Preventing Concussions From Foul Tips and Backswings in Professional Baseball: Catchers' Perceptions of and Experiences With Conventional and Hockey-Style Masks.

OBJECTIVE: To understand catchers' preferences for mask type and perceptions regarding safety, comfort, and fit, and determine whether mask type is correlated with self-reported concussion and related symptoms after impacts from foul tips or backswings. DESIGN: Cross-sectional study. SETTING: Survey of active baseball catchers. PARTICIPANTS: Professional baseball catchers. INTERVENTION: From May 1, 2015, to June 30, 2015, an online survey was administered in English and Spanish to all Major and Minor League catchers (n = 836). MAIN OUTCOME MEASURES: Survey items addressed the type of mask routinely and previously used (conventional or hockey style); brand and material (steel or titanium); perceptions regarding safety, comfort, and fit; and experiences with concussions. RESULTS: The sample consisted of 596 catchers of which 26% reported being diagnosed with a concussion. Some concussions occurred from non-baseball activities, such as car accidents or off the field incidents. For those that occurred playing baseball, 35% resulted from a foul tip. Once catchers entered professional baseball, the use of a conventional mask rose significantly: 71% of catchers reported wearing conventional-style masks, and 30% hockey-style masks at the time the survey was conducted (P < 0.05). Both conventional and hockey-style mask wearers significantly selected hockey-style masks as providing better overall safety and protection than conventional masks (P < 0.05). CONCLUSIONS: This research supports foul tips as an important cause of concussion in catchers and provides important information about preferences among catchers for masks that are not perceived as the safest and strongest. Future research should supplement these data by conducting laboratory testing to determine which masks are stronger and by collecting qualitative data to explore why some players are more likely to wear a mask type that they perceive as offering less safety or protection.

Concordance of common data elements for assessment of subjective cognitive complaints after mild-traumatic brain injury: a TRACK-TBI Pilot Study.

OBJECTIVE: To determine characteristics and concordance of subjective cognitive complaints (SCCs) 6 months following mild-traumatic brain injury (mTBI) as assessed by two different TBI common data elements (CDEs). RESEARCH DESIGN: The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot Study was a prospective observational study that utilized the NIH TBI CDEs, Version 1.0. We examined variables associated with SCC, performance on objective cognitive tests (Wechsler Adult Intelligence Scale, California Verbal Learning Test, and Trail Making Tests A and B), and agreement on self-report of SCCs as assessed by the acute concussion evaluation (ACE) versus the Rivermead Post Concussion Symptoms Questionnaire (RPQ). RESULTS: In total, 68% of 227 participants endorsed SCCs at 6 months. Factors associated with SCC included less education, psychiatric history, and being assaulted. Compared to participants without SCC, those with SCC defined by RPQ performed significantly worse on all cognitive tests. There was moderate agreement between the two measures of SCCs (kappa = 0.567 to 0.680). CONCLUSION: We show that the symptom questionnaires ACE and RPQ show good, but not excellent, agreement for SCCs in an mTBI study population. Our results support the retention of RPQ as a basic CDE for mTBI research. ABBREVIATIONS: BSI-18: Brief Symptom Inventory; 18CDEs: common data elements; CT: computed tomography; CVLT: California Verbal Learning Test; ED: emergency department; GCS: Glasgow coma scale; LOC: loss of consciousnessm; TBI: mild-traumatic brain injury; PTA: post-traumatic amnesia; SCC: subjective cognitive complaints; TBI: traumatic brain injury; TRACK-TBI: Transforming Research and Clinical Knowledge in Traumatic Brain Injury; TMT: Trail Making Test; WAIS-PSI: Wechsler Adult Intelligence Scale, Fourth Edition, Processing Speed Index.

Chronic Upregulation of Cleaved-Caspase-3 Associated with Chronic Myelin Pathology and Microvascular Reorganization in the Thalamus after Traumatic Brain Injury in Rats.

