Search Results (123)

Objective: The primary objective was to identify whether there were differences in performance for the individual subcomponents of the instrumented timed “Up and Go” (iTUG) between adults with traumatic brain injury (TBI) and healthy controls. Methods: Fifteen adults with moderate-to-severe TBI and fifteen age- and sex-matched controls completed two separate trials of the iTUG. Paired t-tests or Wilcoxon signed rank tests were used to determine the differences between groups. Results: Adults with moderate-to-severe TBI took more time to complete the iTUG (14.50 ± 2.36 s vs. 9.85 ± 1.71 s; p-value = 0.0002), had slower chest flexion angular velocities (63.52 ± 23.25 s vs. 88.19 ± 29.20 s; p-value = 0.0486) and vertical acceleration (2.22 [1.23–2.74] s vs. 3.89 [3.36–5.02] s; p-value = 0.0005) during the sit-to-stand movements, and had slower angular velocities during the turns (p-value < 0.05 for both mean and peak turn angular velocities) compared with the controls. Conclusions: Adults with moderate-to-severe TBI completed the iTUG more slowly than healthy controls. Significant differences were noted in the sit-to-stand and turn subcomponents for adults with moderate-to-severe TBI compared with healthy controls, which would not be apparent from evaluating the total time taken alone. Full article

Background: Traumatic brain injury (TBI) is a leading cause of mortality and disability, particularly in patients on anticoagulation therapy. While anticoagulants are linked to higher TBI mortality, the specific impact of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) on severe TBI (sTBI) outcomes remains unclear, especially in light of newer reversal agents. Therefore, this study evaluates long-term mortality and complication risks associated with pre-injury use of DOACs and VKAs in sTBI patients from a large, real-world cohort. Methods: A retrospective cohort study was conducted using the TriNetX global research network, identifying patients with sTBI between 2016 and 2022. Patients were grouped based on pre-injury anticoagulant use: DOAC, VKA, or none. Propensity score matching was performed, adjusting for age, comorbidities, and baseline characteristics. The primary outcome was all-cause mortality at 1-, 3-, 6-, and 12-months post-injury. Secondary outcomes included hospital and surgical complications up to 30 days post-injury. Results: A total of 40,563 patients met the inclusion criteria. At all time intervals, no significant mortality differences were found between the PSM-matched groups. Conclusions: In patients with sTBI, pre-injury DOAC or VKA use was not associated with increased short- or long-term mortality. These findings suggest that, with current perioperative practices, anticoagulation can be managed without adversely affecting outcomes. Full article

Traumatic brain injury (TBI) induces complex molecular and cellular responses, often leading to vision deterioration and potential mortality. Current objective diagnostic methods are limited, necessitating the development of novel tools to assess disease severity. This review focuses on the retina, a readily approachable part of the central nervous system (CNS), as a potential indicator of TBI. We conduct a targeted database search and employ a blinded scoring system, incorporating both human and artificial intelligence (AI) assessments, to identify relevant articles. We then perform a detailed analysis to elucidate the molecular pathways and cellular changes in the retina following TBI. Recent findings highlight the involvement of key molecular markers, such as ionized calcium-binding adapter molecule 1 (IBA1), phosphorylated tau, glial fibrillary acidic protein (GFAP), and various cytokines (IL-1β, IL-6, and TNF). Additionally, the roles of oxidative stress, reactive oxygen species (ROS), and blood–retina barrier (BRB) disruption are explored. Based on these findings, we hypothesize that alterations in these molecular pathways and cellular components, particularly microglia, can serve as direct indicators of brain health and TBI severity. Recent technological advancements in retinal imaging now allow for a direct assessment of retinal cells, including microglia, and related inflammatory processes, facilitating the translation of these molecular findings into clinical practice. This review underscores the retina’s potential as a non-invasive window into the molecular pathophysiology of TBI. Full article

