Outcome Of Traumatic Brain Injury Research Articles

Longitudinal changes in sodium concentration and in clinical outcome in mild traumatic brain injury.

Ionic imbalances and sodium channel dysfunction, well-known sequelae of traumatic brain injury (TBI), promote functional impairment in affected subjects. Therefore, non-invasive measurement of sodium concentrations using 23Na MRI has the potential to detect clinically relevant injury and predict persistent symptoms. Recently, we reported diffusely lower apparent total sodium concentrations (aTSC) in mild TBI patients compared to controls, as well as correlations between lower aTSC and worse clinical outcomes. The main goal of this study was to determine whether these aTSC findings, and their changes over time, predict outcomes at 3- and 12-month from injury. Twenty-seven patients previously studied with 23Na MRI and outcome measures at 22 ± 10 days (average ± standard deviation) after injury (visit-1, v1) were contacted at 3- (visit-2, v2) and 12-month after injury (visit-3, v3) to complete the Rivermead post-concussion symptoms questionnaire (RPQ), the extended Glasgow outcome scale (GOSE), and the brief test of adult cognition by telephone (BTACT). Follow-up 1H and 23Na MRI were additionally scheduled at v2. Linear regression was used to calculate aTSC in global grey and white matters. Six hypotheses were tested in relation to the serial changes in outcome measures and in aTSC, and in relation to the cross-sectional and serial relationships between aTSC and outcome. Twenty patients contributed data at v2 and fifteen at v3. Total RPQ and composite BTACT z-scores differed significantly for v2 and v3 in comparison to v1 (each P < 0.01), reflecting longitudinally reduced symptomatology and improved performance on cognitive testing. No associations between aTSC and outcome were observed at v2. Previously lower grey and white matter aTSC normalized at v2 in comparison to controls, in line with a statistically detectable longitudinal increase in grey matter aTSC between v1 and v2 (P = 0.0004). aTSC values at v1 predicted a subset of future BTACT subtest scores, but not future RPQ scores nor GOSE-defined recovery status. Similarly, aTSC rates of change correlated with BTACT rates of change, but not with those of RPQ. Tissue aTSC, previously shown to be diffusely decreased compared to controls at v1, was no longer reduced by v2, suggesting normalization of the sodium ionic equilibrium. These changes were accompanied by marked improvement in outcome. The results support the notion that early aTSC from 23Na MRI predicts future BTACT, but not RPQ scores, nor future GOSE status.

A strike to the head: Parallels between the pediatric and adult human and the rodent in traumatic brain injury.

Traumatic brain injury (TBI) is a condition that occurs commonly in children from infancy through adolescence and is a global health concern. Pediatric TBI presents with a bimodal age distribution, with very young children (0-4 years) and adolescents (15-19 years) more commonly injured. Because children's brains are still developing, there is increased vulnerability to the effects of head trauma, which results in entirely different patterns of injury than in adults. Pediatric TBI has a profound and lasting impact on a child's development and quality of life, resulting in long-lasting consequences to physical, cognitive, and emotional development. Chronic issues like learning disabilities, behavioral problems, and emotional disturbances can develop. Early intervention and ongoing support are critical for minimizing these long-term deficits. Many animal models of TBI exist, and each varies significantly, displaying different characteristics of clinical TBI. The neurodevelopment differs in the rodent from the human in timing and effect, so TBI outcomes in the juvenile rodent can thus vary from the human child. The current review compares findings from preclinical TBI work in juvenile and adult rodents to clinical TBI research in pediatric and adult humans. We focus on the four brain regions most affected by TBI: the prefrontal cortex, corpus callosum, hippocampus, and hypothalamus. Each has its unique developmental projections and thus is impacted by TBI differently. This review aims to compare the healthy neurodevelopment of these four brain regions in humans to the developmental processes in rodents.

