With the aging population, symptomatic chronic subdural hematoma (CSDH) is becoming increasingly prevalent in neurosurgical practice. While burr-hole drainage remains the mainstay treatment, the optimal drilling site remains controversial. This single-center, randomized controlled noninferiority trial aimed to compare frontal versus parietal burr-hole approaches in patients aged ≥18 years requiring surgical drainage for CSDH. Participants were randomized (1:1) via computer-generated allocation to frontal or parietal burr-hole groups, with blinding maintained for patients and staff except operating neurosurgeons. All patients received postoperative atorvastatin combination therapy. Primary outcomes included 6-month recurrence rates (noninferiority margin: 5.0%), with secondary outcomes assessing functional status (modified Rankin Scale [mRS] 4-6), mortality, and complications. From July 2020 to December 2022, 135 of 147 screened patients (92%) were enrolled (frontal: = 67; parietal: = 68), comprising 79% males ( = 107) and 21% females ( = 28). At 6-month follow-up (completed June 2023), recurrence rates were 1.5% (1/67) in the frontal group versus 4.4% (3/68) in the parietal group (difference: -2.9%; 95% confidence interval [CI]: -8.6 to 2.8; = 0.31), meeting noninferiority criteria. Functional outcomes (mRS 4-6: 3.0% vs. 4.4%, = 0.66) and mortality (3.0% vs. 1.5%, = 0.55) showed no significant intergroup differences. Notably, postoperative pneumocephalus volume was significantly lower in the frontal group (11.6 ± 14.8 mL vs. 20.7 ± 20.4 mL; = 0.038). Adverse event rates were comparable between groups, with pneumonia being most frequent (53.7% vs. 55.9%) and surgical complications similarly distributed (6.0% vs. 5.9%). These findings establish noninferiority of frontal burr-hole while demonstrating reduced postoperative pneumocephalus, supporting its clinical preference and warranting future superiority trials. (Trial registration: chictr.org.cn, ChiCTR2000033967).

Spinal cord injury (SCI) is a debilitating condition resulting in the loss of sensorimotor functioning at and below the site of injury. Despite advances in the treatment and management of SCI, there are no current approved pharmacological therapies to augment motor function and functional recovery. NX210c is a 12-amino acid peptide derived from thrombospondin type 1 (TSP1) repeat sequences from the subcommissural organ-spondin protein. TSPs are glycoproteins present in the extracellular matrix, mediating cell-cell and cell-matrix interactions and axon pathfinding. NX210c was previously shown to improve axonal regeneration and functional recovery in thoracic SCI. The aim of this study was to evaluate the ability of NX210c to promote functional recovery and tissue repair in a traumatic cervical SCI rat model. Adult female Wistar rats were subjected to a C6/C7 bilateral clip compression-contusion injury and treated once daily with intraperitoneal injections of NX210c (8 mg/kg) or its vehicle for 8 weeks, beginning 4 h or 8 h post-injury. Administration of NX210c beginning at 4 h post-injury increased forelimb grip strength post-injury and improved several static and dynamic aspects of locomotion, including interlimb coordination. When the first administration was undertaken at 8 h post-injury, NX210c promoted weight gain, improved trunk balance (inclined plane), trended toward accelerated bladder control recovery, and approached significance for skilled reaching at 8 weeks post-injury. Furthermore, for animals that were treated daily with NX210c starting 8 h post-injury, histological analysis demonstrated greater white and gray matter preservation and reduced cavity size, along with the upregulation of neuronal markers. To conclude, NX210c mitigates various aspects of SCI, including motor function and tissue preservation, with preferential results being obtained with the delayed initial administration of NX210c at 8 h post-injury.

Traumatic spinal cord injury (TSCI) is a debilitating disease that results in a heterogeneous set of symptoms. This includes secondary inflammatory mechanisms, which can perpetuate injury to the spinal cord, as well as negatively affect other organ systems. Standard prognostication, such as magnetic resonance imaging, is cumbersome and provides limited resolution; thus, the development of prognostic biofluid tests is of significant clinical importance. The current study systematically reviewed biomarker studies following acute (within 24 h) TSCI. Four databases were searched for this systematic review, PubMed/MEDLINE, Cochrane (OvidSP), Web of Science, and Scopus, resulting in 702 articles to be screened by two independent reviewers. Thirty-two studies met inclusion criteria and were included in the systemic review. About 116 total markers were examined, and 66.4% were found to be associated with TSCI with three major utilities: diagnostic, injury severity, and prognostics. Results generated from the current study highlight discrepancies between biofluids and recommend biomarkers for clinical utility. Future research should associate these acute biomarkers with long-term outcomes using predictive modeling, in addition to curating a clinical TSCI database for optimal prognostication. As TSCI outcomes are variable and impact many systems, the curation of preventative and interventional treatment strategies is crucial.