Traumatic brain injury (TBI) is associated with long-term disabilities and devastating chronic neurological complications including problems with cognition, motor function, sensory processing, as well as behavioral deficits and mental health problems such as anxiety, depression, personality change and social unsuitability. Clinical data suggest that disruption of the thalamo-cortical system including anatomical and metabolic changes in the thalamus following TBI might be responsible for some chronic neurological deficits following brain trauma. Detailed mechanisms of these pathological processes are not completely understood. The goal of this study was to evaluate changes in the thalamus following TBI focusing on cleaved-caspase-3, a specific effector of caspase pathway activation and myelin and microvascular pathologies using immuno- and histochemistry at different time points from 24 h to 3 months after controlled cortical impact (CCI) in adult Sprague-Dawley rats. Significant increases in cleaved-caspase-3 immunoreactivity in the thalamus were observed starting one month and persisting for at least three months following experimental TBI. Further, the study demonstrated an association of cleaved-caspase-3 with the demyelination of neuronal processes and tissue degeneration in the gray matter in the thalamus, as reflected in alterations of myelinated fiber integrity (luxol fast blue) and decreases in myelin basic protein (MBP) immunoreactivity. The immunofluorescent counterstaining of cleaved-caspase-3 with endothelial barrier antigen (EBA), a marker of blood-brain barrier, revealed limited direct and indirect associations of cleaved caspase-3 with blood-brain barrier damage. These results demonstrate for the first time a significant chronic upregulation of cleaved-caspase-3 in selected thalamic regions associated with cortical regions directly affected by CCI injury. Further, our study is also the first to report that significant upregulation of cleaved-caspase-3 in selected ipsilateral thalamic regions is associated with microvascular reorganization reflected in the significant increases in the number of microvessels with blood-brain barrier alterations detected by EBA staining. These findings provide new insights into potential mechanisms of TBI cell death involving chronic activation of caspase-3 associated with disrupted cortico-thalamic and thalamo-cortical connectivity. Moreover, this study offers the initial evidence that this upregulation of activated caspase-3, delayed degeneration of myelinated nerve fibers and microvascular reorganization with impaired blood-brain barrier integrity in the thalamus might represent reciprocal pathological processes affecting neuronal networks and brain function at the chronic stages of TBI.

DRD2 C957T polymorphism is associated with improved 6-month verbal learning following traumatic brain injury.

Traumatic brain injury (TBI) often leads to heterogeneous clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism (SNP) in the dopamine D2 receptor (DRD2) may influence cognitive deficits following TBI. However, part of the association with DRD2 has been attributed to genetic variability within the adjacent ankyrin repeat and kinase domain containing 1 protein (ANKK1). Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether a novel DRD2 C957T polymorphism (rs6277) influences outcome on a cognitive battery at 6 months following TBI-California Verbal Learning Test (CVLT-II), Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), and Trail Making Test (TMT). Results in 128 Caucasian subjects show that the rs6277 T-allele associates with better verbal learning and recall on CVLT-II Trials 1-5 (T-allele carrier 52.8 ± 1.3 points, C/C 47.9 ± 1.7 points; mean increase 4.9 points, 95% confidence interval [0.9 to 8.8]; p = 0.018), Short-Delay Free Recall (T-carrier 10.9 ± 0.4 points, C/C 9.7 ± 0.5 points; mean increase 1.2 points [0.1 to 2.5]; p = 0.046), and Long-Delay Free Recall (T-carrier 11.5 ± 0.4 points, C/C 10.2 ± 0.5 points; mean increase 1.3 points [0.1 to 2.5]; p = 0.041) after adjusting for age, education years, Glasgow Coma Scale, presence of acute intracranial pathology on head computed tomography scan, and genotype of the ANKK1 SNP rs1800497 using multivariable regression. No association was found between DRD2 C947T and non-verbal processing speed (WAIS-PSI) or mental flexibility (TMT) at 6 months. Hence, DRD2 C947T (rs6277) may be associated with better performance on select cognitive domains independent of ANKK1 following TBI.

Temporal profile of care following mild traumatic brain injury: predictors of hospital admission, follow-up referral and six-month outcome.

