outcomes at 2 weeks and 6 months after injury., Results: A total of 1835 participants (mean [SD] age, 42.2 [17.8] years; 1279 [70%] male; 299 Black, 1412 White, and 96 other) were analyzed, including 1349 nonsurgical participants and 486 participants undergoing EC surgery. The participants undergoing EC surgery across all TBI severities had significantly worse GOSE-ALL scores at 2 weeks and 6 months compared with their nonsurgical counterparts. At 6 months after injury, m/sTBI and CT+ mTBI participants who underwent EC surgery had significantly worse GOSE-TBI scores (B = -1.11 [95% CI, -1.53 to -0.68] in participants with m/sTBI and -0.39 [95% CI, -0.77 to -0.01] in participants with CT+ mTBI) and performed worse on the Trail Making Test Part B (B = 30.1 [95% CI, 11.9-48.2] in participants with m/sTBI and 26.3 [95% CI, 11.3-41.2] in participants with CT+ mTBI)., Conclusions and Relevance: This study found that exposure to EC surgery and anesthesia was associated with adverse functional outcomes and impaired executive function after TBI. This unfavorable association warrants further investigation of the potential mechanisms and clinical implications that could inform decisions regarding the timing of surgical interventions in patients after TBI.

Ischemic stroke prompts a strong inflammatory response, which is associated with exacerbated outcomes. In this study, we investigated mechanistic regulators of neutrophil extracellular trap (NET) formation in stroke and whether they contribute to stroke outcomes. NET-forming neutrophils were found throughout brain tissue of ischemic stroke patients, and elevated plasma NET biomarkers correlated with worse stroke outcomes. Additionally, we observed increased plasma and platelet surface-expressed high-mobility group box 1 (HMGB1) in stroke patients. Mechanistically, platelets were identified as the critical source of HMGB1 that caused NETs in the acute phase of stroke. Depletion of platelets or platelet-specific knockout of HMGB1 significantly reduced plasma HMGB1 and NET levels after stroke, and greatly improved stroke outcomes. We subsequently investigated the therapeutic potential of neonatal NET-inhibitory factor (nNIF) in stroke. Mice treated with nNIF had smaller brain infarcts, improved long-term neurological and motor function, and enhanced survival after stroke. nNIF specifically blocked NET formation without affecting neutrophil recruitment after stroke. Importantly, nNIF also improved stroke outcomes in diabetic and aged mice and was still effective when given 1 hour after stroke onset. These results support a pathological role for NETs in ischemic stroke and warrant further investigation of nNIF for stroke therapy.