Recent advancements in machine learning have increased studies predicting neurological outcomes following spinal cord injury (SCI). However, there is limited research on predictive models for bladder and bowel dysfunction outcomes postinjury. This study aims to develop predictive models for bladder and bowel dysfunction outcomes in patients with traumatic SCI and integrate the models into a web application. This study utilized data from 4181 patients with traumatic SCI, registered in the Japan Association of Rehabilitation Database between 1991 and 2015, to develop and validate predictive models. The explanatory variables were categorized into three groups: neurological findings at admission (such as American Spinal Injury Association scores and Functional Independence Measure scores), patient background (including demographics, comorbidities, and insurance status), and SCI pathology (including injury mechanism, vertebral fractures, surgical history, presence of ossification of the posterior longitudinal ligament/OLF, and time to admission). Feature selection was performed using Boruta, excluding features with more than 25% missing values. The target variables were the bladder and bowel functions at discharge, classified into a binary outcome of whether natural urination and defecation were possible. Machine learning models were implemented using PyCaret, and model performance was evaluated using the area under the curve (AUC). Shapley Additive Explanation (SHAP) values assessed the contribution of individual features. A total of 3,949 cases were analyzed, with an average age of 50.3 years. The model with the highest accuracy for predicting bladder function was the gradient boosting model, achieving an AUC of 0.9064 on the test data. For predicting bowel function, the gradient boosting model showed the highest accuracy with an AUC of 0.8714. The top three key predictive factors identified using SHAP values included L3 motor function, time from injury to admission, and the Functional Independence Measure bowel management score, which were common predictors for both bladder and bowel function. The web application of the predictive models can be found at https://takakikitamura-bladder-prediction.hf.space/ and https://takakikitamura-bowel-prediction.hf.space. In conclusion, we developed a predictive model for bladder and bowel dysfunction outcomes after traumatic SCI using machine learning, confirming its high predictive accuracy. Critical predictors included L3 motor function, time from injury to admission, and the degree of bowel dysfunction, all of which were relevant for predicting both bladder and bowel function. These models were made publicly available as a web application.

Although blast-induced traumatic brain injury (bTBI) is considered as the signature injury of recent combat operations such as Operations Iraqi Freedom and Enduring Freedom, no precise biomechanical and biological mechanisms of injury have been identified. Consequently, to date, there are no FDA-approved countermeasures for the treatment of bTBI. Animal models that are highly translatable to humans are required for studying the injury mechanisms underlying bTBI. As a small animal with a gyrencephalic cerebral cortex, the ferret has been increasingly used for studying the mechanisms of neurological disorders in recent years, especially for mechanically induced brain injuries such as traumatic brain injury. In this study, we used a ferret model to understand both biochemical and neurobehavioral outcome measures following closely coupled blast exposure at ∼19 psi. The neurobehavioral battery was used to assess activity and thigmotaxis (open field test), short-term memory (novel object recognition test), motor and gait (CatWalk XT system), and sleep patterns (actigraphy) up to 1 month post-exposure. For biochemical outcome measures, enzyme-linked immunosorbent assays were performed for the estimation of levels of phosphorylated neurofilament heavy chain (pNFH) protein and corticosterone in the serum at 24 h and 1-month post-blast. Western blotting was performed to measure the differential expressions of known biomarkers of brain injury such as pNFH, neurofilament light chain (NFL) protein present in the neurons undergoing degeneration, phosphorylated protein, and glial fibrillary acidic protein at 24-h and 1-month post-blast. The results revealed that blast exposure caused significant anxiety-like behaviors, short-term memory loss, disrupted front and hind limbs movements, and disturbed sleep pattern in a time-dependent manner. Levels of both pNFH and corticosterone increased in the plasma post-blast. Western blotting revealed that blast exposure increased the levels of the biomarker proteins evaluated in different brain regions. Overall, we observed changes in biochemical and neurobehavioral outcomes after blast exposure that together suggest that ferret is a potentially valuable animal model for understanding the mechanism of bTBI and developing effective countermeasures.