OBJECTIVE: To investigate the clinical management and medical follow-up of patients with mild traumatic brain injury (mTBI) presenting to emergency departments (EDs). METHODS: Overall, 168 adult patients with mTBI from the prospective, multicentre Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot study with Glasgow Coma Scale (GCS) 13-15, no polytrauma and alive at six months were included. Predictors for hospital admission, three-month follow-up referral and six-month functional disability (Glasgow Outcome Scale-Extended (GOSE) ≤ 6) were analysed using multivariable regression. RESULTS: Overall, 48% were admitted to hospital, 22% received three-month referral and 27% reported six-month functional disability. Intracranial pathology on ED head computed tomography (multivariable odds ratio (OR) = 81.08, 95% confidence interval (CI) [10.28-639.36]) and amnesia (>30-minutes: OR = 5.27 [1.75-15.87]; unknown duration: OR = 4.43 [1.26-15.62]) predicted hospital admission. Older age (per-year OR = 1.03 [1.01-1.05]) predicted three-month referral, while part-time/unemployment predicted lack of referral (OR = 0.17 [0.06-0.50]). GCS < 15 (OR = 2.46 [1.05-5.78]) and prior history of seizures (OR = 3.62 [1.21-10.89]) predicted six-month functional disability, while increased education (per-year OR = 0.86 [0.76-0.97]) was protective. CONCLUSIONS: Clinical factors modulate triage to admission, while demographic/socioeconomic elements modulate follow-up care acquisition; six-month functional disability associates with both clinical and demographic/socioeconomic variables. Improving triage to acute and outpatient care requires further investigation to optimize resource allocation and outcome after mTBI. ClinicalTrials.gov registration: NCT01565551.

COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury.

Mild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme which degrades catecholamine neurotransmitters, may influence cognitive deficits following moderate and/or severe head trauma. However, this has been disputed, and its role in mTBI has not been studied. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val (158) Met polymorphism influences outcome on a cognitive battery 6 months following mTBI--Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), Trail Making Test (TMT) Trail B minus Trail A time, and California Verbal Learning Test, Second Edition Trial 1-5 Standard Score (CVLT-II). All patients had an emergency department Glasgow Coma Scale (GCS) of 13-15, no acute intracranial pathology on head CT, and no polytrauma as defined by an Abbreviated Injury Scale (AIS) score of ≥3 in any extracranial region. Results in 100 subjects aged 40.9 (SD 15.2) years (COMT Met (158) /Met (158) 29 %, Met (158) /Val (158) 47 %, Val (158) /Val (158) 24 %) show that the COMT Met (158) allele (mean 101.6 ± SE 2.1) associates with higher nonverbal processing speed on the WAIS-PSI when compared to Val (158) /Val (158) homozygotes (93.8 ± SE 3.0) after controlling for demographics and injury severity (mean increase 7.9 points, 95 % CI [1.4 to 14.3], p = 0.017). The COMT Val (158) Met polymorphism did not associate with mental flexibility on the TMT or with verbal learning on the CVLT-II. Hence, COMT Val (158) Met may preferentially modulate nonverbal cognition following uncomplicated mTBI.Registry: ClinicalTrials.gov Identifier NCT01565551.

Magnetic resonance imaging improves 3-month outcome prediction in mild traumatic brain injury.

OBJECTIVE: To determine the clinical relevance, if any, of traumatic intracranial findings on early head computed tomography (CT) and brain magnetic resonance imaging (MRI) to 3-month outcome in mild traumatic brain injury (MTBI). METHODS: One hundred thirty-five MTBI patients evaluated for acute head injury in emergency departments of 3 LEVEL I trauma centers were enrolled prospectively. In addition to admission head CT, early brain MRI was performed 12 ± 3.9 days after injury. Univariate and multivariate logistic regression were used to assess for demographic, clinical, socioeconomic, CT, and MRI features that were predictive of Extended Glasgow Outcome Scale (GOS-E) at 3 months postinjury. RESULTS: Twenty-seven percent of MTBI patients with normal admission head CT had abnormal early brain MRI. CT evidence of subarachnoid hemorrhage was associated with a multivariate odds ratio of 3.5 (p = 0.01) for poorer 3-month outcome, after adjusting for demographic, clinical, and socioeconomic factors. One or more brain contusions on MRI, and ≥4 foci of hemorrhagic axonal injury on MRI, were each independently associated with poorer 3-month outcome, with multivariate odds ratios of 4.5 (p = 0.01) and 3.2 (p = 0.03), respectively, after adjusting for head CT findings and demographic, clinical, and socioeconomic factors. INTERPRETATION: In this prospective multicenter observational study, the clinical relevance of abnormal findings on early brain imaging after MTBI is demonstrated. The addition of early CT and MRI markers to a prognostic model based on previously known demographic, clinical, and socioeconomic predictors resulted in a >2-fold increase in the explained variance in 3-month GOS-E.

ED disposition of the Glasgow Coma Scale 13 to 15 traumatic brain injury patient: analysis of the Transforming Research and Clinical Knowledge in TBI study.

