Outcome Of Traumatic Brain Injury Research Articles

P.116 Days at home after traumatic brain injury: moving beyond mortality to evaluate patient-centered outcomes using population health data

Background: Despite the utility of administrative health data, there remains a lack of patient-centered outcome measures to meaningfully capture morbidity after traumatic brain injury (TBI). We sought to characterize and validate days at home (DAH) as a feasible measure to assess population-level moderate to severe TBI (msTBI) outcomes and health resource utilization. Methods: We utilized linked health administrative data sources to identify adults with msTBI patients presenting to trauma centers in Ontario injured between 2009-2021. DAH at 180 days reflects the total number of days spent alive and at home excluding the days spent institutionalized in acute care, rehabilitation, inpatient mental health settings or post-acute readmissions. Construct and predictive validity were determined; we additionally estimated minimally important difference (MID) in DAH180days. Results: There were 6340 patients that met inclusion criteria. Median DAH180days were 70 days (interquartile range 0-144). Increased health resource utilization at baseline, older age, increasing cranial injury severity and major extracranial injuries were significantly associated with fewer DAH180days. DAH180days was correlated to DAH counts at 1-3 years. The average MID estimate from anchor-based and distribution-based methods was 18 days. Conclusions: We introduce DAH180days as a feasible and sufficiently responsive patient-centered outcome measure with construct, predictive and face validity in an msTBI population.

The weekend effect in geriatric traumatic brain injury in tertiary hospital: an observational study

IntroductionThere were no previous studies discussing the comparison of the complications among traumatic brain injury (TBI) cases during weekdays and weekends. The current study aims to retrospectively compare the TBI outcome of geriatric patients on weekdays versus weekends in the neurosurgery department in a tertiary hospital in Oman.MethodsThis is a retrospective study, from December 2015 to December 2019. Medical records of 670 patients above 65 years and admitted to the neurosurgery ward were reviewed. From that, only 45 patients over 65 years, diagnosed with TBI and managed surgically were included.ResultsThe study included 28 patients admitted during weekdays and 17 patients admitted during weekends. Nevertheless, the highest number of admissions was during Friday. The male-to-female ratio was 3.6:1 during weekdays and 3.2:1 during weekends. The average length of stay (LOS) was 12.4 days among patients operated on weekdays compared to 36.5 days on weekends. For average ICU stay, it was 3.9 days during weekdays compared to 32.2 during weekends (p = 0.011). Complications were found to be more common among patients admitted on weekends (p = 0.015).ConclusionSignificant differences between weekdays and weekends were found. So, more trauma imaging facilities and neurosurgeons need to be available during the weekends.

Parallel Cerebrospinal Fluid and Serum Temporal Profile Assessment of Axonal Injury Biomarkers Neurofilament-Light Chain and Phosphorylated Neurofilament-Heavy Chain: Associations With Patient Outcome in Moderate-Severe Traumatic Brain Injury.

Neurofilament-light chain (NF-L) and phosphorylated neurofilament-heavy chain (pNF-H) are axonal proteins that have been reported as potential diagnostic and prognostic biomarkers in traumatic brain injury (TBI). However, detailed temporal profiles for these proteins in blood, and interrelationships in the acute and chronic time periods post-TBI have not been established. Our objectives were: 1) to characterize acute-to-chronic serum NF-L and pNF-H profiles after moderate-severe TBI, as well as acute cerebrospinal fluid (CSF) levels; 2) to evaluate CSF and serum NF-L and pNF-H associations with each other; and 3) to assess biomarker associations with global patient outcome using both the Glasgow Outcome Scale-Extended (GOS-E) and Disability Rating Scale (DRS). In this multi-cohort study, we measured serum and CSF NF-L and pNF-H levels in samples collected from two clinical cohorts (University of Pittsburgh [UPITT] and Baylor College of Medicine [BCM]) of individuals with moderate-severe TBI. The UPITT cohort includes 279 subjects from an observational cohort study; we obtained serum (n = 277 unique subjects) and CSF (n = 95 unique subjects) daily for 1 week, and serum every 2 weeks for 6 months. The BCM cohort included 103 subjects from a previous randomized clinical trial of erythropoietin and blood transfusion threshold after severe TBI, which showed no effect on neurological outcome between treatment arms; serum (n = 99 unique subjects) and CSF (n = 54 unique subjects) NF-L and pNF-H levels were measured at least daily during Days (D) 0-10 post-injury. GOS-E and DRS were assessed at 6 months (both cohorts) and 12 months (UPITT cohort only). Results show serum NF-L and pNF-H gradually rise during the first 10 days and peak at D20-30 post-injury. In the UPITT cohort, acute (D0-6) NF-L and pNF-H levels correlate within CSF and serum (Spearman r = 0.44-0.48; p < 0.05). In the UPITT cohort, acute NF-L CSF and serum levels, as well as chronic (Months [M]2-6) serum NF-L levels, were higher among individuals with unfavorable GOS-E and worse DRS at 12 months (p < 0.05, all comparisons). In the BCM cohort, higher acute serum NF-L levels were also associated with unfavorable GOS-E. Higher pNF-H serum concentrations (D0-6 and M2-6), but not CSF pNF-H, were associated with unfavorable GOS-E and worse DRS (p < 0.05, all comparisons) in the UPITT cohort. Relationships between biomarker levels and favorable outcome persisted after controlling for age, sex, and Glasgow Coma Scale. This study shows for the first time that serum levels of NF-L and pNF-H peak at D20-30 post-TBI. Serum NF-L levels, and to a lesser extent pNF-H levels, are robustly associated with global patient outcomes and disability after moderate-severe TBI. Further studies on clinical utility as prognosis and treatment-response indicators are needed.