The Blast Exposure Threshold Survey (BETS) is a recently developed measure of lifetime blast exposure. Although promising, it is considered a fundamental tenet to establish that the BETS (and other measures like it) have good psychometric properties before it can be recommended for clinical use. The purpose of this study was to examine the test-retest reliability of the BETS in a military sample. Participants were 83 United States service members and veterans prospectively recruited from three military medical treatment facilities and from the community. Participants were classified into two broad groups as part of a larger study: traumatic brain injury (TBI; = 41; mild-severe TBI) and controls ( = 42; injured and non-injured controls). Participants completed the BETS, Neurobehavioral Symptom Inventory, and a brief structured interview to gather basic demographic, military, and injury-related information (e.g., age, education, deployments, etc.). In addition, participants completed the BETS on a second occasion (T2) 3 weeks following the first administration (T1). Using Spearman rho correlation analyses, the test-retest reliability of the BETS Generalized Blast Exposure Value (GBEV) was classified as "acceptable" ( = 0.76). However, when comparing individual responses across T1 and T2, 33% of the sample reported significant inconsistencies in the endorsement of the five weapons categories. The most problematic inconsistency (∼10% of the sample) related to the failure of some participants to consistently endorse, or not endorse, exposure to a weapons category at T1 and T2 (e.g., T1 = exposure present; T2 = exposure absent). Less problematic, but also of concern, was the failure of some participants (∼23%) to consistently report the same number of years in which they were exposed to a weapons category from T1 and T2 (e.g., T1 = 10 years; T2 = 5 years). Factors associated with inconsistent reporting from T1 to T2 included higher GBEV scores, older age, higher number of years in the military, higher number of deployments, and higher blast exposure. This is one of the first studies to comprehensively examine the test-retest reliability of the BETS GBEV. Overall, the test-retest reliability of the GBEV was considered statistically acceptable and provides support for the use of the GBEV in both clinical and research settings. Concerningly, however, substantial inconsistencies were found in the basic reporting of weapons exposure in 33% of the sample that need to be addressed. Future researchers should identify ways to improve the BETS to increase response consistency over time.

Intimate partner violence (IPV) is a serious and prevalent problem affecting approximately one in three women globally. Physical IPV can involve non-fatal strangulation (NFS), which can result in an acquired brain injury (ABI), inferred by an alteration in consciousness (AIC). However, there is limited research pertaining to NFS-related ABIs, especially in the context of understanding long-term outcomes. We examined neurobehavioral and traumatic stress symptoms associated with a past history of IPV-related strangulation, focusing on the presence of strangulation and the presence and type of a strangulation-related AIC. A sample of 139 women aged 18 years and older (mean = 40 years) was recruited via flyers shared with community partners (e.g., domestic violence advocates) as well as online advertisements and social media. Assessments included the Brain Injury Severity Assessment, Ohio State University Traumatic Brain Injury Identification Method, revised Conflict Tactics Scale, Neurobehavioral Symptom Inventory, and Post-traumatic Stress Disorder (PTSD) Checklist for the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), the PCL-5. Multivariable linear and ordinal logistic regression models were used to examine the association between strangulation history and neurobehavioral and traumatic stress symptoms. The average time since the most recent strangulation was 8.7 years. Women who experienced strangulation reported greater levels of self-reported vision problems ( < 0.01) and traumatic stress symptoms ( < 0.05) than women who were not strangled, although only vision problems remained significant ( < 0.01) after adjusting for confounders. Women who sustained an AIC during strangulation reported higher levels of current traumatic stress symptoms, dizziness, vision problems, and poor concentration ( < 0.05; < 0.05; < 0.01; < 0.01, respectively) in comparison with women who were strangled but did not sustain a related AIC; after adjusting for confounders, vision problems remained significant ( < 0.01). Women who specifically sustained a loss of consciousness (LOC) compared to another type of AIC, reported higher levels of traumatic stress symptoms ( < 0.05), even after adjusting for potential confounders. We found that long after the most recent IPV-related strangulation event, the presence of strangulation, strangulation-related AIC, and strangulation-related LOC were associated with a range of neurobehavioral symptoms and traumatic stress symptoms. However, after adjusting for potential confounders, strangulation and strangulation-related AICs were associated with self-reported vision problems, and strangulation-related LOC was associated with traumatic stress. This study highlights the potential long-term consequences of IPV-related strangulation and reinforces the importance of IPV prevention and providing treatment for these women in need.