OBJECTIVE: Mild traumatic brain injury (mTBI) patients are frequently admitted to high levels of care despite limited evidence suggesting benefit. Such decisions may contribute to the significant cost of caring for mTBI patients. Understanding the factors that drive disposition decision making and how disposition is associated with outcomes is necessary for developing an evidence-base supporting disposition decisions. We evaluated factors associated with emergency department triage of mTBI patients to 1 of 3 levels of care: home, inpatient floor, or intensive care unit (ICU). METHODS: This multicenter, prospective, cohort study included patients with isolated head trauma, a cranial computed tomography as part of routine care, and a Glasgow Coma Scale (GCS) score of 13 to 15. Data analysis was performed using multinomial logistic regression. RESULTS: Of the 304 patients included, 167 (55%) were discharged home, 76 (25%) were admitted to the inpatient floor, and 61 (20%) were admitted to the ICU. In the multivariable model, admission to the ICU, compared with floor admission, varied by study site, odds ratio (OR) 0.18 (95% confidence interval [CI], 0.06-0.57); antiplatelet/anticoagulation therapy, OR 7.46 (95% CI, 1.79-31.13); skull fracture, OR 7.60 (95% CI, 2.44-23.73); and lower GCS, OR 2.36 (95% CI, 1.05-5.30). No difference in outcome was observed between the 3 levels of care. CONCLUSION: Clinical characteristics and local practice patterns contribute to mTBI disposition decisions. Level of care was not associated with outcomes. Intracranial hemorrhage, GCS 13 to 14, skull fracture, and current antiplatelet/anticoagulant therapy influenced disposition decisions.

Use of MRI in patients with severe diffuse traumatic brain injury: A matched National Trauma Data Bank analysis.

OBJECTIVE: Magnetic resonance imaging (MRI) is increasingly used to evaluate patients with diffuse traumatic brain injury (dTBI). However, the utility of early MRI is understudied. We hypothesize that early MRI patients will have increased length of stay but no changes in intracranial pressure (ICP) management or disposition. METHODS: The 2019 National Trauma Data Bank was queried for patients with dTBI and Glasgow Coma Scale score ≤8. Extra-axial and focal intra-axial hemorrhages were excluded. Clinical characteristics were controlled for. Patients with and without MRI were compared for ICP management, outcome, mortality, and disposition. A propensity score matching algorithm was used to create a 1:1 match cohort. RESULTS: In 2568 patients, MRI was less common in severe dTBI patients with clear reasons for poor examination, including bilaterally unreactive pupils or midline shift. After matching, 501 patients who underwent MRI within 1 week were compared with 501 patients without MRI. Magnetic resonance imaging patients had longer intensive care unit stays (11.6 ± 9.6 vs. 13.4 ± 9.5, p < 0.01; 95% confidence interval [95% CI], -3.03 to -0.66). There was no difference between groups in ICP monitor (23.6% vs. 27.3%; p = 0.17; 95% CI, -0.09 to 0.02) or ventriculostomy placement (13.6% vs. 13.2%, p = 0.85; 95% CI, -0.04 to 0.05) or in withdrawal of care (15.0% vs. 18.6%, p = 0.12; 95% CI, -0.08 to 0.01). MRI patients were more likely to be discharged to inpatient rehabilitation (42.9% vs. 33.5%; p < 0.01; 95% CI, 0.03-0.15) but not to home (9.4% vs. 9.0%; p = 0.83; 95% CI, -0.03 to 0.04). CONCLUSION: The decision to pursue early brain MRI may be driven by lack of obvious reasons for a patient's poor neurologic status. MRI patients had longer intensive care unit stays but no difference in rates of placement of ICP monitors or ventriculostomies or withdrawal of care. Further study is required to define the role of early MRI in dTBI patients. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Clinical Outcomes After Traumatic Brain Injury and Exposure to Extracranial Surgery: A TRACK-TBI Study.