An international, prospective observational study on traumatic brain injury epidemiology study protocol: GEO-TBI: Incidence

Background The epidemiology of traumatic brain injury (TBI) is unclear – it is estimated to affect 27–69 million individuals yearly with the bulk of the TBI burden in low-to-middle income countries (LMICs). Research has highlighted significant between-hospital variability in TBI outcomes following emergency surgery, but the overall incidence and epidemiology of TBI remains unclear. To address this need, we established the Global Epidemiology and Outcomes following Traumatic Brain Injury (GEO-TBI) registry, enabling recording of all TBI cases requiring admission irrespective of surgical treatment. Objective The GEO-TBI: Incidence study aims to describe TBI epidemiology and outcomes according to development indices, and to highlight best practices to facilitate further comparative research. Design Multi-centre, international, registry-based, prospective cohort study. Subjects Any unit managing TBI and participating in the GEO-TBI registry will be eligible to join the study. Each unit will select a 90-day study period. All TBI patients meeting the registry inclusion criteria (neurosurgical/ICU admission or neurosurgical operation) during the selected study period will be included in the GEO-TBI: Incidence. Methods All units will form a study team, that will gain local approval, identify eligible patients and input data. Data will be collected via the secure registry platform and validated after collection. Identifiers may be collected if required for local utility in accordance with the GEO-TBI protocol. Data Data related to initial presentation, interventions and short-term outcomes will be collected in line with the GEO-TBI core dataset, developed following consensus from an iterative survey and feedback process. Patient demographics, injury details, timing and nature of interventions and post-injury care will be collected alongside associated complications. The primary outcome measures for the study will be the Glasgow Outcome at Discharge Scale (GODS) and 14-day mortality. Secondary outcome measures will be mortality and extended Glasgow Outcome Scale (GOSE) at the most recent follow-up timepoint.

A systematic review and meta-analysis of major blood protein biomarkers that predict unfavorable outcomes in severe traumatic brain injury

IntroductionSevere traumatic brain injury (TBI) presentation and late clinical outcomes are usually evaluated by the Glasgow Outcome Scale-Extended (GOS-E), which lacks strong prognostic predictability. Several blood biomarkers have been linked to TBI, such as Tau, GFAP, UCH-L1, S-100B, and NSE. Clinical values of TBI biomarkers have yet to be evaluated in a focused multi-study meta-analysis. We reviewed relevant articles evaluating potential relationships between TBI biomarkers and both early and 6-month outcomes. MethodsAll PubMed article publications from January 2000 to November 2023 with the search criteria “Protein Biomarker” AND “Traumatic Brain Injury” were included. Amongst all comparative studies, the sensitivity means and range values of biomarkers in predicting CT Rotterdam scores, ICU admission in the early period, or predicting GOS-E < 4 at the 6-month period were calculated from confusion matrices. Sensitivity values were modeled for each biomarker across studies and compared statistically for heterogeneity and differences. ResultsFrom the 65 articles that met the criteria, 13 were included in this study. Six articles involved early-period TBI outcomes and seven involved 6-month outcomes. In the early period TBI outcomes, GFAP had a superior sensitivity to UCH-L1 and S-100B, and similar sensitivity to the CT Rotterdam score. In the 6-month period TBI outcomes, total Tau and NSE both had significant interstudy heterogeneity, making them inferior to GFAP, phosphorylated Tau, UCH-L1, and S-100B, all four of which had similar sensitivities at 75 %. This sensitivity range at 6-month outcomes was still relatively inferior to the CT Rotterdam score. Total Tau did not show any prognostic advantage at six months with GOS-E < 4, and phosphorylated Tau was similar in its sensitivity to other biomarkers such as GFAP and UCH-L1 and still inferior to the CT Rotterdam score. ConclusionThis data suggests that TBI protein biomarkers do not possess better prognostic value with regards to outcomes.

