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PurposeTraumatic brain injury (TBI) and potentially traumatic events (PTEs) contribute to increased substance use, mental health issues, and cognitive impairments. However, there's not enough research on how TBI and PTEs combined impact mental heath, substance use, and neurocognition.MethodsThis study leverages a subset of The National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) multi-site dataset with 551 adolescents to assess the combined and distinctive impacts of TBI, PTEs, and TBI+PTEs (prior to age 18) on substance use, mental health, and neurocognitive outcomes at age 18.ResultsTBI, PTEs, and TBI+PTEs predicted greater lifetime substance use and past-year alcohol and cannabis use. PTEs predicted greater internalizing symptoms, while TBI+PTEs predicted greater externalizing symptoms. Varying effects on neurocognitive outcomes included PTEs influencing attention accuracy and TBI+PTEs predicting faster speed in emotion tasks. PTEs predicted greater accuracy in abstraction-related tasks. Associations with working memory were not detected.ConclusionThis exploratory study contributes to the growing literature on the complex interplay between TBI, PTEs, and adolescent mental health, substance use, and neurocognition. The developmental implications of trauma via TBIs and/or PTEs during adolescence are considerable and worthy of further investigation.

Background and purposeTraumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarettes (E-cig) (vaping) on TBI-associated behavioural and biochemical changes.Experimental approachAdult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain-derived neurotrophic factor (mBDNF) and associated downstream proteins (p-Erk, p-Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation.Key resultsPost-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up-regulated mBDNF, p-Erk and p-Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p-Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia-mediated neuroinflammation.Conclusions and implicationsPost-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions.

BACKGROUND: Venous thromboembolism (VTE) is a preventable medical condition which has substantial impact on patient morbidity, mortality, and disability. Unfortunately, adherence to the published best practices for VTE prevention, based on patient centered outcomes research (PCOR), is highly variable across U.S. hospitals, which represents a gap between current evidence and clinical practice leading to adverse patient outcomes. This gap is especially large in the case of traumatic brain injury (TBI), where reluctance to initiate VTE prevention due to concerns for potentially increasing the rates of intracranial bleeding drives poor rates of VTE prophylaxis. This is despite research which has shown early initiation of VTE prophylaxis to be safe in TBI without increased risk of delayed neurosurgical intervention or death. Clinical decision support (CDS) is an indispensable solution to close this practice gap; however, design and implementation barriers hinder CDS adoption and successful scaling across health systems. Clinical practice guidelines (CPGs) informed by PCOR evidence can be deployed using CDS systems to improve the evidence to practice gap. In the Scaling AcceptabLE cDs (SCALED) study, we will implement a VTE prevention CPG within an interoperable CDS system and evaluate both CPG effectiveness (improved clinical outcomes) and CDS implementation. METHODS: The SCALED trial is a hybrid type 2 randomized stepped wedge effectiveness-implementation trial to scale the CDS across 4 heterogeneous healthcare systems. Trial outcomes will be assessed using the RE2-AIM planning and evaluation framework. Efforts will be made to ensure implementation consistency. Nonetheless, it is expected that CDS adoption will vary across each site. To assess these differences, we will evaluate implementation processes across trial sites using the Exploration, Preparation, Implementation, and Sustainment (EPIS) implementation framework (a determinant framework) using mixed-methods. Finally, it is critical that PCOR CPGs are maintained as evidence evolves. To date, an accepted process for evidence maintenance does not exist. We will pilot a Living Guideline process model for the VTE prevention CDS system. DISCUSSION: The stepped wedge hybrid type 2 trial will provide evidence regarding the effectiveness of CDS based on the Berne-Norwood criteria for VTE prevention in patients with TBI. Additionally, it will provide evidence regarding a successful strategy to scale interoperable CDS systems across U.S. healthcare systems, advancing both the fields of implementation science and health informatics. TRIAL REGISTRATION: Clinicaltrials.gov - NCT05628207. Prospectively registered 11/28/2022, https://classic. CLINICALTRIALS: gov/ct2/show/NCT05628207 .

BACKGROUND: Over two decades of research about traumatic brain injury (TBI) rehabilitation emphasized the persistence of racial health disparities in functional outcomes that disproportionately impact Black populations without naming or addressing racism as the root problem. Further, the experiences of Black people with TBI have yet to be documented and accounted for in scientific scholarship from the perspectives of Black persons in Canada. PURPOSE: This study intended to examine the rehabilitation narratives of Black TBI survivors, family caregivers, and rehabilitation providers and use critical race theory as a conceptual framework to understand how anti-Black racism manifests in those experiences. METHODS: Through critical narrative inquiry informed by a critical constructivist paradigm and a critical race theory lens, in-depth narrative interviewing were conducted with seven survivors, three family caregivers, and four rehabilitation providers. Data were analyzed using reflexive thematic analysis within and across groups of participants to conceptualize themes and sub-themes. FINDINGS: Themes captured how racism becomes institutionalized in TBI rehabilitation: (1) the institutional construction of deficient Black bodies, (2) the institutional construction of rehabilitation access, (3) the institutional investment in resisting and approximating whiteness in rehabilitation practice, and (4) the institutional construction of deficient Black futures. CONCLUSION: Study findings point to the dire need to ensure rehabilitation programs, services, and the delivery of care are not determined based on inequitable practices, racial biases and assumptions about Black people, which determine who deserves to get into rehabilitation and have opportunities to be supported in working towards living a full and meaningful life.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinsons disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

AimAstrocytes respond to stressors by acquiring a reactive state characterized by changes in their morphology and function. Molecules underlying reactive astrogliosis, however, remain largely unknown. Given that several studies observed increase in the Amyloid Precursor Protein (APP) in reactive astrocytes, we here test whether APP plays a role in reactive astrogliosis.MethodsWe investigated whether APP instigates reactive astroglios by examining in vitro and in vivo the morphology and function of naive and APP-deficient astrocytes in response to APP and well-established stressors.ResultsOverexpression of APP in cultured astrocytes led to remodeling of the intermediate filament network, enhancement of cytokine production, and activation of cellular programs centered around the interferon (IFN) pathway, all signs of reactive astrogliosis. Conversely, APP deletion abrogated remodeling of the intermediate filament network and blunted expression of IFN-stimulated gene products in response to lipopolysaccharide. Following traumatic brain injury (TBI), mouse reactive astrocytes also exhibited an association between APP and IFN, while APP deletion curbed the increase in glial fibrillary acidic protein observed canonically in astrocytes in response to TBI.ConclusionsThe APP thus represents a candidate molecular inducer and regulator of reactive astrogliosis. This finding has implications for understanding pathophysiology of neurodegenerative and other diseases of the nervous system characterized by reactive astrogliosis and opens potential new therapeutic avenues targeting APP and its pathways to modulate reactive astrogliosis.