Importance: Traumatic brain injury (TBI) is associated with persistent functional and cognitive deficits, which may be susceptible to secondary insults. The implications of exposure to surgery and anesthesia after TBI warrant investigation, given that surgery has been associated with neurocognitive disorders. Objective: To examine whether exposure to extracranial (EC) surgery and anesthesia is related to worse functional and cognitive outcomes after TBI. Design, Setting, and Participants: This study was a retrospective, secondary analysis of data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective cohort study that assessed longitudinal outcomes of participants enrolled at 18 level I US trauma centers between February 1, 2014, and August 31, 2018. Participants were 17 years or older, presented within 24 hours of trauma, were admitted to an inpatient unit from the emergency department, had known Glasgow Coma Scale (GCS) and head computed tomography (CT) status, and did not undergo cranial surgery. This analysis was conducted between January 2, 2020, and August 8, 2023. Exposure: Participants who underwent EC surgery during the index admission were compared with participants with no surgery in groups with a peripheral orthopedic injury or a TBI and were classified as having uncomplicated mild TBI (GCS score of 13-15 and negative CT results [CT- mTBI]), complicated mild TBI (GCS score of 13-15 and positive CT results [CT+ mTBI]), or moderate to severe TBI (GCS score of 3-12 [m/sTBI]). Main Outcomes and Measures: The primary outcomes were functional limitations quantified by the Glasgow Outcome Scale-Extended for all injuries (GOSE-ALL) and brain injury (GOSE-TBI) and neurocognitive outcomes at 2 weeks and 6 months after injury. Results: A total of 1835 participants (mean [SD] age, 42.2 [17.8] years; 1279 [70%] male; 299 Black, 1412 White, and 96 other) were analyzed, including 1349 nonsurgical participants and 486 participants undergoing EC surgery. The participants undergoing EC surgery across all TBI severities had significantly worse GOSE-ALL scores at 2 weeks and 6 months compared with their nonsurgical counterparts. At 6 months after injury, m/sTBI and CT+ mTBI participants who underwent EC surgery had significantly worse GOSE-TBI scores (B = -1.11 [95% CI, -1.53 to -0.68] in participants with m/sTBI and -0.39 [95% CI, -0.77 to -0.01] in participants with CT+ mTBI) and performed worse on the Trail Making Test Part B (B = 30.1 [95% CI, 11.9-48.2] in participants with m/sTBI and 26.3 [95% CI, 11.3-41.2] in participants with CT+ mTBI). Conclusions and Relevance: This study found that exposure to EC surgery and anesthesia was associated with adverse functional outcomes and impaired executive function after TBI. This unfavorable association warrants further investigation of the potential mechanisms and clinical implications that could inform decisions regarding the timing of surgical interventions in patients after TBI.

Performance of the IMPACT and CRASH prognostic models for traumatic brain injury in a contemporary multicenter cohort: a TRACK-TBI study.

OBJECTIVE: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomization After Significant Head Injury (CRASH) prognostic models for mortality and outcome after traumatic brain injury (TBI) were developed using data from 1984 to 2004. This study examined IMPACT and CRASH model performances in a contemporary cohort of US patients. METHODS: The prospective 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years 2014-2018) enrolled subjects aged ≥ 17 years who presented to level I trauma centers and received head CT within 24 hours of TBI. Data were extracted from the subjects who met the model criteria (for IMPACT, Glasgow Coma Scale [GCS] score 3-12 with 6-month Glasgow Outcome Scale-Extended [GOSE] data [n = 441]; for CRASH, GCS score 3-14 with 2-week mortality data and 6-month GOSE data [n = 831]). Analyses were conducted in the overall cohort and stratified on the basis of TBI severity (severe/moderate/mild TBI defined as GCS score 3-8/9-12/13-14), age (17-64 years or ≥ 65 years), and the 5 top enrolling sites. Unfavorable outcome was defined as GOSE score 1-4. Original IMPACT and CRASH model coefficients were applied, and model performances were assessed by calibration (intercept [< 0 indicated overprediction; > 0 indicated underprediction] and slope) and discrimination (c-statistic). RESULTS: Overall, the IMPACT models overpredicted mortality (intercept -0.79 [95% CI -1.05 to -0.53], slope 1.37 [1.05-1.69]) and acceptably predicted unfavorable outcome (intercept 0.07 [-0.14 to 0.29], slope 1.19 [0.96-1.42]), with good discrimination (c-statistics 0.84 and 0.83, respectively). The CRASH models overpredicted mortality (intercept -1.06 [-1.36 to -0.75], slope 0.96 [0.79-1.14]) and unfavorable outcome (intercept -0.60 [-0.78 to -0.41], slope 1.20 [1.03-1.37]), with good discrimination (c-statistics 0.92 and 0.88, respectively). IMPACT overpredicted mortality and acceptably predicted unfavorable outcome in the severe and moderate TBI subgroups, with good discrimination (c-statistic ≥ 0.81). CRASH overpredicted mortality in the severe and moderate TBI subgroups and acceptably predicted mortality in the mild TBI subgroup, with good discrimination (c-statistic ≥ 0.86); unfavorable outcome was overpredicted in the severe and mild TBI subgroups with adequate discrimination (c-statistic ≥ 0.78), whereas calibration was nonlinear in the moderate TBI subgroup. In subjects ≥ 65 years of age, the models performed variably (IMPACT-mortality, intercept 0.28, slope 0.68, and c-statistic 0.68; CRASH-unfavorable outcome, intercept -0.97, slope 1.32, and c-statistic 0.88; nonlinear calibration for IMPACT-unfavorable outcome and CRASH-mortality). Model performance differences were observed across the top enrolling sites for mortality and unfavorable outcome. CONCLUSIONS: The IMPACT and CRASH models adequately discriminated mortality and unfavorable outcome. Observed overestimations of mortality and unfavorable outcome underscore the need to update prognostic models to incorporate contemporary changes in TBI management and case-mix. Investigations to elucidate the relationships between increased survival, outcome, treatment intensity, and site-specific practices will be relevant to improve models in specific TBI subpopulations (e.g., older adults), which may benefit from the inclusion of blood-based biomarkers, neuroimaging features, and treatment data.