The Impact of ADP Inhibition on Traumatic Brain Injury Outcomes.

Platelet inhibition correlates with severity of traumatic brain injury and may be associated with mortality. Adenosine diphosphate participates in platelet aggregation via the activation of the ADP receptors, P2Y1 and P2Y12. Prior work suggests this ADP pathway is significant in managing patients with head injuries. This study aimed to measure the influence of ADP inhibition on outcomes after a traumatic brain injury (TBI), as measured by thromboelastography with platelet mapping (TEG-PM). Outcomes were defined as (a) hospital length of stay; (b) ICU length of stay, (c) mortality, and (d) progression of hemorrhage on CT. The resulting cohort was split into quartiles to compare the effect of increasingly inhibited ADP values on the identified outcomes. Comparisons of 2 groups of patients were also conducted, one defined by ADP inhibition less than or equal to 60% and the other group by ADP inhibition of greater than 60%. 98 patients were included in final analysis, with 72.4% having ADP inhibition less than 60%. These patients were significantly older and had lower global injury severity scores (ISSs), although their head-specific ISS was equivalent. Compared to the group with ADP inhibition over 60%, there was no significant difference in mortality, hospital or ICU length of stay, or progression of lesion on CT. Patients with ADP less than 60% inhibited had smaller ISS and higher GCS, indicating they were less injured than those with greater ADP inhibition, consistent with prior literature. The equivalent ICU and hospital length of stay and mortality suggests that ADP inhibition plays a smaller role in outcomes. Additional study with a larger sample size and guideline-based assessments is necessary to further define the impact of ADP inhibition and to determine the role of platelet transfusion in this population.

A Proof-of-Concept Study Demonstrating How FITBIR Datasets Can be Harmonized to Examine Posttraumatic Stress Disorder-Traumatic Brain Injury Associations

Background: Although posttraumatic stress disorder (PTSD) is common following traumatic brain injury (TBI), the specific associations between these conditions is difficult to elucidate in part due to the diverse methodologies, small samples, and limited longitudinal data in the extant literature. Objective: Conduct a proof-of-concept study demonstrating our ability to compile patient-level TBI data from shared studies in the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System to address these shortcomings and improve our understanding of TBI outcomes including the rates PTSD comorbidity. Method: We searched the FITBIR database for shared studies reporting rates of probable PTSD among participants with no TBI, history of mild TBI, or history of moderate/severe TBI. We merged and harmonized data across the relevant studies and analyzed rates of probable PTSD across TBI history and severity categories. Results: Four FITBIR studies with 2,312 participants included PTSD outcome data. The final sample for comparative analyses comprised 1,633 participants from two studies with TBI group comparison data. Approximately 79% had a history of mild TBI and 32-37% screened positive for probable PTSD. Participants with a history of mild TBI had 2.8 greater odds of probable PTSD compared to those without TBI (95% CI: 2.0, 3.7). Conclusions: Only two FITBIR studies reported data examining PTSD outcomes for mild TBI as of January 2021. The analyses are consistent with prior literature, suggesting mild TBI is associated with higher rates of probable PTSD than no TBI. This study developed the methods, shared the harmonization and analysis code, and publicly shared the TBI and PTSD meta-dataset back to FITBIR for dissemination through their website, allowing future research teams to update these and other, related analyses as more studies are contributed to and shared via the FITBIR platform.

Long-term outcome of pediatric head injuries – A five-year follow-up

Objectives: Traumatic brain injury (TBI) disrupts the developing brain in the pediatric population. This study aims to look at the outcomes of moderate and severe TBI over a five-year follow-up to look for the long-term sequelae of head injury in the pediatric population. Materials and Methods: A prospective observational study was conducted after obtaining the permission of the Institutional Ethics Committee with the primary study participants admitted between 2015 and 2017 with follow-up extending up to 2022 in 118 pediatric patients, aged between 1 and 15 years who required admission in the pediatric intensive care unit with moderate and severe TBI. Results: Language impairment was noted in 33.63% (n = 37) patients during early follow-up, and 12 of them continued to have impaired language skills and communication at the end of five years. With regard to school functioning, children had more difficulty in the arithmetic domain (n = 33) compared to language domains (n = 17). While the parents noted improvements in scholastic performances, some degree of difficulty in learning was noted in most of the children, who sustained TBI. Despite these difficulties, 27 out of 41 participants, who gave their higher secondary examinations have gone on to pursue undergraduate courses in colleges. Conclusion: Our study indicates that over the passage of time, children tend to have a reasonable chance at recovery, and with the potential for plasticity, early and aggressive rehabilitative services may enable the child to have a decent quality of life and in selected cases, even an independent life.