Introduction: Traumatic brain injury (TBI) involves a diverse group of head blunt and/or penetrating injuries and is a leading cause of death in the U.S., accounting for one-third of all injury-related deaths. A post-injury hyperglycemic state may commonly impact TBI prognosis and strongly correlate with injury severity. Diabetes mellitus (DM) may also be a source of concomitant hyperglycemia that can worsen prognosis, with previous literature suggesting that DM could be an independent predictor of poor outcome and mortality after TBI. Methods: Using the multi-center, national TriNetX database, we performed a propensity score-matched analysis of severe TBI patients with (DM) and without DM (NDM) from 2014 to 2024. We examined the risk of mortality and complications, including sepsis, cerebral infarction, and pulmonary embolism. We also performed a sub-group analysis comparing the risk of mortality and complications between patients with either insulin-dependent or insulin-independent forms of DM. Results: A total of 26,019 patients were included (4604 DM vs. 21,415 NDM). After propensity score matching, patients with DM had a significantly lower risk of mortality (RR: 0.815; 95% CI: 0.771–0.861; p < 0.05) and ventilator dependency (RR: 0.902; 95% CI: 0.844–0.963; p < 0.05) compared to NDM patients. However, patients with DM had a significantly higher risk of cerebral infarctions, seizures, pneumonia, and sepsis (p < 0.05). Sub-group analysis found no significant difference in mortality or complications between insulin-dependent and insulin-independent forms of DM. Conclusion: Our results suggest that hyperglycemia secondary to DM plays a complicated role in the outcomes after severe TBI. Unexpectedly, we identified both increased and decreased complications in patients with DM. These results reflect the current challenges in the literature surrounding pre-existing DM in patients’ outcomes, the impact of diabetic medications on patient outcomes, and the changing role of aggressive glucose management in critical care patients. Full article

Severe traumatic brain injury (sTBI) often results in significant impairments in gait stability, symmetry, and smoothness. Inertial measurement units (IMUs) have emerged as powerful tools to quantify these aspects of gait, but their clinometric properties in sTBI populations remain underexplored. This study aimed to assess the test-retest reliability and minimal detectable change (MDC) of three IMU-derived indices—normalized Root Mean Square (nRMS), improved Harmonic Ratio (iHR), and Log Dimensionless Jerk (LDLJ)—during a 10 m walking test for sTBI survivors. Forty-nine participants with sTBI completed the walking test, with IMUs placed on key body segments to capture accelerations and angular velocities. Test-retest analyses revealed moderate to excellent reliability for nRMS and iHR in anteroposterior (ICC: 0.78–0.95 and 0.94, respectively) and craniocaudal directions (ICC: 0.95), with small MDC values, supporting their clinical applicability (MDC: 0.04–0.3). However, iHR in the mediolateral direction exhibited greater variability (ICC: 0.80; MDC: 9.74), highlighting potential sensitivity challenges. LDLJ metrics showed moderate reliability (ICC: 0.57–0.77) and higher MDC values (0.55–0.75), suggesting the need for further validation. These findings underscore the reliability and sensitivity of specific IMU-derived indices in detecting meaningful gait changes in sTBI survivors, paving the way for refined assessments and monitoring the rehabilitation process of sTBI survivors. Future research should explore these indices’ responsiveness to interventions and their correlation with functional outcomes. Full article

The proteasomal system of protein degradation is crucial for various cellular processes, including transduction of signals and differentiation of cells. Proteasome activity rises after various traumatic stressors such as hyperoxia, radiation, or oxidative damage. Removal of damaged proteins is essential to provide the necessary conditions for cell repair. Several studies report the activation of the proteasomal degradation system after thermal injury, CNS injury, abdominal trauma, ischemia-reperfusion injury, and possible clinical implications of the use of proteasome inhibitors. It is important to highlight the distinct and crucial roles of UCHL1, 26S, and 20S proteasome subunits as biomarkers. UCHL1 appears to be particularly relevant for identifying brain and neuronal damage and in advancing the diagnosis and prognosis of traumatic brain injury (TBI) and other neurological conditions. Meanwhile, the 26S and 20S proteasomes may serve as markers for peripheral tissue damage. This differentiation enhances our understanding and ability to target specific types of tissue damage in clinical settings. Full article