Isolated Traumatic Subarachnoid Hemorrhage on Head Computed Tomography Scan May Not Be Isolated: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (TRACK-TBI) Study.

Isolated traumatic subarachnoid hemorrhage (tSAH) after traumatic brain injury (TBI) on head computed tomography (CT) scan is often regarded as a "mild" injury, with reduced need for additional workup. However, tSAH is also a predictor of incomplete recovery and unfavorable outcome. This study aimed to evaluate the characteristics of CT-occult intracranial injuries on brain magnetic resonance imaging (MRI) scan in TBI patients with emergency department (ED) arrival Glasgow Coma Scale (GCS) score 13-15 and isolated tSAH on CT. The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (TRACK-TBI; enrollment years 2014-2019) enrolled participants who presented to the ED and received a clinically-indicated head CT within 24 h of TBI. A subset of TRACK-TBI participants underwent venipuncture within 24 h for plasma glial fibrillary acidic protein (GFAP) analysis, and research MRI at 2-weeks post-injury. In the current study, TRACK-TBI participants age ≥17 years with ED arrival GCS 13-15, isolated tSAH on initial head CT, plasma GFAP level, and 2-week MRI data were analyzed. In 57 participants, median age was 46.0 years [quartile 1 to 3 (Q1-Q3): 34-57] and 52.6% were male. At ED disposition, 12.3% were discharged home, 61.4% were admitted to hospital ward, and 26.3% to intensive care unit. MRI identified CT-occult traumatic intracranial lesions in 45.6% (26 of 57 participants; one additional lesion type: 31.6%; 2 additional lesion types: 14.0%); of these 26 participants with CT-occult intracranial lesions, 65.4% had axonal injury, 42.3% had subdural hematoma, and 23.1% had intracerebral contusion. GFAP levels were higher in participants with CT-occult MRI lesions compared with without (median: 630.6 pg/mL, Q1-Q3: [172.4-941.2] vs. 226.4 [105.8-436.1], p = 0.049), and were associated with axonal injury (no: median 226.7 pg/mL [109.6-435.1], yes: 828.6 pg/mL [204.0-1194.3], p = 0.009). Our results indicate that isolated tSAH on head CT is often not the sole intracranial traumatic injury in GCS 13-15 TBI. Forty-six percent of patients in our cohort (26 of 57 participants) had additional CT-occult traumatic lesions on MRI. Plasma GFAP may be an important biomarker for the identification of additional CT-occult injuries, including axonal injury. These findings should be interpreted cautiously given our small sample size and await validation from larger studies.

Neuroworsening in the Emergency Department Is a Predictor of Traumatic Brain Injury Intervention and Outcome: A TRACK-TBI Pilot Study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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 p < 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 p < 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]). CONCLUSIONS: 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.

The Richmond Acute Subdural Hematoma Score: A Validated Grading Scale to Predict Postoperative Mortality.

