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OBJECTIVES: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort. METHODS: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury. RESULTS: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months. CONCLUSIONS: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed. LEVEL OF EVIDENCE: IV. TRIAL REGISTRATION NUMBER: NCT02119182.

OBJECTIVES: We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate-severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury. DESIGN: Retrospective cohort study. SETTING: ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. PATIENTS: Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate-severe TBI (Glasgow Coma Scale of

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) may be a chronic condition carrying risk of future sequelae; few prospective studies examine long-term postinjury outcomes. We examined the prevalence of functional, cognitive, and psychiatric change outcomes from 1 to 7 years postinjury. METHODS: Transforming Research and Clinical Knowledge in TBI LONG (TRACK-TBI LONG) participants were prospectively enrolled within 24 hours of injury and followed up to 1 year postinjury; a subset participated in long-term follow-up from 2 to 7 years postinjury. Reliable change thresholds for the Brief Test of Adult Cognition by Telephone General Composite (cognition) and Brief Symptom Inventory (BSI)-18 (psychiatric) were derived from orthopedic trauma controls (OTCs). Multiple assessments were completed (postinjury baseline assessment and 2 or 3 visits 2-7 years postinjury) within a sample subset. Change was assessed for functional outcome (Glasgow Outcome Scale-Extended [GOSE]) and self-report/informant report of decline. Prevalence ratios for outcomes classified as stable, improved, and declined were reported individually and collectively. The Fisher exact test and log-binomial regression models examined factors associated with decline and improvement. RESULTS: Of the sample (N = 1,264; mild TBI [mTBI], Glasgow Coma Scale [GCS] 13-15, n = 917; moderate-to-severe TBI [msTBI], GCS 3-12, n = 193; or OTC n = 154), stable was the most prevalent outcome. Functional outcome showed the highest rates of decline, regardless of TBI severity (mild = 29%; moderate/severe = 23%). When measures were collectively considered, rates of decline included mTBI (21%), msTBI (26%), and OTC (15%). Age and preinjury employment status were associated with functional decline (per 10 years; relative risk [RR] 1.16, 95% CI 1.07-1.25, p < 0.001; higher in retired/disabled/not working vs full-time/part-time; RR 1.81, 95% CI 1.33-2.45, respectively) in the mTBI group. Improvement in functional recovery 2-7 years postinjury was associated with higher BSI scores (per 5 points; RR 1.11, 95% CI 1.04-1.18, p = 0.002) and GOSE score of 5-7 (GOSE = 8 as reference; RR 2.64, 95% CI 1.75-3.97, p < 0.001). Higher BSI scores and identifying as Black (RR 2.28, 95% CI 1.59-3.25, p < 0.001) were associated with a greater likelihood of improved psychiatric symptoms in mTBI (RR 1.21, 95% CI 1.14-1.29, p < 0.001). A greater likelihood of cognitive improvement was observed among those with higher educational attainment in msTBI (per 4 years; RR 2.61, 95% CI 1.43-4.79, p = 0.002). DISCUSSION: Function across domains at 1-year postinjury, a common recovery benchmark, undergoes change across the subsequent 6 years. Results support consideration of TBI as a chronic evolving condition and suggest continued monitoring, rehabilitation, and support is required to optimize long-term independence and quality of life.

INTRODUCTION: Early circulatory shock following traumatic brain injury (TBI) is a multifactorial process; however, the impact of brain injury biomarkers on the risk of shock has not been evaluated. We examined the association between neuronal injury biomarker levels and the development of circulatory shock following moderate-severe TBI. METHODS: In this retrospective cohort study, we examined adults with moderate-severe TBI (Glasgow Coma Scale score