Cost-Effectiveness of Sleep Apnea Diagnosis and Treatment in Hospitalized Persons With Moderate to Severe Traumatic Brain Injury.

To assess the cost-effectiveness of alternative approaches to diagnose and treat obstructive sleep apnea (OSA) in patients with traumatic brain injury (TBI) during inpatient rehabilitation. Data collected during the Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and Outcome (C-SAS) clinical trial (NCT03033901) on an inpatient rehabilitation TBI cohort were used in this study. Decision tree analysis was used to determine the cost-effectiveness of approaches to diagnosing and treating sleep apnea. Costs were determined using 2021 Centers for Medicare and Medicaid Services reimbursement codes. Effectiveness was defined in terms of the appropriateness of treatment. Costs averted were extracted from the literature. A sensitivity analysis was performed to account for uncertainty. Analyses were performed for all severity levels of OSA and a subgroup of those with moderate to severe OSA. Six inpatient approaches using various phases of screening, testing, and treatment that conform to usual care or guideline-endorsed interventions were evaluated: (1) usual care; (2) portable diagnostic testing followed by laboratory-quality testing; (3) screening with the snoring, tiredness, observed apnea, high BP, BMI, age, neck circumference, and male gender (STOP-Bang) questionnaire; (4) Multivariable Apnea Prediction Index (MAPI) followed by portable diagnostic testing and laboratory-quality testing; (5) laboratory-quality testing for all; and (6) treatment for all patients. Cost, Effectiveness, and Incremental Cost-Effectiveness Ratio (ICER). Phased approaches utilizing screening and diagnostic tools were more effective in diagnosing and allocating treatment for OSA than all alternatives in patients with mild to severe and moderate to severe OSA. Usual care was more costly and less effective than all other approaches for mild to severe and moderate to severe OSA. Diagnosing and treating OSA in patients with TBI is a cost-effective strategy when compared with usual care.

Age Suppresses the Association Between Traumatic Brain Injury Severity and Functional Outcomes: A Study Using the NIDILRR TBIMS Dataset.

Recovery from traumatic brain injury (TBI) is extremely difficult to predict, with TBI severity usually demonstrating weak predictive validity for functional or other outcomes. A possible explanation may lie in the statistical phenomenon called suppression, according to which a third variable masks the true association between predictor and outcome, making it appear weaker than it actually is. Age at injury is a strong candidate as a suppressor because of its well-established main and moderating effects on TBI outcomes. We tested age at injury as a possible suppressor in the predictive chain of effects between TBI severity and functional disability, up to 10years post-TBI. Follow-up interviews were conducted during telephone interviews. We used data from the 2020 NDILRR Model Systems National Dataset for 4 successive follow-up interviews: year 1 (n =10,734), year 2 (n =9174), year 5 (n =6,201), and year 10 (n =3027). Successive cross-sectional multiple regression analyses. Injury severity was operationalized using a categorical variable representing duration of posttrauma amnesia. The Glasgow Outcomes Scale-Extended (GOS-E) operationally defined functioning. Sociodemographic characteristics having significant bivariate correlations with GOS-E were included. Entry of age at injury into the regression models significantly increases the association between TBI severity and functioning up to 10years post-TBI. Age at injury is a suppressor variable, masking the true effect of injury severity on functional outcomes. Identifying the mediators of this suppression effect is an important direction for TBI rehabilitation research.

Traumatic brain injury and occupational risk of low-level blast exposure on adverse career outcomes: an examination of administrative and medical separations from Service (2005-2015).