BACKGROUND: Traumatic acute subdural hematomas (aSDHs) are common, life-threatening injuries often requiring emergency surgery. OBJECTIVE: To develop and validate the Richmond acute subdural hematoma (RASH) score to stratify patients by risk of mortality after aSDH evacuation. METHODS: The 2016 National Trauma Data Bank (NTDB) was queried to identify adult patients with traumatic aSDHs who underwent craniectomy or craniotomy within 4 h of arrival to an emergency department. Multivariate logistic regression modeling identified risk factors independently associated with mortality. The RASH score was developed based on a factor's strength and level of association with mortality. The model was validated using the 2017 NTDB and the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 2516 cases met study criteria. The patients were 69.3% male with a mean age of 55.7 yr and overall mortality rate of 36.4%. Factors associated with mortality included age between 61 and 79 yr (odds ratio [OR] = 2.3, P < .001), age ≥80 yr (OR = 6.3, P < .001), loss of consciousness (OR = 2.3, P < .001), Glasgow Coma Scale score of ≤8 (OR = 2.6, P < .001), unilateral (OR = 2.8, P < .001) or bilateral (OR = 3.9, P < .001) unresponsive pupils, and midline shift >5 mm (OR = 1.7, P < .001). Using these risk factors, the RASH score predicted progressively increasing mortality ranging from 0% to 94% for scores of 0 to 8, respectively (AUC = 0.72). Application of the RASH score to 3091 cases from 2017 resulted in similar accuracy (AUC = 0.74). CONCLUSION: The RASH score is a simple and validated grading scale that uses easily accessible preoperative factors to predict estimated mortality rates in patients with traumatic aSDHs who undergo surgical evacuation.

From the Defense Health Board: Military Accessions and the Continuum of Mental Health Research.

The Defense Health Board conducted a year-long examination of mental health accession screening and related issues. In its August 2020 report, Examination of Mental Health Accession Screening: Predictive Value of Current Measures and Processes, the Board recommends a paradigm shift in how mental health impacts on readiness are understood and addressed. This shift can only occur with the development and implementation of a research plan that follows cohorts of military personnel from recruitment through their military career. The following article describes this research plan as an excerpt of the larger report.

Developing a National Trauma Research Action Plan: Results from the Neurotrauma Research Panel Delphi Survey.

BACKGROUND: In 2016, the National Academies of Science, Engineering and Medicine called for the development of a National Trauma Research Action Plan. The Department of Defense funded the Coalition for National Trauma Research to generate a comprehensive research agenda spanning the continuum of trauma and burn care. Given the public health burden of injuries to the central nervous system, neurotrauma was one of 11 panels formed to address this recommendation with a gap analysis and generation of high-priority research questions. METHODS: We recruited interdisciplinary experts to identify gaps in the neurotrauma literature, generate research questions, and prioritize those questions using a consensus-driven Delphi survey approach. We conducted four Delphi rounds in which participants generated key research questions and then prioritized the importance of the questions on a 9-point Likert scale. Consensus was defined as 60% or greater of panelists agreeing on the priority category. We then coded research questions using an National Trauma Research Action Plan taxonomy of 118 research concepts, which were consistent across all 11 panels. RESULTS: Twenty-eight neurotrauma experts generated 675 research questions. Of these, 364 (53.9%) reached consensus, and 56 were determined to be high priority (15.4%), 303 were deemed to be medium priority (83.2%), and 5 were low priority (1.4%). The research topics were stratified into three groups-severe traumatic brain injury (TBI), mild TBI (mTBI), and spinal cord injury. The number of high-priority questions for each subtopic was 46 for severe TBI (19.7%), 3 for mTBI (4.3%) and 7 for SCI (11.7%). CONCLUSION: This Delphi gap analysis of neurotrauma research identified 56 high-priority research questions. There are clear areas of focus for severe TBI, mTBI, and spinal cord injury that will help guide investigators in future neurotrauma research. Funding agencies should consider these gaps when they prioritize future research. LEVEL OF EVIDENCE: Diagnostic Test or Criteria, Level IV.

Predictors of six-month inability to return to work in previously employed subjects after mild traumatic brain injury: A TRACK-TBI pilot study.