Neurogenic lower urinary tract dysfunction (NLUTD) is a major cause of morbidity and reduced quality of life after spinal cord injury (SCI). In pre-clinical research, small and large animal models such as rats, dogs, and minipigs have been used to investigate NLUTD through urodynamic studies (UDS) such as conventional filling cystometry. Although filling cystometry is currently considered the gold standard for bladder monitoring in pre-clinical research, this approach has several well-recognized limitations. The aim of this study was to develop and evaluate the feasibility of an implantable, radiotelemetric system for monitoring bladder pressure in a Yucatan minipig model of SCI. The transmitter was surgically implanted in the dome of the bladder and several UDS experiments were conducted to evaluate the system's effectiveness at measuring pressure compared to conventional UDS equipment. We observed a strong correlation and agreement between the transmural telemetry sensor and the UDS system. There was no significant difference between bladder compliance and baseline bladder pressure between the two sensor systems. However, the telemetry system recorded significantly lower voiding and non-voiding contraction pressure amplitudes as well as lower voiding threshold pressures and detrusor after-contraction measured with the telemetry system. The telemetry system appeared to be a reliable and accurate method for assessing bladder pressure and allowed for an evaluation of urodynamics in a pig model of SCI for several months. The application of this method could enable a more detailed in vivo evaluation of NLUTD after SCI and a better understanding of micturition behavior during natural-filling, ambulatory urodynamics.

Traumatic brain injury (TBI) is a major health problem worldwide. Approximately 2.8 million people in the United States sustain a TBI each year, the majority of which can be classified as mild TBI (mTBI) or concussive injuries. Although mTBI may not cause overt brain damage, it triggers many cellular and molecular changes in brain cells, resulting in neurological, cognitive, and behavioral impairments. Metabolites are released in response to mTBI and can serve as diagnostic markers, as well as potentially contributing to ongoing pathophysiological changes. N-formylmethionine (fMet) is used as the first amino acid for protein synthesis in mitochondria, bacteria, and chloroplasts. Both formylated peptides and free fMet have been detected in human plasma. While a number of studies have demonstrated that formylated peptides can activate the innate immune response, less is known about the role of free fMet in health and disease. In this study, we quantified the free fMet concentration in plasma samples obtained from persons who have sustained an mTBI and compared it with the plasma concentrations detected in healthy volunteers. Our results show that the plasma levels of fMet increased within 24 h of a documented mTBI in both males and females. Receiver operator characteristic (ROC) analysis indicated that the acute change in plasma fMet (<48 h after an injury) has an area under ROC (AUROC) of 0.82 in identifying an mTBI. Interestingly, when fMet was measured in plasma samples collected from these patients 3 months later, it remained elevated and had an AUROC of 0.88. The systemic administration of fMet to mTBI mice impaired brain mitochondrial function, suggesting that it may affect ongoing mTBI pathophysiology.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI). In CTE, hyperphosphorylated tau (p-tau) aggregates are found in neurons at the depth of cortical sulci close to the gray matter/white matter (GM/WM) boundary. To date, CTE can only be diagnosed postmortem by neuropathological examination. Traumatic encephalopathy syndrome (TES) is the clinical syndrome purported to be associated with CTE pathology. The aim of this study is to investigate microstructural properties at the GM/WM boundary in individuals with a history of exposure to RHI and clinical features of CTE (i.e., TES). Diffusion magnetic resonance imaging (dMRI), TES diagnoses, and cerebrospinal fluid (CSF) biomarkers were acquired from 165 male former American football players (age: 57.29 ± 8.23 years) from the DIAGNOSE CTE Research Project, a multicenter, observational cohort study. Fractional anisotropy (FA) was measured at the GM/WM boundary of the whole brain. In addition, a widely used method (tract-based spatial statistics [TBSS]) was applied to measure FA of central WM. We used analyses of covariance to test associations between FA and TES. Furthermore, we used linear regressions to test associations between FA and nine CSF biomarkers (i.e., p-tau-181, -217, -231, total tau, amyloid β [Aβ], Aβ, glial fibrillary acidic protein [GFAP], neurofilament light [NfL], and soluble triggering receptor expressed on myeloid cells-2 [sTREM2]). We report an association between higher FA at the GM/WM boundary and higher levels of certainty for CTE pathology ((1, 147) = 5.781, 95% confidence interval (CI) = 0.0003-0.003, = 0.035) as well as neurobehavioral dysregulation ((1, 148) = 7.559, 95% CI = 0.001-0.009, = 0.020), and functional dependence/dementia ((1, 148) = 5.046, 95% CI = 0.0004-0.006, = 0.039). In addition, we report an association between higher FA at the GM/WM boundary and higher CSF p-tau-181 (β = 0.272, 95% CI = 0.078-0.466, = 0.029) and p-tau-217 (β = 0.295, 95% CI = 0.102-0.488, = 0.027). FA of the central WM was not associated with TES diagnoses. Taken together, these findings suggest that dMRI at the GM/WM boundary could be used to investigate microstructural alterations suggestive of tau pathology-associated neurodegeneration in individuals with TES, the clinical presentation of CTE. Future studies are needed to validate this approach and to identify clinically useful cutoff values for dMRI metrics.