Neuroprotection or Sex Bias: A Protective Response to Traumatic Brain Injury in the Females

Traumatic brain injury (TBI) is a major healthcare problem and a common cause of mortality and morbidity. Clinical and preclinical research suggests sex-related differences in short- and long-term outcomes following TBI; however, males have been the main focus of TBI research. Females show a protective response against TBI. Female animals in preclinical studies and women in clinical trials have shown comparatively better outcomes against mild, moderate, or severe TBI. This reflects a favorable protective nature of the females compared to the males, primarily attributed to various protective mechanisms that provide better prognosis and recovery in the females after TBI. Understanding the sex difference in the TBI pathophysiology and the underlying mechanisms remains an elusive goal. In this review, we provide insights into various mechanisms related to the anatomical, physiological, hormonal, enzymatic, inflammatory, oxidative, genetic, or mitochondrial basis that support the protective nature of females compared to males. Furthermore, we sought to outline the evidence of multiple biomarkers that are highly potential in the investigation of TBI's prognosis, pathophysiology, and treatment and which can serve as objective measures and novel targets for individualized therapeutic interventions in TBI treatment. Implementations from this review are important for the understanding of the effect of sex on TBI outcomes and possible mechanisms behind the favorable response in females. It also emphasizes the critical need to include females as a biological variable and in sufficient numbers in future TBI studies.

Derivation of the Quebec Brain Injury Categories for complicated mild traumatic brain injuries.

Approximately 10% of patients with mild traumatic brain injury (TBI) present with intracranial bleeding, and only 3.5% eventually require neurosurgical intervention, which often necessitates interhospital transfer. Better guidelines and recommendations are needed to manage complicated mild TBI in the emergency department (ED). The main objective of this study was to derive a clinical decision rule, the Quebec Brain Injury Categories (QueBIC), to predict the risk of adverse outcomes for complicated mild TBI in the ED. The secondary objective was to compare the QueBIC's performance with those of other existing guidelines. The authors conducted a retrospective multicenter cohort study in 3 level I trauma centers. Consecutive patients with complicated mild TBI (Glasgow Coma Scale [GCS] score 13-15) who were aged ≥ 16 years were included. The primary outcome was a combination of neurosurgical intervention, mild TBI-related death, and clinical deterioration. Statistical analyses included set covering machine analyses. In total, 477 patients were included in the study. The mean age was 62.9 years, and 68.1% were male. The algorithm classified patients into three risk categories (low, moderate, and high risk). The high-risk group (128 patients) (subdural hemorrhage [SDH] width > 7 mm or any midline shift) presented a sensitivity of 84% (95% CI 71%-93%) and a specificity of 80% (95% CI 76%-84%) to detect neurosurgical intervention and mild TBI-related death, leaving 8 undetected cases. Patients in the moderate-risk group (169 patients) had at least 1 variable: SDH width > 4 mm, initial GCS score ≤ 14, > 1 intraparenchymal hemorrhage, or intraparenchymal hemorrhage width > 4 mm. The combined QueBIC high- and moderate-risk category had a sensitivity of 100% (95% CI 63%-100%) and a specificity of 53% (95% CI 47%-58%) to detect mild TBI-related death or neurosurgical intervention. The sensitivity and specificity values for clinical deterioration when no death or neurosurgical intervention occurred were 81% (95% CI 64%-93%) and 44% (95% CI 39%-49%), respectively. The remaining 180 patients (37.7%) did not meet any high-risk or moderate-risk criteria and were considered low risk. None had neurosurgical intervention or mild TBI-related death. Only 6 (3.3%) low-risk patients showed clinical deterioration. QueBIC is a safe and effective tool to guide the management of patients presenting to the ED with complicated mild TBI. It accurately identifies patients at low risk for specialized neurotrauma or neurosurgical care. Further validation is required before its use in EDs.

Loss of AMPK potentiates inflammation by activating the inflammasome after traumatic brain injury in mice.

