J. Neurotrauma [JOURNAL]
Sun
200 papers
The Evolving Role of Neuroimaging in Traumatic Brain Injury Research.
Dennis EL, Keleher F, McCabe C … +2 more , Tate DF, Wilde EA
J Neurotrauma · 2026 Mar · PMID 41449717 · Publisher ↗
Neuroimaging technologies such as computed tomography and magnetic resonance imaging (MRI) have been widely adopted in the clinical diagnosis and management of traumatic brain injury (TBI), particularly at the more acute...
Neuroimaging technologies such as computed tomography and magnetic resonance imaging (MRI) have been widely adopted in the clinical diagnosis and management of traumatic brain injury (TBI), particularly at the more acute and severe levels of injury. Additionally, a number of advanced applications of MRI have been employed in TBI-related clinical research with great promise, and researchers have used these techniques to better understand the underlying mechanisms, progression of secondary injury and tissue perturbation over time, and relation of focal and diffuse injury to outcome. However, the acquisition and analysis time, the cost of these and other imaging modalities, and the need for specialized expertise have represented historical barriers in extending these tools in clinical practice. While group studies are important in detecting patterns, heterogeneity among patient presentation and limited sample sizes from which to compare individual-level data to well-developed normative data have also played a role in the limited translatability of imaging to wider clinical application. Fortunately, the field of TBI has benefited from increased public and scientific awareness of the prevalence and impact of TBI, particularly related to recent military conflicts and sport-related concussion. This awareness parallels an increase in federal funding in the United States and other countries allocated to investigation in these areas. In 2025, funding for TBI research in the United States is less certain due to the changing administrative priorities, so we hope this article can highlight the incredible productivity of the TBI neuroimaging research community. In this article, we summarize funding and publication trends since the mainstream adoption of imaging in TBI to elucidate evolving trends and priorities in the application of different techniques and patient populations. A total of 4872 articles over 82 years are categorized. We also review recent and ongoing efforts to advance the field through promoting reproducibility, data sharing, big data analytic methods, and team science. Finally, we discuss international collaborative efforts to combine and harmonize neuroimaging, cognitive, and clinical data, both prospectively and retrospectively. Each of these represents unique, but related, efforts that facilitate closing gaps between the use of advanced imaging solely as a research tool and the use of it in clinical diagnosis, prognosis, and treatment planning and monitoring.
Effect of Two Glasgow Outcome Scale-Extended Scoring Methods on Traumatic Brain Injury Clinical Trial Design: A TRACK-TBI Study.
Temkin N, Barber J, Machamer J … +9 more , Boase K, Hwang P, Bodien YG, Giacino JT, McCrea MA, Nelson LD, Manley G, Dikmen S, TRACK-TBI Investigators
J Neurotrauma · 2025 Dec · PMID 41449672 · Publisher ↗
The Glasgow Outcome Scale-Extended (GOSE) is the most frequently used outcome measure for traumatic brain injury (TBI) clinical trials. The GOSE may be administered several ways, the choice depending on the purpose of th...
The Glasgow Outcome Scale-Extended (GOSE) is the most frequently used outcome measure for traumatic brain injury (TBI) clinical trials. The GOSE may be administered several ways, the choice depending on the purpose of the research. For example, the GOSE can be administered to reflect functional limitations attributed to the overall injury, including extracranial injuries (GOSE-All), or to discount limitations attributed to extracranial injuries (GOSE-TBI). In this investigation, we assessed the effect of using GOSE-All versus GOSE-TBI in clinical trial design. We estimated the impact of the differences in assessment strategy on sample size and power for a clinical trial of an intervention that affects only TBI-related limitations. Inclusion criteria based on TBI severity and extracranial injury severity were examined, as were primary assessments at 2 weeks or 3, 6, or 12 months after injury. Data from 2,288 participants in the prospective observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study were used to simulate the effects. If the trial were analyzed by a Mann-Whitney test comparing GOSE-All scores between treatment groups, sample size would need to increase 8-158% to account for the apparent decreased effect of a treatment that affects only the brain injury. If the sample size were not adjusted, power to detect a treatment effect would decrease from 80% to as low as 41%. If the outcome were dichotomized (favorable=GOSE 8 if including only patients with Glasgow Coma Scale [GCS]=13-15, GOSE 5-8 if GCS = 3-12), the sample size would need to increase 6-165%. The ratios of sample size are largest when the trial population consists of people with milder brain injuries and decrease with time since injury in those with GCS 13-15. It is crucial for researchers, given the aims of their studies, to decide in advance whether the classification of the GOSE should be based on effects attributed to the brain injury, despite the fact that extracranial injuries may not have allowed one to experience the extent of limitation due to the TBI, or all injuries, including extracranial injuries, and to power their studies accordingly. Instructions to the respondent and outcomes examiner need to be clear about what causes of disability are to be included. The assessment method should be accounted for in the power and sample size calculations, clearly indicated in the protocol and publications and documentation accompanying shared data, and emphasized in the training of the outcome examiners so all are collecting the desired information.