OBJECTIVE: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomization After Significant Head Injury (CRASH) prognostic models for mortality and outcome after traumatic brain injury (TBI) were developed using data from 1984 to 2004. This study examined IMPACT and CRASH model performances in a contemporary cohort of US patients. METHODS: The prospective 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years 2014-2018) enrolled subjects aged ≥ 17 years who presented to level I trauma centers and received head CT within 24 hours of TBI. Data were extracted from the subjects who met the model criteria (for IMPACT, Glasgow Coma Scale [GCS] score 3-12 with 6-month Glasgow Outcome Scale-Extended [GOSE] data [n = 441]; for CRASH, GCS score 3-14 with 2-week mortality data and 6-month GOSE data [n = 831]). Analyses were conducted in the overall cohort and stratified on the basis of TBI severity (severe/moderate/mild TBI defined as GCS score 3-8/9-12/13-14), age (17-64 years or ≥ 65 years), and the 5 top enrolling sites. Unfavorable outcome was defined as GOSE score 1-4. Original IMPACT and CRASH model coefficients were applied, and model performances were assessed by calibration (intercept [< 0 indicated overprediction; > 0 indicated underprediction] and slope) and discrimination (c-statistic). RESULTS: Overall, the IMPACT models overpredicted mortality (intercept -0.79 [95% CI -1.05 to -0.53], slope 1.37 [1.05-1.69]) and acceptably predicted unfavorable outcome (intercept 0.07 [-0.14 to 0.29], slope 1.19 [0.96-1.42]), with good discrimination (c-statistics 0.84 and 0.83, respectively). The CRASH models overpredicted mortality (intercept -1.06 [-1.36 to -0.75], slope 0.96 [0.79-1.14]) and unfavorable outcome (intercept -0.60 [-0.78 to -0.41], slope 1.20 [1.03-1.37]), with good discrimination (c-statistics 0.92 and 0.88, respectively). IMPACT overpredicted mortality and acceptably predicted unfavorable outcome in the severe and moderate TBI subgroups, with good discrimination (c-statistic ≥ 0.81). CRASH overpredicted mortality in the severe and moderate TBI subgroups and acceptably predicted mortality in the mild TBI subgroup, with good discrimination (c-statistic ≥ 0.86); unfavorable outcome was overpredicted in the severe and mild TBI subgroups with adequate discrimination (c-statistic ≥ 0.78), whereas calibration was nonlinear in the moderate TBI subgroup. In subjects ≥ 65 years of age, the models performed variably (IMPACT-mortality, intercept 0.28, slope 0.68, and c-statistic 0.68; CRASH-unfavorable outcome, intercept -0.97, slope 1.32, and c-statistic 0.88; nonlinear calibration for IMPACT-unfavorable outcome and CRASH-mortality). Model performance differences were observed across the top enrolling sites for mortality and unfavorable outcome. CONCLUSIONS: The IMPACT and CRASH models adequately discriminated mortality and unfavorable outcome. Observed overestimations of mortality and unfavorable outcome underscore the need to update prognostic models to incorporate contemporary changes in TBI management and case-mix. Investigations to elucidate the relationships between increased survival, outcome, treatment intensity, and site-specific practices will be relevant to improve models in specific TBI subpopulations (e.g., older adults), which may benefit from the inclusion of blood-based biomarkers, neuroimaging features, and treatment data.

Resting state functional magnetic resonance imaging (rsfMRI) provides researchers and clinicians with a powerful tool to examine functional connectivity across large-scale brain networks, with ever-increasing applications to the study of neurological disorders, such as traumatic brain injury (TBI). While rsfMRI holds unparalleled promise in systems neurosciences, its acquisition and analytical methodology across research groups is variable, resulting in a literature that is challenging to integrate and interpret. The focus of this narrative review is to address the primary methodological issues including investigator decision points in the application of rsfMRI to study the consequences of TBI. As part of the ENIGMA Brain Injury working group, we have collaborated to identify a minimum set of recommendations that are designed to produce results that are reliable, harmonizable, and reproducible for the TBI imaging research community. Part one of this review provides the results of a literature search of current rsfMRI studies of TBI, highlighting key design considerations and data processing pipelines. Part two outlines seven data acquisition, processing, and analysis recommendations with the goal of maximizing study reliability and between-site comparability, while preserving investigator autonomy. Part three summarizes new directions and opportunities for future rsfMRI studies in TBI patients. The goal is to galvanize the TBI community to gain consensus for a set of rigorous and reproducible methods, and to increase analytical transparency and data sharing to address the reproducibility crisis in the field.

In this Viewpoint, we provide an overview of the worsening trend of traumatic injuries across the United States-Mexico border after its recent fortification and height extension to 30-feet. We further characterize the international factors driving migration and the current U.S. policies and political climate that will allow this public health crisis to progress. Finally, we provide recommendations involving prevention efforts, effective resource allocation, and advocacy that will start addressing the humanitarian and economic consequences of current U.S. border policies and infrastructure.

BACKGROUND: Adult patients with mild traumatic brain injury (mTBI) exhibit distinct phenotypes of emotional and cognitive functioning identified by latent profile analysis of clinical neuropsychological assessments. When discerned early after injury, these latent clinical profiles have been found to improve prediction of long-term outcomes from mTBI. The present study hypothesized that white matter (WM) microstructure is better preserved in an emotionally resilient mTBI phenotype compared with a neuropsychiatrically distressed mTBI phenotype. METHODS: The present study used diffusion magnetic resonance imaging to investigate and compare WM microstructure in major association, projection, and commissural tracts between the two phenotypes and over time. Diffusion magnetic resonance images from 172 patients with mTBI were analyzed to compute individual diffusion tensor imaging maps at 2 weeks and 6 months after injury. RESULTS: By comparing the diffusion tensor imaging parameters between the two phenotypes at global, regional, and voxel levels, emotionally resilient patients were shown to have higher axial diffusivity compared with neuropsychiatrically distressed patients early after mTBI. Longitudinal analysis revealed greater compromise of WM microstructure in neuropsychiatrically distressed patients, with greater decrease of global axial diffusivity and more widespread decrease of regional axial diffusivity during the first 6 months after injury compared with emotionally resilient patients. CONCLUSIONS: These results provide neuroimaging evidence of WM microstructural differences underpinning mTBI phenotypes identified from neuropsychological assessments and show differing longitudinal trajectories of these biological effects. These findings suggest that diffusion magnetic resonance imaging can provide short- and long-term imaging biomarkers of resilience.

Traumatic brain injury (TBI) is a common diagnosis requiring acute hospitalization. Long-term, TBI is a significant source of health and socioeconomic impact in the United States and globally. The goal of clinicians who manage TBI is to prevent secondary brain injury. In this population, post-traumatic cerebral infarction (PTCI) acutely after TBI is an important but under-recognized complication that is associated with negative functional outcomes. In this comprehensive review, we describe the incidence and pathophysiology of PTCI. We then discuss the diagnostic and treatment approaches for the most common etiologies of isolated PTCI, including brain herniation syndromes, cervical artery dissection, venous thrombosis, and post-traumatic vasospasm. In addition to these mechanisms, hypercoagulability and microcirculatory failure can also exacerbate ischemia. We aim to highlight the importance of this condition and future clinical research needs with the goal of improving patient outcomes after TBI.

BackgroundTraumatic brain injury (TBI) and repetitive head impacts (RHI) have been linked to increased risk for multiple types of neurodegenerative disease, higher dementia risk, and earlier age of dementia symptom onset, suggesting transdiagnostic implications for later-life brain health. Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) represent a spectrum of clinical phenotypes that are neuropathologically diverse. FTD/PPA diagnoses bring unique challenges due to complex cognitive and behavioral symptoms that disproportionately present as an early-onset dementia (before age 65). We performed a detailed characterization of lifetime head trauma exposure in individuals with FTD and PPA compared to healthy controls to examine frequency of lifetime TBI and RHI and associated clinical implications.MethodsWe studied 132 FTD/PPA (age 68.9 ± 8.1, 65% male) and 132 sex-matched healthy controls (HC; age 73.4 ± 7.6). We compared rates of prior TBI and RHI (contact/collision sports) between FTD/PPA and HC (chi-square, logistic regression, analysis of variance). Within FTD/PPA, we evaluated associations with age of symptom onset (analysis of variance). Within behavioral variant FTD, we evaluated associations with cognitive function and neuropsychiatric symptoms (linear regression controlling for age, sex, and years of education).ResultsYears of participation were greater in FTD/PPA than HC for any contact/collision sport (8.5 ± 6.7yrs vs. 5.3 ± 4.5yrs, p = .008) and for American football (6.2yrs ± 4.3yrs vs. 3.1 ± 2.4yrs; p = .003). Within FTD/PPA, there were dose-dependent associations with earlier age of symptom onset for TBI (0 TBI: 62.1 ± 8.1, 1 TBI: 59.9 ± 6.9, 2 + TBI: 57.3 ± 8.4; p = .03) and years of American football (0yrs: 62.2 ± 8.7, 1-4yrs: 59.7 ± 7.0, 5 + yrs: 55.9 ± 6.3; p = .009). Within bvFTD, those who played American football had worse memory (z-score: -2.4 ± 1.2 vs. -1.4 ± 1.6, p = .02, d = 1.1).ConclusionsLifetime head trauma may represent a preventable environmental risk factor for FTD/PPA. Dose-dependent exposure to TBI or RHI influences FTD/PPA symptom onset and memory function in bvFTD. Clinico-pathological studies are needed to better understand the neuropathological correlates linking RHI or TBI to FTD/PPA onset and symptoms.