Although traumatic brain injury (TBI) has been linked with adverse long-term health, less research has examined whether TBI is linked with non-clinical outcomes including involuntary job loss. Symptoms associated with TBI may influence one's ability to maintain gainful employment including employment in the U.S. military. That influence may impact military service members with exposure to repetitive low-level blast (LLB). Understanding the association between TBI and involuntary job loss outcomes among military populations is particularly important as it may be associated with differences in eligibility for post-service benefits. The purpose of the present research was to determine whether (1) TBI and related conditions are associated with involuntary job loss (i.e., medical and administrative separations from service) among military personnel, and (2) occupational risk of LLB is associated with involuntary job loss in both the presence and absence of clinical diagnoses of TBI and related conditions. This research leveraged population-level data from the Career History Archival Medical and Personnel System for enlisted personnel who served on active duty between 2005-2015. Risk of LLB exposure was categorized using military occupational specialty as a proxy. Medical diagnoses were identified using ICD-9 codes. Separations for medical and administrative reasons were identified. Risk for administrative separation differed across medical diagnoses of interest, but those who worked in high-risk occupations were more likely to be administratively separated than those working in low-risk occupations. Risk for medical separation was associated with occupational risk of LLB and each of the diagnoses of interest, though significant interactions suggested that the effects of certain diagnoses of interest (e.g., concussion, cognitive problems, postconcussive syndrome, migraines) on medical separations was greater among those working in high-risk occupations. Taken together, the present research suggests that TBI and associated medical conditions, as well as occupational risk of LLB, are associated with long-term involuntary job loss for medical reasons. This study is the first to demonstrate involuntary military job loss outcomes associated with TBI, mental health conditions, and conditions associated with blast exposure using both inpatient and outpatient population-level data and may have important implications for civilian employment and post-service benefits.

Impact of menopause-associated frailty on traumatic brain injury

Navigating menopause involves traversing a complex terrain of hormonal changes that extend far beyond reproductive consequences. Menopausal transition is characterized by a decrease in estradiol-17β (E2), and the impact of menopause resonates not only in the reproductive system but also through the central nervous system, musculoskeletal, and gastrointestinal domains. As women undergo menopausal transition, they become more susceptible to frailty, amplifying the risk and severity of injuries, including traumatic brain injury (TBI). Menopause triggers a cascade of changes leading to a decline in muscle mass, accompanied by diminished tone and excitability, thereby restricting the availability of irisin, a crucial hormone derived from muscles. Concurrently, bone mass undergoes reduction, culminating in the onset of osteoporosis and altering the dynamics of osteocalcin, a hormone originating from bones. The diminishing levels of E2 during menopause extend their influence on the gut microbiota, resulting in a reduction in the availability of tyrosine, tryptophan, and serotonin metabolites, affecting neurotransmitter synthesis and function. Understanding the interplay between menopause, frailty, E2 decline, and the intricate metabolisms of bone, gut, and muscle is imperative when unraveling the nuances of TBI after menopause. The current review underscores the significance of accounting for menopause-associated frailty in the incidence and consequences of TBI. The review also explores potential mechanisms to enhance gut, bone, and muscle health in menopausal women, aiming to mitigate frailty and improve TBI outcomes.

Visualization of Cerebral Pressure Autoregulatory Insults in Traumatic Brain Injury.

The first aim was to investigate the combined effect of insult intensity and duration of the pressure reactivity index (PRx) and deviation from the autoregulatory cerebral perfusion pressure target (∆CPPopt = actual CPP - optimal CPP [CPPopt]) on outcome in traumatic brain injury. The second aim was to determine if PRx influenced the association between intracranial pressure (ICP), CPP, and ∆CPPopt with outcome. Observational cohort study. Neurocritical care unit, Cambridge, United Kingdom. Five hundred fifty-three traumatic brain injury patients with ICP and arterial blood pressure monitoring and 6-month outcome data (Glasgow Outcome Scale [GOS]). None. The insult intensity (mm Hg or PRx coefficient) and duration (minutes) of ICP, PRx, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In these plots, there was a transition from favorable to unfavorable outcome when PRx remained positive for 30 minutes and this was also the case for shorter durations when the intensity was higher. In a similar plot of ∆CPPopt, there was a gradual transition from favorable to unfavorable outcome when ∆CPPopt went below -5 mm Hg for 30-minute episodes of time and for shorter durations for more negative ∆CPPopt. Furthermore, the percentage of monitoring time with certain combinations of PRx with ICP, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In the combined PRx/ICP heatmap, ICP above 20 mm Hg together with PRx above 0 correlated with unfavorable outcome. In a PRx/CPP heatmap, CPP below 70 mm Hg together with PRx above 0.2-0.4 correlated with unfavorable outcome. In the PRx-/∆CPPopt heatmap, ∆CPPopt below 0 together with PRx above 0.2-0.4 correlated with unfavorable outcome. Higher intensities for longer durations of positive PRx and negative ∆CPPopt correlated with worse outcome. Elevated ICP, low CPP, and negative ∆CPPopt were particularly associated with worse outcomes when the cerebral pressure autoregulation was concurrently impaired.

Gender Disparities in Neurobehavioral Symptoms and the Role of Post-Traumatic Symptoms in US Service Members Following Mild Traumatic Brain Injury.