Background: Cerebral edema is a major cause of morbidity in patients with severe traumatic brain injury (TBI). Intraparenchymal thermal conductivity-based probes that measure local cerebral blood flow can measure percent brain tissue water (%BTW) content, but such measures have been insufficiently characterized in patients with TBI., Methods: We retrospectively reviewed physiologic data from patients with severe TBI treated at our institution (2014-2016) who underwent cerebral blood flow monitoring., Results: Sixteen patients underwent focal %BTW measurements at a 15-minute sampling rate. %BTW measurements showed characteristic temporal profiles, with a mean time to peak of 3.7 ± 1.7 days. The mean minimum and maximum %BTWs were 71.0 ± 3.9% and 82.7 ± 7.4%, respectively (overall mean %BTW, 77.0 ± 2.9%). Intracranial pressure (ICP) values of 22 mm Hg (the current treatment threshold for patients with trauma) corresponded to 75.8 ± 5.4 %BTW. Repeated measures correlation showed that %BTW is negatively correlated with serum sodium concentration (r = -0.3; P < 0.001) and weakly positively correlated with ICP (r = 0.08; P = 0.01) and regional cerebral blood flow (r = 0.06; P < 0.001). These effects were consistent in a multivariable model including time from injury. In the best model, time was modeled as a quadratic term because the %BTW followed a parabolic trajectory., Conclusions: %BTW may be a clinically useful, real-time measurement of cerebral edema in patients with TBI. It is closely associated with the serum sodium concentration and follows a characteristic temporal course with characteristic trajectory and stability over time., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Previous studies of traumatic brain injury (TBI) outcomes in elderly patients on oral antithrombotic (OAT) therapies have yielded conflicting results. Our objective was to examine the effect of premorbid OAT medications on outcomes among elderly TBI patients with intracranial hemorrhage., Methods: We performed a retrospective analysis of elderly TBI patients (≥65 years) with closed head injury and evidence of brain hemorrhage on computed tomography scan from 2006 to 2010. Patient demographics, injury severity, clinical course, hospital and intensive care unit length of stay, and disposition were collected. Comparison of patients stratified by premorbid OAT use was performed using nonparametric Kruskal-Wallis and Fisher's exact tests. Multivariable logistic regression was used to compare groups and identify predictors of primary outcomes, including mortality, neurosurgical intervention, hemorrhage progression, complications, and infection., Results: A total of 1,552 patients were identified: 543 on aspirin only, 97 on clopidogrel only, 218 on warfarin only, 193 on clopidogrel and aspirin, and 501 on no antithrombotic agent. Blood products were administered to reverse coagulopathy in 77.3% of patients on antithrombotic medications. After adjusting for covariates, including medication reversal, OAT use was associated with increased mortality (p = 0.04). Warfarin use was identified as a key predictor (odds ratio, 2.27; p = 0.05), in contrast to the preinjury use of antiplatelet medications, which was not associated with increased risk of in-hospital death. Rates of neurosurgical intervention differed between groups, with patients on warfarin undergoing intervention more frequently. Survivor subset analysis demonstrated that hemorrhage progression was not associated with preinjury antithrombotic therapy, nor were rates of complication or infection, hospital and intensive care unit lengths of stay, or ventilator days., Conclusion: Preinjury use of warfarin, but not antiplatelet medications, influences survival and need for neurosurgical intervention in elderly TBI patients with intracranial hemorrhage; hemorrhage progression and morbidity are not affected. The importance of antithrombotic therapy may lie in its impact on initial injury severity., Level of Evidence: Epidemiologic study, level III.

Purpose: In previous studies, collagen based matrices have been implanted into the site of lesion in different models of brain injury. We hypothesized that semisynthetic collagen matrix can have neuroprotective function in the setting of traumatic brain injury., Methods: Rats were subjected to sham injury or controlled cortical impact. They either received extracellular matrix graft (DuraGen) over the injury site or did not receive any graft and underwent beam balance/beam walking test at post injury days 1-5 and Morris water maze at post injury days 14-18. Animals were sacrificed at day 18 for tissue analysis., Results: Collagen matrix implantation in injured rats did not affect motor function (beam balance test: p = 0.627, beam walking test: p = 0.921). However, injured group with collagen matrix had significantly better spatial memory acquisition (p < 0.05). There was a significant reduction in lesion volume, as well as neuronal loss in CA1 (p < 0.001) and CA3 (p < 0.05) regions of the hippocampus in injured group with collagen matrix (p < 0.05)., Conclusions: Collagen matrix reduces contusional lesion volume, neuronal loss, and cognitive deficit after traumatic brain injury. Further studies are needed to demonstrate the mechanisms of neuroprotection by collagen matrix.