INTRODUCTION: Intracranial pressure (ICP) monitoring is a very commonly performed neurosurgical procedure but there is a wide variation in how it is reported, hindering analysis of it. The current study sought to generate consensus on the reporting of ICP monitoring recording data. RESEARCH QUESTION: What should be included in an ICP monitoring report? MATERIAL AND METHODS: The exercise was completed via a modified eDelphi survey. An expert panel discussion was held from which themes were identified and used to produce a code to annotate the transcript of the discussion. Statements were generated for a further two rounds of electronic questionnaires distributed via the REDcap platform. A Likert scale was used to grade agreement with each statement in the survey. A statement was accepted if more than 70% agreement was achieved between respondents. Data was collated using Microsoft Excel and analysed using R. RESULTS: 149 relevant statements were identified from the transcript and categorised into recording parameters, waveform characteristics or reporting. A total of 22 statements were generated for the first round of the survey which was answered by 39 respondents. Following the electronic round of surveys consensus was achieved for all but one statement regarding the acceptability of automating ICP reporting. This was put forward to a second round after which 79% agreement was reached. DISCUSSION AND CONCLUSION: The themes and statements from this eDelphi can be used as a framework to allow the standardisation of the reporting of intracranial pressure monitoring data.

OBJECTIVES: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort. METHODS: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury. RESULTS: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months. CONCLUSIONS: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed. LEVEL OF EVIDENCE: IV. TRIAL REGISTRATION NUMBER: NCT02119182.

BackgroundTraumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are potential risk factors for the development of dementia including Alzheimer's disease (AD) in later life. The findings of studies investigating this question are inconsistent though.ObjectiveTo investigate if these inconsistencies are caused by the existence of subgroups with different vulnerability for AD pathology and if these subgroups are characterized by atypical tau load/atrophy pattern.MethodsThe MRI and PET data of 89 subjects with or without previous TBI and/or PTSD from the DoD ADNI database were used to calculate an age-corrected gray matter tau mismatch metric (ageN-T mismatch-score and matrix) for each subject. This metric provides a measure to what degree regional tau accumulation drives regional gray matter atrophy (matrix) and can be used to calculate a summary score (score) reflecting the severity of AD pathology in an individual.ResultsThe ageN-T mismatch summary score was positively correlated with whole brain beta-amyloid load and general cognitive function but not with PTSD or TBI severity. Hierarchical cluster analysis identified five different spatial patterns of tau-gray matter interactions. These clusters reflected the different stages of the typical AD tau progression pattern. None was exclusively associated with PTSD and/or TBI.ConclusionsThese findings suggest that a) although subsets of patients with PTSD and/or TBI develop AD-pathology, a history of TBI or PTSD alone or both is not associated with a significantly higher risk to develop AD pathology in later life. b) remote TBI or PTSD do not modify the typical AD pathology distribution pattern.

ObjectiveProject 1 of the Preclinical Multicenter Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) consortium aims to identify preclinical biomarkers for antiepileptogenic therapies following traumatic brain injury (TBI). The international participating centers in Finland, Australia, and the United States have made a concerted effort to ensure protocol harmonization. Here, we evaluate the success of harmonization process by assessing the timing, coverage, and performance between the study sites.MethodWe collected data on animal housing conditions, lateral fluid-percussion injury model production, postoperative care, mortality, post-TBI physiological monitoring, timing of blood sampling and quality, MR imaging timing and protocols, and duration of video-electroencephalography (EEG) follow-up using common data elements. Learning effect in harmonization was assessed by comparing procedural accuracy between the early and late stages of the project.ResultsThe animal housing conditions were comparable between the study sites but the postoperative care procedures varied. Impact pressure, duration of apnea, righting reflex, and acute mortality differed between the study sites (p  0.05). Plasma quality was poor in 4% of the samples in UEF, 1% in Monash and 14% in UCLA. More than 97% of the final cohort were MR imaged at all timepoints in all study sites. The timing of imaging did not differ on D2 and D9 (p > 0.05), but varied at D30, 5 months, and ex vivo timepoints (p  0.05). A decrease in acute mortality and increase in plasma quality across time reflected a learning effect in the TBI production and blood sampling protocols.SignificanceOur study is the first demonstration of the feasibility of protocol harmonization for performing powered preclinical multi-center trials for biomarker and therapy discovery of post-traumatic epilepsy.

• Self-care deficits first emerged eight weeks after a single closed-head injury. • Injured animals lost social novelty preference within the first month post-injury. • Loss of desire for social interaction developed over a twelve week period. • GluN1 expression increased chronically in the injured frontal cortex and amygdala. • Hippocampal GLT-1 expression was decreased chronically following injury. Mild traumatic brain injury (mTBI) is known to result in chronic somatic, cognitive, and emotional symptoms. Depression is commonly reported among individuals suffering from persistent concussion symptoms; however, the underlying mechanisms are not understood. The glutamatergic system has recently been linked with mTBI and depression due to reports of similar changes in expression of glutamatergic proteins. Using a closed-head controlled cortical impact (cCCI) model in adult male rats (n = 8/group), this study investigated the emergence of self-care deficits and changes in social interaction behaviors at four, eight and twelve weeks post-injury. Western blotting was used to assess associated changes in expression of glutamate transporters and N-methyl-D-aspartate (NMDA) receptor subunits at twelve weeks. Splash test results revealed deficits in self-care behaviors beginning at eight weeks, which continued through twelve weeks in the injury group. Injured animals also exhibited decreased preference for social novelty at four weeks and loss of desire for social interaction as a whole by twelve weeks. GluN1 was increased in injured animals compared to shams in the frontal cortex and amygdala, while decreased GLT-1 was observed in the hippocampus. Linear regression was performed to evaluate relationships between behavioral and molecular variables; the results suggested that injury affects these relationships in a region-dependent manner. Together, these results suggest that the development of chronic depression-like behavior was associated with changes in glutamatergic protein expression. Deeper investigations into how injury influences glutamatergic synaptic protein expression are needed, as this has the potential to affect circuit-level neurotransmission that drives depression-like behavior following mTBI. [ABSTRACT FROM AUTHOR]