Women are more directly involved in combat operations today than ever before, currently making up 18.6% of officers and 16.8% of enlisted personnel in the United States military. However, women continue to be under-represented in military research. Studies that do consider gender differences in traumatic brain injury (TBI) outcomes have shown that women report significantly more post-concussive symptoms than men. Conclusions for true gender differences related to TBI are hard to make without controlling for non-TBI factors. The effects previously identified in the literature may be an artifact of how men and women differ in their response to injury, unrelated to the neurological recovery process associated with TBI. The objective of this study was to examine the effects of gender specifics on mild TBI (mTBI) sequelae on injured and uninjured control groups, and to investigate the role of post-traumatic stress disorder (PTSD) on symptom reporting. It should be noted that the terms "gender" and "men/women" are used in this article in place of "sex" or "males/females" given that we are not discussing biological attributes. A total of 966 United States military service members and veterans were included in the study. Of the total sample, 455 men and 46 women were in the mTBI group, 285 men and 31 women were in the injured controls group (IC), and 111 men and 38 women in the non-injured controls group (NIC). Post-concussive and quality of life symptoms were compared for men and women while controlling for combat exposure. MTBI and IC groups were also stratified by PTSD presentation. Measures used included the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist (PCL-C), Traumatic Brain Injury Quality of Life (TBI-QOL), and Combat Exposure Scale. In the mTBI group, women had worse scores on NSI total, NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety, Fatigue, and Headache scales (n2 = 0.018-0.032, small to small-medium effect sizes). When PTSD was present, women had worse scores on the NSI Somatosensory cluster only (n2 = 0.029, small-medium effect size). In contrast, when PTSD was absent, women had worse scores than men on the NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety and Headache scales (n2 = 0.032-0.063, small to medium effect sizes). In the IC group, women had worse scores on the NSI Cognitive cluster and the TBI-QOL Fatigue and Pain Interference scales (n2 = 0.024-0.042, small to small-medium effect sizes). However, group differences were no longer found when stratified by PTSD sub-groups. In the NIC group, there were no significant group differences for any analyses. We were able to identify symptoms unique to women recovering from mTBI that were not present following other forms of physical injury or in healthy controls. However, the impact of PTSD exacerbates the symptom profile and its comorbidity with mTBI equates to most of the noted gender differences.

Bi-directional neuro-immune dysfunction after chronic experimental brain injury

BackgroundIt is well established that traumatic brain injury (TBI) causes acute and chronic alterations in systemic immune function and that systemic immune changes contribute to posttraumatic neuroinflammation and neurodegeneration. However, how TBI affects bone marrow (BM) hematopoietic stem/progenitor cells chronically and to what extent such changes may negatively impact innate immunity and neurological function has not been examined.MethodsTo further understand the role of BM cell derivatives on TBI outcome, we generated BM chimeric mice by transplanting BM from chronically injured or sham (i.e., 90 days post-surgery) congenic donor mice into otherwise healthy, age-matched, irradiated CD45.2 C57BL/6 (WT) hosts. Immune changes were evaluated by flow cytometry, multiplex ELISA, and NanoString technology. Moderate-to-severe TBI was induced by controlled cortical impact injury and neurological function was measured using a battery of behavioral tests.ResultsTBI induced chronic alterations in the transcriptome of BM lineage−c-Kit+Sca1+ (LSK+) cells in C57BL/6 mice, including modified epigenetic and senescence pathways. After 8 weeks of reconstitution, peripheral myeloid cells from TBI→WT mice showed significantly higher oxidative stress levels and reduced phagocytic activity. At eight months after reconstitution, TBI→WT chimeric mice were leukopenic, with continued alterations in phagocytosis and oxidative stress responses, as well as persistent neurological deficits. Gene expression analysis revealed BM-driven changes in neuroinflammation and neuropathology after 8 weeks and 8 months of reconstitution, respectively. Chimeric mice subjected to TBI at 8 weeks and 8 months post-reconstitution showed that longer reconstitution periods (i.e., time post-injury) were associated with increased microgliosis and leukocyte infiltration. Pre-treatment with a senolytic agent, ABT-263, significantly improved behavioral performance of aged C57BL/6 mice at baseline, although it did not attenuate neuroinflammation in the acutely injured brain.ConclusionsTBI causes chronic activation and progressive dysfunction of the BM stem/progenitor cell pool, which drives long-term deficits in hematopoiesis, innate immunity, and neurological function, as well as altered sensitivity to subsequent brain injury.

Management of traumatic brain injury in Africa: Challenges and opportunities.

