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 (
= 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.
Guideline recommendations for surgical management of traumatic epidural hematomas (EDHs) do not directly address EDHs that co-occur with other intracranial hematomas; the relative rates of isolated ...vs nonisolated EDHs and guideline adherence are unknown. We describe characteristics of a contemporary cohort of patients with EDHs and identify factors influencing acute surgery.
This research was conducted within the longitudinal, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury cohort study which prospectively enrolled patients with traumatic brain injury from 65 hospitals in 18 European countries from 2014 to 2017. All patients with EDH on the first scan were included. We describe clinical, imaging, management, and outcome characteristics and assess associations between site and baseline characteristics and acute EDH surgery, using regression modeling.
In 461 patients with EDH, median age was 41 years (IQR 24-56), 76% were male, and median EDH volume was 5 cm3 (IQR 2-20). Concomitant acute subdural hematomas (ASDHs) and/or intraparenchymal hemorrhages were present in 328/461 patients (71%). Acute surgery was performed in 99/461 patients (21%), including 70/86 with EDH volume ≥30 cm3 (81%). Larger EDH volumes (odds ratio OR 1.19 95% CI 1.14-1.24 per cm3 below 30 cm3), smaller ASDH volumes (OR 0.93 95% CI 0.88-0.97 per cm3), and midline shift (OR 6.63 95% CI 1.99-22.15) were associated with acute surgery; between-site variation was observed (median OR 2.08 95% CI 1.01-3.48). Six-month Glasgow Outcome Scale-Extended scores ≥5 occurred in 289/389 patients (74%); 41/389 (11%) died.
Isolated EDHs are relatively infrequent, and two-thirds of patients harbor concomitant ASDHs and/or intraparenchymal hemorrhages. EDHs ≥30 cm3 are generally evacuated early, adhering to Brain Trauma Foundation guidelines. For heterogeneous intracranial pathology, surgical decision-making is related to clinical status and overall lesion burden. Further research should examine the optimal surgical management of EDH with concomitant lesions in traumatic brain injury, to inform updated guidelines.
The guiding principle for data stewardship dictates that data be FAIR: findable, accessible, interoperable, and reusable. Data reuse allows researchers to probe data that may have been originally ...collected for other scientific purposes in order to gain novel insights. The current study reuses the Transforming Research and Clinical Knowledge for Traumatic Brain Injury (TRACK-TBI) Pilot dataset to build upon prior findings and ask new scientific questions. Specifically, we have previously used a multivariate analytics approach to multianalyte serum protein data from the TRACK-TBI Pilot dataset to show that an inflammatory ensemble of biomarkers can predict functional outcome at 3 and 6 months post-TBI. We and others have shown that there are quantitative and qualitative changes in inflammation that come with age, but little is known about how this interaction affects recovery from TBI. Here we replicate the prior proteomics findings with improved missing value analyses and non-linear principal component analysis and then expand upon this work to determine whether age moderates the effect of inflammation on recovery. We show that increased age correlates with worse functional recovery on the Glasgow Outcome Scale-Extended (GOS-E) as well as increased inflammatory signature. We then explore the interaction between age and inflammation on recovery, which suggests that inflammation has a more detrimental effect on recovery for older TBI patients.
The admission noncontrast head computed tomography (CT) scan has been demonstrated to be one of several key early clinical and imaging features in the challenging problem of prediction of long-term ...outcome after acute traumatic brain injury (TBI). In this study, we employ two novel approaches to the problem of imaging classification and outcome prediction in acute TBI. First, we employ the novel technique of quantitative CT (qCT) image analysis to provide more objective, reproducible measures of the abnormal features of the admission head CT in acute TBI. We show that the incorporation of quantitative, rather than qualitative, CT features results in a significant improvement in prediction of the 6-month Extended Glasgow Outcome Scale (GOS-E) score over a wide spectrum of injury severity. Second, we employ principal components analysis (PCA) to demonstrate the interdependence of certain predictive variables. Relatively few prior studies of outcome prediction in acute TBI have used a multivariate approach that explicitly takes into account the potential covariance among clinical and CT predictive variables. We demonstrate that several predictors, including midline shift, cistern effacement, subdural hematoma volume, and Glasgow Coma Scale (GCS) score are related to one another. Rather than being independent features, their importance may be related to their status as surrogate measures of a more fundamental underlying clinical feature, such as the severity of intracranial mass effect. We believe that objective computational tools and data-driven analytical methods hold great promise for neurotrauma research, and may ultimately have a role in image analysis for clinical care.