OBJECTIVE: To evaluate associations of preinjury vascular risk factors with traumatic brain injury (TBI) outcomes. SETTING: The level 1 trauma center-based T ransforming R esearch a nd C linical K nowledge in TBI (TRACK-TBI) Study. PARTICIPANTS: A total of 2361 acute TBI patients 18 years or older who presented to the emergency department within 24 hours of head trauma warranting clinical evaluation with a noncontrast head CT between February 26, 2014, and August 8, 2018. DESIGN: A multicenter prospective cohort study. MAIN MEASURES: Vascular risk factors (hypertension, diabetes, hyperlipidemia, and smoking) were assessed at baseline by self- or proxy-report and chart review. The primary outcome was the 6-month Glasgow Outcome Scale-Extended TBI version (GOSE-TBI). Secondary 6-month outcomes included the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), the Satisfaction with Life Scale (SWLS), and the 18-item Brief Symptom Inventory Global Severity Index (BSI-18-GSI). RESULTS: Mean age of participants was 42 years, 31% were women, and 16% were Black. Current smoking was the most common vascular risk factor (29%), followed by hypertension (17%), diabetes (8%), and hyperlipidemia (6%). Smoking was the only risk factor associated with worse scores on all 4 outcome indices. Hypertension and diabetes were associated with worse RPQ scores, and hypertension was associated with worse BSI-18-GSI scores (all P < .05). Compared with individuals with no vascular risk factors, individuals with 1 but not 2 or more vascular risk factors had significantly worse GOSE-TBI and SWLS scores, while a higher burden of vascular risk factors was significantly associated with worse RPQ and BSI-18-GSI scores. CONCLUSION: Our study found that preinjury vascular risk factors, especially smoking, are associated with worse outcomes after TBI. Aggressive postinjury treatment of vascular risk factors may be a promising strategy to improve TBI outcomes.

The effects of traumatic brain injury (TBI) are difficult to measure in longitudinal cohort studies, because disparate pre-injury characteristics and injury mechanisms produce variable impairment profiles and recovery trajectories. In preparation for the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, which followed patients with injuries ranging from uncomplicated mild TBI to coma, we designed a multi-dimensional Flexible outcome Assessment Battery (FAB). The FAB relies on a decision-making algorithm that assigns participants to a Comprehensive (CAB) or Abbreviated Assessment Battery (AAB) and guides test selection across all phases of recovery. To assess feasibility of the FAB, we calculated the proportion of participants followed at 2 weeks (2w) and at 3, 6, and 12 months (3m, 6m, 12m) post-injury who completed the FAB and received valid scores. We evaluated utility of the FAB by examining differences in 6m and 12m Glasgow Outcome Scale-Extended (GOSE) scores between participant subgroups derived from the FAB-enabled versus traditional approach to outcome assessment applied at 2w. Among participants followed at 2w (n = 2094), 3m (n = 1871), 6m (n = 1736), and 12m (n = 1607) post-injury, 95-99% received valid completion scores on the FAB, in full or in part, either in person or by telephone. Level of function assessed by the FAB-enabled approach at 2w was associated with 6m and 12m GOSE scores (proportional odds p

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 (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

BACKGROUND: Extracranial multisystem organ failure is a common sequela of severe traumatic brain injury (TBI). Risk factors for developing circulatory shock and long-term functional outcomes of this patient subset are poorly understood. OBJECTIVE: To identify emergency department predictors of circulatory shock after moderate-severe TBI and examine long-term functional outcomes in patients with moderate-severe TBI who developed circulatory shock. METHODS: We conducted a retrospective cohort study using the Transforming Clinical Research and Knowledge in TBI database for adult patients with moderate-severe TBI, defined as a Glasgow Coma Scale (GCS) score of

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.

Background and objectivesThe objectives of this study were to develop and establish concurrent validity of a clinically relevant definition of poor cognitive outcome 1 year after mild traumatic brain injury (mTBI), to compare baseline characteristics across cognitive outcome groups, and to determine whether poor 1-year cognitive outcome can be predicted by routinely available baseline clinical variables.MethodsProspective cohort study included 656 participants ≥17 years of age presenting to level 1 trauma centers within 24 hours of mTBI (Glasgow Coma Scale score 13-15) and 156 demographically similar healthy controls enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Poor 1-year cognitive outcome was defined as cognitive impairment (below the ninth percentile of normative data on ≥2 cognitive tests), cognitive decline (change score [1-year score minus best 2-week or 6-month score] exceeding the 90% reliable change index on ≥2 cognitive tests), or both. Associations of poor 1-year cognitive outcome with 1-year neurobehavioral outcomes were performed to establish concurrent validity. Baseline characteristics were compared across cognitive outcome groups, and backward elimination logistic regression was used to build a prediction model.ResultsMean age of participants with mTBI was 40.2 years; 36.6% were female; 76.6% were White. Poor 1-year cognitive outcome was associated with worse 1-year functional outcome, more neurobehavioral symptoms, greater psychological distress, and lower satisfaction with life (all p < 0.05), establishing concurrent validity. At 1 year, 13.5% of participants with mTBI had a poor cognitive outcome vs 4.5% of controls (p = 0.003). In univariable analyses, poor 1-year cognitive outcome was associated with non-White race, lower education, lower income, lack of health insurance, hyperglycemia, preinjury depression, and greater injury severity (all p < 0.05). The final multivariable prediction model included education, health insurance, preinjury depression, hyperglycemia, and Rotterdam CT score ≥3 and achieved an area under the curve of 0.69 (95% CI 0.62-0.75) for the prediction of a poor 1-year cognitive outcome, with each variable associated with >2-fold increased odds of poor 1-year cognitive outcome.DiscussionPoor 1-year cognitive outcome is common, affecting 13.5% of patients with mTBI vs 4.5% of controls. These results highlight the need for better understanding of mechanisms underlying poor cognitive outcome after mTBI to inform interventions to optimize cognitive recovery.

