Brain Injury Research Research Articles

Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study

Several studies have reported an association between serum biomarker values and functional outcome following traumatic brain injury. We aimed to examine the incremental (added) prognostic value of serum biomarkers over demographic, clinical, and radiological characteristics and over established prognostic models, such as IMPACT and CRASH, for prediction of functional outcome. We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study. We included patients aged 14 years or older who had blood sampling within 24 h of injury, results from a CT scan, and outcome assessment according to the Glasgow Outcome Scale-Extended (GOSE) at 6 months. Amounts in serum of six biomarkers (S100 calcium-binding protein B, neuron-specific enolase, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 [UCH-L1], neurofilament protein-light, and total tau) were measured. The incremental prognostic value of these biomarkers was determined separately and in combination. The primary outcome was the GOSE 6 months after injury. Incremental prognostic value, using proportional odds and a dichotomised analysis, was assessed by delta C-statistic and delta R2 between models with and without serum biomarkers, corrected for optimism with a bootstrapping procedure. Serum biomarker values and 6-month GOSE were available for 2283 of 4509 patients. Higher biomarker levels were associated with worse outcome. Adding biomarkers improved the C-statistic by 0·014 (95% CI 0·009-0·020) and R2 by 4·9% (3·6-6·5) for predicting GOSE compared with demographic, clinical, and radiological characteristics. UCH-L1 had the greatest incremental prognostic value. Adding biomarkers to established prognostic models resulted in a relative increase in R2 of 48-65% for IMPACT and 30-34% for CRASH prognostic models. Serum biomarkers have incremental prognostic value for functional outcome after traumatic brain injury. Our findings support integration of biomarkers-particularly UCH-L1-in established prognostic models. European Union's Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences.

Risk Factors for High Symptom Burden Three Months after Traumatic Brain Injury and Implications for Clinical Trial Design: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study.

More than 75% of patients presenting to level I trauma centers in the United States with suspicion of TBI sufficient to require a clinical computed tomography scan report injury-related symptoms 3 months later. There are currently no approved treatments, and few clinical trials have evaluated possible treatments. Efficient trials will require subject inclusion and exclusion criteria that balance cost-effective recruitment with enrolling individuals with a higher chance of benefiting from the interventions. Using data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, we examined the relationship of 3-month symptoms to pre-injury, demographic, and acute characteristics as well as 2-week symptoms and blood-based biomarkers to identify and evaluate factors that may be used for sample enrichment for clinical trials. Many of the risk factors for TBI symptoms reported in the literature were supported, but the effect sizes of each were small or moderate (< 0.5). The only factors with large effect sizes when predicting 3-month symptom burden were TBI-related (i.e., post-concussive) and post-traumatic stress symptom levels at 2 weeks (respective effect sizes 1.13 and 1.34). TBI severity was not significantly associated with 3-month symptom burden (p = 0.37). Using simulated data to evaluate the effect of enrichment, we showed that including only people with high symptom burden at 2 weeks would permit trials to reduce the sample size by half, with minimal increase in screening, as compared with enrolling an unenriched sample. Clinical trials aimed at reducing symptoms after TBI can be efficiently conducted by enriching the included sample with people reporting a high early symptom burden.

Diffusion Tensor Imaging Reveals Elevated Diffusivity of White Matter Microstructure that Is Independently Associated with Long-Term Outcome after Mild Traumatic Brain Injury: A TRACK-TBI Study.