Traumatic brain injury (TBI) is a significant public health concern characterized by a complex cascade of cellular events. TBI induces adenosine monophosphate-activated protein kinase (AMPK) dysfunction impairs energy balance activates inflammatory cytokines and leads to neuronal damage. AMPK is a key regulator of cellular energy homeostasis during inflammatory responses. Recent research has revealed its key role in modulating the inflammatory process in TBI. Following TBI the activation of AMPK can influence various important pathways and mechanisms including metabolic pathways and inflammatory signaling. Our study investigated the effects of post-TBI loss of AMPK function on functional outcomes inflammasome activation, and inflammatory cytokine production. Male C57BL/6 adult wild-type (WT) and AMPK knockout (AMPK-KO) mice were subjected to a controlled cortical impact (CCI) model of TBI or sham surgery. The mice were tested for behavioral impairment at 24 h post-TBI thereafter, mice were anesthetized, and their brains were quickly removed for histological and biochemical evaluation. In vitro we investigated inflammasome activation in mixed glial cells stimulated with lipopolysaccharides+ Interferon-gamma (LI) (0.1 μg/20 ng/ml LPS/IFNg) for 6 h to induce an inflammatory response. Estimating the nucleotide-binding domain, leucine-rich-containing family pyrin domain containing western blotting ELISA and qRT-PCR performed 3 (NLRP3) inflammasome activation and cytokine production. Our findings suggest that TBI leads to reduced AMPK phosphorylation in WT mice and that the loss of AMPK correlates with worsened behavioral deficits at 24 h post-TBI in AMPK-KO mice as compared to WT mice. Moreover compared with the WT mice AMPK-KO mice exhibit exacerbated NLRP3 inflammasome activation and increased expression of proinflammatory mediators such as IL-1b IL-6 TNF-a iNOS and Cox 2. These results align with the in vitro studies using brain glial cells under inflammatory conditions, demonstrating greater activation of inflammasome components in AMPK-KO mice than in WT mice. Our results highlighted the critical role of AMPK in TBI outcomes. We found that the absence of AMPK worsens behavioral deficits and heightens inflammasome-mediated inflammation thereby exacerbating brain injury after TBI. Restoring AMPK activity after TBI could be a promising therapeutic approach for alleviating TBI-related damage.

Mapping the institutionalization of racism in the research about race and traumatic brain injury rehabilitation: implications for Black populations

Purpose Traumatic brain injury (TBI) is a chronic disease process and a public health concern that disproportionately impacts Black populations. While there is an abundance of literature on race and TBI outcomes, there is a lack of scholarship that addresses racism within rehabilitation care, and it remains untheorized. This article aims to illuminate how racism becomes institutionalized in the scientific scholarship that can potentially inform rehabilitation care for persons with TBI and what the implications are, particularly for Black populations. Material and methods Applying Bacchi’s What’s the Problem Represented to be approach, the writings of critical race theory (CRT) are used to examine the research about race and TBI rehabilitation comparable to CRT in other disciplines, including education and legal scholarship. Results A CRT examination illustrates that racism is institutionalized in the research about race and TBI rehabilitation through colourblind ideologies, meritocracy, reinforcement of a deficit perspective, and intersections of race and the property functions of whiteness. A conceptual framework for understanding institutional racism in TBI rehabilitation scholarship is presented. Conclusions The findings from this article speak to the future of TBI rehabilitation research for Black populations, the potential for an anti-racist agenda, and implications for research and practice.