Background/Objectives: Suicides among U.S. military veterans are alarmingly high, driven by factors such as mental health issues, combat exposure, and history of mild traumatic brain injury (mTBI)/concussion. This study aims to examine the relationship between concussion history, combat experience, and their effects on mental health issues and suicide ideation among military veterans. Additionally, this study investigates the impact of post-traumatic stress disorder (PTSD) on these variables. Methods: A total of 78 veterans (62 males, 16 females) participated in this study. Participants completed a demographic survey and the Global Well-being Index (GWI) to assess concussion history and residual symptoms. A licensed social worker interviewed the veterans using the 9-Item Patient Health Questionnaire (PHQ-9) for depression, the Generalized Anxiety Disorder survey (7 Items) (GAD-7) for anxiety, and the Columbia-Suicide Severity Rating Scale (C-SSRS) for suicide ideation. A 2 × 2 cross-tabulation analysis examined the relationships between concussion history, combat experience, and outcomes of anxiety, depression, and suicide ideation. PTSD was also assessed as both a predictor and an outcome. Statistical analyses yielded odds ratios (OR) with 95% confidence intervals (CI), Chi-square, and Cramer’s V (V) correlations along with associated p-values. Results: The combination of concussion history and combat experience strongly predicted either anxiety, depression, or suicide ideation (OR = 7.97, 95% CI: 1.70, 37.44; V = 0.334, (p = 0.003)), more than either factor alone. Combat experience was the strongest predictor of PTSD (OR = 11.12, 95% CI: 3.30, 37.47; V = 0.485, p ≤ 0.001), both individually and when combined with concussion history. PTSD strongly influenced mental health issues and suicide ideation (OR = 8.16, 95% CI: 1.74, 38.25; V = 0.339, p = 0.003). Stratification by PTSD status (positive or negative) affected the relationships between independent and dependent variables. Small cell counts resulted in a wide 95% CI for some ORs, though some statistically significant Fisher’s Exact Test results were observed. Credibility analysis using the critical prior interval (CPI) metric confirmed the intrinsic credibility of the results. Conclusions: This study provides insights into the relationships between concussion history, combat experience, and their impacts on mental health issues and suicide ideation among military veterans. Full article

Introduction: Traumatic brain injury (TBI) in pediatric population is responsible for significant mortality and morbidity, particularly among children aged 0–4 and young adults aged 15–24. The developing brain’s unique characteristics may increase vulnerability to injuries, potentially leading to long-term cognitive and motor deficits. Current therapeutic options for neuronal regeneration post-TBI are limited, although neurotrophins, especially nerve growth factor (NGF), show promise in enhancing recovery. NGF can mitigate excitotoxicity and promote neuroprotection, particularly by intranasal administration, which is attractive because of its non-invasive nature. Case Presentation: A three-year-old boy suffered from severe TBI due to a car accident, leading to multiple complications, including a basilar skull fracture and cerebral venous sinus thrombosis. Initial assessments revealed significant neurological impairments. After intensive care and rehabilitation, the child exhibited gradual improvements in consciousness and motor functions but continued to face challenges, particularly with left-sided hemiparesis. Nine months post-injury, he began intranasal administration of human-recombinant NGF (hr-NGF) as part of a clinical trial. Discussion: Following hr-NGF treatment, the child demonstrated notable advancements in motor function, achieving independent standing and walking. Cognitive assessments indicated improvements in various domains, including verbal comprehension and executive functioning. EEG results showed reduced epileptiform activity. These findings suggest that hr-NGF may facilitate recovery in pediatric TBI cases by enhancing both motor and cognitive outcomes. Conclusions: This case highlights the potential role of intranasal hr-NGF administration as a therapeutic strategy for improving neurological recovery in children with severe TBI. The positive clinical outcomes support further exploration of NGF as a viable treatment option to mitigate long-term sequelae associated with pediatric brain injuries. Full article

