Journal of neurotrauma最新文献

The Australian Traumatic Brain Injury Initiative (AUS-TBI) is developing a data resource to enable improved outcome prediction for people with moderate-severe TBI (msTBI) across Australia. Fundamental to this resource is the collaboratively designed data dictionary. This systematic review and consultation aimed to identify acute interventions with potential to modify clinical outcomes for people after msTBI, for inclusion in a data dictionary. Standardized searches were implemented across bibliographic databases from inception through April 2022. English-language reports of randomized controlled trials (RCTs) evaluating any association between any acute intervention and clinical outcome in at least 100 patients with msTBI, were included. A predefined algorithm was used to assign a value to each observed association. Consultation with AUS-TBI clinicians and researchers formed the consensus process for interventions to be included in a single data dictionary. Searches retrieved 14,455 records, of which 124 full-length RCTs were screened, with 35 studies included. These studies evaluated 26 unique acute interventions across 21 unique clinical outcomes. Only 4 interventions were considered to have medium modifying value for any outcome from the review, with an additional 8 interventions agreed upon through the consensus process. The interventions with medium value were tranexamic acid and phenytoin, which had a positive effect on an outcome; and decompressive craniectomy surgery and hypothermia, which negatively affected outcomes. From the systematic review and consensus process, 12 interventions were identified as potential modifiers to be included in the AUS-TBI national data resource.

In this series of eight articles, the Australian Traumatic Brain Injury Initiative (AUS-TBI) consortium describes the Australian approach used to select the common data elements collected acutely that have been shown to predict outcome following moderate-severe traumatic brain injury (TBI) across the lifespan. This article presents the unified single data dictionary, together with additional measures chosen to facilitate comparative effectiveness research and data linkage. Consultations with the AUS-TBI Lived Experience Expert Group provided insights on the merits and considerations regarding data elements for some of the study areas, as well as more general principles to guide the collection of data and the selection of meaningful measures. These are presented as a series of guiding principles and themes. The AUS-TBI Aboriginal and Torres Strait Islander Advisory Group identified a number of key points and considerations for the project approach specific to Aboriginal and Torres Strait Islander peoples, including key issues of data sovereignty and community involvement. These are outlined in the form of principles to guide selection of appropriate methodologies, data management, and governance. Implementation of the AUS-TBI approach aims to maximize ongoing data collection and linkage, to facilitate personalization of care and improved outcomes for people who experience moderate-severe TBI.

Adverse childhood experiences (ACEs) and traumatic brain injuries (TBI) are highly prevalent globally, and both are associated with long-term negative health outcomes across the lifespan. Past research exploring the potential association between ACEs and TBI occurrence has demonstrated mixed findings. Thus, we conducted a systematic review and meta-analysis to examine the association between the ACEs measure and TBI occurrence. Moderator analyses were conducted to determine whether certain factors, including participant age, sex, and geographical location, modified the association between ACEs score and TBI occurrence. Searches were conducted in PsycINFO, MEDLINE, Embase, and CINHAL for studies published between January 1, 1998, and February 19, 2024. A total of 42 full-text articles were screened against inclusion criteria (i.e., measure of ACEs using the original 8- or 10-item scale or another composite measure of ACEs, TBI occurrence, and effect size for the association between ACEs score and TBI). Eight studies and 10 samples (N = 4954) were included in the meta-analysis. The data were synthesized using a random-effects multilevel meta-analysis, which revealed a significant large positive association between ACEs score and TBI occurrence, r = 0.31, 95% confidence interval [0.13, 0.49], p < 0.001. Moderator analyses did not yield significant results. The current findings demonstrate that individuals who reported a higher ACEs score were more likely to have reported sustaining a TBI, highlighting a need for trauma-informed efforts to prevent TBI and its adverse effects.