The Glasgow Outcome Scale-Extended (GOSE) is a functional outcome measure intended to place individuals with traumatic brain injury (TBI) into one of eight broad levels of injury-related disability. This simplicity is not always optimal, particularly when more granular assessment of individuals' injury recovery is desired. The GOSE, however, is customarily assessed using a multi-question interview that contains richer information than is reflected in the GOSE score. Using data from the multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study (N = 1544), we used item response theory (IRT) to evaluate whether rescoring the GOSE using IRT, which posits that a continuous latent variable (disability) underlies responses, can yield a more precise index of injury-related functional limitations. We fit IRT models to GOSE interview responses collected at three months post-injury. Each participant's level of functional limitation was estimated from the model (GOSE-IRT) and comparisons were made between IRT-based and standard (GOSE-Ordinal) scores. The IRT scoring resulted in 141 possible scores (vs. 7 GOSE-Ordinal scores in this sample of individuals with GOSE scores ranging between 2 and 8). Moreover, GOSE-IRT scores were significantly more strongly associated with measures of TBI-related symptoms, psychological symptoms, and quality of life. Our findings demonstrate that rescoring the GOSE interview using IRT yields more granular, meaningful measurement of injury-related functional limitations, while adding no additional respondent or examiner burden. This technique may have utility for many applications, such as clinical trials aiming to detect small treatment effects, and small-scale studies that need to maximize statistical efficiency.

Traumatic brain injury (TBI) is a widespread and expensive problem globally. The standard diagnostic workup for new TBI includes obtaining a noncontrast computed tomography image of the head, which provides quick information on operative pathologies. However, given the limited sensitivity of computed tomography for identifying subtle but meaningful changes in the brain, magnetic resonance imaging (MRI) has shown better utility for ongoing management and prognostication after TBI. In recent years, advanced applications of MRI have been further studied and are being implemented as clinical tools to help guide care. These include functional MRI, diffusion tensor imaging, MR perfusion, and MR spectroscopy. In this review, we discuss the scientific basis of each of the above techniques, the literature supporting their use in TBI, and how they may be clinically implemented to improve the care of TBI patients.

Objective: It is not currently possible to predict long‐term functional dependency in patients with disorders of consciousness (DoC) after traumatic brain injury (TBI). Our objective was to fit and externally validate a prediction model for 1‐year dependency in patients with DoC ≥2 weeks after TBI. Methods: We included adults with TBI enrolled in TBI Model Systems (TBI‐MS) or Transforming Research and Clinical Knowledge in TBI (TRACK‐TBI) studies who were not following commands at rehabilitation admission or 2 weeks post‐injury, respectively. We fit a logistic regression model in TBI‐MS and validated it in TRACK‐TBI. The primary outcome was death or dependency at 1 year post‐injury, defined using the Disability Rating Scale. Results: In the TBI‐MS Discovery Sample, 1,960 participants (mean age 40 [18] years, 76% male, 68% white) met inclusion criteria, and 406 (27%) were dependent 1 year post‐injury. In a TBI‐MS held out cohort, the dependency prediction model's area under the receiver operating characteristic curve was 0.79 (95% CI 0.74–0.85), positive predictive value was 53% and negative predictive value was 86%. In the TRACK‐TBI external validation (n = 124, age 40 [16] years, 77% male, 81% white), the area under the receiver operating characteristic curve was 0.66 (0.53, 0.79), equivalent to the standard IMPACTcore + CT score (p = 0.8). Interpretation: We developed a 1‐year dependency prediction model using the largest existing cohort of patients with DoC after TBI. The sensitivity and negative predictive values were greater than specificity and positive predictive values. Accuracy was diminished in an external sample, but equivalent to the IMPACT model. Further research is needed to improve dependency prediction in patients with DoC after TBI. ANN NEUROL 2023;94:1008–1023 [ABSTRACT FROM AUTHOR]

This document is a response to a letter regarding an article on venous thromboembolism (VTE) in patients with traumatic brain injury. The authors acknowledge the comment that oral estrogen is associated with an increased risk of VTE, although this data was not specifically collected in their study. They also note that diabetes mellitus was not examined individually as a risk factor, but was included in the Charlson Comorbidity Index. Mechanical prophylaxis was assumed for all patients in the study, as per institutional policy. The authors appreciate the discussion and look forward to further research on VTE risk factors in patients with neurotrauma. [Extracted from the article]