Background/Objectives: Intentional injury due to violent acts is associated with significant morbidity and mortality. However, intentional traumatic brain injury (TBI) has received little attention and there is limited research on the relationship of injury intent to injury mechanism, severity, mortality, hospital disposition and demographic factors. In this study, the aim was to examine the factors associated with intentional TBI and evaluate the differences in outcomes based on injury intent. Methods: We conducted a retrospective analysis of patients with diagnosed TBI at an urban trauma center. Hospital data were obtained from the Department of Surgery’s trauma registry for the years 2017–2022. Intentional and unintentional TBI patients were compared using descriptive, univariate and multivariate methods. Results: In this study, 123 (9.28%) intentional TBIs and 1203 (90.72%) unintentional TBIs were identified. Younger age, male gender, minority status, Medicaid coverage, alcohol use and the lack of orthopedic injury were associated with intentional TBI. Patients with intentional TBI were more likely to be discharged to home and with admissions had shorter hospital lengths of stay and were less likely to be discharged to rehabilitation. Multivariate analysis found that Black race and alcohol use near the time of injury were predictive of intentional injury when adjusting for other demographic variables. Conclusions: Overall, patients with intentional TBI had less severe and more focal injury events with shorter hospital stays if admitted. Multiple demographic- and injury-related variables were associated with intentional TBI. Further study is needed to evaluate the long-term patient outcomes and re-injury after intentional TBI. Full article

Goal: Current methodologies for assessing cerebral compliance using pressure sensor technologies are prone to errors and issues with inter- and intra-observer consistency. RAP, a metric for measuring intracranial compensatory reserve (and therefore compliance), holds promise. It is derived using the moving correlation between intracranial pressure (ICP) and the pulse amplitude of ICP (AMP). RAP remains largely unexplored in cases of moderate to severe acute traumatic neural injury (also known as traumatic brain injury (TBI)). The goal of this work is to explore the general description of (a) RAP signal patterns and behaviors derived from ICP pressure transducers, (b) temporal statistical relationships, and (c) the characterization of the artifact profile. Methods: Different summary and statistical measurements were used to describe RAP’s pattern and behaviors, along with performing sub-group analyses. The autoregressive integrated moving average (ARIMA) model was employed to outline the time-series structure of RAP across different temporal resolutions using the autoregressive (p-order) and moving average orders (q-order). After leveraging the time-series structure of RAP, similar methods were applied to ICP and AMP for comparison with RAP. Finally, key features were identified to distinguish artifacts in RAP. This might involve leveraging ICP/AMP signals and statistical structures. Results: The mean and time spent within the RAP threshold ranges ([0.4, 1], (0, 0.4), and [−1, 0]) indicate that RAP exhibited high positive values, suggesting an impaired compensatory reserve in TBI patients. The median optimal ARIMA model for each resolution and each signal was determined. Autocorrelative function (ACF) and partial ACF (PACF) plots of residuals verified the adequacy of these median optimal ARIMA models. The median of residuals indicates that ARIMA performed better with the higher-resolution data. To identify artifacts, (a) ICP q-order, AMP p-order, and RAP p-order and q-order, (b) residuals of ICP, AMP, and RAP, and (c) cross-correlation between residuals of RAP and AMP proved to be useful at the minute-by-minute resolution, whereas, for the 10-min-by-10-min data resolution, only the q-order of the optimal ARIMA model of ICP and AMP served as a distinguishing factor. Conclusions: RAP signals derived from ICP pressure sensor technology displayed reproducible behaviors across this population of TBI patients. ARIMA modeling at the higher resolution provided comparatively strong accuracy, and key features were identified leveraging these models that could identify RAP artifacts. Further research is needed to enhance artifact management and broaden applicability across varied datasets. Full article