Dynamic Glasgow Coma Scale Trajectories Improve Mortality Prediction in Traumatic Brain Injury: A Multicenter Intensive Care Unit Cohort Study.
Wang J, Li HB, Xu MM … +5 more , Li WJ, Cheng LY, Li SY, Hang CH, Zhao PL
J Neurotrauma · 2025 Dec · PMID 41449136 · Publisher ↗
Traumatic brain injury (TBI) is a leading cause of death and disability. While the Glasgow Coma Scale (GCS) guides initial assessment, single values miss evolving neurological change. In this multicenter ICU cohort integ...
Traumatic brain injury (TBI) is a leading cause of death and disability. While the Glasgow Coma Scale (GCS) guides initial assessment, single values miss evolving neurological change. In this multicenter ICU cohort integrating NSICU, MIMIC-IV, and eICU databases, we analyzed adults (≥18 years) with TBI who had ≥3 GCS measurements within the first 120 ICU hours. Using 12-hourly measures, latent class growth modeling identified four dynamic GCS trajectories (Stable High, Rapidly Improving, Persistently Moderate, Persistently Low), and we quantified cumulative neurological burden with a mean threshold-based area-under-the-curve (TBM-AUC) summarizing time above prespecified GCS thresholds. Among 3,132 patients, mortality increased monotonically across trajectories, highest in the Persistently Low group (adjusted hazard ratio [HR] 4.95, 95% confidence interval: 3.14-7.81 vs. Stable High). Lower TBM-AUC was strongly associated with mortality; most pronounced at threshold 13 (HR 0.34). Age-stratified analyses showed a trajectory-by-age interaction ( = 0.013), with Persistently Low conferring the greatest risk in both younger and older adults. Adding trajectory class to baseline predictors improved discrimination (AUC: 0.820-0.861, < 0.001) with consistent gains in integrated discrimination improvement, net reclassification improvement, and median risk score across Boruta-, LASSO-, and best-subset-based models. Dynamic GCS trajectories and TBM-AUC provide prognostic information beyond conventional assessments and may enhance risk stratification and clinical decision-making in neurocritical care; prospective validation is warranted. [Figure: see text].
Spinal Cord Injury Disrupts Inflammatory Signaling and Impairs Skin Wound Healing: Evidence from Two Models of Decubitus Ulcers.
Marbourg JM, Vadala CP, Pyter LM … +3 more , Sen CK, Schwab JM, Popovich PG
J Neurotrauma · 2025 Dec · PMID 41449090 · Publisher ↗
Traumatic spinal cord injury (SCI) increases the risk for skin complications, including the development of decubitus ulcers, that is, pressure sores. The mechanisms by which SCI adversely affects skin health are poorly u...
Traumatic spinal cord injury (SCI) increases the risk for skin complications, including the development of decubitus ulcers, that is, pressure sores. The mechanisms by which SCI adversely affects skin health are poorly understood. To better understand how SCI affects the normal progression of wound healing, two mouse models of cutaneous wound healing were used. Mice received a high-level (T3) SCI or sham injury (Lam) over the first week postinjury. Mice received standardized skin wounds on the dorsum below the injury level (punch biopsy or compression/ischemia wounds). Planimetric analysis revealed that wound closure was consistently delayed and impaired after SCI. Subsequent analyses of the expression of genes and proteins responsible for regulating cell migration and recruitment, particularly of neutrophils, were reduced in SCI mice as early as 1 day post-wounding. This impaired chemotactic signaling was associated with a corresponding decrease in neutrophil recruitment to the wounds of SCI mice. At later phases of healing, the expression of inflammatory genes and the accumulation of wound myeloid cells with an elevated capacity for arginine catabolism was enhanced in SCI mice relative to Lam. Overall, data in this report show that impaired wound closure in SCI mice is associated with early and prolonged disruption of the expression of genes and proteins needed to coordinate the sequential progression through all phases of wound healing. Consequently, skin wounds in SCI mice exhibit prolonged inflammation, characteristic of complicated wound healing. Thus, targeting signaling pathways during the inflammatory phase of healing of decubitus ulcers after SCI could improve wound closure and limit further complications.