In 2023, the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest Group (ACRM BI-ISIG) Mild Traumatic Brain Injury (TBI) Task Force published updated diagnostic criteria for mild TBI. These criteria were developed in collaboration with a panel of 32 subject matter experts in mild TBI using the Delphi method. The 2023 ACRM diagnostic criteria marked the first update since 1993, incorporating three decades of research advancements in our understanding of mild TBI. To facilitate the consistent use of the new diagnostic criteria, the ACRM BI-ISIG Mild TBI Task Force initiated a special project in September 2023 to develop a structured interview to apply the ACRM diagnostic criteria for mild TBI in clinical and research settings. The purpose of this article is to describe the development of the ACRM Structured TBI Interview and the accompanying documents. The ACRM Structured TBI Interview was developed in four phases: (1) initial development of a draft interview by two project leads, (2) review and revision over three rounds by 17 members of the ACRM BI-ISIG Mild TBI Task Force, (3) external review by 19 subject matter experts in mild TBI, and (4) field testing of the ACRM Structured TBI Interview by 11 interviewers who completed 25 diagnostic interviews. In addition to the ACRM Structured TBI Interview, three other documents were developed to help facilitate the administration of the interview (Administration Guide) and to apply the diagnostic criteria (Diagnostic Coding Form and Diagnostic Flow Diagram). A Short Form was also developed for use in contexts where administering the full structured interview is not feasible due to time constraints.

Secondary loss of initially spared white and grey matter is a major driver of morbidity after spinal cord injury (SCI). Current treatments have not substantially changed in decades and are limited to surgical decompression and blood pressure management. White matter atrophy after SCI is primarily caused by secondary axonal degeneration (SAD), which is triggered by maladaptive axonal uptake of sodium and calcium through a multitude of ion channels and transporters. While specific inhibitors have been studied, none have been translated into clinical use, in part due to the diverse array of involved channels. Here, we studied whether amiodarone, an FDA-approved antiarrhythmic drug that exerts pleotropic inhibition of multiple sodium and calcium channels, might be neuro- and axonoprotective after SCI precisely because of its broad inhibitory profile. Mice were submitted to off-midline thoracic SCI versus sham surgery and treated with amiodarone versus vehicle control within 15 min and after 4 h of injury. We found that amiodarone treatment after SCI improved locomotor function, which was longitudinally measured over 28 days with the Basso mouse scale, accelerating rotarod, and inclined plane tests. Amiodarone treatment reduced spinal cord atrophy and white matter loss at 28 days after injury, assessed by spinal cord wet weights and by volumetric measurements of grey and white matter in serial coronal sections of spinal cords stained with luxol fast blue and cresyl violet. Amiodarone was directly axonoprotective after SCI, with reduced losses of neurofilament heavy positive axons at 28 days. Interestingly, long-term amiodarone-mediated axonoprotection was accompanied by a reduction of SAD at early time points, measured by counting axonal spheroids 24 h after SCI in fluorescently labeled corticospinal tract axons imaged with light sheet imaging. Overall, these data identify amiodarone as a potentially axonoprotective agent that could be repurposed to treat secondary injury after SCI.