Background: Traumatic brain injury (TBI) is a leading cause of mortality worldwide and often results in substantial cognitive, motor, and psychological impairments, triggering oxidative stress, neuroinflammation, and neurodegeneration. This study examined the neuroprotective effects of azithromycin (AZI) in TBI. Methods: TBI was induced in rats using the weight-drop method. Subsequently, rats received a daily intraperitoneal (I.P.) dose of AZI (150 mg/kg) for 28 days. Behavioral tests (Morris water maze, rotarod, and open field tests) were performed to assess cognitive and motor functions. Neurochemical analyses included oxidative stress markers (GSH, SOD, MDA, catalase), inflammatory cytokines (TNF-α, IL-1β), apoptotic markers (caspase-3, Bax, Bcl-2), mitochondrial complexes (complex I, II, III, IV, and V), and the transforming growth factor- beta (TGF-β) as a neurofilament marker. Histological evaluations focused on neuronal integrity in the cortex, hippocampus, and striatum. Results: Treatment with AZI significantly facilitated motor and cognitive function recovery in TBI-affected rats. At the molecular level, AZI effectively reduced oxidative stress markers, ameliorated neuroinflammation by decreasing TNF-α, IL-1β, and neuronal apoptosis, and differentially modulated mitochondrial complexes. Histological assessments revealed enhanced neuronal integrity and fewer pathological changes in AZI-treated rats compared to untreated TBI controls. Conclusions: AZI was shown to interfere with several pathways involved in TBI’s pathophysiology. While preclinical results are promising, further studies are necessary to establish the long-term safety and efficacy of AZI in a clinical setting. This research supports the potential re-purposing of AZI as a novel treatment strategy for TBI and related neurodegenerative disorders. Full article

Background: Diffusion tensor imaging (DTI), a variant of Diffusion Weighted Imaging (DWI), enables a neuroanatomical microscopic-like examination of the brain, which can detect brain damage using physical parameters. DTI’s application to traumatic brain injury (TBI) has the potential to reveal radiological features that can assist in predicting the clinical outcomes of these patients. What is the ongoing role of DTI in detecting brain alterations and predicting neurological outcomes in patients with moderate to severe traumatic brain injury and/or diffuse axonal injury? Methods: A scoping review of the PubMed, Scopus, EMBASE, and Cochrane databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The aim was to identify all potentially relevant studies concerning the role of DTI in TBI. From an initial pool of 3527 publications, 26 articles were selected based on relevance. These studies included a total of 729 patients with moderate to severe TBI and/or diffuse axonal injury. DTI parameters were analyzed to determine their relationship with neurological outcomes post-TBI, with assessments of several brain functions and regions. Results: The studies included various DTI parameters, identifying significant relationships between DTI variations and neurological outcomes following TBI. Multiple brain functions and regions were evaluated, demonstrating the capability of DTI to detect brain alterations with higher accuracy, sensitivity, and specificity than MRI alone. Conclusions: DTI is a valuable tool for detecting brain alterations in TBI patients, offering enhanced accuracy, sensitivity, and specificity compared to MRI alone. Recent studies confirm its effectiveness in identifying neurological impairments and predicting outcomes in patients following brain trauma, underscoring its utility in clinical settings for managing TBI. Full article

Traumatic brain injuries (TBIs) are a leading cause of mortality and morbidity, particularly in forensic settings where determining the cause of death and timing of injury is critical. Glial fibrillary acidic protein (GFAP), a biomarker specific to astrocytes, has emerged as a valuable tool in post-mortem analyses of TBI. A PRISMA-based literature search included studies examining GFAP in human post-mortem samples such as brain tissue, cerebrospinal fluid (CSF), serum, and urine. The results highlight that GFAP levels correlate with the severity of brain injury, survival interval, and pathological processes such as astrocyte damage and blood–brain barrier disruption. Immunohistochemistry, ELISA, and molecular techniques were commonly employed for GFAP analysis, with notable variability in protocols and thresholds among studies. GFAP demonstrated high diagnostic accuracy in distinguishing TBI-related deaths from other causes, particularly when analyzed in CSF and serum. Furthermore, emerging evidence supports its role in complementing other biomarkers, such as S100B and NFL, to improve diagnostic precision. However, the review also identifies significant methodological heterogeneity and gaps in standardization, which limit the generalizability of findings. Future research should focus on establishing standardized protocols, exploring biomarker combinations, and utilizing advanced molecular tools to enhance the forensic application of GFAP. Full article