Diffusion tensor imaging (DTI) literature on single-center studies contains conflicting results regarding acute effects of mild traumatic brain injury (mTBI) on white matter (WM) microstructure and the prognostic significance. This larger-scale multi-center DTI study aimed to determine how acute mTBI affects WM microstructure over time and how early WM changes affect long-term outcome. From Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI), a cohort study at 11 United States level 1 trauma centers, a total of 391 patients with acute mTBI ages 17 to 60 years were included and studied at two weeks and six months post-injury. Demographically matched friends or family of the participants were the control group (n = 148). Axial diffusivity (AD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were the measures of WM microstructure. The primary outcome was the Glasgow Outcome Scale Extended (GOSE) score of injury-related functional limitations across broad life domains at six months post-injury. The AD, MD, and RD were higher and FA was lower in mTBI versus friend control (FC) at both two weeks and six months post-injury throughout most major WM tracts of the cerebral hemispheres. In the mTBI group, AD and, to a lesser extent, MD decreased in WM from two weeks to six months post-injury. At two weeks post-injury, global WM AD and MD were both independently associated with six-month incomplete recovery (GOSE <8 vs = 8) even after accounting for demographic, clinical, and other imaging factors. DTI provides reliable imaging biomarkers of dynamic WM microstructural changes after mTBI that have utility for patient selection and treatment response in clinical trials. Continued technological advances in the sensitivity, specificity, and precision of diffusion magnetic resonance imaging hold promise for routine clinical application in mTBI.

A-31 Examining Interactions between Concussion Population and Biological Sex on Post-Concussive Symptom Reporting in FITBIR

Abstract Purpose: The purpose of this study was to examine interactions between population (sport/civilian vs. military) and biological sex (females vs. males) on post-concussive symptom reporting using Federal Interagency Traumatic Brain Injury Research (FITBIR) data. Methods: Data were obtained from the national FITBIR informatics system. Studies released as of 04/07/21 that included both males and females with a history of concussion were included. In total, 6 studies with 9957 participants (8918 sport/civilian, 1039 military; 3209 females, 6748 males) were evaluated. Symptom measures included the Sport Concussion Assessment Tool-3rd Edition, Neurobehavioral Symptom Inventory, and Rivermead Post Concussion Symptoms Questionnaire. These measures were harmonized to generate an overall composite score and three symptom domains (somatic, affective, and cognitive). Data were analyzed using linear mixed-effects models. Symptom scores were regressed onto population, sex, and the population-by-sex interaction. Results: We found significant main effects of population (military&amp;gt;sport/civilian; beta(β) = 0.30, p = 0.003) and sex (females&amp;gt;males; β = 0.06, p &amp;lt; 0.001) on the overall composite, as well as a significant population-by-sex interaction such that female service members/veterans endorsed the highest rates of symptoms (β = 0.27, p &amp;lt; 0.001). Similar patterns of significance and effect sizes were observed for the somatic and affective composites. Cognitive symptom composites showed a similar pattern, but with smaller effect sizes overall. Conclusions: Findings increase our understanding of population and sex-specific experiences following concussion, suggesting a need for individually-tailored treatments and interventions for these groups. Future studies are planned using FITBIR data to further explore the population-by-sex interaction on post-injury outcomes.

Employment and Economic Outcomes of Participants With Mild Traumatic Brain Injury in the TRACK-TBI Study

Mild traumatic brain injury (mTBI) may impair the ability to work. Strategies to facilitate return to work are understudied. To assess employment and economic outcomes for employed, working-age adults with mTBI in the 12 months after injury and the association between return to work and employer assistance. Using data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a cohort study of patients with mTBI presenting to emergency departments of 11 level I US trauma centers was performed. Patients with mTBI enrolled in the TRACK-TBI cohort study from February 26, 2014, to May 4, 2016, were followed up at 2 weeks and 3, 6, and 12 months after injury. Work status and income decline of participants were documented in the first year after injury. Associations between work status, injury characteristics, and offer of employer assistance and associations between follow-up care and employer assistance were investigated. Results were adjusted for unobserved outcomes using inverse probability weighting. Data were extracted July 12, 2020; analyses were completed March 24, 2021. Analyses included 435 participants aged 18 to 64 years who were working before the injury, had a Glasgow Coma Scale score of 13 to 15, and completed all postinjury follow-up surveys. Primary outcomes were work status (working or not working) at each study follow-up milestone. Employer assistance included sick leave, reduced hours, modified schedule, transfer to different tasks, assistive technology, and coaching offered during the first 3 months after injury. Of 435 participants (147 [34%] female; 320 [74%] White; mean [SD] age 37.3 [12.9] years), 258 (59%) reported not working at 2 weeks after injury and 74 (17%) reported not working at 12 months after injury. More than one-fifth (92 [21%]) experienced a decline in annual income. Work status at 12 months was significantly associated with postconcussion symptoms experienced at 3 months after injury (73% of patients with 3 or more symptoms reported working at 12 months after injury vs 89% of patients with 2 or fewer symptoms; P < .001) but not with other injury characteristics. Participants offered employer assistance in the first 3 months after injury were more likely to report working after injury than those not offered such assistance (at 6 months: 88% vs 78%; P = .02; at 12 months: 86% vs 72%; P = .005). In this cohort study, mTBI was associated with substantial employment and economic consequences for some patients. Clinicians should systematically follow up with patients with mTBI and coordinate with employers to promote successful return to work.