Background: Recent interest in the study of concussion and other neurological injuries has heightened awareness of the medical implications of American tackle football injuries amongst the public. Objective: Using the National Emergency Department Sample (NEDS) and the National Inpatient Sample (NIS), the largest publicly available all-payer emergency department and inpatient healthcare databases in the United States, we sought to describe the impact of tackle football injuries on the American healthcare system by delineating injuries, specifically neurological in nature, suffered as a consequence of tackle football between 2010 and 2013. Methods: The NEDS and NIS databases were queried to collect data on all patients presented to the emergency department (ED) and/or were admitted to hospitals with an ICD code for injuries related to American tackle football between the years 2010 and 2013. Subsequently those with football-related neurological injuries were abstracted using ICD codes for concussion, skull/face injury, intracranial injury, spine injury, and spinal cord injury (SCI). Patient demographics, length of hospital stay (LOS), cost and charge data, neurosurgical interventions, hospital type, and disposition were collected and analyzed. Results: A total of 819,000 patients presented to EDs for evaluation of injuries secondary to American tackle football between 2010 and 2013, with 1.13% having injuries requiring inpatient admission (average length of stay 2.4 days). 80.4% of the ED visits were from the pediatric population. Of note, a statistically significant increase in the number of pediatric concussions over time was demonstrated (OR = 1.1, 95% CI 1.1 to 1.2). Patients were more likely to be admitted to trauma centers, teaching hospitals, the south or west regions, or with private insurance. There were 471 spinal cord injuries and 1,908 total spine injuries. Ten patients died during the study time period. The combined ED and inpatient charges were $1.35 billion. Conclusion: Injuries related to tackle football are a frequent cause of emergency room visits, specifically in the pediatric population, but severe acute trauma requiring inpatient admission or operative interventions are rare. Continued investigation in the long-term health impact of football related concussion and other repetitive lower impact trauma is warranted. [ABSTRACT FROM AUTHOR]

Mild traumatic brain injury (mTBI) is commonly encountered in clinical practice. While the cognitive ramifications of mTBI are frequently described in the literature, the impact of mTBI on emotional, sensory, and motor function is not as commonly discussed. Chronic pain is a phenomenon more prevalent among patients with mTBI compared to those with moderate or severe traumatic brain injury. Chronic pain can become a primary disorder of the central nervous system (CNS) expressed as widespread pain, and cognitive, mood, and movement dysfunction. Shared mechanisms across chronic pain conditions can account for how pain is generated and maintained in the CNS, irrespective of the underlying structural pathology. Herein, we review the impact of mTBI on cognitive, emotional, sensory, and motor domains, and the role of pain as an important confounding variable in patient recovery and dysfunction following mTBI. [ABSTRACT FROM AUTHOR]

Background: Patients with traumatic brain injuries (TBIs) have an increased risk of developing a deep vein thrombosis (DVT), but the risk of hemorrhage expansion with intracranial monitoring devices remains unknown. We sought to determine the safety of chemical DVT prophylaxis in severe TBI patients with invasive intracranial pressure monitors.Methods: We retrospectively reviewed all patients with severe TBI admitted to the neurosurgical intensive care unit of a large tertiary care center over a three-year period.Results: 155 patients were included with an incidence of DVT of 12 %. The median length of time to a stable head CT was 2 days, and the median time to initiation of chemical DVT prophylaxis was 3.6 days. The odds of DVT increased with intraparenchymal hemorrhage [OR 7.21, 95 % CI (1.43-36.47), p = 0.0169], non-White ethnicity [OR 7.86, 95 % CI (1.23-50.35), p = 0.0295], female gender [OR 13.93, 95 % CI (2.47-78.73), p = 0.0029], smoking [OR 4.32, 95 % CI (1.07-17.51), p = 0.0405], no anticoagulation [OR 25.39, 95 % CI (4.26-151.48), p < 0.001], and an IVC filter [OR 15.82, 95 % CI (3.14-79.76), p < 0.001]. Twenty-eight (18 %) of these subjects experienced in-hospital mortality. The risk of in-hospital death was significantly increased among those who did not receive anticoagulation. This study found no association between DVT formation, hemorrhage expansion, or increased risk from invasive monitoring devices between various doses of unfractionated heparin (UH) and low-molecular-weight heparin (LMWH).Conclusion: We conclude that DVT prophylaxis with either LMWH or UH is safe with intracranial pressure monitors in place. [ABSTRACT FROM AUTHOR]