Glial fibrillary acidic protein and its breakdown products (GFAP-BDP) are brain-specific proteins released into serum as part of the pathophysiological response after traumatic brain injury (TBI). We ...performed a multi-center trial to validate and characterize the use of GFAP-BDP levels in the diagnosis of intracranial injury in a broad population of patients with a positive clinical screen for head injury. This multi-center, prospective, cohort study included patients 16-93 years of age presenting to three level 1 trauma centers with suspected TBI (loss of consciousness, post-trauma amnesia, and so on). Serum GFAP-BDP levels were drawn within 24 h and analyzed, in a blinded fashion, using sandwich enzyme-linked immunosorbent assay. The ability of GFAP-BDP to predict intracranial injury on admission computed tomography (CT) as well as delayed magnetic resonance imaging was analyzed by multiple regression and assessed by the area under the receiver operating characteristic curve (AUC). Utility of GFAP-BDP to predict injury and reduce unnecessary CT scans was assessed utilizing decision curve analysis. A total of 215 patients were included, of which 83% suffered mild TBI, 4% moderate, and 12% severe; mean age was 42.1±18 years. Evidence of intracranial injury was present in 51% of the sample (median Rotterdam Score, 2; interquartile range, 2). GFAP-BDP demonstrated very good predictive ability (AUC=0.87) and demonstrated significant discrimination of injury severity (odds ratio, 1.45; 95% confidence interval, 1.29-1.64). Use of GFAP-BDP yielded a net benefit above clinical screening alone and a net reduction in unnecessary scans by 12-30%. Used in conjunction with other clinical information, rapid measurement of GFAP-BDP is useful in establishing or excluding the diagnosis of radiographically apparent intracranial injury throughout the spectrum of TBI. As an adjunct to current screening practices, GFAP-BDP may help avoid unnecessary CT scans without sacrificing sensitivity (Registry: ClinicalTrials.gov Identifier: NCT01565551).
Identifying the principal determinants of life satisfaction following mild TBI (mTBI) may inform efforts to improve subjective well-being in this population. We examined life satisfaction among ...participants in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study who presented with mTBI (Glasgow Coma Scale GCS score = 13-15;
= 1152). An L1-regularization path algorithm was used to select optimal sets of baseline and concurrent symptom measures for prediction of scores on the Satisfaction with Life Scale (SWLS) at 2 weeks and 3, 6, and 12 months post-injury. Multi-variable linear regression models (all
= 744-894) were then fit to evaluate associations between the empirically selected predictors and SWLS scores at each follow-up visit. Results indicated that emotional post-TBI symptoms (all b = -1.27 to -0.77, all
< 0.05), anhedonia (all b = -1.59 to -1.08, all
< 0.01), and pain interference (all b = -1.38 to -0.89, all
< 0.001) contributed to the prediction of lower SWLS scores at all follow-ups. Insomnia predicted lower SWLS scores at 2 weeks, 3 months, and 6 months (all b = -1.11 to -0.83, all
s < 0.01); and negative affect predicted lower SWLS scores at 2 weeks, 3 months, and 12 months (all b = -1.38 to -0.80, all
< 0.005). Other post-TBI symptom domains and baseline socio-demographic, injury-related, and clinical characteristics did not emerge as robust predictors of SWLS scores during the year after mTBI. Efforts to improve satisfaction with life following mTBI may benefit from a focus on the detection and treatment of affective symptoms, pain, and insomnia. The results reinforce the need for tailoring of evidence-based treatments for these conditions to maximize efficacy in patients with mTBI.
The idea that multiple traumatic brain injury (TBI) can have a cumulative detrimental effect on functioning is widely accepted. Most research supporting this idea comes from athlete samples, and it ...is not known whether remote history of previous TBI affects functioning after subsequent TBI in community-based samples. This study investigates whether a previous history of TBI with loss of consciousness (LOC) is associated with worse health and functioning in a sample of individuals who require emergency department care for current TBI. Twenty-three percent of the 586 individuals with current TBI in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study reported having sustained a previous TBI with LOC. Individuals with previous TBI were more likely to be unemployed (χ(2)=17.86; p=0.000), report a variety of chronic medical and psychiatric conditions (4.75≤χ(2)≥24.16; p<0.05), and report substance use (16.35≤χ(2)≥27.57; p<0.01) before the acute injury, compared to those with no previous TBI history. Those with a previous TBI had less-severe acute injuries, but experienced worse outcomes at 6-month follow-up. Results of a series of regression analyses controlling for demographics and acute injury severity indicated that individuals with previous TBI reported more mood symptoms, more postconcussive symptoms, lower life satisfaction, and had slower processing speed and poorer verbal learning, compared to those with no previous TBI history. These findings suggest that history of TBI with LOC may have important implications for health and psychological functioning after TBI in community-based samples.