Symptom endorsement after traumatic brain injury (TBI) is common acutely post-injury and is associated with other adverse outcomes. Prevalence of persistent symptoms has been debated, especially in mild TBI (mTBI). A cohort of participants ≥17 years with TBI (n = 2039), 257 orthopedic trauma controls (OTCs), and 300 friend controls (FCs) were enrolled in the TRACK-TBI study and evaluated at 2 weeks and 3, 6, and 12 months post-injury using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). TBI participants had significantly higher symptom burden than OTCs or FCs at all times, with average scores more than double. TBI cases showed significant decreases in RPQ score between each evaluation (p 50% of each of the mild and moderate/severe TBI subsamples, continued to endorse three or more symptoms as worse than pre-injury through 12 months post-injury. A majority of TBI participants who endorsed a symptom at 3 months or later did so at the next evaluation as well. Contrary to reviews that report symptom resolution by 3 months post-injury among those with mTBI, this study of participants treated at level 1 trauma centers and having a computed tomography ordered found that persistent symptoms are common to at least a year after TBI. Additionally, although symptom endorsement was not specific to TBI given that they were also reported by OTC and FC participants, TBI participants endorsed over twice the symptom burden compared with the other groups.

BackgroundEarly hypotension following moderate to severe traumatic brain injury (TBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors to support blood pressure following TBI; however, guidelines do not specify vasopressor type, resulting in variation in clinical practice. Minimal data are available to guide clinicians on optimal early vasopressor choice to support blood pressure following TBI. Therefore, we conducted a multicenter study to examine initial vasopressor choice for the support of blood pressure following TBI and its association with clinical and functional outcomes after injury.MethodsWe conducted a retrospective cohort study of patients enrolled in the transforming research and clinical knowledge in traumatic brain injury (TRACK-TBI) study, an 18-center prospective cohort study of patients with TBI evaluated in participating level I trauma centers. We examined adults with moderate to severe TBI (defined as Glasgow Coma Scale score

It is important to measure quality of life (QoL) after traumatic brain injury (TBI), yet limited studies have compared QoL inventories. In 2579 TBI patients, orthopedic trauma controls, and healthy friend control participants, we compared the Quality of Life After Brain Injury-Overall Scale (QOLIBRI-OS), developed for TBI patients, to the Satisfaction with Life Scale (SWLS), an index of generic life satisfaction. We tested the hypothesis that group differences (TBI and orthopedic trauma vs. healthy friend controls) would be larger for the QOLIBRI-OS than the SWLS and that the QOLIBRI-OS would manifest more substantial changes over time in the injured groups, demonstrating more relevance of the QOLIBRI-OS to traumatic injury recovery. (1) We compared the group differences (TBI vs. orthopedic trauma control vs. friend control) in QoL as indexed by the SWLS versus the QOLIBRI-OS and (2) characterized changes across time in these two inventories across 1 year in these three groups. Our secondary objective was to characterize the relationship between TBI severity and QoL. As compared with healthy friend controls, the QOLIBRI reflected greater reductions in QoL than the SWLS for both the TBI group (all time points) and the orthopedic trauma control group (2 weeks and 3 months). The QOLIBRI-OS better captured expected improvements in QoL during the injury recovery course in injured groups than the SWLS, which demonstrated smaller changes over time. TBI severity was not consistently or robustly associated with self-reported QoL. The findings imply that, as compared with the SWLS, the QOLIBRI-OS appears to identify QoL issues more specifically relevant to traumatically injured patients and may be a more appropriate primary QoL outcome measure for research focused on the sequelae of traumatic injuries.

