Journal of neurotrauma最新文献

The Glasgow Outcome Scale Extended (GOSE) is the most widely used outcome measure for hospital-based studies of traumatic brain injury (TBI). The GOSE may be administered several ways, the choice depending on the purpose of the research. In this investigation, we evaluated the effect of administering the GOSE to collect functional disability attributed to all injuries sustained (GOSE-All) or excluding the impact of extracranial injuries (GOSE-TBI). We examined the differences in reported disability between the two administration methods at 2 weeks, 3 months, 6 months, and 12 months after injury. Data are summarized from 2288 individuals who were enrolled in the prospective observational Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) cohort study. The distribution of scores is summarized by time after injury, brain injury severity, and extracranial injury severity. Dichotomizing the GOSE varying ways, differences in the prevalence of unfavorable outcomes for GOSE-All versus GOSE-TBI range from none to 42 percentage points. Discrepancies in disability captured by GOSE-All and GOSE-TBI decrease with greater TBI severity, no serious extracranial injuries, and longer time post-injury. It is important for researchers, given the aims of their studies, to decide in advance whether GOSE classification should be based on the effects of all injuries sustained or excluding the effects of extracranial injuries so as to emphasize the effects of the brain injury, as well as how disability due to emotional consequences of injury and other circumstances will be scored. Instructions to the respondent and outcomes examiner need to be clear about what causes of disability are to be included. The TBI Common Data Elements should include information that reflects the method that was used to collect the GOSE data and data repositories should disclose which data collection method was used for a given study.

Because most traumatic brain injuries (TBIs) do not present with objective indicators (e.g., neuroimaging findings) to confirm the diagnosis, clinicians often rely on self- or observer-reporting of alteration of consciousness (AOC; e.g., loss of consciousness [LOC], amnesia, other signs of altered mental status), and symptoms to make diagnoses. Moreover, there is no universal agreement on signs and symptoms to sufficiently diagnose TBI, which leads to variability and ambiguity in how TBI is diagnosed in clinical and research settings. The lack of standardized procedures for the diagnosis of acute TBI is a major challenge that hampers the ability to evaluate and compare TBI studies and advance the science and treatment of TBI. We present a new semi-structured TBI Diagnostic Interview (TBI-DI), developed for prospective TBI research to collect injury information important to verifying eligibility for the diagnosis of TBI. Specifically, the TBI-DI collects patient (and/or witness) reports of head trauma, AOC (including LOC and amnesia), and TBI-related symptomology. We describe the protocol, interrater reliability of the TBI-DI items to the same audio-recorded interview, and observed injury characteristics for interviews conducted at 2 weeks post-injury. The sample comprised 335 interviews (320 self-reported, 10 informant-reported, and 5 both) collected on individuals with TBI who were prospectively recruited from 4 U.S. level 1 trauma centers from 2019 to 2023. Cohen's kappa was calculated to summarize interrater reliability n = 288 interviews. UpSet plots were created to illustrate the prevalence of distinct profiles of signs of AOC and symptom reporting. Overall, there was a near-perfect agreement between raters for all AOC descriptors (κ = 0.85-0.92) and symptom items (κ ranging from 0.92 to 0.99). We observed diverse profiles of AOC, with 45% manifesting witnessed LOC, post-traumatic amnesia, or other altered mental status. Patients (n = 325) self-reported 256 different combinations of the 14 acute symptoms included in the interview (most commonly experiencing headache, dizziness, fatigue, and difficulty concentrating). The TBI-DI and associated SOP appear well-suited for use in a multicenter prospective study of TBI. Future research should examine the stability of reporting by respondents and the alignment between interview and objective clinical information. The TBI-DI solicits diverse acute diagnostic information that, when combined with clinical information (including confounding factors) and objective injury indicators, may inform more rigorous scientific reporting and evidence-based TBI diagnostic practices.

An extensive library of symptom inventories has been developed over time to measure clinical symptoms of traumatic brain injury (TBI), but this variety has led to several long-standing issues. Most notably, results drawn from different settings and studies are not comparable. This creates a fundamental problem in TBI diagnostics and outcome prediction, namely that it is not possible to equate results drawn from distinct tools and symptom inventories. Here, we present an approach using semantic textual similarity (STS) to link symptoms and scores across previously incongruous symptom inventories by ranking item text similarities according to their conceptual likeness. We tested the ability of four pretrained deep learning models to screen thousands of symptom description pairs for related content-a challenging task typically requiring expert panels. Models were tasked to predict symptom severity across four different inventories for 6,607 participants drawn from 16 international data sources. The STS approach achieved 74.8% accuracy across five tasks, outperforming other models tested. Correlation and factor analysis found the properties of the scales were broadly preserved under conversion. This work suggests that incorporating contextual, semantic information can assist expert decision-making processes, yielding broad gains for the harmonization of TBI assessment.

Bowel dysfunction, is a prevalent and life-impacting comorbidity of spinal cord injury (SCI) with no long-term treatment available. SCI-induced colon changes including motility and fibrosis are understudied as are strategies to address SCI bowel dysfunction. This need remains partly due to the lack of a mouse model that recapitulates the human condition. We hypothesized that a high thoracic spinal transection in mice would trigger bowel dysfunction with coincident colon pathology similar to humans and rats after SCI. We observed bowel dysfunction as increased fecal pellet numbers within the colon, smaller pellet size, and decreased motility. Fecal pellets numbers in the colon increased significantly in SCI animals versus sham (laminectomy only) injuries by 4 days postinjury (dpi) and persisted to 7 and 21 dpi. The number of pellets expelled (fecal output) significantly decreased in SCI versus sham animals at both 7 and 20 dpi. Pellet size was significantly decreased in SCI animals at 7 and 14 dpi, collectively indicative of decreased motility with SCI. SCI caused non-significant reductions in colonic motility (bead expulsion assay) at all three timepoints. Through ex vivo myograph analyses of live colon sections, we detected significant increase in the maximal contractility of the circular musculature from both the proximal and distal colon after SCI at 21 dpi. At the same time point, distal colons displayed significant collagen deposition in the musculature after SCI. Collectively, these findings demonstrate bowel dysfunction immediately after injury that continues in the distal colon over time. Establishing this mouse model enables further interrogation using transgenic models.