Differential DNA Methylation of the Brain-Derived Neurotrophic Factor Gene is Observed after Pediatric Traumatic Brain Injury Compared with Orthopedic Injury.
Heinsberg LW, Kesbhat A, Petersen B … +8 more , Kaseman L, Stec Z, Anton N, Kochanek PM, Yeates KO, Weeks DE, Conley YP, Treble-Barna A
J Neurotrauma · 2026 Apr · PMID 41376515 · Full text
Pediatric traumatic brain injury (TBI) triggers biological changes that may differ from those observed in non-brain injuries. Brain-derived neurotrophic factor () DNA methylation (DNAm) may serve as a novel, dynamic biom...
Pediatric traumatic brain injury (TBI) triggers biological changes that may differ from those observed in non-brain injuries. Brain-derived neurotrophic factor () DNA methylation (DNAm) may serve as a novel, dynamic biomarker of the brain's response and help identify TBI-specific epigenetic patterns relevant to later recovery. Therefore, the purpose of this study was to examine whether DNAm differed between children with TBI and those with orthopedic injury (OI, comparison group) acutely and over time. Data were derived from the Epigenetic Effects on TBI Recovery study, a prospective, longitudinal cohort study conducted at UPMC Children's Hospital of Pittsburgh. Children aged 3-18 years hospitalized at a minimum of overnight for complicated mild-to-severe TBI or OI without head trauma were enrolled. Exclusion criteria included prior hospitalization for TBI, pre-existing neurological or psychiatric conditions, or sensory or motor impairments precluding study participation. Blood samples were collected during hospitalization (mean = 31.6 h post-injury) and at 6 (mean = 216.9 days) and 12 months (mean = 405.9 days) post-injury. The primary outcome variable was DNAm assessed via pyrosequencing at five quality-controlled CpG sites in the gene (chromosome 11, Genome Reference Consortium Human Build 38 positions 27722033, 27722036, 27722047, 27701612, and 27701614). The primary exposure was injury type (TBI vs. OI), with severity (measured via Glasgow Coma Scale [GCS]) examined as a secondary exposure within the TBI group. Primary covariates included age, sex, and race; secondary covariates included pubertal status, age-adjusted body mass index, non-head injury severity, socioeconomic status, and psychosocial adversity. The final analysis sample included = 189 participants with TBI and = 105 participants with OI. Participants were 66.3% male, 83.2% White, and had a mean age of 10.6 (±4.3) years at the time of enrollment. Acutely, children with TBI showed significantly lower DNAm at three of five sites (3.17-5.83% lower; = 0.0044 to 6.48E-06) while controlling for age, sex, and race. One site remained significantly lower at 12 months (8.56% lower; = 0.0045); no significant differences were observed at 6 months. Observed differences remained robust across sensitivity models adjusting for secondary covariates. GCS-measured TBI severity was not associated with DNAm at any time point. These findings suggest that DNAm differs between children with TBI and those with OI, particularly in the acute period. DNAm differences may reflect early biological responses that are specific to TBI.
Plasma and Imaging Biomarker Changes Following Rotational and Contusional Models of Traumatic Brain Injury in Adolescent Pigs.
Shin SS, Browne KD, Viaene AN … +16 more , Keim G, Han DJ, Degani R, Mazandi V, Morton S, Starr J, Weeks K, Widmann N, Hobson L, Gaudio H, Ko TS, Menezes-Forti R, Jang DH, Cullen DK, Kilbaugh TJ, Kao SH
J Neurotrauma · 2026 Jun · PMID 41371769 · Publisher ↗
Given the heterogeneity of traumatic brain injury (TBI), the development of a therapeutic strategy has been difficult despite decades of research. To develop an accurate classification system to guide individualized trea...
Given the heterogeneity of traumatic brain injury (TBI), the development of a therapeutic strategy has been difficult despite decades of research. To develop an accurate classification system to guide individualized treatment, new protein biomarkers of TBI have been studied. We explored if different subtypes of TBI have unique biomarker profiles and histological findings using four pig models of TBI: moderate rotational injury (100-110 r/s), mild rotational injury (85-95 r/s), moderate contusional injury (8-9 mm), and mild contusional injury (6-7 mm). Among these groups, we identified unique profile of plasma neurofilament light (NFL) and glial fibrillary acidic protein (GFAP): whereas moderate contusion animals had early peak of NFL (2-3 days) and GFAP (1 day), mild contusion animals had delayed peak of NFL (8 days) and GFAP (3 days). Diffusion tensor imaging analysis found reduced fractional anisotropy in corona radiata for contusional injured animals but rotational injured animals showed no significant changes compared to control animals. Histological analysis showed prominent vascular inflammation and axonal injury in the pericontusional cortex in contusional injured animals. In rotational injured animals, prominent axonal injury was found in perivascular white matter. Future studies for mechanistic underpinning of biomarker changes are needed to establish therapeutic targets, predict severity of injury, and determine clinical trial enrollment and therapeutic response.