Admission levels of serum biomarkers have additive and cumulative prognostic value in traumatic brain injury

Elevated levels of CNS-derived serum proteins are associated with poor outcome in traumatic brain injury (TBI), but the value of adding acute serum biomarker levels to common clinical outcome predictors lacks evaluation. We analyzed admission serum samples for Total-Tau (T-Tau), Neurofilament light chain (Nfl), Glial fibrillary acidic protein (GFAP), and Ubiquitin C-terminal hydrolase L1 (UCHL1) in a cohort of 396 trauma patients including 240 patients with TBI. We assessed the independent association of biomarkers with 1-year mortality and 6–12 months Glasgow Outcome Scale Extended (GOSE) score, as well as the additive and cumulative value of biomarkers on Glasgow Coma Scale (GCS) and Marshall Score for outcome prediction. Nfl and T-Tau levels were independently associated with outcome (OR: Nfl = 1.65, p = 0.01; T-Tau = 1.99, p < 0.01). Nfl or T-Tau improved outcome prediction by GCS (Wald Chi, Nfl = 6.8–8.8, p < 0.01; T-Tau 7.2–11.3, p < 0.01) and the Marshall score (Wald Chi, Nfl = 16.2–17.5, p < 0.01; T-Tau 8.7–12.4, p < 0.01). Adding T-Tau atop Nfl further improved outcome prediction in majority of tested models (Wald Chi range 3.8–9.4, p ≤ 0.05). Our data suggest that acute levels of serum biomarkers are independently associated with outcome after TBI and add outcome predictive value to commonly used clinical scores.

Factors Affecting Outcome of Traumatic Brain Injury in Alcohol Dependence in the Absence of Intoxication: A Study from Goa

Abstract Background Alcohol dependence is common in certain parts of the world and it contributes to increased incidence of head injury. The effect of alcohol dependence on head injury outcome separate from intoxication has not received much attention. Aims We evaluate the factors affecting outcome in head injury patients with a history of alcohol dependence. Materials and Methods A prospective study of alcohol-dependent patients with head injury was conducted. The patients were treated using standard head injury protocols and information regarding duration of alcohol use was assessed with investigations relating to alcoholic liver disease. The outcome was measured up to 1 month and analyzed with respect to the factors measured. Results The Extended Glasgow Outcome Score at 1 month was lower in patients with increasing duration of alcohol use. Increased duration of alcohol use also led to increased incidence of liver disease and coagulopathy, which independently affected the outcome negatively. Higher duration of alcohol use also resulted in increased risk of seizures and infection. Conclusion Alcohol dependence negatively affects head injury outcome at 1 month. In addition, increased duration of alcohol use shows a linear trend with poor outcome. Although the exact mechanisms for this are not clear, detection and management of complications like coagulopathy may improve outcome.

Immunohistochemical Detection of Axonal Injury in Chimpanzee (Pan troglodytes) with Traumatic and Fatal Brain Injury

Abstract Estimating the time of death after traumatic brain injury (TBI) in wildlife is a significant challenge in forensic veterinary medicine. The understanding of histopathological changes and predicting the survival time can prompt critical emergency measures and health management strategies for animals in managed care. Glial fibrillary acidic protein (GFAP) is a well-established astrocytic biomarker for diagnosing, monitoring, and predicting TBI outcomes. Moreover, the buildup of Beta-Amyloid Precursor Protein (βAPP) resulting from axonal damage is an energetic process intricately connected to the survival period following the injury. To date, no study has explored the accumulation of GFAP and βAPP in TBI chimpanzees. In human studies, the earliest reported time for detecting axonal injury postmortem in TBI using βAPP is approximately 30 minutes. This study aimed to investigate whether GFAP and βAPP staining can be used to detect postmortem axonal injury within 30 minutes in TBI chimpanzees. Cerebral and cerebellar tissues from a postmortem TBI chimpanzee and control samples were screened for immunopositivity for GFAP and βAPP in neurons using immunohistochemistry and immunofluorescence. The results suggested that neuronal immunopositivity for GFAP was likely a staining artifact, as negative controls also showed neuronal GFAP staining. However, it was not easy to assume the absence of post-traumatic neuronal GFAP. Conversely, the βAPP assay results indicated that axonal damage can be detected within 22 minutes after death, marking the fastest recorded time to date and aiding in diagnosing severe TBI with short survival times. In conclusion, we demonstrated that the axonal damage in captivated chimpanzee caused by severe and sudden concussion can be detected with βAPP staining within 22 minutes.