Background: In the new era, microbial-based medicine is one of the best strategies that try to modify the normal flora with the aim of treating some disorders. This systematic review and meta-analysis was performed to evaluate the use of probiotics in the treatment of the clinical outcomes in cases with traumatic brain injury.. Methods: In this regard, the search strategy was done using databases such as PubMed, Embase, Scopus, CENTRAL, and Google Scholar, from 2006 until April 2024. All studies about the efficacy of probiotic supplementation on the clinical outcomes in traumatic brain injury patients were retrieved. During the assessment process of the eligible studies, we evaluated clinical characteristics such as the Glasgow Coma Scale score, the Sequential Organ Failure Assessment score, the Acute Physiology and Chronic Health Evaluation II score, referral rate and hospitalization period in the intensive care unit, mortality rate, as well as opportunistic infections in both groups of case and control.. Results: In this study, the authors analyzed data from 6 articles including 391 cases with traumatic brain injury. Our results showed that the probiotic therapy increases the Glasgow Coma Scale score in patients with the average age of more than 50 years. However, there was no a significant difference in the Sequential Organ Failure Assessment and the Acute Physiology and Chronic Health Evaluation scores between the group that had received probiotics and the control group. Although probiotic-based treatment did not significantly affect the intensive care unit admission (or length of stay), but, the risk of infection, and also mortality was significantly lower in the probiotic group (OR: 0.53; 95% CI: 0.3 to 0.8, as well as OR: 0.41; 95% CI: 0.2 to 0.7, respectively).. Conclusions: Overall, due to the modification of microbial flora, probiotic supplements can balance microflora disturbances, which in turn leads to improvement the clinical outcomes in patients with brain injury. Therefore, probiotic-based therapy can be considered as a promising strategy for the treatment of the central nervous system disorders. However, given the limited evidence, more clinical trial studies need to strengthen our results.. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) increases the risk of developing Alzheimer's disease (AD), and a growing number of studies support a potential link between the two disorders. Therefore, the objective of this study is to systematically map the knowledge structure surrounding this topic over the past and to summarize the current state of research and hot frontiers in the field. Methods: Data were retrieved from the Web of Science Core Collection (WOSCC) starting from the beginning until December 31, 2023, focusing on articles and reviews in English. Bibliometric tools including Bibliometrix R, VOSviewer, and Microsoft Excel were utilized for data analysis. The analysis included citations, authors, institutions, countries, journals, author keywords, and references. Results: A total of 1,515 publications were identified, comprising 872 articles (57.56%) and 643 reviews (42.44%). The annual number of publications increased steadily, especially after 2013, with an R2 value of 0.978 indicating a strong upward trend. The USA was the leading country in terms of publications (734 articles), followed by China (162 articles) and the United Kingdom (77 articles). Meanwhile Boston University was the most productive institution. Collaborative networks show strong collaborative author links between the USA and the United Kingdom, as well as China. The analysis also showed that the Journal of Alzheimer's Disease was the most productive journal, while the article authored by McKee achieved the highest local citations value. The top three author keywords, in terms of occurrences, were "Alzheimer's disease," "traumatic brain injury," and "neurodegeneration." Thematic mapping showed a consolidation of research themes over time, decreasing from 11 main themes to 8. Emerging themes such as "obesity" and "diffusion tensor imaging" indicate new directions in the field. Conclusion: The research on AD after TBI has attracted a great deal of interest from scientists. Notably, the USA is at the forefront of research in this field. There is a need for further collaborative research between countries. Overall, this study provides a comprehensive overview of developments in TBI and AD research, highlighting key contributors, emerging topics, and potential areas for future investigation. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) remains a significant global public health epidemic with adverse health and cost implications. Due to its complex, heterogeneous nature and wide-ranging impacts, definitive TBI treatments remain elusive. As such, continued laboratory research using animal models is warranted. In accordance with guidelines set forth for the humane treatment of research animals, TBI animal models are often administered analgesics for pain management. The choice of drug, timing, dose, and formulation of analgesic can vary depending on the study's unique needs and can potentially and unintentionally influence experimental results. In TBI studies utilizing rats as animal models, buprenorphine is a common analgesic administered. In addition to pain management in such studies, investigators must also monitor the research animals post-operatively and make the decision for humane euthanasia before intended experimental survival timepoint if the animals are assessed to be excessively suffering. This study investigated the differences in adult, male Sprague Dawley rats used for various TBI studies that reached weight-loss-induced humane endpoints following a single administration of buprenorphine slow-release LAB (bup-SR-LAB) or buprenorphine slow-release HCl (bup-SR-HCl). Our findings indicate that TBI-induced rats receiving bup-SR-LAB in conjunction with a secondary surgical insult such as artificial intracranial pressure elevation and/or osmotic pump implantation reach a weight-loss-induced humane euthanasia endpoint more often compared to sham-injured rats. When stratifying into the same groups, we did not find this pattern to hold true for rats administered bup-SR-HCl. Overall, this study contributes to the limited body of literature addressing different analgesic formulations' effects on laboratory animals. [ABSTRACT FROM AUTHOR]

Introduction: Acute subdural hematomas are major causes of morbidity which warrant immediate treatment. If surgical intervention is warranted, craniotomy (CO) and decompressive craniectomy (DC) are employed, largely based on a loosely defined criteria and the neurosurgeon's best judgment. The primacy of one approach over another is a matter of dispute. Objective: We attempt to further clarify any advantages in the two techniques, and include a propensity score matched (PSM) subgroup analysis to eliminate bias. Design: This meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Data Sources and Methods: A literature review was conducted on PubMed/Medline, Cochrane Central, and Google Scholar from inception to September 2023. 15 studies were extracted, and three outcomes were meta-analyzed: Mortality, Glasgow Outcome Scale (GOS) scores and patients undergoing re-operations/revisions. Odds Ratios (OR) and Mean Difference (MD) were used in dichotomous and continuous variables respectively. PSM data was used wherever possible. A subgroup analysis was conducted with 5 PSM studies and a trial. Heterogeneity was addressed if above 40% and the P -value is significant (≤.05). Results: A total of 15 studies were meta-analyzed with a total of 2327 and 2171 patients undergoing CO and DC respectively. Patients undergoing DC had a significantly worse GOS 5 outcome (OR:.63 [95% CI:.45-.87]; P =.005; I2 = 0%) and higher mortality (OR: 1.58 [95% CI: 1.20-2.08]; P =.001; I2 = 67%). In subgroup analysis of adjusted studies, DC still had significantly higher mortality. (OR: 1.50 [95% CI: 1.03-2.18]; P =.001; I2 = 83%). Conclusions: This meta-analysis determines that CO is more viable than DC as a surgical option due to its less invasive nature. DC can be employed, albeit under strict preprocedural patient selection and for highly specific indications. [ABSTRACT FROM AUTHOR]

Objective: Cranial computed tomography (CT) scan is the most widely used tool to rule out intracranial lesions after pediatric traumatic brain injury (TBI). However, in pediatric population, the radiation exposure can lead to an increased risk of hematological and brain neoplasm. Defined in 2019 National Institute for Health and Care Excellence (NICE) guidelines as "troponins for the brain", serum biomarkers measurements, particularly S100B, have progressively emerged as a supplementary tool in the management of TBI thanks to their capacity to predict intracranial post-traumatic lesions. Methods: This systematic review was conducted following the PRISMA protocol (preferred reporting items for systematic reviews and meta-analyses). No chronological limits of study publications were included. Studies reporting data from children with TBI undergoing serum S100B measurement and computed tomography (CT) scans were included. Results: Of 380 articles screened, 10 studies met the inclusion criteria. Patients admitted with mild-TBI in the Emergency Department (ED) were 1325 (80.25%). The overall pooled sensitivity and specificity were 98% (95% CI, 92–99%) and 45% (95% CI, 29–63%), respectively. The meta-analysis revealed a high negative predictive value (NVP) (99%; 95% CI, 94–100%) and a low positive predictive value (PPV) (41%; 95% CI, 16–79%). Area under the curve (AUC) was 76% (95% CI, 65–85%). The overall pooled negative predictive value (NPV) was 99% (95% CI, 99–100%). Conclusions: The measurement of serum S100B in the diagnostic workflow of mTBI could help informed decision-making in the ED setting, potentially safely reducing the use of CT scan in the pediatric population. The high sensitivity and excellent negative predictive values look promising and seem to be close to the values found in adults. Despite this, it must be pointed out the high heterogeneity (> 90%) found among studies. In order for S100B to be regularly introduced in the pediatric workflow for TBI, it is important to conduct further studies to obtain cut-off levels based on pediatric reference intervals. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are key effector molecules in innate immunity, both systemically and locally. AMPs also play important roles in brain functions such as memory and sleep in the absence of infection. The expression of many AMPs is increased during aging, neurodegeneration, and brain injuries. Overactivation of certain AMPs contributes to neuronal cell death in several neurodegenerative disease models. Antimicrobial peptides (AMPs), a collection of small proteins with important roles in classical innate immunity, have been extensively studied in multiple organisms, particularly in Drosophila melanogaster. Advances in CRISPR/Cas9 genome editing have allowed individual AMP functions to be dissected, revealing specific and selective roles in host defense. Recent findings have also revealed many unexpected contributions of endogenous AMPs to neuronal functions and neurodegenerative diseases, and have shed light on the intersections between innate immunity and neurobiology. We explore the intricate relationships between AMPs and sleep regulation, memory formation, as well as traumatic brain injury and several neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia (FTD), and Parkinson's disease (PD). Understanding the diverse functions of AMPs opens new avenues for neuroinflammation and neurodegenerative disease research and potential therapeutic development. [ABSTRACT FROM AUTHOR]