YAP Regulates Microglial Anti-Inflammatory Responses and Alleviates Cognitive Impairment Through the IL-33/ST2 Pathway after Traumatic Brain Injury.
Zhao R, Gao SQ, Wang X … +9 more , Li T, Gao CC, Han YL, Qiu JY, Miao SH, Sun Y, Zheng XB, Jin WX, Zhou ML
J Neurotrauma · 2026 Apr · PMID 41371749 · Publisher ↗
Traumatic brain injury (TBI) is a neurological disease that seriously endangers human life and has a poor prognosis. In particular, neuroinflammation during secondary injury after TBI affects the course of TBI, and inter...
Traumatic brain injury (TBI) is a neurological disease that seriously endangers human life and has a poor prognosis. In particular, neuroinflammation during secondary injury after TBI affects the course of TBI, and interleukin-33 (IL-33) plays an important regulatory role in neuroinflammation after TBI. Meanwhile, the Yes-associated protein (YAP) can influence the prognosis after TBI. In this study, we explored whether the upregulation of YAP in astrocytes can enhance the protective effect of IL-33 against neuroinflammation after TBI. In the current study, the markers of microglial proinflammatory/anti-inflammatory responses both and were assessed after the administration of exogenous IL-33. Adeno-associated virus targeting astrocytes and lentivirus transfecting astrocytes were used to overexpress YAP, and the expression and localization of proteins were evaluated by Western blotting and immunofluorescence staining. Chromatin immunoprecipitation-quantitative Polymerase Chain Reaction (qPCR) assays were performed to confirm that YAP transcriptionally regulates the gene by binding directly to its promoter region. Astegolimab was administered to block Growth Stimulation Express Gene 2 Protein (ST2) receptors and . Morris water maze and Y-maze tests were employed to assess cognitive function after TBI. The results demonstrated that the expression levels of both YAP and IL-33 were significantly decreased during the early phase of TBI. Concurrently, the anti-inflammatory marker CD206 in microglia was also markedly reduced in the acute stage post-TBI. Importantly, YAP was found to enhance IL-33 secretion by binding to its gene promoter, thereby activating the IL-33/ST2 signaling pathway. This activation promoted anti-inflammatory responses in microglia, which were mediated through the NF-κB signaling pathway, and ultimately led to improved cognitive function. These beneficial effects were effectively reversed by the administration of astegolimab, confirming the specificity of the YAP/IL-33/ST2 mechanism. Above all, we found that YAP produced by astrocytes regulates microglial anti-inflammatory responses through the IL-33/ST2 pathway, thereby improving cognitive function after TBI.
Artificial Intelligence Chatbot Responses to Patient Queries on Traumatic Brain Injury: An Expert Assessment of Reliability and Accuracy.
Schuss P, Gonschorek AS, Kämper M … +9 more , Lemcke J, Meisel HJ, Rogge W, Schaan M, Schwenkreis P, Strowitzki M, Wohlfahrt K, Schmehl I, Neuro-Trauma Working Group
J Neurotrauma · 2025 Nov · PMID 41335521 · Publisher ↗
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 performa...
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.
Administration of a Novel Peptide Derived From Thrombospondin Repeat Sequences Enhances Recovery after Cervical Spinal Cord Injury.
Punjani N, Lemarchant S, Altamentova S … +5 more , Chio JCT, Hong J, Wang J, Godfrin Y, Fehlings MG
J Neurotrauma · 2026 May · PMID 41335520 · Publisher ↗
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 approv...
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.
The Impact of Mild Traumatic Brain Injury Sustained with Blast or Nonblast Mechanism During Combat or Noncombat Deployment on Community Reintegration.
Remigio-Baker RA, Dismuke-Greer C, Pugh MJ … +3 more , Eppich KG, Allen CM, Walker WC
J Neurotrauma · 2025 Nov · PMID 41334709 · Publisher ↗
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 ad...
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.
Development of Prognostic Models for Bladder and Bowel Dysfunction in Traumatic Spinal Cord Injury Patients Using Machine Learning.