In nearly all clinical and research contexts, the initial severity of a traumatic brain injury (TBI) is measured using the Glasgow Coma Scale (GCS) total score. The GCS total score however, may not accurately reflect level of consciousness, a critical indicator of injury severity. We investigated the relationship between GCS total scores and level of consciousness in a consecutive sample of 2455 adult subjects assessed with the GCS 69,487 times as part of the multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. We assigned each GCS subscale score combination a level of consciousness rating based on published criteria for the following disorders of consciousness (DoC) diagnoses: coma, vegetative state/unresponsive wakefulness syndrome, minimally conscious state, and post-traumatic confusional state, and present our findings using summary statistics and four illustrative cases. Participants had the following characteristics: mean (standard deviation) age 41.9 (17.6) years, 69% male, initial GCS 3-8 = 13%; 9-12 = 5%; 13-15 = 82%. All GCS total scores between 4-14 were associated with more than one DoC diagnosis; the greatest variability was observed for scores of 7-11. Further, a wide range of total scores was associated with identical DoC diagnoses. Importantly, a diagnosis of coma was only possible with GCS total scores of 3-6. The GCS total score does not accurately reflect level of consciousness based on published DoC diagnostic criteria. To improve the classification of patients with TBI and to inform the design of future clinical trials, clinicians and investigators should consider individual subscale behaviors and more comprehensive assessments when evaluating TBI severity.

ObjectivesTraumatic brain injury is a leading cause of death and disability in the United States. While the impact of early multiple organ dysfunction syndrome has been studied in many critical care paradigms, the clinical impact of early multiple organ dysfunction syndrome in traumatic brain injury is poorly understood. We examined the incidence and impact of early multiple organ dysfunction syndrome on clinical, functional, and disability outcomes over the year following traumatic brain injury.DesignRetrospective cohort study.SettingPatients enrolled in the Transforming Clinical Research and Knowledge in Traumatic Brain Injury study, an 18-center prospective cohort study of traumatic brain injury patients evaluated in participating level 1 trauma centers.SubjectsAdult (age > 17 yr) patients with moderate-severe traumatic brain injury (Glasgow Coma Scale < 13). We excluded patients with major extracranial injury (Abbreviated Injury Scale score ≥ 3).InterventionsDevelopment of early multiple organ dysfunction syndrome, defined as a maximum modified Sequential Organ Failure Assessment score greater than 7 during the initial 72 hours following admission.Measurements and main resultsThe main outcomes were: hospital mortality, length of stay, 6-month functional and disability domains (Glasgow Outcome Scale-Extended and Disability Rating Scale), and 1-year mortality. Secondary outcomes included: ICU length of stay, 3-month Glasgow Outcome Scale-Extended, 3-month Disability Rating Scale, 1-year Glasgow Outcome Scale-Extended, and 1-year Disability Rating Scale. We examined 373 subjects with moderate-severe traumatic brain injury. The mean (sd) Glasgow Coma Scale in the emergency department was 5.8 (3.2), with 280 subjects (75%) classified as severe traumatic brain injury (Glasgow Coma Scale 3-8). Among subjects with moderate-severe traumatic brain injury, 252 (68%) developed early multiple organ dysfunction syndrome. Subjects that developed early multiple organ dysfunction syndrome had a 75% decreased odds of a favorable outcome (Glasgow Outcome Scale-Extended 5-8) at 6 months (adjusted odds ratio, 0.25; 95% CI, 0.12-0.51) and increased disability (higher Disability Rating Scale score) at 6 months (adjusted mean difference, 2.04; 95% CI, 0.92-3.17). Subjects that developed early multiple organ dysfunction syndrome experienced an increased hospital length of stay (adjusted mean difference, 11.4 d; 95% CI, 7.1-15.8), with a nonsignificantly decreased survival to hospital discharge (odds ratio, 0.47; 95% CI, 0.18-1.2).ConclusionsEarly multiple organ dysfunction following moderate-severe traumatic brain injury is common and independently impacts multiple domains (mortality, function, and disability) over the year following injury. Further research is necessary to understand underlying mechanisms, improve early recognition, and optimize management strategies.