Individuals who experience intimate partner violence (IPV) sometimes self-report balance and vestibular problems; however, objectively measured balance has rarely been investigated in this population. Given the risk for persistent physical, neurocognitive, and psychological effects of brain injury (BI) in women who experience IPV, the present study evaluated the association between mild IPV-BIs, objective balance, and self-reported vestibular symptoms in women with at least one instance of physical IPV (n = 144). IPV-BIs and accident-related BIs were assessed using the Ohio State University traumatic BI (TBI) identification method and the Brain Injury Severity Assessment Interview. Psychological symptoms were measured with the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Posttraumatic Stress Disorder Checklist for DSM-5. Vestibular symptoms were measured with the Neurobehavioral Symptom Inventory (NSI). Static balance and postural sway were measured with the Sway Medical System Balance Test, for which lower scores reflect worse balance. Hierarchical regression analyses revealed that having a greater number of mild IPV-related BIs was related to (1) lower objectively measured balance scores (adjusting for age, accident-related BIs, and moderate-severe IPV-BIs) and (2) worse self-reported vestibular symptoms on the NSI (adjusting for age, accident-BIs, moderate-severe IPV-BIs, and symptoms of depression, anxiety, and traumatic stress). Worse self-reported vestibular symptoms were also related to lower balance scores. Results from the present study add to the literature describing the complex health problems experienced by women who experience IPV and IPV-related brain injuries. Future research could include in-person evaluations designed to identify treatable vestibular symptoms and problems.

Disturbed cerebral autoregulation (represented by a positive pressure reactivity index [PRx]), elevated intracranial pressure (ICP), and decreased cerebral perfusion pressure (CPP) are key treatment targets following severe traumatic brain injury (sTBI). This study investigated neuroinflammation as a potential mechanism underlying these intracranial disturbances. Plasma samples from 11 sTBI patients (from a prior Phase II drug trial) were analyzed for 174 proteins using an antibody-based suspension bead array, with intervention effects accounted for where possible. Dimensionality reduction techniques, including principal component analysis (PCA) and supervised methods, were applied to protein data, informed by physiological variables (ICP, CPP, and PRx). PCA revealed distinct protein clustering patterns related to ICP >20 mmHg and PRx > 0, with PC1 linked to patient ID, time from injury, and intervention, and PC2/PC3 significantly associated with PRx dose (p < 0.001). Markers relating to inflammation of the vascular system comprised 20% of the top 50 proteins influencing PC2, implicating complement inflammation in these processes. Notably, MASP-2 (p = 0.027) and complement factor I (p = 0.039) were significantly associated with PRx dose in a mixed-effects model. These findings suggest that vascular inflammation, particularly complement activation, may contribute to intracranial physiological disturbances in sTBI, highlighting the complement pathway as a potential target for further investigation.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.

The first aim of the Australian Traumatic Brain Injury Initiative (AUS-TBI) encompasses development of a set of measures that comprehensively predict outcomes for people with moderate-severe TBI across Australia. This process engaged diverse stakeholders and information sources across six areas: social, health, and clinical factors; biological markers; treatments; and longer-term outcomes. Here, we report the systematic review of pre-existing health conditions as predictors of outcome for people with moderate-severe TBI. Standardized searches were implemented across databases until March 31, 2022. English-language reports of studies evaluating association between pre-existing health conditions and clinical outcome in at least 10 patients with moderate-severe TBI were included. A predefined algorithm was used to assign a judgement of predictive value to each observed association. The list of identified pre-existing health conditions was then discussed with key stakeholders during a consensus meeting to determine the feasibility of incorporating them into standard care. The searches retrieved 22,217 records, of which 47 articles were included. The process led to identification of 88 unique health predictors (homologized to 21 predictor categories) of 55 outcomes (homologized to 19 outcome categories). Only pre-existing health conditions with high and moderate predictive values were discussed during the consensus meeting. Following the consensus meeting, 5 out of 11 were included (migraine, mental health conditions, ≥4 pre-existing health conditions, osteoporosis, and body mass index [BMI]) as common data elements in the AUS-TBI data dictionary. Upon further discussion, 3 additional pre-existing health conditions were included. These are pre-existing heart disease, frailty score, and previous incidence of TBI.