Traumatic Brain Injury and Posttraumatic Stress Disorder Are Associated with Physical Health Burden among Post-9/11 Women Veterans.

Background: Little research focuses on physical health outcomes of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) among post-9/11 women veterans (WVs). This study examined lifetime TBI, current PTSD, and their associations with biomarkers of cardiometabolic health, sleep, pain, and functional disability among post-9/11 WVs. Methods: WVs (n = 90) from the Translational Research Center for TBI and Stress Disorders longitudinal cohort study were included in this study. Gold standard clinician administered interviews assessed lifetime TBI (Boston Assessment of TBI-Lifetime) and current PTSD symptoms (Clinician-Administered PTSD Scale-IV). Objective measures of health included waist-hip ratio (WHR) and fasted blood biomarker (high density lipoprotein [HDL], low density lipoprotein [LDL], blood glucose, triglycerides) levels. Self-reported surveys assessed sleep, pain, and functional disability. Results: Just under two-thirds (58.9%) of WVs experienced a lifetime TBI, and just over half (53.3%) of this sample had a current PTSD diagnosis at the time of testing. Lifetime TBI was significantly associated with higher WHR, triglycerides levels, and worse pain and sleep (ps = <0.01 to 0.02; ds = 0.01 to 1.12). Current PTSD was significantly associated with higher WHR, lower HDL, and worse pain and sleep (ps = <0.01 to 0.02; ds = 0.009 to 1.19). PTSD was significantly associated with lower total functioning and each of its subdomains (βs = -0.58 to 0.63; ps = <0.001 to 0.02). Lifetime TBI was significantly associated with total functioning, mobility, and life/work (βs = -0.20 to 0.30; ps = <0.01 to 0.02). Conclusions: These findings highlight the importance of screening for lifetime TBI and cardiovascular disease for WVs and support transdiagnostic treatment approaches targeting physical health outcomes.

Prediction Value of Initial Serum Levels of SERPINA3 in Intracranial Pressure and Long-Term Neurological Outcomes in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a severe neurological condition characterized by inflammation in the central nervous system. SERPINA3 has garnered attention as a potential biomarker for assessing this inflammation. Our study aimed to explore the predictive value of postoperative serum SERPINA3 levels in identifying the risk of cerebral edema and its prognostic implications in TBI. This study is a prospective observational study, including 37 patients with TBI who finally met our criteria. The Glasgow Outcome Scale (GOS), Levels of Cognitive Functioning (LCF), Disability Rating Scale (DRS), and Early Rehabilitation Barthel Index (ERBI) scores at six months after trauma were defined as the main study endpoint. We further calculated the ventricle-to-intracranial-volume ratio (VBR) at 6 months from CT scans. The study included patients with Glasgow Coma Scale (GCS) scores ranging from 3 to 8, who were subsequently categorized into two groups: the critical TBI group (GCS 3-5 points) and the severe TBI group (GCS 6-8 points). Within the critical TBI group, SERPINA3 levels were notably lower. However, among patients with elevated SERPINA3 levels, both the peak intracranial pressure (ICP) and average mannitol consumption were significantly reduced compared with those of patients with lower SERPINA3 levels. In terms of the 6-month outcomes measured via the GOS, LCF, DRS, and ERBI, lower levels of SERPINA3 were indicative of poorer prognosis. Furthermore, we found a negative correlation between serum SERPINA3 levels and the VBR. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) demonstrated the predictive performance of SERPINA3. In conclusion, incorporating the novel biomarker SERPINA3 alongside traditional assessment tools offers neurosurgeons an effective and easily accessible means, which is readily accessible early on, to predict the risk of intracranial pressure elevation and long-term prognosis in TBI patients.