Community reintegration serves an integral role to enhance veterans' quality of life as they transition to civilian life. Unsuccessful reintegration after military separation may contribute to the relative increase in adverse outcomes such as homelessness and suicide in this population. Mild traumatic brain injury (TBI) has been linked to poor mental health, which, in turn, may compromise community reintegration; however, little is known about how the characteristics of mild TBI may impact community reintegration either directly or indirectly. The objectives of this study are to: (1) evaluate the association of the characteristics of mild TBI, including blast versus nonblast mechanism and combat versus noncombat deployment (i.e., outside of combat deployment) setting on community reintegration; (2) determine whether this association varies by the level of perceived social support; and (3) explore the potential mediation effect of mental health symptom levels. This cross-sectional analysis used data from the Long-term Impact of Military-relevant Brain Injury Consortium Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) Prospective Longitudinal Study on 2,177 service members and veterans (SMVs) who were registered for clinical care at a Department of Defense and/or Veterans' Affairs Medical Facility. The exposure of interest was the characteristics of each mild TBI, including from blast/nonblast mechanism, combat deployment/noncombat deployment setting, or lack of any lifetime mild TBI. The outcome was community reintegration measured by the Community Reintegration of Injured Service Members survey. Perceived social support was measured using the Deployment Risk & Resilience Inventory-2 Post-deployment Social Support Scale. Mental health symptoms (post-traumatic stress and depressive) were evaluated using the post-traumatic stress disorder checklist, DSM-5, and the Patient Health Questionnaire-9, respectively. Community reintegration among SMVs who sustained mild TBI(s) only with a nonblast mechanism outside of a combat deployment was better compared with those sustaining mild TBI(s) during a combat deployment or by blast mechanism. Those with no mild TBI history had a similar level of community reintegration as those who sustained nonblast mild TBI(s) outside of combat deployment. The level of perceived social support did not significantly alter these relationships; however, inclusion of variables to account for mental health symptoms in the models attenuated the results to nonsignificance, supporting potential mediation by mental health symptoms. This study found mild TBI sustained during combat deployment (either blast or nonblast mechanism) may be a risk factor for poor community reintegration. These results support clinical care processes that include identifying SMs with sustained mild TBI during combat deployment (particularly those with blast mechanism) for targeted interventions that may facilitate transition into the community. Future studies are needed to evaluate the mechanism through which mild TBI sustained during combat deployment for both blast and nonblast type injuries may impact community reintegration.

Traumatic brain injury (TBI) results from a primary injury that impacts the brain in a spatially dependent manner. In this study, we investigated the topographical relationship of early transcriptional responses to a single, focal TBI in mice by controlled cortical impact. Guided by the presence of the anterior commissure (AC) in coronal sections at the rostro-caudal point of impact, we compared gene expression changes in the neocortex (CTX) and corpus callosum-external capsule (CC-EC), striatum (STR), and AC. Injury-induced gene expression changes were detected in the CTX, CC-EC, and STR but not AC and were principally segregated based on cytoarchitecture and secondarily by proximity to the site of impact. In addition, unbiased spatial clustering revealed a positive relationship between proximity to the impact and the number of acutely differentially expressed genes within the laminar CTX. Gene pathways for interferon gamma response and for leukocyte-mediated migration and immunity were acutely enhanced across the injured CTX, CC-EC, and STR. Within 1 week post-injury, transcriptional responses to injury in the CTX and CC-EC included gene pathways for adaptive T- and B cell mediated immunity, whereas gene expression changes in the STR were largely resolved. Next, we examined the effects of systemic depletion of neutrophils and monocytes on spatial gene expression changes in the injured brain. The systemic depletion and attenuated infiltration of these immune cells into the damaged brain post-injury led to the upregulation of gene pathways functioning in synaptic transmission and an alternating down- and then upregulation of genes functioning in ribosomal messenger RNA translation and aerobic metabolism in mitochondria. These data suggest that infiltrating neutrophils and monocytes play an evolving, multifaceted role in modulating the metabolic, transcriptional, and synaptic activity of brain tissue post-injury.

Traumatic brain injury (TBI) remains a global health challenge, with computed tomography serving as the primary diagnostic tool for initial evaluation. However, significant variability exists in repeat computed tomography (CT) scanning protocols, ranging from routine scheduled imaging to selective approaches based on clinical deterioration. This systematic review synthesized evidence from 1247 initially identified records, ultimately including 26 studies that met inclusion criteria, to determine optimal timing strategies for repeat CT scanning in patients with TBI. The analysis revealed dramatic heterogeneity in hemorrhagic progression rates (0.4-65%) and intervention requirements across studies, largely explained by differences in TBI severity. Patients with mild TBI (Glasgow Coma Scale [GCS] 13-15) demonstrated consistently lower progression rates (0.4-42%), intervention rates (0.13-0.9%), and mortality (0.13-1.2%) compared with moderate-severe TBI cohorts, which exhibited progression rates of 42.3-61%, intervention rates of 8.9-24%, and mortality of 13-18%. Critical temporal patterns emerged, with Fletcher-Sandersjöö demonstrating that 94% of hematomas ceased progressing within 24 h postinjury, establishing a crucial surveillance window. Multiple predictors of progression were identified, including concomitant intracranial lesions (subarachnoid hemorrhage odds ratio [OR] 3.28, subdural hemorrhage OR 4.35), advanced age, and antiplatelet therapy. Notably, patients undergoing initial CT scanning within 2-3 h postinjury showed higher rates of subsequent progression, suggesting that early scans warrant scheduled follow-up regardless of clinical status. These findings support severity-stratified approaches to repeat imaging, with routine protocols potentially justified in moderate-severe TBI, while selective strategies may be appropriate for patients with stable mild TBI. The evidence emphasizes balancing diagnostic yield against radiation exposure concerns, advocating for personalized protocols based on individual risk factors rather than universal approaches.