Background: Mild traumatic brain injury (mTBI) is becoming a more common emergency department (ED) presentation. Towards this end, many types of testing in the acute setting are being investigated. One of these is screening for convergence insufficiency (CI) symptoms. These are common problems reported by patients with mTBI, but such oculomotor testing is rarely performed in the ED. Objective: To assess the feasibility of convergence insufficiency screening in the ED and investigate whether CI is associated with adverse events such as post-concussive symptoms or hospital admission. Methods: Written informed consent was obtained from patients age 18 years or older who experienced a mild head injury from any mechanism resulting in an mTBI. Patients underwent screening for CI symptoms using a standardized instrument of 15 questions, known as the convergence insufficiency symptom survey (CISS), with responses based on the Likert scale. These data were correlated to outcomes of hospital admission, occurrence of post-concussive symptoms, and 30-day hospital re-admission. Results: A total of 116 patients were prospectively enrolled, of which 58 were male. The median age was 31 years, with a range of 18 to 95 years of age. The median CISS score was 13, with an interquartile range (IQR) of 6 to 21 and an overall range of 0 to 53. Females presented with a median CISS score of 14, which was higher compared to the male median score of 10. The higher the CISS score, the more likely the patient was to be admitted to the hospital (p = 0.0378), develop symptoms of post-concussive syndrome at 30-day follow up (p = 0.0322), and be readmitted within 30 days (p = 0.0098). Conclusions: Screening for CI symptoms using the CISS can be a solid adjunct in the evaluation of mTBI in the ED. The CISS is easy and fast to administer, and it is a useful tool to stratify patients in terms of who is at the highest risk of developing complications related to the mTBI. [ABSTRACT FROM AUTHOR]

ObjectiveMethodsResultsSignificanceTo investigate phenotypes of comorbidity before and after an epilepsy diagnosis in a national cohort of post‐9/11 Service Members and Veterans and explore phenotypic associations with mortality.Among a longitudinal cohort of Service Members and Veterans receiving care in the Veterans Health Administration (VHA) from 2002 to 2018, annual diagnoses for 26 conditions associated with epilepsy were collected over 5 years, ranging from 2 years prior to 2 years after the year of first epilepsy diagnosis. Latent class analysis (LCA) was used to identify probabilistic comorbidity phenotypes with distinct health trajectories. Descriptive statistics were used to describe the characteristics of each phenotype. Fine and Gray cause‐specific survival models were used to measure mortality outcomes for each phenotype up to 2021.Six distinct phenotypes were identified: (1) relatively healthy, (2) post‐traumatic stress disorder, (3) anxiety and depression, (4) chronic disease, (5) bipolar/substance use disorder, and (6) polytrauma. Accidents were the most common cause of death overall, followed by suicide/mental health and cancer, respectively. Each phenotype exhibited unique associations with mortality and cause of death, highlighting the differential impact of comorbidity patterns on patient outcomes.By delineating clinically meaningful epilepsy comorbidity phenotypes, this study offers a framework for clinicians to tailor interventions. Moreover, these data support systems of care that facilitate treatment of epilepsy and comorbidities within an interdisciplinary health team that allows continuity of care. Targeting treatment toward patients with epilepsy who present with specific heightened risks could help mitigate adverse outcomes and enhance overall patient care. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injuries (TBIs) are one of the leading causes of death or long‐term disability around the world. As a result of improvements in supportive care, patients are surviving more severe insults with more pronounced dependency on their families, hospitals, and long‐term care facilities. The introduction of brain tissue oxygenation (PbtO2) monitoring aims to recognize episodes of reduced cerebral perfusion with and without associated increased intracranial pressure (ICP). Aim: The aim of this review is to determine the impact of PbtO2 on the Glasgow Outcome Scale/Glasgow Outcome Scale Extended (GOS/GOSE) in patients with moderate to severe TBI. Study Design: Systematic review with narrative and meta‐analysis. All original research in which adult patients undergoing PbtO2 were compared with a control group of traditional ICP/cerebral perfusion pressure (CPP) monitoring. Both randomized controlled trials and observational studies were included in this review. Methods: Databases were searched in September 2022. The primary outcome of the review was the impact of PbtO2 monitoring on GOS/GOSE, while secondary outcomes were mortality and length of stay (LOS) in the intensive care unit (ICU). Results: Seven studies with a combined number of 770 patients were included in the review. These patients were adults ≥16 years of age. Only two of the studies included found a statistically significant association between PbtO2 monitoring and improved long‐term neurological outcomes in patients with TBI (p =.01, p <.01). A meta‐analysis of the secondary outcomes identified an associated reduction of mortality in favour of the group treated with PbtO2 monitoring (p <.0001). Results from studies examining LOS in ICU have demonstrated an associated increase of LOS in ICU in patients treated with PbtO2‐guided therapy. Conclusion: From the studies included in this review, only two found a statistically significant association between PbtO2 monitoring and long‐term outcomes. It is unclear whether PbtO2 goal‐directed therapy has a positive impact on the long‐term neurological functions and mortality of patients suffering from TBI. A multicentre randomized controlled trial may provide further evidence, but not necessarily conclusive. Relevance to Clinical Practice: Further research is warranted to determine the efficacy of the introduction of this new monitoring system to guide local policy change. [ABSTRACT FROM AUTHOR]

Purpose/Objective: Psychometric network analysis (PNA) is an application of dynamic systems theory that can inform measurement of complex rehabilitation phenomena such as depressive symptom patterns in veterans and service members (V/SMs) after traumatic brain injury (TBI). This study applied PNA to the Patient Health Questionnaire-9 (PHQ-9), a common measure of depressive symptoms, in a sample of V/SMs with TBI at Years 1 and 2 (Y1–2) postinjury. Research Method/Design: A sample of 808 V/SMs with TBI participated, 594 contributing PHQ-9 data at Y1 and 585 at Y2. Participants were recruited while or after receiving inpatient postacute rehabilitation from one of five Veterans Affairs Polytrauma Rehabilitation Centers. Results: The networks were stable and invariant over time. At both times, network structure revealed the cardinal depressive symptom "feeling down, depressed, or hopeless," as evidenced by its strength centrality. In the Y1 network, the suicidal ideation node was connected exclusively to the network through the guilt node, and in the Y2 network, the suicidal ideation node formed a second connection through the low mood node. The guilt node was the second most influential node at Y1 but was replaced by anhedonia node at Y2. Conclusions/Implications: This study demonstrated the potential of PNA in rehabilitation research and identified the primacy of feeling down, depressed, and hopeless after TBI at both Y1 and Y2, with guilt being the second most influential symptom at Y1, but replaced by anhedonia at Y2, providing supportive evidence that the relationships among depressive symptoms after TBI are dynamic over time. Impact and Implications: Psychometric network analysis (PNA) represents a promising avenue for understanding how key rehabilitation variables influence one another, making it a valuable tool for unraveling the complexities of depressive symptoms after traumatic brain injury (TBI) and other psychological phenomena. This study demonstrated the application of PNA by modeling the structure of depression and the relationships among depressive symptoms over time in veterans and service members at 1 and 2 years post-TBI. Findings demonstrated the potential of PNA in rehabilitation research and identified the main symptom of depression after TBI at both time points to be feeling down, depressed, and hopeless, with secondary symptoms that change over time. [ABSTRACT FROM AUTHOR]

Stem cell therapies are progressively redefining the treatment landscape for a spectrum of neurological and age-related disorders. This review discusses the molecular and functional attributes of stem cells, emphasizing the roles of neural stem cells and mesenchymal stem cells in the context of neurological diseases such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson's disease, and Alzheimer's disease. The review also explores the potential of stem cells in addressing the aging process. The paper analyzes stem cells' intrinsic properties of self-renewal, differentiation, and paracrine effects, alongside the importance of laboratory-modified stem cells like induced pluripotent stem cells and transgenic stem cells. Insights into disease-specific stem cell treatments are offered, reviewing both successes and challenges in the field. This includes the translational difficulties from rodent studies to human trials. The review concludes by acknowledging the uncharted territories that warrant further investigation, emphasizing the potential roles of stem cell-derived exosomes and indole-related molecules, and aiming at providing a basic understanding of stem cell therapies. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the potential of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) as biomarkers for diagnosis and prognosis in mild and severe TBI cases, including TBI-related deaths. Methods: This prospective cohort study includes 40 cases each of mild, severe, fatal TBI cases, and 40 healthy controls. Serum samples were collected from live patients at 8 and 20 h post injury for UCH-L1 and GFAP respectively, and from deceased patients within 6 h of death. Results: Elevated levels of both GFAP and UCH-L1 were observed in patients with severe and fatal TBI cases. These biomarkers exhibited promising potential for predicting various Glasgow Outcome Scale Extended (GOSE) categories. Combining GFAP and UCH-L1 yielded higher predictive accuracy both for diagnosis and prognosis in TBI cases. The study additionally established specific cut-off levels for GFAP and UCH-L1 stratified according to the severity and prognosis. Conclusion: GFAP and UCH-L1 individually demonstrated moderate to good discrimination capacity in predicting TBI severity and functional outcomes. However, combining these biomarkers is recommended for improved diagnostic and prognostic utility. This precision tool can enhance patient care, enabling tailored treatment plans, ultimately reducing morbidity and mortality rates in TBI cases. [ABSTRACT FROM AUTHOR]