Traumatic brain injury (TBI) is a major public health concern globally, with significant implications for morbidity, mortality, and long-term disability. While extensive research has been conducted on TBI management in high-income countries, limited attention has been given to the specific challenges and opportunities faced by healthcare systems in Sub-Saharan Africa (SSA). This perspective study aims to provide a comprehensive overview of the current status of TBI management in SSA, focusing on the unique challenges and potential opportunities for improvement. The findings highlight several key challenges faced by SSA healthcare systems in managing TBIs, including limited resources, inadequate infrastructure, and a shortage of trained healthcare professionals. Furthermore, social and cultural factors, such as ignorance of driving laws, financial constraints, and limited access to modern technology services. However, the study also identifies potential opportunities for improving TBI management in SSA. These include strengthening healthcare infrastructure, enhancing pre-hospital care and transportation systems, and increasing public awareness and education about TBI. This perspective study emphasizes the urgent need for tailored interventions and strategies to address the unique challenges faced by SSA in managing TBIs. Addressing the challenges and opportunities in brain injury management in sub-Saharan Africa requires a comprehensive approach which can be through investing in health infrastructure, addressing socioeconomic inequalities, implementing prevention strategies, and fostering evidence-based research collaboration. Through this, the region can significantly improve TBI care and outcomes, thereby improving the well-being of people affected by TBI in sub-Saharan Africa.

Neuromonitoring in neurocritical care for traumatic brain injury in the Thai context

The purposes of this review were to identify the incidence and types of traumatic brain injury (TBI) in Thailand, and recommend neuro-monitoring for limited resources in Thai patients. The monitoring methods focus on the targeted and personalized management in severe TBI such as intracranial pressure (ICP), pressure reactivity index (PRx), regional cerebral saturation (rSO2), cerebral autoregulation (CA), as well as noninvasive methods for example near-infrared spectroscopy (NIRS) and optic nerve sheath diameter (ONSD). These monitors are aimed to optimize brain oxygen delivery and prevent further neurologic deterioration in terms of increased ICP and decreased cerebral perfusion pressure (CPP). Some of these were implemented in neurological monitoring protocol and clinical practice guidelines for severe TBI. However, cost - effectiveness is concerned. Even though considering CA and the advance monitoring methods in continuous assessment are widely used, current therapeutic interventions which appear entirely to bedside approach for correct dysregulated CA are limited. In addition, understanding of basic molecular and cellular pathways involved in cerebral homeostasis ( brain oxygen delivery, cerebral blood flow, CA and cerebral vascular reactivity to oxygen and carbon dioxide) as well as secondary brain injury prevention are still necessary for improving TBI outcomes. In summary, further study in Thailand is required to determine optimal cerebral physiologic-based technology, monitoring parameters, and individualized thresholds to optimize CA and potentially improve neurologic outcomes across a spectrum of TBI patients, which focus in Thai rural areas where invasive monitoring is not routinely performed due to resources limitation. Encourage and training of non invasive methods might solve these issues.

437 Pressure Reactivity Index (PRx) as a Predictor for Outcome in Severe Traumatic Brain Injury

INTRODUCTION: The pressure reactivity index (PRx) is a surrogate for vascular cerebral autoregulation that evaluates moving correlation coefficients between intracranial pressure (ICP) and mean arterial blood pressure (MAP). Ideal threshold PRx values for distinguishing between poor and good outcome in severe traumatic brain injury (sTBI) is unclear. METHODS: Retrospective evaluation of consecutive patients over a three-year period with sTBI and polytrauma who received continuous ICP, MAP, and PRx monitoring. Good outcome was defined as patients who upon hospital discharge had a modified Rankin score &lt; 4 and were discharged to an acute rehabilitation facility or home. RESULTS: 36 patients received continuous monitoring. Nine patients were excluded for the following reasons: early palliative withdrawal, early death through multi-organ dysfunction not related to the sTBI, and continuous neuromonitoring &lt; 24 hrs. Of the 27 patients evaluated, average PRx values for the good outcome group was 0.18 (+0.17) and 0.37 (+0.24) for the poor outcome group. Receiver operating characteristics (ROC) analysis showed that a PRx threshold value &gt; 0.34 had the highest combined sensitivity and specificity for predicting poor outcome with an AUC (95% CI) = 0.775 (0.583-0.967). When dichotomized using ROC curve analysis, a threshold PRx value of greater than 0.34 was independently associated with higher odds of poor outcome (OR 18.63, 95% CI 1.17-297.21, p = 0.038) after adjustment for potential confounders. CONCLUSIONS: Higher mean PRx is an independent predictor for poor outcome in patients with sTBI. Further study is required to evaluate the temporal role of PRx changes to improve neuroprognostication.