INTRODUCTION: Return to work (RTW) is an important milestone of mild traumatic brain injury (mTBI) recovery. The objective of this study was to evaluate whether baseline clinical variables, three-month RTW, and three-month postconcussional symptoms (PCS) were associated with six-month RTW after mTBI. METHODS: Adult subjects from the prospective multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot study with mTBI (Glasgow Coma Scale 13-15) who were employed at baseline, with completed three-and six-month RTW status, and three-month Acute Concussion Evaluation (ACE), were extracted. Univariate and multivariable analyses were performed for six-month RTW, with focus on baseline employment, three-month RTW, and three-month ACE domains (physical, cognitive, sleep, and/or emotional postconcussional symptoms (PCS)). Odds ratios (OR) and 95% confidence intervals [CI] were reported. Significance was assessed at p < 0.05. RESULTS: In 152 patients aged 40.7 ± 15.0years, 72% were employed full-time at baseline. Three- and six-month RTW were 77.6% and 78.9%, respectively. At three months, 59.2%, 47.4%, 46.1% and 31.6% scored positive for ACE physical, cognitive, sleep, and emotional PCS domains, respectively. Three-month RTW predicted six-month RTW (OR = 19.80, 95% CI [7.61-51.52]). On univariate analysis, scoring positive in any three-month ACE domain predicted inability for six-month RTW (OR = 0.10-0.11). On multivariable analysis, emotional symptoms predicted inability to six-month RTW (OR = 0.19 [0.04-0.85]). Subjects who scored positive in all four ACE domains were more likely to be unable to RTW at six months (4 domains: 58.3%, vs. 0-to-3 domains: 9.5%; multivariable OR = 0.09 [0.02-0.33]). CONCLUSIONS: Three-month post-injury is an important time point at which RTW status and PCS should be assessed, as both are prognostic markers for six-month RTW. Clinicians should be particularly vigilant of patients who present with emotional symptoms, and patients with symptoms across multiple PCS categories, as these patients are at further risk of inability to RTW and may benefit from targeted evaluation and support.

Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus attacks multiple organs of coronavirus disease 2019 (COVID-19) patients, including the brain. There are worldwide descriptions of neurological deficits in COVID-19 patients. Central nervous system (CNS) symptoms can be present early in the course of the disease. As many as 55% of hospitalized COVID-19 patients have been reported to have neurological disturbances three months after infection by SARS-CoV-2. The mutability of the SARS-COV-2 virus and its potential to directly affect the CNS highlight the urgency of developing technology to diagnose, manage, and treat brain injury in COVID-19 patients. The pathobiology of CNS infection by SARS-CoV-2 and the associated neurological sequelae of this infection remain poorly understood. In this review, we outline the rationale for the use of blood biomarkers (BBs) for diagnosis of brain injury in COVID-19 patients, the research needed to incorporate their use into clinical practice, and the improvements in patient management and outcomes that can result. BBs of brain injury could potentially provide tools for detection of brain injury in COVID-19 patients. Elevations of BBs have been reported in cerebrospinal fluid (CSF) and blood of COVID-19 patients. BB proteins have been analyzed in CSF to detect CNS involvement in patients with infectious diseases, including human immunodeficiency virus and tuberculous meningitis. BBs are approved by the U.S. Food and Drug Administration for diagnosis of mild versus moderate traumatic brain injury and have identified brain injury after stroke, cardiac arrest, hypoxia, and epilepsy. BBs, integrated with other diagnostic tools, could enhance understanding of viral mechanisms of brain injury, predict severity of neurological deficits, guide triage of patients and assignment to appropriate medical pathways, and assess efficacy of therapeutic interventions in COVID-19 patients.

Intracranial Pressure Monitoring in Experimental Traumatic Brain Injury: Implications for Clinical Management.

Traumatic brain injury (TBI) is often associated with long-term disability and chronic neurological sequelae. One common contributor to unfavorable outcomes is secondary brain injury, which is potentially treatable and preventable through appropriate management of patients in the neurosurgical intensive care unit. Intracranial pressure (ICP) is currently the predominant neurological-specific physiological parameter used to direct the care of severe TBI (sTBI) patients. However, recent clinical evidence has called into question the association of ICP monitoring with improved clinical outcome. The detailed cellular and molecular derangements associated with intracranial hypertension (IC-HTN) and their relationship to injury phenotype and neurological outcomes are not completely understood. Various animal models of TBI have been developed, but the clinical applicability of ICP monitoring in the pre-clinical setting has not been well-characterized. Linking basic mechanistic studies in translational TBI models with investigation of ICP monitoring that more faithfully replicates the clinical setting will provide clinical investigators with a more informed understanding of the pathophysiology of IC-HTN, thus facilitating development of improved therapies for sTBI patients.