We present a case of a child with a suprasellar arachnoid cyst and hydrocephalus who developed a massive traumatic epidural hematoma following a fall. This represents the first reported case of such a condition. The case is characterized by a progressive increase in hemorrhage leading to a massive hematoma, yet with relatively mild clinical symptoms. The hemorrhage originated from extensive blood seepage from the dura mater. Intraoperative hemostasis was challenging, and there was a large residual cavity of the epidural hematoma without repositioning of brain tissue after removal of the hematoma. Surgical measures such as extensive continuous compression hemostasis with Surgicel, the half-suspension technique, and continuous external drainage were employed to address these challenges. A second-stage surgery for the treatment of the suprasellar arachnoid cyst was performed 1.5 months after hematoma evacuation, utilizing neuroendoscopic ventriculocisternostomy (VCC). We recommend that for patients with traumatic brain injury and hydrocephalus, especially those with skull fractures or minimal intracranial hemorrhage, relying solely on clinical symptom observation and monitoring is insufficient. Timely and close monitoring with cranial CT is crucial for the early detection of progressive intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

Objective: Morbid hunger and hyperphagia (MHH) is a rare neurological disorder that can manifest following damage to the right frontal and temporal lobes. It can lead to detrimental short and long-term complications such as electrolyte imbalances, obesity, and cardiovascular diseases. This report details the case of a young male patient who developed MHH five months post-traumatic brain injury. Method: Single-case report. The patient exhibited colossal appetite, overeating, food-demanding behavior, and rapid weight gain. The prescription of quetiapine to manage his visual and auditory hallucinations was suspected of exacerbating the hyperphagia. A comprehensive, multidisciplinary rehabilitation approach was implemented, encompassing a meticulous dietary regime, environmental modifications, behavioral management, physical activities, therapeutic exercises, and pharmacological interventions, which included switching the anti-psychotics and introducing low-dose escitalopram. Results: Over the course of 6 months, the MHH gradually subsided, and the patient achieved the target bodyweight. The Glasgow Outcome Scale-Extended improved from 3 to 5. Conclusion: This is the first report on the use of escitalopram to manage secondary eating disorders. Our findings underscore the necessity to formally catalog and recognize disorders like MHH in diagnostic classifications to facilitate the systematic study of their pathophysiology, natural history, prognosis, and management strategies. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between on-road driving remediation and achieving fitness to drive following acquired brain injury. Design: Randomized controlled trial. Setting: Tertiary hospital outpatient driver assessment and rehabilitation service, Australia. Participants: Thirty-five participants (54.3% male), aged 18–65 years, 41 days-20 years post-acquired brain injury (including stroke, aneurysm, traumatic brain injury) recommended for on-road driving remediation following occupational therapy driver assessment were randomly assigned to intervention (n = 18) and waitlist control (n = 17) groups. Intervention: Intervention group received on-road driving remediation delivered by a qualified driving instructor in a dual-control vehicle. The waitlist control group completed a 6 week period of no driving-related remediation. Main measure: Fitness to drive rated following the conduct of an on-road occupational therapy driver assessment with a qualified driving instructor where outcome assessors were blinded to group allocation. Results: The intervention group were significantly more likely to achieve a fit to drive recommendation than no driving specific intervention (p = 0.003). Conclusion: Following comprehensive assessment, individualized on-road driving remediation programs devised by an occupational therapist with advanced training in driver assessment and rehabilitation and delivered by a qualified driving instructor are significantly associated with achieving fitness to drive after acquired brain injury. [ABSTRACT FROM AUTHOR]

Background: The Brain Injury Guidelines (BIG) categorize the severity of Traumatic Brain Injury (TBI). The efficacy of BIG in predicting radiological deterioration and the necessity for neurosurgical intervention remains uncertain, as there is a lack of examination of pooled data from current literature despite validation in numerous single and multi-institutional studies. The aim of this study was to analyze existing studies to determine the diagnostic accuracy of BIG scoring criteria. Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPEROID CRD42021277542). Three databases were searched, and articles published from 2000 to October 2022 were included (last search date: 25 November 2022). Pooled sensitivity and specificity were calculated using random effects meta-analysis. Results: Of the 1130 articles identified, 13 were included in the analysis (9032 patients – 1433 BIG1, 2136 BIG2 & 3189 BIG3). A total of 2274 patients were not classified under either group. Pooled sensitivity for predicting neurosurgical intervention was 1.00 (95%CI:1.00–1.00), and 0.98 for radiological deterioration (95% CI: 0.927–0.996). The specificity in predicting radiological deterioration was 0.18 (95% CI: 0.16–0.21) and 0.05 for neurosurgical intervention (95% CI 0.05–0.05). Conclusions: The BIG score is highly sensitive at excluding TBI cases that do not require neurosurgical intervention; however, BIG-2 and BIG-3 might not be useful for ruling in TBI patients who require neurosurgical intervention. [ABSTRACT FROM AUTHOR]

Withdrawal of life-sustaining therapies (WDLST) in young individuals with traumatic brain injury (TBI) is an overwhelming situation often made more stressful by socioeconomic factors that shape health outcomes. Identifying these factors is crucial to developing equitable and goal-concordant care for patients and families. We aimed to identify predictors of WDLST in young patients with 1-TBI. We hypothesized uninsured payment method, race, and co-morbid status are associated with WDLST. We queried the 2021 Trauma Quality Improvement Program database for patients <45 years with TBI. Patients with WDLST were compared to patients without WDLST. Multivariable logistic regression (MLR) was performed. 61,115 patients were included, of whom 2,487 (4.1%) underwent WDLST. Patients in the WDLST cohort were older (29 vs 27, P <0.001), more likely to suffer from a penetrating mechanism (29% vs 11%, P <.0001), and have uninsured (22% vs 18%) or other payment method (5% vs 3%) when compared to the non-WDLST cohort. MLR identified age (AOR:1.019, 95% CI 1.014 – 1.024, P <.0001), non-Hispanic ethnicity (AOR:1.590, 95% CI 1.373–1.841, P <.0001), penetrating mechanism (AOR:3.075, 95% CI 2.727–3.467, P <.0001), systolic blood pressure (AOR: 0.992, 95% CI 0.990–0.993, P <0.0001), advanced directive (AOR:4.987, 95% CI 2.823–8.812, P <.0001), cirrhosis (AOR:3.854, 95% CI 2.641–5.625, P <.0001), disseminated cancer (AOR:6.595, 95% CI 2.370–18.357, P =0.0003), and interfacility transfer (AOR:1.457, 95% CI 1.295–1.640, P <0.0001) as factors associated with WDLST. Black patients were less likely to undergo WDLST when compared to white patients (AOR:0.687, 95% CI 0.603–0.782, P <.0001). The decision for WDLST in young patients with severe TBI may be influenced by cultural and socioeconomic factors in addition to clinical considerations. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the difference in oculomotor functioning between Olympic-level contact and non-contact sports participants. In total, 67 male and female Olympic-level contact (n = 27) and non-contact (n = 40) athletes completed oculomotor tasks, including Horizontal Saccade (HS), Circular Smooth Pursuit (CSP), Horizontal Smooth Pursuit (HSP), and Vertical Smooth Pursuit (VSP) using a remote eye tracker. No significant differences for sex or age occurred. Each variable indicated higher scores for contact compared to non-contact athletes (p <.05) except for VSP Pathway differences and CSP Synchronization. A logistic regression was performed to determine the degree that HS measures, CSP synchronization, and VSP pathway predicted sport type. The model was significant, χ2(6) = 37.08, p <.001, explaining 57.4% of the variance and correctly classified 88.1% of cases. The sensitivity was 87.5% and specificity was 88.9%. CSP synchronization did not increase the likelihood of participating in a contact sport. This was the first study to identify oculomotor differences between Olympic athletes of contact and non-contact sports, which adds to the growing evidence that oculomotor functioning may be a reliable, quick, real-time tool to help detect mTBI in sport. [ABSTRACT FROM AUTHOR]