Kitamura T, Maki S, Furuya T … +15 more , Nagashima Y, Maruyama J, Toki Y, Kitagawa K, Yazaki M, Iwata S, Gushiken S, Noguchi Y, Inoue M, Shiga Y, Inage K, Eguchi Y, Orita S, Kawakami E, Ohtori S
J Neurotrauma · 2025 Dec · PMID 41334701 · Publisher ↗
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 dysfunctio...
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.
Biofluid Biomarkers of Acute Traumatic Spinal Cord Injury: A Systematic Review.
Schaeffer EA, Levy AS, Errante EL … +5 more , Costello MC, Smartz T, Levi AD, Burks SS, Papa L
J Neurotrauma · 2026 May · PMID 41334695 · Publisher ↗
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 n...
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.
Frontal Burr-Hole Compared with Parietal Burr-Hole in the Management of Chronic Subdural Hematoma: A Single-Center, Randomized Controlled, Noninferiority Trial.
Chen P, Ou P, Xiao Z … +6 more , Nie Z, Niu J, Zhou M, Wang T, Jiang Y, Wang B
J Neurotrauma · 2026 Jun · PMID 41334693 · Publisher ↗
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 rem...
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).
Amiodarone Improves Locomotor Function in Experimental Spinal Cord Injury by Reducing Secondary Axonal Degeneration and White Matter Atrophy.
Stokum JA, Wilhelmy B, Bragança C … +6 more , Tosun C, Serra R, Tsymbalyuk O, Keledjian K, Gerzanich V, Simard JM
J Neurotrauma · 2026 May · PMID 41314966 · Publisher ↗
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 decompressi...
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.
Development of a Structured Interview for the American Congress of Rehabilitation Medicine Diagnostic Criteria for Mild Traumatic Brain Injury.
Lange RT, Gillow KC, ACRM Brain Injury Special Interest Group Mild TBI Task Force members: … +18 more , Silverberg ND, Wallace T, Panenka WJ, Rabinowitz A, Stephens JA, Dams-O'Connor K, Delmonico R, Graf MJP, Kam ASH, Khan Q, Lequerica AH, Al Lawati Z, McKinney G, McPherson JI, Nagele D, Snell D, Kamins J, Wethe J
J Neurotrauma · 2026 Jun · PMID 41293888 · Publisher ↗
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 T...
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.
Timing Is Everything: A Systematic Review of Optimal Repeat Computed Tomography Protocols in Traumatic Brain Injury.
Taddei G, Pietrantonio A, Petrella G … +8 more , Piragine G, Bertini R, Aloisi M, Sampirisi L, Ciarlo S, Mastino L, Toccaceli G, Pompucci A
J Neurotrauma · 2026 Feb · PMID 41293885 · Publisher ↗
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 tomograph...
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.
Response to Letter to the Editor on "Exoskeletal-Assisted Walking During Acute Inpatient Rehabilitation Enhances Recovery for Persons with Spinal Cord Injury-A Pilot Randomized Controlled Trial".
Tsai CY, Weinrauch WJ, Manente N … +3 more , Huang V, Bryce TN, Spungen AM
J Neurotrauma · 2025 Nov · PMID 41293864 · Publisher ↗
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High-Frequency Physiological Measures Predict Post-Admission Surgical Intervention After Severe Traumatic Brain Injury.
Hinds S, Robertson C, Chen J … +6 more , Yaseen A, Diaz-Arrastia R, Temkin NR, Cruz Navarro J, DeSantis SM, Yamal JM
J Neurotrauma · 2026 Jun · PMID 41274778 · Publisher ↗
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 intracrania...
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.
Validation of A Wireless Telemetric Bladder Pressure Monitoring System in Traumatic Thoracic Spinal Cord Injury in Yucatan Minipigs.
Doelman AW, Ethridge J, Streijger F … +12 more , Warner A, Webster M, Billingsley A, Gunamalai S, So K, Kankroliwala H, Keung MSM, Manouchehri N, Kavanagh A, Majerus SJA, Damaser MS, Kwon BK
J Neurotrauma · 2026 May · PMID 41269117 · Publisher ↗
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...
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.
History of Strangulation Is Associated with Current Traumatic Stress, Self-Reported Vision Problems, and Other Neurobehavioral Symptoms in Women Who Have Experienced Intimate Partner Violence.
Xu MC, Tanriverdi A, Iverson GL … +1 more , Valera EM
J Neurotrauma · 2026 Jun · PMID 41269098 · Full text
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...
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.
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