Patients with severe traumatic brain injury (STBI) often experience an abnormal hemostasis that contributes to mortality and unfavorable neurological outcomes. Objectives: We aimed to analyze epidemiologic, clinical, and laboratory factors associated with mortality in patients with STBI during the first 48 h after in-hospital admission. Methods: We performed an observational retrospective study of STBI patients with associated extracranial trauma [defined as Injury Severity Score (ISS) ≥ 16 with an Abbreviated Injury Scale (AIS) head and neck ≥ 3 and Glasgow Coma Scale (GCS) ≤ 8] admitted to a Level II trauma center over seven years (2015–2021). Patients were divided into two groups: survivors and dead. We assessed differences regarding demographics, trauma severity, hemodynamics, disability, need for surgery, length of stay, transfusions, need for massive transfusion protocol, and hemostatic laboratory parameters at different time points. Results: A total of 134 STBI patients were included. Patients who died were older, mostly men, and showed higher trauma severity and disability. Hemoglobin, platelets, and clotting parameters deteriorated after admission to the emergency department (ED) with significant differences between groups within the first 24 h after admission. Platelet count < 150 × 10³/μL at ED arrival, GCS, and age were independent risk factors for mortality. Conclusions: Older age, GCS, and platelet count at ED arrival were independent risk factors for mortality in STBI patients with associated extracranial trauma. Early thrombocytopenia < 150 × 10³/μL at ED arrival may be used as a simple prognostic tool to early predict mortality between non-isolated STBI. Full article

Background: There is currently increasing interest in the implication of traumatic brain injury (TBI) as a potential risk factor for long-term neurodegenerative conditions, such as dementia and Alzheimer’s disease (AD). In this context, we performed a systematic review and meta-analysis to evaluate the association between TBI and the risk of dementia. Methods: A systematic search was performed across multiple electronic databases, including PubMed, Embase, and Cochrane Library, to identify relevant meta-analyses and cohort studies. Studies were included if they reported effect sizes (odds ratios [ORs] or relative risks [RRs]) for the association between TBI, its severity, and the risk of dementia or AD. Meta-analyses were performed using random-effects models to account for heterogeneity, and sensitivity analyses were conducted. Results: A total of six studies were included in the analysis. The pooled results showed that TBI significantly increases the risk of dementia, with an overall odds ratio of 1.81 (95% CI: 1.53–2.14). Mild TBI was associated with a modest increase in dementia risk (OR = 1.96, 95% CI: 1.70–2.26), while moderate-to-severe TBI showed a stronger association (OR = 1.95, 95% CI: 1.55–2.45). In contrast, the association between TBI and AD was less consistent, with the pooled OR for AD being 1.18 (at 95% CI: 1.11–1.25) for mild TBI; however, in several studies, no significant association was observed (OR = 1.02, 95% CI: 0.91–1.15). The results also indicated substantial heterogeneity across studies, particularly in relation to AD outcomes. Conclusions: The findings from this umbrella meta-analysis confirm that TBI is a significant risk factor for dementia, with more severe TBIs conferring a higher risk. While mild TBIs also increase the risk of dementia, the effect is more pronounced in moderate-to-severe injuries. The evidence linking TBI to AD is less robust, with inconsistent findings across studies. Clinicians should consider long-term cognitive screening and management for individuals with a history of TBI, particularly those with moderate-to-severe injuries. Full article