Antibiotic treatment induces microbiome dysbiosis and reduction of neuroinflammation following traumatic brain injury in mice.

The gut microbiome is linked to brain pathology in cases of traumatic brain injury (TBI), yet the specific bacteria that are implicated are not well characterized. To address this gap, in this study, we induced traumatic brain injury (TBI) in male C57BL/6J mice using the controlled cortical impact (CCI) injury model. After 35 days, we administered a broad-spectrum antibiotics (ABX) cocktail (ampicillin, gentamicin, metronidazole, vancomycin) through oral gavage for 2 days to diminish existing microbiota. Subsequently, we inflicted a second TBI on the mice and analyzed the neuropathological outcomes five days later. Longitudinal analysis of the microbiome showed significant shifts in the diversity and abundance of bacterial genera during both acute and chronic inflammation. These changes were particularly dramatic following treatment with ABX and after the second TBI. ABX treatment did not affect the production of short-chain fatty acids (SCFA) but did alter intestinal morphology, characterized by reduced villus width and a lower count of goblet cells, suggesting potential negative impacts on intestinal integrity. Nevertheless, diminishing the intestinal microbiome reduced cortical damage, apoptotic cell density, and microglial/macrophage activation in the cortical and thalamic regions of the brain. Our findings suggest that eliminating colonized gut bacteria via broad-spectrum ABX reduces neuroinflammation and enhances neurological outcomes in TBI despite implications to gut health.

Cerebral hypoperfusion exacerbates traumatic brain injury in male but not female mice.

Mild-moderate traumatic brain injuries (TBIs) are prevalent, and while many individuals recover, there is evidence that a significant number experience long-term health impacts, including increased vulnerability to neurodegenerative diseases. These effects are influenced by other risk factors, such as cardiovascular disease. Our study tested the hypothesis that a pre-injury reduction in cerebral blood flow (CBF), mimicking cardiovascular disease, worsens TBI recovery. We induced bilateral carotid artery stenosis (BCAS) and a mild-moderate closed-head TBI in male and female mice, either alone or in combination, and analyzed CBF, spatial learning, memory, axonal damage, and gene expression. Findings showed that BCAS and TBI independently caused a ~10% decrease in CBF. Mice subjected to both BCAS and TBI experienced more significant CBF reductions, notably affecting spatial learning and memory, particularly in males. Additionally, male mice showed increased axonal damage with both BCAS and TBI compared to either condition alone. Females exhibited spatial memory deficits due to BCAS, but these were not worsened by subsequent TBI. Gene expression analysis in male mice highlighted that TBI and BCAS individually altered neuronal and glial profiles. However, the combination of BCAS and TBI resulted in markedly different transcriptional patterns. Our results suggest that mild cerebrovascular impairments, serving as a stand-in for preexisting cardiovascular conditions, can significantly worsen TBI outcomes in males. This highlights the potential for mild comorbidities to modify TBI outcomes and increase the risk of secondary diseases.

Exploratory assessment of the effect of systemic administration of soluble glycoprotein 130 on cognitive performance and chemokine levels in a mouse model of experimental traumatic brain injury

