Journal of neurotrauma最新文献

Prognostication after moderate-to-severe traumatic brain injury (TBI) remains challenging in the intensive care unit (ICU) despite the existence of well-validated online prognostication tools. Changes in brain activity related to TBI can be measured using electroencephalography (EEG), making it a potentially interesting diagnostic tool to refine prognostication. The primary objective of this systematic review was to evaluate the literature concerning the prognostic value of EEG among patients with TBI in the ICU. Five databases were searched from inception until August 13, 2024. The search identified 1492 unique records. Eventually, 27 manuscripts met the inclusion criteria (>18 years old, Glasgow Coma Scale ≤12, EEG performed in the ICU). The QUIPS (QUality In Prognostic Studies) and PROBAST (Prediction model Risk Of Bias ASsessment Tool) tools were used to assess the study quality and bias. Due to high heterogeneity in EEG feature and outcome definitions and a lack of correction for confounding factors, all studies had a moderate-to-high risk of bias. Nonetheless, specific EEG features (identified through visual and quantitative EEG, EEG reactivity, and machine learning techniques) were found to be predictive of neurological outcomes up to 1.5 years after TBI. While epileptiform discharges and seizures were not consistently associated with outcomes, a higher alpha variability, a more continuous EEG, present EEG reactivity, and present EEG sleep features were predictive of better outcomes. The combination of EEG features with clinical parameters demonstrated improved predictive performance compared with models using standard clinical parameters alone. Still, the EEG features described and their potential additional value in outcome prediction after TBI merit further investigation.

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.

There is limited information about long-term outcomes following severe acquired brain injury (ABI). This is due, in part, to the lack of validated longitudinal assessment measures that can be administered remotely. To address this gap, we developed a caregiver-administered telephone interview designed for the remote evaluation of the functional status of patients who are too impaired to provide reliable self-report. The interview comprises items drawn from three existing standardized instruments: the Coma Recovery Scale-Revised (CRS-R), Cognitive Impairment subscale of the Confusion Assessment Protocol (CAP-Cog), and Galveston Orientation and Amnesia Test (GOAT) (subsequently referred to as the CRS-RT, CAP-CogT, and GOAT-T to reflect telephone administration). The CRS-RT items evaluate the level of consciousness, while the CAP-CogT and GOAT-T items assess basic aspects of cognition. We administered the caregiver interview to 48 caregivers of persons with severe acquired disability (i.e., vegetative state to confusional state) and validated caregiver responses by conducting in-person patient examinations using the original versions of the assessment instruments. To establish the concurrent validity of the caregiver interview, we assessed the correlation between the findings from the caregiver interview and the patient examination, using Lin's concordance correlation coefficient (CCC). The mean (standard error) sensitivity, specificity, and accuracy across both sets of interview items were 0.82 (0.03), 0.68 (0.04), and 0.75 (0.03), respectively. Lin's CCC between caregiver responses to the nine interview items addressing the level of consciousness and the corresponding patient examination findings was 0.78 (95% confidence interval [CI]: 0.65, 0.90), with six items exceeding our a priori cut-off of ≥0.70. However, the correlation between caregiver responses to the eight basic cognition items and the patient examination findings was poor (Lin's CCC = 0.37, 95% CI: -0.09, 0.82), with only three items at or above the cut-off. These results indicate that the CRS-RT can be administered remotely to caregivers of persons with severe ABI-related disability to monitor neurobehavioral status longitudinally. The CAP-CogT and GOAT-T items require further study before they can be used for clinical outcome assessment.

Cerebrovascular reactivity (CVR) mapping is a promising biomarker for evaluating vascular dysfunction following traumatic brain injury (TBI). Traditional CVR assessment requires carbon dioxide (CO₂) administration. Assessing CVR from resting-state blood-oxygen-level-dependent (BOLD) sequences (RS-CVR) offers a task-free alternative, but its validity in TBI has not yet been established. We aimed to evaluate whether RS-CVR can reliably detect cerebrovascular impairment in patients with TBI by comparing it with CO₂-inhalation CVR (CO₂-CVR). We enrolled 23 chronic moderate-to-severe TBI patients and 13 healthy controls (HC) who underwent both CO₂-CVR and RS-CVR imaging using BOLD functional magnetic resonance imaging (BOLD fMRI). RS-CVR maps were computed using a voxel-wise general linear model (GLM) across 120 bandpass filters. Spatial correlations between RS-CVR and CO₂-CVR were calculated to identify the optimal frequency bands. Z-score analyses and lesion-based comparisons were performed to assess CVR reductions in TBI. In the TBI cohort, lesion-based CVR was correlated with clinical outcomes using GLM adjusted for age and sex. The highest whole-brain spatial correlation between RS-CVR and CO₂-CVR in HC occurred at [0-116.4 mHz] (r = 0.5239 ± 0.1107). In TBI, the peak correlation slightly shifted to [0-74.5 mHz] (r = 0.5217 ± 0.1108) but remained comparable at [0-116.4 mHz] (r = 0.5093 ± 0.1263). As expected, regions of encephalomalacia, fluid-attenuated inversion recovery hyperintensity, showed CVR reductions on RS-CVR and CO₂-CVR maps, but low CVR was also identified through both methods in normal-appearing brain tissue. Across lesion areas, RS-CVR detected deficits consistent with CO₂-CVR, with mean z-scores of -0.217 ± 0.334 and -0.391 ± 0.294 for encephalomalacia and hyperintensities, respectively. Lesion-based CVR values were associated with clinical outcomes, with both CO₂-CVR and RS-CVR positively correlated with days in the intensive care unit (ICU; p < 0.05) and showing negative associations with Rivermead post-concussion symptoms questionnaire scores, statistically significant for CO₂-CVR (p = 0.031) and trending for RS-CVR (p = 0.089). RS-CVR closely mirrors CO₂-CVR in both global and lesion-specific analyses, validating its use as a noninvasive method for detecting vascular deficits in TBI. This task-free and scalable tool for cerebrovascular assessment offers a valuable approach for characterizing vascular health relevant to TBI prognosis and guiding neurorehabilitation efforts.