Background End-of-life (EoL) decisions are routine in neurosurgical care due to frequent devastating and life-threatening diagnoses. Advance directives, discussions with patients' relatives, and evaluation of the alleged will of the patient play an increasing important role in clinical decision-making. Institutional standards, ethical values, different ethnical backgrounds, and individual physician's experiences influence clinical judgments and decisions. We hypothesize that the implementation of palliative care in neurosurgical wards needs optimization. The aim of this study is to identify possible sources of error and to share our experiences. Methods This is a retrospective observational analysis. One hundred and sixty-eight patients who died on a regular neurosurgical ward between 2014 and 2019 were included. Medical reports were analyzed in detail. A differentiation between consistent and nonconsistent palliation was made, with consistent palliative care consisting of discontinuation of medication that was no longer indicated, administration of medication for symptom control, and consequent discontinuation of nutrition and fluid substitution that went beyond satisfying hunger or thirst. Results EoL decisions were made in 127 (84.1%) of all 168 cases; 100 patients were included in our analysis. Of these patients, only 24 had an advance directive, and the relatives were included in the communication about the therapy goals in 71 cases. Discontinuation of medication that is not for symptom control was performed in 63 patients, food withdrawal in 66 patients, and fluid substitution that went beyond the quenching of thirst was withdrawn in 27 patients. Thus, consistent palliative care was realized in 25% of all patients. The mean duration from the EoL decision until death was 2.1 days (range: 0–20 days). If a consistent palliative care was carried out, patients survived significantly shorter (nonconsistent palliative care: 2.4 days; range: 0–10 days vs. consistent palliative care: 1.2 days; range: 0–4 days; p = 0.008). Conclusions The therapy goal should be thoroughly considered and determined at an early stage. If an EoL decision is reached, consistent palliative care should be carried out in order to limit suffering of moribund patients. [ABSTRACT FROM AUTHOR]

The Response Bias Scale (RBS) is a measure of protocol validity that is composed of items from the Minnesota Multiphasic Personality Inventory − 2. The RBS has been successfully cross-validated as a whole, but the composition of the scale has not been reexamined until recently when three types of items were identified. In this study we sought to examine the reliability of the scale as a whole, as well as the items that are (a) empirically supported and conceptually similar (ES/CS), (b) empirically supported but not conceptually similar (ES/NS), and (c) not empirically supported (NES). Participants included 56 veterans undergoing neuropsychological evaluation for suspected traumatic brain injury. Results generally replicated Ratcliffe et al. finding that removing key NES items improved the internal consistency of the RBS from 0.706 to 0.747. Examined separately, ES/CS and ES/NS had internal consistencies of 0.629 and 0.605, respectively. One of the nine NES items had strong internal consistency, but none of the remaining eight had corrected item-total correlations above 0.194. NES items had an internal consistency of 0.177. Although the RBS is well-validated in detecting non-credible cognitive presentations, it may prove even more valuable after further item refinement whereby items detracting from its reliability and validity are excised. [ABSTRACT FROM AUTHOR]

Targeting single monitoring modalities such as intracranial pressure (ICP) or cerebral perfusion pressure alone has shown to be insufficient in improving outcome after traumatic brain injury (TBI). Multimodality monitoring (MMM) allows for a more complete description of brain function and for individualized management. Transcranial Doppler (TCD) represents the gold standard for continuous cerebral blood flow velocity assessment, but requires high levels skill and time. In TBI, the practical aspects of conducting extended TCD monitoring sessions have yet to be evaluated. Patients with acute moderate-to-severe TBI admitted to the neurocritical care unit between March 2022 and December 2023 receiving invasive ICP measurements were evaluated for inclusion. Exclusion criteria included trauma incompatible with TCD monitoring and if MMM was unwarranted. Daily MMM sessions (in addition to regular monitoring) were performed using TCD (Delica EMS 9D System or the DWL Doppler Box) for ≤5 d. Quantitative and qualitative feasibility, safety, and quality metrics were assessed. Of 74 patients, 36 (75% male; mean age, 44 ± 17 y) were included. Common reasons for exclusion were skull fractures (n = 12) and decompressive craniectomy (n = 9). We acquired 88 recordings (mean, 275 ± 88 min). Overall monitoring times increased, and set-up times decreased. Physiologic variables (including ICP/brain temperature) did not change with TCD application. A single adverse event (dislodging of a microdialysis catheter) occurred. Implementing extended TCD monitoring in MMM protocols is feasible and safe. Considering these results, inclusion of long-term TCD as part of the MMM is strongly encouraged to allow for in-depth description and direct evaluation of hemodynamic changes after TBI. [ABSTRACT FROM AUTHOR]

Objective: To determine whether YTHDF1 and YTHDF3 play the same role in brain and gut damage after traumatic brain injury (TBI). Methods: We generated YTHDF1-/- and YTHDF3-/- mice using CRISPR/Cas9 technology, established a mouse brain injury model through severe controlled cortical impact (CCI), and finally observed the different types of damage between YTHDF1-/- and YTHDF3-/- mice by analysing the levels of oedema proteins in cortical tissue and inflammatory proteins and histopathological lesions in brain and gut tissues in mice at 3 days after CCI. Result: Compared with WT mice, YTHDF1-/- mice had decreased levels of oedema in cortical tissue and inflammation and histopathological lesions in brain and gut tissues at 3 days post-CCI, but YTHDF3-/- mice did not. Conclusion: Our results suggest that deletion of YTHDF1, but not YTHDF3, could reduce damage to the brain and gut following TBI. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a prevalent and debilitating condition, which often leads to the development of post-traumatic epilepsy (PTE), a condition that yet lacks preventive strategies. Biperiden, an anticholinergic drug, is a promising candidate that has shown efficacy in murine models of PTE. MicroRNAs (miRNAs), small regulatory RNAs, can help in understanding the biological basis of PTE and act as TBI- and PTE-relevant biomarkers that can be detected peripherally, as they are present in extracellular vesicles (EVs) that cross the blood–brain barrier. This study aimed to investigate miRNAs in serum EVs from patients with TBI, and their association with biperiden treatment and PTE. Blood samples of 37 TBI patients were collected 10 days after trauma and treatment initiation in a double-blind clinical trial. A total of 18 patients received biperiden, with three subjects developing PTE, and 19 received placebo, with two developing PTE. Serum EVs were characterized by size distribution and protein profiling, followed by high-throughput sequencing of the EV miRNome. Differential expression analysis revealed no significant differences in miRNA expression between TBI patients with and without PTE. Interestingly, miR-9-5p displayed decreased expression in biperiden-treated patients compared to the placebo group. This miRNA regulates genes enriched in stress response pathways, including axonogenesis and neuronal death, relevant to both PTE and TBI. These findings indicate that biperiden may alter miR-9-5p expression in serum EVs, which may play a role in TBI resolution. [ABSTRACT FROM AUTHOR]

Family members frequently provide both physical and emotional support to patients. Previous studies have focused primarily on the experiences of patients with traumatic brain injury (TBI) and their caregivers during home care and the transition from hospital care to the community, with less emphasis on their experiences during acute hospital care immediately after TBI. This study aimed to explore the experiences of caregivers of patients with TBI during acute hospitalizations. A qualitative descriptive study using individual semistructured interviews was conducted at the trauma center of a tertiary hospital in western China. A purposive sample of 21 caregivers of patients with TBI were recruited. The interviews were conducted face to face in the inpatient ward from July to September 2023. Conventional content analysis was used to conduct the framework analysis. The experiences of caregivers were identified within three key themes: TBI consequences in patients (physical impairments, psychological distress, and cognitive dysfunctions), challenges of caregivers (physiological/emotional/economic burdens, conflicts, and concerns regarding recovery), and needs of caregivers (health information, medical services, and recovery expectations). This study highlights the experiences of caregivers of patients with TBI during hospital stays in western China. The challenges faced by caregivers and the needs of caregivers are multidimensional. Appropriate support should be provided to alleviate the burden of caregiving. [ABSTRACT FROM AUTHOR]