There has been limited exploration of blood-based biomarkers in the chronic period following traumatic brain injury (TBI). Our objective was to conduct a systematic review of studies examining blood-based protein biomarkers with at least one sample collected 12 months post-TBI in adults (≥16 years). Database searches were conducted in Embase, MEDLINE, and Science Citation Index-Expanded on July 24, 2023. Risk of bias was assessed using modified Joanna Briggs Institute critical appraisal tools. Only 30 of 12,523 articles met inclusion criteria, with samples drawn from 12 months to 48 years. Higher quality evidence (low risk of bias; large samples) identified promising inflammatory biomarkers at 12 months post-injury in both moderate-severe TBI (GFAP) and mild TBI (eotaxin-1, IFN-y, IL-8, IL-9, IL-17A, MCP-1, MIP-1β, FGF-basic, and TNF-α). Studies with low risk of bias but smaller samples also suggest NSE, MME, and CRP may be informative, alongside protein variants for α-syn (10H, D5), amyloid-β (A4, C6T), TDP-43 (AD-TDP 1;2;3;9;11), and tau (D11C). Findings for NfL were inconclusive. Longitudinal data were mostly available for acute samples followed until 12 months post-injury, with limited evaluation of changes beyond 12 months. Associations of some blood-based biomarkers with cognitive, sleep, and functional outcomes were reported. The overall strength of the evidence in this review was limited by the risk of bias and small sample sizes. Replication is required within prospective longitudinal studies that move beyond 12 months post-injury. Novel efforts should be guided by promising neurodegenerative-disease markers and use panels to model polypathology.

Balance and mobility problems are common consequences after mild traumatic brain injury (mTBI). However, turning and nonstraight gait, which are required for daily living, are rarely assessed in clinical tests of function after mTBI. Therefore, the primary goals of this study were to assess (1) the added value of clinic-based turning task variables, obtained using wearable sensors, over standard general assessments of mobility, and (2) assess the associations between general assessments of mobility, objective variables from clinic-based turning tasks, and ecologically relevant functional tasks. Fifty-three civilians with mTBI, 57 healthy civilian controls, and 36 healthy active-duty military controls participated across three sites. Participants were tested in a single session that encompassed self-reported questionnaires including demographic information and balance and mobility testing including the use of wearable sensors. Lasso regression models and the area under the receiver-operator characteristic curve (AUC) assessed diagnostic accuracy. Partial correlation coefficients assessed the relationship between each variable with ecologically relevant functional tasks. Multivariate models revealed high diagnostic accuracy, with an AUC of 0.92, using multiple variables from instrumented clinic-based turning tasks. The complex turning course (CTC) yielded the highest multivariate AUC (95% confidence interval [CI]) of 0.90 (0.84, 0.95) for a single task, and the average lap time from the CTC had the highest univariate AUC (95% CI) of 0.70 (0.58, 0.78). Turning variables provided added value, indicated by higher AUCs, over standard general assessments of mobility. Turning variables had strong associations with ecologically relevant functional tasks and outperformed general assessments of mobility, though there were slight differences in the relationship based on civilian versus military population. Clinic-based turning tasks, especially the CTC and modified Illinois Agility Test (mIAT), have high diagnostic accuracy, strong associations with ecologically relevant functional tasks, and require relatively short time(s) to complete. Compared to general assessments of mobility, clinic-based turning tasks may be more ecologically relevant to daily function. Future work should continue to examine the CTC and mIAT alongside other promising tools for return-to-activity assessments.

Traumatic brain injury (TBI) after high-energy, behind helmet blunt trauma (BHBT) is an important but poorly understood clinical entity often associated with apnea and death in humans. In this study, we use a swine model of high-energy BHBT to characterize key neuropathologies and their association with acute respiratory decompensation. Animals with either stable or critical vital signs were euthanized within 4 h after injury for neuropathological assessment, with emphasis on axonal and vascular pathologies in the brainstem. The majority of cases were characterized by fractures of the cranium at or about the impact site, extensive subarachnoid hemorrhages, coup and contrecoup contusions, and primarily diffuse axonal and vascular lesions throughout the cerebrum, particularly in the brainstem. Absence of spontaneous respiration that was encountered frequently was associated with both severity of impact and the severity of brainstem axonal and vascular lesions. A focused regional examination of brainstem pathology indicated a link between adverse outcomes and diffuse axonal lesions within the medial medulla or vascular lesions within the anteroventral brainstem, a pattern suggesting that injury to brainstem respiratory centers may play a role in apnea following BHBT. In addition, while the overall burden of diffuse axonal and vascular pathologies correlated with each other, we found minimal overlap in their regional distribution. Our findings indicate that high-energy, blunt-force impact TBI causes diffuse lesions in axons and blood vessels associated with poor outcomes. They also suggest that axons and vessels may have distinct responses to tissue deformation and that commonly used markers of vascular pathology, for example, in diagnostic radiology, cannot be used as direct surrogates of diffuse axonal injury. In concert, our study underscores the role of regional axonal and vascular injuries in the brainstem in acute respiratory decompensation after high-rate blunt TBI, even in the presence of head protection; it also emphasizes the importance of detailed clinicopathological work in complex brains in the field of TBI.