Tailoring Multi-Dimensional Outcomes to Level of Functional Recovery after Traumatic Brain Injury.

There is increasing emphasis on assessing multi-dimensional outcomes in traumatic brain injury (TBI), but achieving this aim is hampered by a plethora of overlapping assessment tools. There is a clear need for advice on the choice of outcomes and we examined level of functional recovery as a framework to guide selection of assessments. In this cohort study we analysed cross-sectional data from 2604 patients enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) project. Patients were followed up 6 months after injury and assessed on the Glasgow Outcome Scale-Extended (GOSE), cognitive tests, and patient-reported outcomes. We describe assessment completeness and prevalence of impairment. Relationships between outcomes were visualized using UpSet plots and hierarchical cluster analysis. GOSE categories varied markedly for both completion rates, 34-91% for patient-reported outcomes and 9-81% for cognitive tests, and prevalence of impairment, 3-82% for patient-reported outcomes and 9-59% for cognitive tests. In complete case samples, the GOSE identified impairment in 59-61%, whereas the most impaired patient-reported outcome was the Short Form-12 version 2 (SF-12v2) Physical Component Summary (28% overall), and the most impaired cognitive test was Trail Making Test (TMT) Part A (19% overall). The findings show that degree of disability is a key context of use for cognitive tests and patient-reported outcomes. Level of functional recovery provides a guide to the feasibility of different types of assessment and the likelihood of impairment, and can help tailor suitable assessment approaches in clinical practice and research studies.

Comparison Groups Matter in Traumatic Brain Injury Research: An Example with Dementia.

The association between traumatic brain injury (TBI) and risk for Alzheimer disease and related dementias (ADRD) has been investigated in multiple studies, yet reported effect sizes have varied widely. Large differences in comorbid and demographic characteristics between individuals with and without TBI could result in spurious associations between TBI and poor outcomes, even when control for confounding is attempted. Yet, inadvertent control for post-TBI exposures (e.g., psychological and physical trauma) could result in an underestimate of the effect of TBI. Choice of the unexposed or comparison group is critical to estimating total associated risk. The objective of this study was to highlight how selection of the comparison group impacts estimates of the effect of TBI on risk for ADRD. Using data on Veterans aged ≥55 years obtained from the Veterans Health Administration (VA) for years 1999-2019, we compared risk of ADRD between Veterans with incident TBI (n = 9440) and (1) the general population of Veterans who receive care at the VA (All VA) (n = 119,003); (2) Veterans who received care at a VA emergency department (VA ED) (n = 111,342); and (3) Veterans who received care at a VA ED for non-TBI trauma (VA ED NTT) (n = 65,710). In inverse probability of treatment weighted models, TBI was associated with increased risk of ADRD compared with All VA (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.84, 2.04), VA ED (HR 1.42; 95% CI 1.35, 1.50), and VA ED NTT (HR 1.12; 95% CI 1.06, 1.18). The estimated effect of TBI on incident ADRD was strongly impacted by choice of the comparison group.

Combined Traumatic Brain Injury and Hemorrhagic Shock in Ferrets Leads to Structural, Neurochemical, and Functional Impairments.