Uncontrolled neuroinflammation mediates traumatic brain injury (TBI) pathology and impairs recovery. Interleukin-6 (IL-6), a pleiotropic inflammatory regulator, is associated with poor clinical TBI outcomes. IL-6 operates via classical-signaling through membrane-bound IL-6 receptor (IL-6R) and trans-signaling through soluble IL-6 receptor (s)IL-6R. IL-6 trans-signaling specifically contributes to neuropathology, making it a potential precision therapeutic TBI target. Soluble glycoprotein 130 (sgp130) prevents IL-6 trans-signaling, sparing classical signaling, thus is a possible treatment. Mice received either controlled cortical impact (CCI) (6.0 ± 0.2 m/s; 2 mm; 50-60ms) or sham procedures. Vehicle (VEH) or sgp130-Fc was subcutaneously administered to sham (VEH or 1 µg) and CCI (VEH, 0.25 µg or 1 µg) mice on days 1, 4, 7, 10 and 13 post-surgery to assess effects on cognition [Morris Water Maze (MWM)] and ipsilateral hemisphere IL-6 related biomarkers (day 21 post-surgery). CCI + sgp130-Fc groups (0.25 µg and 1 µg) were combined for analysis given similar behavior/biomarker outcomes. CCI + VEH mice had longer latencies and path lengths to the platform and increased peripheral zone time versus Sham + VEH and Sham + sgp130-Fc mice, suggesting injury-induced impairments in learning and anxiety. CCI + sgp130-Fc mice had shorter platform latencies and path lengths and had decreased peripheral zone time, indicating a therapeutic benefit of sgp130-Fc after injury on learning and anxiety. Interestingly, Sham + sgp130-Fc mice had shorter platform latencies, path lengths and peripheral zone times than Sham + VEH mice, suggesting a beneficial effect of sgp130-Fc, independent of injury. CCI + VEH mice had increased brain IL-6 and decreased sgp130 levels versus Sham + VEH and Sham + sgp130-Fc mice. There was no treatment effect on IL-6, sIL6-R or sgp130 in Sham + VEH versus Sham + sgp130-Fc mice. There was also no treatment effect on IL-6 in CCI + VEH versus CCI + sgp130-Fc mice. However, CCI + sgp130-Fc mice had increased sIL-6R and sgp130 versus CCI + VEH mice, demonstrating sgp130-Fc treatment effects on brain biomarkers. Inflammatory chemokines (MIP-1β, IP-10, MIG) were increased in CCI + VEH mice versus Sham + VEH and Sham + sgp130-Fc mice. However, CCI + sgp130-Fc mice had decreased chemokine levels versus CCI + VEH mice. IL-6 positively correlated, while sgp130 negatively correlated, with chemokine levels. Overall, we found that systemic sgp130-Fc treatment after CCI improved learning, decreased anxiety and reduced CCI-induced brain chemokines. Future studies will explore sex-specific dosing and treatment mechanisms for sgp130-Fc therapy.

Study Analysis of Serum Phosphorylated Tau (P-Tau) Levels with Severity and Outcome in Traumatic Brain Injury Patients: A Single Center Observational Study at Dr. M. Djamil General Hospital, Padang, Indonesia

Background: Traumatic brain injury (TBI) is a global health problem that can cause death and disability in people of productive age. The diagnosis and assessment of TBI severity currently still rely on clinical examination and neuroimaging. However, limited access and cost of neuroimaging are obstacles in many health facilities. Therefore, blood-based biomarkers are needed that can help the diagnosis and prognosis of TBI. Phosphorylated Tau (p-tau) is a potential biomarker that can be measured in serum. This study aims to assess the relationship between serum p-tau levels and severity and outcome in TBI patients. Methods: This research is a comparative study with a cross-sectional design involving 70 TBI patients who came to the emergency room (ER) of Dr. M. Djamil General Hospital Padang. TBI severity was assessed using the Glasgow coma scale (GCS) and grouped into mild (GCS 13-15) and moderate to severe (GCS 3-12). Outcomes were assessed using the Glasgow outcome scale (GOS) and grouped into good (GOS 4-5) and poor (GOS 1-3). Serum p-tau levels were measured using the ELISA method. Data analysis was carried out using SPSS. Results: The median serum p-tau level in the mild TBI group was 165.84 ng/L (IQR 126.18-463.85), while in the moderate to severe TBI group, it was 177.68 ng/L (IQR 87.62-591 .93). There was a significant difference between serum p-tau levels in the mild and moderate to severe TBI groups (p=0.029). The median serum p-tau level in the good outcome group was 167.21 ng/L (IQR 87.62-463.85), while in the poor outcome group it was 187.04 ng/L (IQR 137.75-591.93). There was a significant difference between serum p-tau levels in the good and bad outcome groups (p=0.014). Conclusion: Serum p-tau levels have a significant relationship with severity and outcome in TBI patients. Elevated serum p-tau levels are associated with increased severity of TBI and poor outcomes. Further research is needed to confirm these findings and explore the potential of p-tau as a biomarker in TBI management.