Neuroworsening may be a sign of progressive brain injury and is a factor for treatment of traumatic brain injury (TBI) in intensive care settings. The implications of neuroworsening for clinical ...management and long-term sequelae of TBI in the emergency department (ED) require characterization.
Adult TBI subjects from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study with ED admission and disposition Glasgow Coma Scale (GCS) scores were extracted. All patients received head computed tomography (CT) scan <24 h post-injury. Neuroworsening was defined as a decline in motor GCS at ED disposition (vs. ED admission). Clinical and CT characteristics, neurosurgical intervention, in-hospital mortality, and 3- and 6-month Glasgow Outcome Scale-Extended (GOS-E) scores were compared by neuroworsening status. Multivariable regressions were performed for neurosurgical intervention and unfavorable outcome (GOS-E ≤ 3). Multivariable odds ratios (mOR) with 95% confidence intervals were reported.
In 481 subjects, 91.1% had ED admission GCS 13-15 and 3.3% had neuroworsening. All neuroworsening subjects were admitted to intensive care unit (vs. non-neuroworsening: 26.2%) and were CT-positive for structural injury (vs. 45.4%). Neuroworsening was associated with subdural (75.0%/22.2%), subarachnoid (81.3%/31.2%), and intraventricular hemorrhage (18.8%/2.2%), contusion (68.8%/20.4%), midline shift (50.0%/2.6%), cisternal compression (56.3%/5.6%), and cerebral edema (68.8%/12.3%; all
< 0.001). Neuroworsening subjects had higher likelihoods of cranial surgery (56.3%/3.5%), intracranial pressure (ICP) monitoring (62.5%/2.6%), in-hospital mortality (37.5%/0.6%), and unfavorable 3- and 6-month outcome (58.3%/4.9%; 53.8%/6.2%; all
< 0.001). On multivariable analysis, neuroworsening predicted surgery (mOR = 4.65 1.02-21.19), ICP monitoring (mOR = 15.48 2.92-81.85, and unfavorable 3- and 6-month outcome (mOR = 5.36 1.13-25.36; mOR = 5.68 1.18-27.35).
Neuroworsening in the ED is an early indicator of TBI severity, and a predictor of neurosurgical intervention and unfavorable outcome. Clinicians must be vigilant in detecting neuroworsening, as affected patients are at increased risk for poor outcomes and may benefit from immediate therapeutic interventions.
Several proteins have proven useful as blood-based biomarkers to assist in evaluation and management of traumatic brain injury (TBI). The objective of this study was to determine whether two ...day-of-injury blood-based biomarkers are predictive of posttraumatic stress disorder (PTSD). We used data from 1143 individuals with mild TBI (mTBI; defined as admission Glasgow Coma Scale GCS score 13-15) enrolled in TRACK-TBI, a prospective longitudinal study of level 1 trauma center patients. Plasma glial fibrillary acidic protein (GFAP) and serum high sensitivity C-reactive protein (hsCRP) were measured from blood collected within 24 h of injury. Two hundred and twenty-seven (19.9% of) patients had probable PTSD (PCL-5 score ≥ 33) at 6 months post-injury. GFAP levels were positively associated (Spearman's rho = 0.35, p < 0.001) with duration of posttraumatic amnesia (PTA). There was an inverse association between PTSD and (log)GFAP (adjusted OR = 0.85, 95% CI 0.77-0.95 per log unit increase) levels, but no significant association with (log)hsCRP (adjusted OR = 1.11, 95% CI 0.98-1.25 per log unit increase) levels. Elevated day-of-injury plasma GFAP, a biomarker of glial reactivity, is associated with reduced risk of PTSD after mTBI. This finding merits replication and additional studies to determine a possible neurocognitive basis for this relationship.
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