Aeromedical evacuation-relevant hypobaria after traumatic brain injury (TBI) leads to increased neurological injury and death in rats relative to those maintained under normobaria. Applicability of rodent brain injury research to humans may be limited, however, by differences in neuroanatomy. Therefore, we developed a model in which ferrets are exposed to polytrauma consisting of controlled cortical impact TBI and hemorrhagic shock subjected 24 h later to 6 h of hypobaria or normobaria. Our objective was to determine whether the deleterious effects of hypobaria observed in rats, with lissencephalic brains, are also present in a species with a human-like gyrencephalic brain. While no deaths were observed, magnetic resonance spectroscopy (MRS) results obtained two days post-injury indicated reduced cortical creatine, N-acetylaspartate, gamma-aminobutyric acid, myo-inositol, and glutamate that were not affected by hypobaria. T2-weighted magnetic resonance imaging quantification revealed increased hyperintensity volume representing cortical edema at the site of impact after polytrauma. Hypobaria did not exacerbate this focal edema but did lead to overall reductions in total cortical volume. Both normobaric and hypobaric ferrets exhibited impaired spatial memory six days post-injury on the Object Location Test, but no differences were noted between groups. Finally, cortical lesion volume was not exacerbated by hypobaria exposure on day 7 post-injury. Results suggest that air travel 24 h after polytrauma is associated with structural changes in the ferret brain. Future studies should investigate secondary injury from hypobaria after polytrauma in greater detail including alternative outcome measures, time points, and exposure to multiple flights.

A daily temperature rhythm in the human brain predicts survival after brain injury.

Patients undergo interventions to achieve a ‘normal’ brain temperature; a parameter that remains undefined for humans. The profound sensitivity of neuronal function to temperature implies the brain should be isothermal, but observations from patients and non-human primates suggest significant spatiotemporal variation. We aimed to determine the clinical relevance of brain temperature in patients by establishing how much it varies in healthy adults.We retrospectively screened data for all patients recruited to the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High Resolution Intensive Care Unit Sub-Study. Only patients with direct brain temperature measurements and without targeted temperature management were included. To interpret patient analyses, we prospectively recruited 40 healthy adults (20 males, 20 females, 20–40 years) for brain thermometry using magnetic resonance spectroscopy. Participants were scanned in the morning, afternoon, and late evening of a single day.In patients (n = 114), brain temperature ranged from 32.6 to 42.3°C and mean brain temperature (38.5 ± 0.8°C) exceeded body temperature (37.5 ± 0.5°C, P < 0.0001). Of 100 patients eligible for brain temperature rhythm analysis, 25 displayed a daily rhythm, and the brain temperature range decreased in older patients (P = 0.018). In healthy participants, brain temperature ranged from 36.1 to 40.9°C; mean brain temperature (38.5 ± 0.4°C) exceeded oral temperature (36.0 ± 0.5°C) and was 0.36°C higher in luteal females relative to follicular females and males (P = 0.0006 and P < 0.0001, respectively). Temperature increased with age, most notably in deep brain regions (0.6°C over 20 years, P = 0.0002), and varied spatially by 2.41 ± 0.46°C with highest temperatures in the thalamus. Brain temperature varied by time of day, especially in deep regions (0.86°C, P = 0.0001), and was lowest at night. From the healthy data we built HEATWAVE—a 4D map of human brain temperature. Testing the clinical relevance of HEATWAVE in patients, we found that lack of a daily brain temperature rhythm increased the odds of death in intensive care 21-fold (P = 0.016), whilst absolute temperature maxima or minima did not predict outcome. A warmer mean brain temperature was associated with survival (P = 0.035), however, and ageing by 10 years increased the odds of death 11-fold (P = 0.0002).Human brain temperature is higher and varies more than previously assumed—by age, sex, menstrual cycle, brain region, and time of day. This has major implications for temperature monitoring and management, with daily brain temperature rhythmicity emerging as one of the strongest single predictors of survival after brain injury. We conclude that daily rhythmic brain temperature variation—not absolute brain temperature—is one way in which human brain physiology may be distinguished from pathophysiology.