Background: Head injuries are the leading cause of trauma in Emergency Departments (EDs). Recent studies have shown epidemiological changes in patients consulting ED for head injuries. The main objective of this study was to describe the profile of head injury patients consulting in the EDs in France and assess i) head injury severity across age groups; ii) the delay between the occurrence of head injury and ED arrival; iii) factors associated with traumatic intracranial hemorrhage (ICH). Methods: This cross-sectional study collected patient data over a three-day period in March 2023. All adult patients (≥ 18 years old) admitted to the ED with a head injury (defined as a trauma to the head) were included. TBI severity was classified according to patients’ initial Glasgow Coma Scale score in the ED: severe (3–8); moderate (9 -12); mild (13–15); and simple head trauma in the absence of transient or persistent neurological symptoms. Results: Among the 71 participating EDs, 26,008 patients visited EDs and a total of 1070 patients (4.1%, IC 95 3.9—4.4) presented a head injury were included in the study, with a median age of 68.5 [37–85] years old. Most of the patients (66.7%) were referred to ED after a call to the Emergency Medical Dispatcher (EMD). The median time from head injury to ED visit was 2 h [1.0 – 5.5]. Ground-level falls were the leading cause of head injury (60.3%). Most of patient presented a simple head trauma (n = 715, 66.8%) followed by mild TBI (n = 337, 31.5%). CT head scans were performed for 636 patients (59.6%), of which 58 were positive. Traumatic ICH prevalence was 5.4% (95% CI: 4.1–6.9) and three patients (0.3%) required an urgent neurosurgical intervention. Neither preinjury anticoagulant (p = 0.97) nor antiplatelet (p = 0.93) use was associated with an increased risk of traumatic ICH. Conclusions: One head injury patient out of two presenting in the ED is aged over 65 years. Patients referred by EMD were more likely to visit ED promptly. The majority of older patients underwent a head CT scan and preinjury anticoagulant use was not associated with increased risk of traumatic ICH. [ABSTRACT FROM AUTHOR]

AbstractPurposeMaterials and methodsResultsConclusions\nIMPLICATIONS FOR REHABILITATIONThe aim of this study was to explore spirituality in inpatient rehabilitation care from the patient’s perspective.Participants were recruited from three inpatient rehabilitation services in Sydney, Australia. A qualitative research design was adopted. Demographic data collected included religious affiliation, age and gender. Participants completed a short survey, where they indicated the level of acceptability for 14 items which could be used in a spiritual history. This was followed by a semi-structured interview where participants discussed how they would like to be asked about spirituality, and by whom.Eighteen participants were recruited (10 females, 8 males; mean age 68.8 years) and were undertaking either general rehabilitation (n = 9) or neurorehabilitation (spinal cord injury n = 6, traumatic brain injury n = 3). The impact of loss and existential struggle was evident for participants with long-lasting injuries. These participants could identify sources of spiritual strength which helped them engage with hardship and described how staff could facilitate access to these sources of strength.Rehabilitation inpatients are willing to explore issues around spirituality. Staff can support inpatients to access sources of spiritual strength by creating a safe and trusting environment and finding out what is most meaningful to the patient.Rehabilitation inpatients can experience losses which lead to a reconsideration of life’s meaning and a greater drawing upon sources of spiritual strength.Spirituality may often be understood to refer to religion only yet can encompass a broader range of connection and experience that relate to the source of a person’s ultimate meaning and purpose.By creating a safe and trusting environment for rehabilitation inpatients, staff can find out what is most meaningful for a person.Rehabilitation inpatients can experience losses which lead to a reconsideration of life’s meaning and a greater drawing upon sources of spiritual strength.Spirituality may often be understood to refer to religion only yet can encompass a broader range of connection and experience that relate to the source of a person’s ultimate meaning and purpose.By creating a safe and trusting environment for rehabilitation inpatients, staff can find out what is most meaningful for a person. [ABSTRACT FROM AUTHOR]

IntroductionMethodsResultsConclusionsCognitive impairment is a highly impactful consequence of traumatic brain injury (TBI) and there are limited evidence-based treatment practices to combat these impairments. Evidence from other populations suggest that aerobic exercise training (AET) is beneficial for a variety of cognitive deficits, but the research in persons with TBI to date is equivocal. One potential reason is the heterogeneity of exercise prescriptions and outcome measures. This stems from the fact that studies have not been designed based on previous data supporting a specific AET prescription to target a cognitive domain. The primary purpose of this cross-sectional analysis was to examine the relationship between cardiorespiratory fitness (CRF), as a cross-sectional surrogate of AET, and cognition in persons with TBI to inform future research.Cross-sectional analysis was conducted on baseline data of persons with TBI who completed neuropsychological assessments to evaluate several cognitive domains and a cardiopulmonary exercise test (CPET) to measure CRF. Based on the normal distribution of an outcome, Pearson’s r or Spearman’s ρ was calculated to measure the relationship between CRF and cognition.Data were analyzed for all participants who demonstrated valid CPETs (n = 21 of 29). Based on the cycle ergometer-based norms of CRF, males in this sample were in the 69th percentile and females in this sample were in the 56th percentile, with high variability across individuals. Higher CRF, as measured by peak power output (Wpeak), was significantly associated with greater working memory (ρ = 0.465, p = 0.017), even after post-hoc corrections.These data suggest average and highly variable CRF in persons with TBI of all severity and support cycle ergometry-based CPET testing in this population. Further, these data provide support for future research applying AET to target working memory and possibly other executive functions in persons with TBI. This research is a small step toward large-scale randomized controlled trials that can directly impact clinical care to treat cognitive symptoms post-TBI. [ABSTRACT FROM AUTHOR]

Background Aims Methods Results Conclusions Trauma‐induced coagulopathy (TIC) is associated with negative outcomes. Pediatric TIC has been described most often in older children. Children undergo normal developmental hemostasis, but it is unknown how this process impacts the risk of TIC across childhood.To understand variations in coagulation testing and TIC across pediatric age groups.We evaluated testing patterns of coagulation studies at presentation and over the first 72 h of hospitalization by pediatric age group at a large, Level I trauma center, 2015–2020. The frequency of TIC was determined using published, age‐specific reference ranges and controlling for injury severity. We performed subgroup analyses of those with isolated severe traumatic brain injury (TBI) and those who presented directly from the scene of injury.Data from 2409 pediatric patients were available; 333 patients had isolated severe TBI. Children <1 year were least likely to be tested for TIC at presentation and over the first 72 h, even among the most injured. Fibrinogen testing was uncommon, regardless of injury severity. TIC was common: 22% of patients had TIC at presentation and 35% by 72 h. Greater injury severity was associated with TIC. Children 1–4 and 5–9 years had a higher frequency of TIC at presentation and over 72 h compared to older children in the least injured cohort. We saw no difference in frequency of TIC between age groups in the subset with isolated severe TBI. Using age‐specific criteria, patients most often met TIC criteria by INR/PT, followed by platelet count, and least commonly by aPTT. The presence of TIC was associated with in‐hospital mortality (OR 4.10, 95% CI 2.06–8.17).Significant sampling bias exists in clinical data collection among injured children and adolescents. Contrary to previous reports and using age‐specific TIC criteria, younger children are not at lower risk of TIC than older children when controlling for injury severity. [ABSTRACT FROM AUTHOR]

Hyperbaric oxygen therapy (HBOT) has recently emerged as a promising neuromodulatory modality for treating several neurological and psychological disorders. Various studies indicate that HBOT can promote brain recovery and neuroplasticity through the modulation of key cellular and molecular mechanisms. HBOT affects multiple primary pathways and cellular functions including mitochondrial biogenesis and function (increased Bcl-2, reduced Bax, and enhanced ATP production), neurogenesis (upregulation of Wnt-3 and VEGF/ERK signaling), synaptogenesis (elevated GAP43 and synaptophysin expression), and anti-inflammatory responses (reduced TNF-a and IL-6). These mechanisms contribute to significant clinical benefits, such as enhanced cognitive function, improved recovery from traumatic brain injury and post-concussion syndrome, and symptom reduction in conditions like post-traumatic stress disorder and fibromyalgia. By influencing these molecular targets, HBOT offers a novel approach to neuromodulation that warrants further exploration. This review discusses the representative mechanisms of action of HBOT and highlights its therapeutic neuromodulatory effects and potential clinical applications across various neurological and psychiatric conditions. [ABSTRACT FROM AUTHOR]