Acute brain injury (ABI) is a severe neurological disorder in which inflammation and immune responses play a key role, with the Triggering Receptor Expressed on Myeloid Cells-1 (TREM1) being involved. Inhibition of TREM1 can alleviate neuroinflammation and damage, but the evidence from these pre-clinical studies remains unclear. This study summarizes and evaluates the results of animal experiments on the treatment of ABI with the TREM1 inhibitor LP17, exploring the effects of using LP17 to treat ABI animal models on neurological function, inflammatory indicators, and brain barrier function. As of April 30, 2025, this review conducted a detailed search of eight databases for studies on LP17 in ABI animal models. It performed a systematic review and meta-analysis of the included studies. The literature was independently screened, and data were extracted and assessed. RevMan 5.4 software was used for the meta-analysis. Compared with controls, the TREM1 inhibitor LP17 significantly reduced brain water content (standardized mean difference [SMD]: -1.36; 95% confidence interval [CI]: -1.77, -0.94; < 0.00001) and neurological deficit scores (SMD: -1.37; 95% CI: -1.76, -0.97; < 0.00001). It also decreased the expression of pro-inflammatory cytokines, including IL-1β (SMD: -1.88; 95% CI: -2.63, -1.13; < 0.00001) and TNF-α (SMD: -2.91; 95% CI: -3.89, -1.92; < 0.00001). LP17 mitigated blood-brain barrier (BBB) disruption (SMD: -1.58; 95% CI: -2.47, -0.68; = 0.0005) and enhanced ZO-1 expression (SMD: 2.77; 95% CI: 1.73, 3.80; < 0.00001). It also inhibited the activation of nuclear factor-κB (SMD: -1.70; 95% CI: -2.58, -0.83; = 0.0001), NLRP3 (SMD: -2.33; 95% CI: -3.27, -1.39; < 0.00001), and Caspase-1 (SMD: -2.03; 95% CI: -2.92, -1.14; < 0.00001). LP17 has neuroprotective effects in ABI animal models, likely through reducing neuroinflammation, preserving BBB integrity, and inhibiting apoptotic pathways. Further studies are needed to explore its mechanisms to better guide clinical use.

The family environment plays an important role in children's recovery from traumatic brain injury (TBI); however, parental and family factors have not been examined in-depth in pediatric mild TBI (mTBI). Existing research on postconcussive symptoms (PCS) typically employs conventional statistical analyses that assume that children with mTBI are a homogenous group. However, children may display distinct trajectories of PCS across time after mTBI. Group-based multitrajectory modeling can identify latent clusters of individuals following similar trajectories across multiple indicators of an outcome. This study sought to: (1) identify trajectories of PCS after mTBI in children, and (2) examine their association with parental and family functioning. Participants were 506 children and adolescents aged 8- to 16-years-old who were recruited during emergency department (ED) visits within 48 h of injury at five Pediatric Emergency Research Canada hospitals. Injury information was collected in the ED, and parental and family functioning was measured at approximately 7 days postinjury. Child and parent PCS ratings were obtained weekly to 3 months and biweekly to 6 months postinjury using the Health and Behavior Inventory. Parental and family functioning were assessed using validated measures of family functioning, parental adjustment, perceived social support from parents, and parental responses to children's symptom complaints. Group-based multitrajectory modeling was used to classify individual children into distinct trajectories of child- and parent-reported cognitive and somatic PCS over time and to examine predictors of those trajectories. Six distinct trajectories were identified: "low acute/resolved PCS" ( 98), "low acute/declining PCS" ( = 64), "moderate acute/elevated cognitive PCS" ( = 106), "moderate acute/declining PCS" ( = 118), "high acute/declining PCS" ( = 88), and "high acute/persisting PCS" ( = 32). Parental adjustment, protectiveness, and social support were independent predictors of trajectory membership after adjusting for demographic and injury characteristics. The identification of different symptom trajectories and specific aspects of parental and family functioning as predictors of these trajectories provides guidance for developing family-based treatments and targeting treatments to children at risk for poor recovery.