Traumatic brain injury (TBI) represents a significant global health challenge, but a systematic, severity-stratified analysis of its epidemiology and risk factors is lacking. Using data from the Global Burden of Disease (GBD) 2021 study, this study compares the burden of mild TBI (mTBI) and moderate-to-severe TBI (msTBI) from 1990 to 2021. We analyzed incidence, prevalence, and years lived with disability (YLDs) for TBI across 204 countries and territories and by sociodemographic index (SDI) quintiles. Analysis included the characterization of age and sex distributions, assessment of temporal trends, and evaluation of risk factor attributions for both mTBI and msTBI. The results revealed that while the global age-standardized incidence rate (ASIR) of TBI declined, low-SDI regions experienced rising prevalence and YLD rates despite falling incidence. The ASIR of mTBI decreased significantly (average annual percentage change [AAPC]: -0.587; 95% confidence interval [CI]: -1.211-0.059), whereas the ASIR of msTBI showed no statistically significant decline (AAPC: -0.483; 95% CI: -1.235-0.275). The absolute number of mTBI cases peaked among young and elderly males, while the ASIR of msTBI increased with age in both sexes but remained consistently higher in males. Falls and road injuries remained the leading causes; however, the absolute number of msTBI cases due to these causes continued to rise. Notably, violence-related factors-including conflict and terrorism as well as police conflict and executions-were among the most rapidly increasing risk factors for both TBI subtypes. In conclusion, the global TBI burden is characterized by a stagnant crisis of msTBI, underscoring an urgent need for severity-specific prevention strategies that target high-risk mechanisms and populations to mitigate the devastating impact of msTBI worldwide.

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.

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 (p = 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, p < 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].

The long-term sequelae of severe penetrating traumatic brain injury (TBI) include neurological and psychiatric disability, impaired cognitive function, and the development of post-traumatic epilepsy. The present study evaluated the therapeutic effects of intravenous immunoglobin (IVIg), a well-established immunomodulatory treatment, in a controlled cortical impact model of severe TBI in mice. The beneficial effects of IVIg treatment on acute neurological status, motor function, anxiety level, and spatial learning ability were demonstrated by reduced Neurological Severity Scores, increased Rotarod latency and cumulative movement durations in open-field tests, and improved active place avoidance performance. IVIg treatment also significantly reduced brain tissue loss, which was examined using Nissl staining at 16 weeks after TBI. Furthermore, brain microRNAs (miRNAs) were profiled to identify the biological pathways potentially associated with the actions of IVIg treatment using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. To identify potential peripheral biomarkers reflecting the changes in the brain, differentially expressed miRNAs in plasma and brain samples from the same animals were compared. Our immunostaining results showed that IVIg treatment significantly attenuated the upregulation of IL-1β and complement 3 (C3) and altered the activation of microglia and astrocytes. This proof-of-concept study provided strong evidence for the beneficial effects of IVIg treatment in severe penetrating TBI.

Neurogenic bowel (NB) affects roughly 60% of people with a spinal cord injury (SCI), and these patients present with slow colonic transit, constipation, and chronic abdominal pain. The mechanisms by which NB bowel develops are unclear, thereby limiting interventions to being primarily symptom-focused and ineffective. Therefore, the main goal of this study was to identify the mechanisms that initiate and maintain NB after SCI as a critical step to develop evidence-based, novel therapeutic options to prevent NB. In previous studies, the neurogenic inflammatory mediator calcitonin gene-related peptide (CGRP) was identified as a high-priority candidate gene. Therefore, in a midthoracic rodent spinal contusion model that presents with clinically translatable NB-like phenotypes, we conducted intrarectal antagonism of CGRP activity using CGRP_8-37 (compared to vehicle administration) in mice with SCI. This was followed by histological, molecular, and functional (Ca²⁺ imaging) approaches to assess the prevention of previously reported phenotypes of NB. CGRP_8-37 significantly prevented colonic dysmotility and structural defects of the colon (i.e., expanded lymphoid nodules). There was also a prevention of microbial invasion into the colon wall and neuronal hyperresponsiveness to autologous fecal supernatants. These data support the role of CGRP/CGRP as a candidate mechanism for NB after SCI and highlight the potential for novel therapeutic treatments for the prevention of NB.