Magnetoencephalography (MEG) is a functional brain imaging technique with high temporal resolution compared with techniques that rely on metabolic coupling. MEG has an important role in traumatic brain injury (TBI) research, especially in mild TBI, which may not have detectable features in conventional, anatomical imaging techniques. This review addresses the original research articles to date that have reported on the use of MEG in TBI. Specifically, the included studies have demonstrated the utility of MEG in the detection of TBI, characterization of brain connectivity abnormalities associated with TBI, correlation of brain signals with post-concussive symptoms, differentiation of TBI from post-traumatic stress disorder, and monitoring the response to TBI treatments. Although presently the utility of MEG is mostly limited to research in TBI, a clinical role for MEG in TBI may become evident with further investigation. [ABSTRACT FROM AUTHOR]

The gut microbiome and its role in health and disease have recently been major focus areas of research. In this review, we summarize the different ways in which the gut microbiome interacts with the rest of the body, with focus areas on its relationships with immunity, the brain, and injury. The gut–brain axis, a communication network linking together the central and enteric nervous systems, represents a key bidirectional pathway with feed-forward and feedback mechanisms. The gut microbiota has a central role in this pathway and is significantly altered following injury, leading to a pro-inflammatory state within the central nervous system (CNS). Herein, we examine traumatic brain injury (TBI) in relation to this axis and explore potential interventions, which may serve as targets for improving clinical outcomes and preventing secondary brain injury. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine early sedation patterns, as well as the association of dexmedetomidine exposure, with clinical and functional outcomes among mechanically ventilated patients with moderate-severe traumatic brain injury (msTBI). DESIGN: Retrospective cohort study with prospectively collected data. SETTING: Eighteen Level-1 Trauma Centers, United States. PATIENTS: Adult (age > 17) patients with msTBI (as defined by Glasgow Coma Scale < 13) who required mechanical ventilation from the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using propensity-weighted models, we examined the association of early dexmedetomidine exposure (within the first 5 d of ICU admission) with the primary outcome of 6-month Glasgow Outcomes Scale Extended (GOS-E) and the following secondary outcomes: length of hospital stay, hospital mortality, 6-month Disability Rating Scale (DRS), and 6-month mortality. The study population included 352 subjects who required mechanical ventilation within 24 hours of admission. The initial sedative medication was propofol for 240 patients (68%), midazolam for 59 patients (17%), ketamine for 6 patients (2%), dexmedetomidine for 3 patients (1%), and 43 patients (12%) never received continuous sedation. Early dexmedetomidine was administered in 77 of the patients (22%), usually as a second-line agent. Compared with unexposed patients, early dexmedetomidine exposure was not associated with better 6-month GOS-E (weighted odds ratio [OR] = 1.48; 95% CI, 0.98-2.25). Early dexmedetomidine exposure was associated with lower DRS (weighted OR = -3.04; 95% CI, -5.88 to -0.21). In patients requiring ICP monitoring within the first 24 hours of admission, early dexmedetomidine exposure was associated with higher 6-month GOS-E score (OR 2.17; 95% CI, 1.24-3.80), lower DRS score (adjusted mean difference, -5.81; 95% CI, -9.38 to 2.25), and reduced length of hospital stay (hazard ratio = 1.50; 95% CI, 1.02-2.20). CONCLUSION: Variation exists in early sedation choice among mechanically ventilated patients with msTBI. Early dexmedetomidine exposure was not associated with improved 6-month functional outcomes in the entire population, although may have clinical benefit in patients with indications for ICP monitoring. [ABSTRACT FROM AUTHOR]