Automated soccer head impact exposure tracking using video and deep learning

Head impacts are highly prevalent in sports and there is a pressing need to investigate the potential link between head impact exposure and brain injury risk. Wearable impact sensors and manual video analysis have been utilized to collect impact exposure data. However, wearable sensors suffer from high deployment cost and limited accuracy, while manual video analysis is a long and resource-intensive task. Here we develop and apply DeepImpact, a computer vision algorithm to automatically detect soccer headers using soccer game videos. Our data-driven pipeline uses two deep learning networks including an object detection algorithm and temporal shift module to extract visual and temporal features of video segments and classify the segments as header or nonheader events. The networks were trained and validated using a large-scale professional-level soccer video dataset, with labeled ground truth header events. The algorithm achieved 95.3% sensitivity and 96.0% precision in cross-validation, and 92.9% sensitivity and 21.1% precision in an independent test that included videos of five professional soccer games. Video segments identified as headers in the test data set correspond to 3.5 min of total film time, which can be reviewed through additional manual video verification to eliminate false positives. DeepImpact streamlines the process of manual video analysis and can help to collect large-scale soccer head impact exposure datasets for brain injury research. The fully video-based solution is a low-cost alternative for head impact exposure monitoring and may also be expanded to other sports in future work.

Health care utilization and outcomes in older adults after Traumatic Brain Injury: A CENTER-TBI study

IntroductionThe incidence of Traumatic Brain Injury (TBI) is increasingly common in older adults aged ≥65 years, forming a growing public health problem. However, older adults are underrepresented in TBI research. Therefore, we aimed to provide an overview of health-care utilization, and of six-month outcomes after TBI and their determinants in older adults who sustained a TBI. MethodsWe used data from the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. In-hospital and post-hospital health care utilization and outcomes were described for patients aged ≥65 years. Ordinal and linear regression analyses were performed to identify determinants of the Glasgow Outcome Scale Extended (GOSE), health-related quality of life (HRQoL), and mental health symptoms six-months post-injury. ResultsOf 1254 older patients, 45% were admitted to an ICU with a mean length of stay of 9 days. Nearly 30% of the patients received inpatient rehabilitation. In total, 554/1254 older patients completed the six-month follow-up questionnaires. The mortality rate was 9% after mild and 60% after moderate/severe TBI, and full recovery based on GOSE was reported for 44% of patients after mild and 6% after moderate/severe TBI. Higher age and increased injury severity were primarily associated with functional impairment, while pre-injury systemic disease, psychiatric conditions and lower educational level were associated with functional impairment, lower generic and disease-specific HRQoL and mental health symptoms. ConclusionThe rate of impairment and disability following TBI in older adults is substantial, and poorer outcomes across domains are associated with worse preinjury health. Nonetheless, a considerable number of patients fully or partially returns to their preinjury functioning. There should not be pessimism about outcomes in older adults who survive.

Novel Injury Scoring Tool for Assessing Brain Injury following Neonatal Hypoxia-Ischemia in Mice

The variability of severity in hypoxia-ischemia (HI)-induced brain injury among research subjects is a major challenge in developmental brain injury research. Our laboratory developed a novel injury scoring tool based on our gross pathological observations during hippocampal extraction. The hippocampi received scores of 0–6 with 0 being no injury and 6 being severe injury post-HI. The hippocampi exposed to sham surgery were grouped as having no injury. We have validated the injury scoring tool with T2-weighted MRI analysis of percent hippocampal/hemispheric tissue loss and cell survival/death markers after exposing the neonatal mice to Vannucci’s rodent model of neonatal HI. In addition, we have isolated hippocampal nuclei and quantified the percent good quality nuclei to provide an example of utilization of our novel injury scoring tool. Our novel injury scores correlated significantly with percent hippocampal and hemispheric tissue loss, cell survival/death markers, and percent good quality nuclei. Caspase-3 and Poly (ADP-ribose) polymerase-1 (PARP1) have been implicated in different cell death pathways in response to neonatal HI. Another gene, sirtuin1 (SIRT1), has been demonstrated to have neuroprotective and anti-apoptotic properties. To assess the correlation between the severity of injury and genes involved in cell survival/death, we analyzed caspase-3, PARP1, and SIRT1 mRNA expressions in hippocampi 3 days post-HI and sham surgery, using quantitative reverse transcription polymerase chain reaction. The ipsilateral (IL) hippocampal caspase-3 and SIRT1 mRNA expressions post-HI were significantly higher than sham IL hippocampi and positively correlated with the novel injury scores in both males and females. We detected a statistically significant sex difference in IL hippocampal caspase-3 mRNA expression with comparable injury scores between males and females with higher expression in females.