After a traumatic brain injury, around 12% of patients require surgical interventions during their index hospitalization due to delayed or progressive intracranial hemorrhage or complications such as elevated intracranial pressure (ICP). Compiling data from four harmonized studies with 288 patients that have high-frequency physiological measurements, including ICP, we aimed to determine factors associated with those surgeries and whether longitudinal physiological measurements could be used to predict the need for craniectomy or craniotomy at least 1 h before the surgery occurred. The outcome was the occurrence of the first cranial surgery 6-120 h post-injury with 2:1 matched controls for those without surgery. Covariates included baseline characteristics and dynamic physiological measurements. Univariate associations were assessed, and the area under the receiving operating characteristic curve (AUC) was used to compare various machine learning and multivariable statistical models for the prediction of surgery. It was found that means, medians, and transgressions of both ICP and mean arterial pressure, as well as the linear regression slope of ICP by time in the 6 h prior to surgery, were significantly and independently related to whether a patient had cranial surgery or not. The best-performing model was found using random forests supervised learning algorithm (AUC = 0.75, 95% confidence interval 0.61-0.88). This model may assist clinicians in predicting when they may need to perform an emergent neurosurgical procedure, thus preventing more damage from elevated ICPs.

Traumatic brain injury (TBI) is common, disabling, and a growing public health concern. There are limited large-scale studies providing insight into factors associated with recovery in the general TBI population. Our aim was to identify factors associated with concussion/TBI symptom severity and return-to-work. We performed a prospective cohort study of concussion/TBI (predominantly mild to moderate) patients with data collected over a 20-year period (1998-2018). This is the first study presenting data from the Sunnybrook TBI (SUNTBI) cohort. Primary outcome at approximately 3-month postinjury was the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), and secondary outcome was return-to-work. Outcomes were analyzed using multivariable linear regression and logistic regression models, respectively. There were 2924 TBI patients included in the study. General Health Questionnaire (GHQ), a screening measure of current psychiatric symptoms, and all its subscales (depression, anxiety, somatic, and social) ( < 0.0001), and active litigation ( < 0.001) were significantly associated with higher RPQ scores. Notably, factors related to injury characteristics and severity were not (e.g., injury mechanism, TBI severity, and neuroimaging abnormalities). For return-to-work, having a professional occupation ( < 0.001) was significantly positively associated with return, while abnormal CT scan ( = 0.001), admission to hospital ( < 0.001), and higher GHQ score ( < 0.001) were negatively associated. In one of the largest observational studies of general population concussion/TBI patients to date, we found that psychiatric symptoms and litigation status were significantly associated with symptoms at 3 months, while factors related to the injury severity were not. We also observed a decoupling of factors that impact symptom score outcomes from return-to-work outcomes. These results have important implications for the management of at-risk TBI subpopulations and wider public policy considerations.

The increasing use of artificial intelligence-driven chatbots for medical queries requires a systematic evaluation of their accuracy, reliability, and potential role in patient education. This study assesses the performance of three widely used chatbots-ChatGPT, Google Gemini, and Microsoft CoPilot-in answering patient-oriented questions related to traumatic brain injury (TBI). A standardized set of questions related to TBI was developed, divided into eight subtopics, and presented to each chatbot using unified prompts. The responses were evaluated together with reference answers prepared by experts from a group of specialists in the fields of neurology, neurosurgery, and neurorehabilitation, and subsequently assessed in a survey of patients undergoing rehabilitation for TBI. Performance was evaluated using a modified scoring framework in five key dimensions of quality. Statistical analysis included multivariate analysis of variance to compare chatbot performance and logistic regression analysis to determine the likelihood of chatbot responses being considered an adequate substitute for expert advice. Significant differences between the chatbots were found in several quality dimensions, with ChatGPT scoring higher than Gemini and CoPilot on reliability, responsiveness, and perceived trustworthiness ( < 0.05). No chatbot consistently demonstrated an advantage in conveying empathy. Logistic regression analysis revealed that responses from ChatGPT were significantly more likely to be rated as an adequate substitute for expert input ( < 0.0001, OR = 4.3, 95% CI: 2.4-7.6). AI-driven chatbots vary in their ability to provide high-quality medical information, with significant differences in reliability and responsiveness. While ChatGPT outperformed other models in providing structured information, further improvements in context awareness and empathy are needed before broader clinical integration can be considered.