Mean apparent propagator MRI (MAP-MRI) quantifies subtle alterations in tissue microstructure noninvasively and provides a more nuanced and comprehensive assessment of tissue architectural and structural integrity compared with other diffusion MRI techniques. We investigate the sensitivity of MAP-MRI-derived quantitative imaging biomarkers to detect previously unseen microstructural damage in patients with mild traumatic brain injuries (mTBI), whose clinical scans otherwise appeared normal. We developed and validated an MAP-MRI data processing pipeline for analyzing diffusion-weighted images for use in healthy controls and mTBI patients whose longitudinal scans were obtained from the GE/NFL/mTBI MRI database. A regional outlier analysis of longitudinal tissue changes in a pilot cohort during a 90-day period of observation showed that several MAP-MRI-derived parameters had increased intersession variability in white matter tracts and deep gray matter nuclei of mTBI patients relative to healthy controls. In summary, longitudinal monitoring of changes in MAP-MRI metrics may provide a comprehensive means to study pathological mTBI alterations that evolve at different timescales, while current image-based biomarkers lack the sensitivity and specificity and are unable to predict patient outcome.

Traumatic brain injury (TBI) leads to significant public health concerns due to cognitive decline and increased risks of neurological conditions like Alzheimer's disease and chronic traumatic encephalopathy. Preclinical models are essential for exploring how mild TBI leads to neuronal dysfunction and neurodegeneration. Using a mouse model, we applied repetitive, mild, side-alternating impacts to induce rapid head rotational acceleration-deceleration. A novel odor-based learning and memory task was developed to address TBI-related vision impairments. Our findings revealed that this side-impact model specifically affects the hippocampus, evidenced by activated CD68+ microglia appearing in the dentate gyrus, stratum lacunosum-moleculare, and corpus callosum. Importantly, no olfactory dysfunction was observed. However, injured mice exhibited learning and memory deficits in an olfaction-based task. These results suggest that repetitive mild TBI damages hippocampal regions, leading to cognitive dysfunction characterized by impaired learning and memory, as demonstrated by this novel behavioral method.

Cerebral autoregulation (CA) plays a critical role in maintaining cerebral blood flow (CBF) amid fluctuations in systemic blood pressure, with dysfunction increasing vulnerability to secondary brain injury, particularly after traumatic brain injury (TBI). While extensively studied in adults, CA dynamics in pediatric TBI (pTBI) remain relatively unexplored. Studying Trends in AutoRegulation in Severe Head Injury in Pediatrics (STARSHIP), the first multicenter, prospective study on CA in pTBI, investigates the pressure reactivity index (PRx) and its association with outcomes. PRx, calculated as the Pearson's correlation between mean arterial pressure and intracranial pressure, provides insights into the patient's CA status. In this article, STARSHIP Part 2 characterizes PRx disturbances using dose metrics that take the magnitude of PRx disturbance, and the time in which the patient experiences this derangement, into consideration. We calculated the dose (overall and hourly) and percentage time spent with a PRx above thresholds 0-0.4 in 135 children with TBI. Associations with outcome were explored via summary metrics and over time, using uni- and multivariable, and ordinal regression with propensity score matching, correcting for known outcome predictors. Patients with poor outcomes exhibited higher PRx dose and percentage time above threshold, even after adjusting for clinical predictors. Time trend analyses highlighted elevated PRx metrics in poor outcome groups during the first-week post-injury. Duration of impaired pressure reactivity, as denoted by the percentage time a patient spent with a PRx >0, is robustly and independently associated with dichotomized outcome at 12 months post-ictus. Our results highlight the predictive strength of PRx metrics, with percentage time above a threshold of 0 emerging as the most robust indicator of 12-month outcome. This work supports further investigation into the feasibility and impact of interventions guided by real-time CA monitoring in severe pTBI.