Investigating Brain White Matter in Football Players with and without Concussion Using a Biophysical Model from Multishell Diffusion MRI.

There have been growing concerns around potential risks related to sports-related concussion and contact sport exposure to repetitive head impacts in young athletes. Here we investigate WM microstructural differences between collegiate football players with and without sports-related concussion. The study included 78 collegiate athletes (24 football players with sports-related concussion, 26 football players with repetitive head impacts, and 28 non-contact-sport control athletes), available through the Federal Interagency Traumatic Brain Injury Research registry. Diffusion metrics of diffusion tensor/kurtosis imaging and WM tract integrity were calculated. Tract-Based Spatial Statistics and post hoc ROI analyses were performed to test group differences. Significantly increased axial kurtosis in those with sports-related concussion compared with controls was observed diffusely across the whole-brain WM, and some focal areas demonstrated significantly higher mean kurtosis and extra-axonal axial diffusivity in sports-related concussion. The extent of significantly different WM regions decreased across time points and remained present primarily in the corpus callosum. Similar differences in axial kurtosis were found between the repetitive head impact and control groups. Other significant differences were seen at unrestricted return-to-play with lower radial kurtosis and intra-axonal diffusivity in those with sports-related concussion compared with the controls, mainly restricted to the posterior callosum. This study highlights the fact that there are differences in diffusion microstructure measures that are present not only between football players with sports-related injuries and controls, but that there are also measurable differences between football players with repetitive head impacts and controls. This work reinforces previous work showing that the corpus callosum is specifically implicated in sports-related concussion and also suggests this to be true for repetitive head impacts.

Serum metabolome associated with severity of acute traumatic brain injury

Complex metabolic disruption is a crucial aspect of the pathophysiology of traumatic brain injury (TBI). Associations between this and systemic metabolism and their potential prognostic value are poorly understood. Here, we aimed to describe the serum metabolome (including lipidome) associated with acute TBI within 24 h post-injury, and its relationship to severity of injury and patient outcome. We performed a comprehensive metabolomics study in a cohort of 716 patients with TBI and non-TBI reference patients (orthopedic, internal medicine, and other neurological patients) from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We identified panels of metabolites specifically associated with TBI severity and patient outcomes. Choline phospholipids (lysophosphatidylcholines, ether phosphatidylcholines and sphingomyelins) were inversely associated with TBI severity and were among the strongest predictors of TBI patient outcomes, which was further confirmed in a separate validation dataset of 558 patients. The observed metabolic patterns may reflect different pathophysiological mechanisms, including protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

A Narrative Review on Translational Research in Acute Brain Injury

AbstractThere has been a constant endeavor to reduce the mortality and morbidity associated with acute brain injury. The associated complex mechanisms involving biomechanics, markers, and neuroprotective drugs/measures have been extensively studied in preclinical studies with an ultimate aim to improve the patients' outcomes. Despite such efforts, only few have been successfully translated into clinical practice. In this review, we shall be discussing the major hurdles in the translation of preclinical results into clinical practice. The need is to choose an appropriate animal model, keeping in mind the species, age, and gender of the animal, choosing suitable outcome measures, ensuring quality of animal trials, and carrying out systematic review and meta-analysis of experimental studies before proceeding to human trials. The interdisciplinary collaboration between the preclinical and clinical scientists will help to design better, meaningful trials which might help a long way in successful translation. Although challenging at this stage, the advent of translational precision medicine will help the integration of mechanism-centric translational medicine and patient-centric precision medicine.