445 Performance of the IMPACT and CRASH Prognostic Models for Traumatic Brain Injury in a Contemporary Multicenter Cohort: A TRACK-TBI Study

INTRODUCTION: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomisation After Significant Head Injury (CRASH) prognostic models for mortality and functional outcome in traumatic brain injury (TBI) were developed using historical data from 1984-2004. METHODS: The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury study enrolled participants aged = 17-years who presented to Level 1 trauma center and received head computed tomography (CT) scan &lt;24-hours of TBI. Data was extracted from participants meeting IMPACT (Glasgow Coma Scale (GCS) 3-12; completed 6-month Glasgow Outcome Scale-Extended (GOSE); N = 441) and CRASH criteria (GCS 3-14; completed 2-week and 6-month GOSE; N = 831). Original model coefficients were applied, and performances were assessed using discrimination (area under the receiver-operating characteristic curve (AUC)) and calibration (intercept; slope; [95% confidence interval]). RESULTS: IMPACT and CRASH models discriminated mortality (AUC = 0.77-0.81, 0.90-0.91, respectively) and unfavorable outcome (0.77-0.81; 0.83, respectively). The IMPACT Lab model overestimated mortality (intercept = -0.79 [-1.05, -0.53]; slope = 1.37 [1.05-1.69]) and acceptably estimated unfavorable outcome (intercept = 0.07 [-0.14, 0.29]; slope = 1.19 [0.96-1.42]). The CRASH CT model overestimated mortality (intercept = -1.06 [-1.36, -0.75]; slope = 0.96 [0.79-1.14]) and unfavorable outcome (intercept = -0.60 [-0.78, -0.41]; slope = 1.20 [1.03-1.37]). Calibration performance differences were observed across the 5 leading enrollment centers (IMPACT Lab model: intercept -1.66 to -0.35, slope 1.07-1.86; CRASH CT model: intercept -1.81 to -0.67, slope 0.67-1.56) and unfavorable outcome (IMPACT Lab model: intercept -0.57 to 0.34, slope 1.28-2.89; CRASH CT model: intercept -1.15 to -0.10, slope 1.02-1.44). CONCLUSIONS: IMPACT and CRASH models discriminated mortality and unfavorable outcome. Observed overestimations of mortality and unfavorable outcome underscore the need to develop prognostic models that incorporate contemporary changes in TBI casemix. Investigations to elucidate the relationships between increased survival, functional outcome, treatment intensity, and center-specific practices will be highly relevant.

240 Impact of a Large Geographical Area on Outcomes in Acute Traumatic Intracranial Extra-axial Haemorrhage Requiring Urgent Surgical Evacuatio

INTRODUCTION: The Princess Alexandra Hospital (PAH) Department of Neurosurgery services a population of 1.85 million people over a 420,000 km2 area in Queensland, Australia. Increased distance from a neurosurgical centre has previously been correlated with poorer outcomes in traumatic brain injury. METHODS: This single-centre retrospective study identified patients aged 16-85 who underwent evacuation of an acute traumatic subdural (ASDH) or extradural haemorrhage (EDH) between 2016 and 2022. Initial Glasgow Coma Score (GCS), pupillary abnormalities, time to intervention, distance from PAH and the Extended Glasgow Outcome Scale (GOS-E) at 6 months were recorded. RESULTS: 106 and 50 patients underwent evacuation of ASDH and EDH respectively. In the ASDH group, age was inversely correlated (p = 0.03, r2 = 0.04) and the motor component of the initial GCS was directly correlated (p = 0.002, r2 = 0.09) with GOS-E at 6 months. Distance from PAH directly correlated with an increased time to intervention (p&lt;0.0001, r2 = 0.23) but did not correlate with GOS-E at 6 months (p = 0.09). There was no difference between survivors and non-survivors regarding distance from PAH (43.43 ± 75.05 km vs. 25.56 ± 41.32 km, p = 0.15) or time to operation (276.14 ± 192.77 mins vs. 217.40 ± 147.27 mins, p = 0.08). This was also found for survivors with poor (GOS-E &lt;6) and fair (GOS-E = 6) recovery at 6 months. In the EDH group there was no correlation between distance, time to operative intervention, age or initial motor score with outcomes at 6 months. CONCLUSIONS: Whilst increased distance from treatment centre correlated with increased time to surgical intervention for ASDH, it did not impact on survival or functional outcomes at 6 months. For ASDH requiring urgent evacuation, increasing age and severity of primary brain injury are predictors of poorer long-term outcomes.