BackgroundTraumatic brainstem injury has yet to be incorporated into widely used imaging classification systems for traumatic brain injury (TBI), and questions remain regarding prognostic implications for this TBI subgroup. To address this, retrospective data on patients from the multicenter prospective Transforming Research and Clinical Knowledge in TBI study were studied.MethodsPatients with brainstem and cerebrum injury (BSI+) were matched by age, sex, and admission Glasgow Coma Scale (GCS) score to patients with cerebrum injuries only. All patients had an interpretable head computed tomography (CT) scan from the first 48 hours after injury and a 6-month Glasgow Outcome Scale Extended (GOSE) score. CT scans were reviewed for brainstem lesions and, when present, characterized by location, size, and type (traumatic axonal injury, contusion, or Duret hemorrhage). Clinical, demographic, and outcome data were then compared between the two groups.ResultsMann-Whitney U-tests showed no significant difference in 6-month GOSE scores in patients with BSI+ (mean 2.7) compared with patients with similar but only cerebrum injuries (mean 3.9), although there is a trend (p = 0.10). However, subclassification by brainstem lesion type, traumatic axonal injury (mean 4.0) versus Duret hemorrhage or contusion (mean 1.4), did identify a proportion of BSI+ with significantly less favorable outcome (p = 0.002). The incorporation of brainstem lesion type (traumatic axonal injury vs. contusion/Duret), along with GCS into a multivariate logistic regression model of favorable outcome (GOSE score 4-8) did show a significant contribution to the prognostication of this brainstem injury subgroup (odds ratio 0.08, 95% confidence interval 0.00-0.67, p = 0.01).ConclusionsThese findings suggest two groups of patients with brainstem injuries may exist with divergent recovery potential after TBI. These data support the notion that newer CT imaging classification systems may augment traditional clinical measures, such as GCS in identifying those patients with TBI and brainstem injuries that stand a higher chance of favorable outcome.

The Glasgow Outcome Scale (GOS) in its original or extended (GOSE) form is the most widely used assessment of global disability in traumatic brain injury (TBI) research. Several publications have reported concerns about assessor scoring inconsistencies, but without documentation of contributing factors. We reviewed 6801 GOSE assessments collected longitudinally, across 18 sites in the 5-year, observational Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. We recorded error rates (i.e., corrections to a section or an overall rating) based on site assessor documentation and categorized scoring issues, which then informed further training. In cohort 1 (n = 1261; February 2014 to May 2016), 24% of GOSEs had errors identified by central review. In cohort 2 (n = 1130; June 2016 to July 2018), acquired after curation of cohort 1 data, feedback, and further training of site assessors, the error rate was reduced to 10%. GOSE sections associated with the most frequent interpretation and scoring difficulties included whether current functioning represented a change from pre-injury (466 corrected ratings in cohort 1; 62 in cohort 2), defining dependency in the home and community (163 corrections in cohort 1; three in cohort 2) and return to work/school (72 corrections in cohort 1; 35 in cohort 2). These results highlight the importance of central review in improving consistency across sites and over time. Establishing clear scoring criteria, coupled with ongoing guidance and feedback to data collectors, is essential to avoid scoring errors and resultant misclassification, which carry potential to result in "failure" of clinical trials that rely on the GOSE as their primary outcome measure.

Diffusion tractography magnetic resonance imaging (MRI) can infer changes in network connectivity in patients with traumatic brain injury (TBI), but the pathological substrates of disconnected tracts have not been well defined because of a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750-μm isotropic resolution, followed by histopathological evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. Analysis of 74 cerebral hemispheric white matter regions revealed a heterogeneous distribution of tract disruptions. Associated histopathology identified variable white matter injury with patchy deposition of amyloid precursor protein (APP), loss of neurofilament-positive axonal processes, myelin dissolution, astrogliosis, microgliosis, and perivascular hemosiderin-laden macrophages. Multiple linear regression revealed that tract disruption strongly correlated with the density of APP-positive axonal swellings and neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.

Our objective was to examine the construct validity of the Brief Test of Adult Cognition by Telephone (BTACT) and its relationship to traumatic brain injury (TBI) of differing severities. Data were analyzed on 1422 patients with TBI and 170 orthopedic trauma controls (OTC) from the multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Participants were assessed at 6 months post-injury with the BTACT and an in-person neuropsychological battery. We examined the BTACT's factor structure, factorial group invariance, convergent and discriminant validity, and relationship to TBI and TBI severity. Confirmatory factor analysis supported both a 1-factor model and a 2-factor model comprising correlated Episodic Memory and Executive Function (EF) factors. Both models demonstrated strict invariance across TBI severity and OTC groups. Correlations between BTACT and criterion measures suggested that the BTACT memory indices predominantly reflect verbal episodic memory, whereas the BTACT EF factor correlated with a diverse range of cognitive tests. Although the EF factor and other BTACT indices showed significant relationships with TBI and TBI severity, some group effect sizes were larger for more comprehensive in-person cognitive tests than the BTACT. The BTACT is a promising, brief, phone-based cognitive screening tool for patients with TBI. Although the BTACT's memory items appear to index verbal Episodic Memory, items that purport to assess EFs may reflect a broader array of cognitive domains. The sensitivity of the BTACT to TBI severity is lower than domain-specific neuropsychological measures, suggesting it should not be used as a substitute for comprehensive, in-person cognitive testing at 6 months post-TBI.