Surgery versus conservative treatment for traumatic acute subdural haematoma: a prospective, multicentre, observational, comparative effectiveness study

Despite being well established, acute surgery in traumatic acute subdural haematoma is based on low-grade evidence. We aimed to compare the effectiveness of a strategy preferring acute surgical evacuation with one preferring initial conservative treatment in acute subdural haematoma. We did a prospective, observational, comparative effectiveness study using data from participants enrolled in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We included patients with no pre-existing severe neurological disorders who presented with acute subdural haematoma within 24 h of traumatic brain injury. Using an instrumental variable analysis, we compared outcomes between centres according to treatment preference for acute subdural haematoma (acute surgical evacuation or initial conservative treatment), measured by the case-mix-adjusted percentage of acute surgery per centre. The primary endpoint was functional outcome at 6 months as rated with the Glasgow Outcome Scale Extended, which was estimated with ordinal regression as a common odds ratio (OR) and adjusted for prespecified confounders. Variation in centre preference was quantified with the median OR (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Between Dec 19, 2014 and Dec 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI, of whom 1407 (31%) presented with acute subdural haematoma and were included in our study. Acute surgical evacuation was done in 336 (24%) patients, by craniotomy in 245 (73%) of those patients and by decompressive craniectomy in 91 (27%). Delayed decompressive craniectomy or craniotomy after initial conservative treatment (n=982) occurred in 107 (11%) patients. The percentage of patients who underwent acute surgery ranged from 5·6% to 51·5% (IQR 12·3-35·9) between centres, with a two-times higher probability of receiving acute surgery for an identical patient in one centre versus another centre at random (adjusted MOR for acute surgery 1·8; p<0·0001]). Centre preference for acute surgery over initial conservative treatment was not associated with improvements in functional outcome (common OR per 23·6% [IQR increase] more acute surgery in a centre 0·92, 95% CI 0·77-1·09). Our findings show that treatment for patients with acute subdural haematoma with similar characteristics differed depending on the treating centre, because of variation in the preferred approach. A treatment strategy preferring an aggressive approach of acute surgical evacuation over initial conservative treatment was not associated with better functional outcome. Therefore, in a patient with acute subdural haematoma for whom a neurosurgeon sees no clear superiority for acute surgery over conservative treatment, initial conservative treatment might be considered. The Hersenstichting Nederland (also known as the Dutch Brain Foundation), the European Commission Seventh Framework Programme, the Hannelore Kohl Stiftung (Germany), OneMind (USA), Integra LifeSciences Corporation (USA), and NeuroTrauma Sciences (USA).

Challenges Encountered in Surgical Traumatic Brain Injury Research: A Need for Methodological Improvement of Future Studies

Investigating neurosurgical interventions for traumatic brain injury (TBI) involves complex methodological and practical challenges. In the present report, we have provided an overview of the current state of neurosurgical TBI research and discussed the key challenges and possible solutions. The content of our report was based on an extensive literature review and personal knowledge and expert opinions of senior neurosurgeon researchers and epidemiologists. Current best practice research strategies include randomized controlled trials (RCTs) and comparative effectiveness research. The performance of RCTs has been complicated by the heterogeneity of TBI patient populations with the associated sample size requirements, the traditional eminence-based neurosurgical culture, inadequate research budgets, and the often acutely life-threatening setting of severe TBI. Statistical corrections can mitigate the effects of heterogeneity, and increasing awareness of clinical equipoise and informed consent alternatives can improve trial efficiency. The substantial confounding by indication, which limits the interpretability of observational research, can be circumvented by using an instrumental variable analysis. Traditional TBI outcome measures remain relevant but do not adequately capture the subtleties of well-being, suggesting a need for multidimensional approaches to outcome assessments. In settings in which traditional RCTs are difficult to conduct and substantial confounding by indication can be present, observational studies using an instrumental variable analysis and "pragmatic" RCTs are promising alternatives. Embedding TBI research into standard clinical practice should be more frequently considered but will require fundamental modifications to the current health care system. Finally, multimodality outcome assessment will be key to improving future surgical and nonsurgical TBI research.

Outcome Prediction in Patients with Severe Traumatic Brain Injury Using Deep Learning from Head CT Scans.