CGRP as a potential mediator for the sexually dimorphic responses to traumatic brain injury

BackgroundThe outcomes of traumatic brain injury (TBI) exhibit variance contingent upon biological sex. Although female sex hormones exert neuroprotective effects, the administration of estrogen and progesterone has not yielded conclusive results. Hence, it is conceivable that additional mediators, distinct from female sex hormones, merit consideration due to their potential differential impact on TBI outcomes. Calcitonin gene-related peptide (CGRP) exhibits sexually dimorphic expression and demonstrates neuroprotective effects in acute brain injuries. In this study, we aimed to examine sex-based variations in TBI structural and functional outcomes with respect to CGRP expression.MethodsMale and female Sprague Dawley rats were exposed to controlled cortical impact to induce severe TBI, followed by interventions with and without CGRP inhibition. In the acute phase of TBI, the study centered on elucidating the influence of CGRP on oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) and endothelial nitric oxide synthase (eNOS) signaling in the peri-impact tissue. Subsequently, during the chronic phase of TBI, the investigation expanded to evaluate CGRP expression in relation to lesion volume, microvascular dysfunction, and white matter injury, as well as working and spatial memory, anxiety-like, and depression-like behaviors in subjects of both sexes.ResultsFemale rats exhibited elevated levels of CGRP in the peri-impact brain tissue during both baseline conditions and in the acute and chronic phases of TBI, in comparison to age-matched male counterparts. Enhanced CGRP levels in specific brain sub-regions among female rats correlated with superior structural and functional outcomes following TBI compared to their male counterparts. CGRP inhibition induced heightened oxidative stress and a reduction in the expression of Nrf2 and eNOS in both male and female rats, with the observed alteration being more pronounced in females than in males.ConclusionsThis study marks the inaugural identification of CGRP as a downstream mediator contributing to the sexually dimorphic response observed in TBI outcomes.

Implementation and outcomes of a statewide TBI screening program for underserved populations.

The purpose of this paper is to describe the implementation and outcomes of a unique traumatic brain injury (TBI) screening initiative serving the community, with a focus on underserved populations. Idaho's definition of underserved populations includes people living in rural/frontier areas, people experiencing homelessness or intimate partner violence, people with co-occurring disorders, and people with cultural and/or linguistically diverse backgrounds. The goals of screenings are to help participants gain awareness about the likelihood of having experienced a TBI, bridge the gap in TBI reporting, and provide needed support to underserved populations in a rural state. Our work represents a cross-sectional study. Beginning in 2014, TBI screenings were conducted by the Institute of Rural Health (IRH) within a public health university with several internal and external partners, as well as grant funding for work. Trained interprofessional health students and/or members of the IRH performed TBI screenings using the Ohio State University TBI Identification Method - Interview Form. Those who screened as likely experiencing a TBI received resources for care and follow-up telephone calls. Data was collected on the number of individuals screened and their results, and reported using descriptive statistics. From 2014-2022, a total of 1,333 individuals were screened at 23 different community events across Idaho. Over 30% of screened individuals reported a history of head or neck injury, primarily due to falls and being hit by objects. The majority of identified cases of traumatic brain injury were characterized by no loss of consciousness or less than 30 minutes of unconsciousness. Screenings targeting underserved populations showed higher TBI prevalence. Targeting underserved populations proved valuable in identifying TBI cases. The collaborative and interprofessional approach of this screening is unique and highlights the potential to address complex health issues effectively. These findings offer valuable insights for others implementing TBI screening programs in community settings.

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.

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.