BackgroundBrain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury.MethodsUsing data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13-15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices.ResultsOverall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors.ConclusionsResults, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury.

ObjectiveWhile a select population of pediatric patients with Chiari malformation type I (CM-I) remain asymptomatic, some patients present with tussive headaches, neurological deficits, progressive scoliosis, and other debilitating symptoms that necessitate surgical intervention. Surgery entails a variety of strategies to restore normal CSF flow, including increasing the posterior fossa volume via bone decompression only, or bone decompression with duraplasty, with or without obex exploration. The indications for duraplasty and obex exploration following bone decompression remain controversial. The objective of this study was to describe an institutional series of pediatric patients undergoing surgery for CM-I, performed by a single neurosurgeon. For patients presenting with a syrinx, the authors compared outcomes following bone-only decompression with duraplasty only and with duraplasty including obex exploration. Clinical outcomes evaluated included resolution of syrinx, scoliosis, presenting symptoms, and surgical complications.MethodsA retrospective review was conducted of the medical records of 276 consecutive pediatric patients with CM-I operated on at a single institution between 2001 and 2015 by the senior author. Imaging findings of tonsillar descent, associated syrinx (syringomyelia or syringobulbia), basilar invagination, and clinical assessment of CM-I-attributable symptoms and scoliosis were recorded. In patients presenting with a syrinx, clinical outcomes, including syrinx resolution, symptom resolution, and impact on scoliosis progression, were compared for three surgical groups: bone-only/posterior fossa decompression (PFD), PFD with duraplasty (PFDwD), and PFD with duraplasty and obex exploration (PFDwDO).ResultsPFD was performed in 25% of patients (69/276), PFDwD in 18% of patients (50/276), and PFDwDO in 57% of patients (157/276). The mean follow-up was 35 ± 35 months. Nearly half of the patients (132/276, 48%) had a syrinx. In patients presenting with a syrinx, PFDwDO was associated with a significantly higher likelihood of syrinx resolution relative to PFD only (HR 2.65, p = 0.028) and a significant difference in time to symptom resolution (HR 2.68, p = 0.033). Scoliosis outcomes did not differ among treatment groups (p = 0.275). Complications were not significantly higher when any duraplasty (PFDwD or PFDwDO) was performed following bone decompression (p > 0.99).ConclusionsIn this series of pediatric patients with CM-I, patients presenting with a syrinx who underwent expansile duraplasty with obex exploration had a significantly greater likelihood of syrinx and symptom resolution, without increased risk of CSF-related complications, compared to those who underwent bone-only decompression.

OBJECTIVE: The Functional Status Examination (FSE) is a comprehensive measure of functional status post-traumatic brain injury (TBI) that has primarily been used in studies of moderate-to-severe TBI. The present observational study examines functional status using the FSE among patients who sustained mild TBIs (mTBIs; defined as Glasgow Coma Scale [GCS] = 13-15 at admission) seen in a Level 1 trauma center. Study aims included examining the course of functional status following mTBI, as well as exploring relationships of the FSE and other relevant constructs among those with GCS = 13-15. METHOD: Participants were assessed at 2 weeks (n = 112), 3 months (n = 113), 6 months (n = 106), and 12 months (n = 88) post-injury for changes in functional status resulting both (a) from all injuries and (b) from TBI only. RESULTS: Among seven domains of day-to-day functioning, participants generally experienced the greatest disruption in their primary activity (work or school) and in leisure and recreation. Subjects overall functional status tended to improve over time, with sharpest increases in functionality occurring in the first 3 months post-injury. However, some subjects continued to report functional limitations even at 12 months post-injury. Functional status was largely unrelated to neurocognitive functioning, but related strongly to post-traumatic symptoms, life satisfaction, and emotional well-being, particularly at 3 months post-injury and beyond. CONCLUSION: Findings indicate that functional impairments related to mTBI may be more likely to persist than widely believed, with those who experience lingering functional deficits at particular risk for emotional health difficulties.