Background After severe traumatic brain injury (sTBI), physicians use long-term prognostication to guide acute clinical care yet struggle to predict outcomes in comatose patients. Purpose To develop and evaluate a prognostic model combining deep learning of head CT scans and clinical information to predict long-term outcomes after sTBI. Materials and Methods This was a retrospective analysis of two prospectively collected databases. The model-building set included 537 patients (mean age, 40 years ± 17 [SD]; 422 men) from one institution from November 2002 to December 2018. Transfer learning and curriculum learning were applied to a convolutional neural network using admission head CT to predict mortality and unfavorable outcomes (Glasgow Outcomes Scale scores 1-3) at 6 months. This was combined with clinical input for a holistic fusion model. The models were evaluated using an independent internal test set and an external cohort of 220 patients with sTBI (mean age, 39 years ± 17; 166 men) from 18 institutions in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study from February 2014 to April 2018. The models were compared with the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model and the predictions of three neurosurgeons. Area under the receiver operating characteristic curve (AUC) was used as the main model performance metric. Results The fusion model had higher AUCs than did the IMPACT model in the prediction of mortality (AUC, 0.92 [95% CI: 0.86, 0.97] vs 0.80 [95% CI: 0.71, 0.88]; P < .001) and unfavorable outcomes (AUC, 0.88 [95% CI: 0.82, 0.94] vs 0.82 [95% CI: 0.75, 0.90]; P = .04) on the internal data set. For external TRACK-TBI testing, there was no evidence of a significant difference in the performance of any models compared with the IMPACT model (AUC, 0.83; 95% CI: 0.77, 0.90) in the prediction of mortality. The Imaging model (AUC, 0.73; 95% CI: 0.66-0.81; P = .02) and the fusion model (AUC, 0.68; 95% CI: 0.60, 0.76; P = .02) underperformed as compared with the IMPACT model (AUC, 0.83; 95% CI: 0.77, 0.89) in the prediction of unfavorable outcomes. The fusion model outperformed the predictions of the neurosurgeons. Conclusion A deep learning model of head CT and clinical information can be used to predict 6-month outcomes after severe traumatic brain injury. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Haller in this issue.

Evaluation of brain injury caused by stick type blunt instruments based on convolutional neural network and finite element method

The finite element method is a new method to study the mechanism of brain injury caused by blunt instruments. But it is not easy to be applied because of its technology barrier of time-consuming and strong professionalism. In this study, a rapid and quantitative evaluation method was investigated to analyze the craniocerebral injury induced by blunt sticks based on convolutional neural network and finite element method. The velocity curve of stick struck and the maximum principal strain of brain tissue (cerebrum, corpus callosum, cerebellum and brainstem) from the finite element simulation were used as the input and output parameters of the convolutional neural network The convolutional neural network was trained and optimized by using the 10-fold cross-validation method. The Mean Absolute Error (MAE), Mean Square Error (MSE), and Goodness of Fit ( R 2) of the finally selected convolutional neural network model for the prediction of the maximum principal strain of the cerebrum were 0.084, 0.014, and 0.92, respectively. The predicted results of the maximum principal strain of the corpus callosum were 0.062, 0.007, 0.90, respectively. The predicted results of the maximum principal strain of the cerebellum and brainstem were 0.075, 0.011, and 0.94, respectively. These results show that the research and development of the deep convolutional neural network can quickly and accurately assess the local brain injury caused by the sticks blow, and have important application value for understanding the quantitative evaluation and the brain injury caused by the sticks struck. At the same time, this technology improves the computational efficiency and can provide a basis reference for transforming the current acceleration-based brain injury research into a focus on local brain injury research.

The Value of Patient Registries to Advance Basic and Translational Research in the Area of Traumatic Brain Injury.

The number of individuals affected by traumatic brain injury (TBI) is growing globally. TBIs may cause a range of physical, cognitive, and psychiatric deficits that can negatively impact employment, academic attainment, community independence, and interpersonal relationships. Although there has been a significant decrease in the number of injury related deaths over the past several decades, there has been no corresponding reduction in injury related disability over the same time period. We propose that patient registries with large, representative samples and rich multidimensional and longitudinal data have tremendous value in advancing basic and translational research and in capturing, characterizing, and predicting individual differences in deficit profile and outcomes. Patient registries, together with recent theoretical and methodological advances in analytic approaches and neuroscience, provide powerful tools for brain injury research and for leveraging the heterogeneity that has traditionally been cited as a barrier inhibiting progress in treatment research and clinical practice. We report on our experiences, and challenges, in developing and maintaining our own patient registry. We conclude by pointing to some future opportunities for discovery that are afforded by a registry model.