Neutrophil Gene Expression Patterns in Multiple Trauma Patients Indicate Distinct Clinical Outcomes.

INTRODUCTION: Patients after polytrauma suffer from posttraumatic immune system dysregulation and multiple organ dysfunction. Genome-wide microarray profiling in monocytes revealed a regulatory network of inflammatory markers around the transcription factor AP-1 in severely injured patients. Recent research focuses on the role of neutrophils in posttraumatic inflammation. The aim of this study was, therefore, to evaluate the impact of this inflammatory network in neutrophils. MATERIALS AND METHODS: Blood sampling and neutrophil separation were performed on admission of the patient and at 6 h, 12 h, 24 h, 48 h, and 72 h after trauma. Neutrophil expression levels of the target genes c-Jun, c-Fos, BCL2A, MMP-9, TIMP-1, ETS-2, IL-1ß, and MIP-1ß were quantified by RT-qPCR. Patients were assorted into groups according to distinct clinical parameters like massive transfusion (>10 RBC units/24 h), injury severity (ISS), 90-d survival, and the presence of traumatic brain injury (defined by ICI on head CT). Statistics were calculated by Mann-Whitney Rank-Sum Test, Receiver Operating Curves, and binary multiple logistic regression. RESULTS: Forty severely injured patients (mean ISS 36 ± 14) were included. BCL2A, MMP-9, TIMP-1, and ETS2 levels showed a significant correlation to 90-d-survival in the early posttraumatic period (6 h-24 h). Furthermore, differential BCL2A, IL-1ß, MIP-1ß, and MMP-9 regulation was observed in patients requiring massive transfusion. We could further show a significant TIMP-1 response in trauma PMN associated with traumatic brain injury. CONCLUSIONS: This study of seriously injured patients highlights very early posttraumatic transcriptional changes in PMNs, which were clearly associated with posttraumatic events and outcomes.

ErbB Signaling Pathway Genes Are Differentially Expressed in Monozygotic Twins Discordant for Sports-Related Concussion.

Transcriptional changes involved in neuronal recovery after sports-related concussion (SRC) may be obscured by inter-individual variation in mRNA expression and nonspecific changes related to physical exertion. Using a co-twin study, the objective of this study was to identify important differences in mRNA expression among a single pair of monozygotic (MZ) twins discordant for concussion. A pair of MZ twins were enrolled as part of a larger study of concussion biomarkers among collegiate athletes. During the study, Twin A sustained SRC, allowing comparison of mRNA expression to the nonconcussed Twin B. Twin A clinically recovered by Day 7. mRNA expression was measured pre-injury and at 6 h and 7 days postinjury using Affymetrix HG-U133 Plus 2.0 microarray. Changes in mRNA expression from pre-injury to each postinjury time point were compared between the twins; differences >1.5-fold were considered important. Kyoto Encyclopedia of Genes and Genomes identified biologic networks associated with important transcripts. Among 38,000 analyzed genes, important changes were identified in 153 genes. The ErbB (epidermal growth factor receptor) signaling pathway was identified as the top transcriptional network from pre-injury to 7 days postinjury. Genes in this pathway with important transcriptional changes included epidermal growth factor (2.41), epiregulin (1.73), neuregulin 1 (1.54) and mechanistic target of rapamycin (1.51). In conclusion, the ErbB signaling pathway was identified as a potential regulator of clinical recovery in a MZ twin pair discordant for SRC. A co-twin study design may be a useful method for identifying important gene pathways associated with concussion recovery.

Short-Term Neurologic Manifestations of Repetitive Head Impacts Among Athletes: A Scoping Review.

OBJECTIVE: To summarize the evidence linking contact sports-related repetitive head impacts (RHIs) and short-term declines in neurologic function. METHODS: A scoping review following the guidelines in the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and searching 3 databases (PubMed, EMBASE, and Web of Science) was performed. Peer-reviewed research articles were eligible for inclusion if they were full-length English language articles published between 1999 and 2019 examining athletes between the ages of 14 and 40 years exposed to RHIs, and reporting cognitive, vestibular, and/or oculomotor outcomes within 4 weeks of last head hit exposure. RESULTS: Fifty-two articles met criteria for review: 14 reported oculomotor outcomes, 23 reported vestibular outcomes, and 36 reported cognitive function. Short-term RHI-related declines in neurologic function were reported in 42.9% of oculomotor studies, in 20.8% of vestibular studies, and in 33.3% of cognitive studies. Most of the 52 studies involved American football, soccer, or ice hockey athletes at the collegiate ( n = 23) or high school ( n = 14) level. Twenty-four (46%) studies involved only male athletes. Wearable sensors were used to measure RHIs in 24 studies (46%), while RHIs were not measured in 26 studies (50%). In addition, many studies failed to control for attention-deficit/hyperactivity disorder/learning disability and/or concussion history. CONCLUSION: The results of this scoping review suggest that the evidence linking RHIs to short-term declines in neurologic function is relatively sparse and lacking in methodological rigor. Although most studies failed to find a link, those that did were more likely to use objective measures of RHIs and to control for confounders. More careful trial design may be needed to definitively establish a causal link between RHIs and short-term neurologic dysfunction.

A Prospective Study of Acute Blood-Based Biomarkers for Sport-Related Concussion.

OBJECTIVE: Prospectively characterize changes in serum proteins following sport-related concussion and determine whether candidate biomarkers discriminate concussed athletes from controls and are associated with duration of symptoms following concussion. METHODS: High school and collegiate athletes were enrolled between 2015 and 2018. Blood was collected at preinjury baseline and within 6 hours (early acute) and at 24 to 48 hours (late acute) following concussion in football players (n = 106), matched uninjured football players (n = 84), and non-contact-sport athletes (n = 50). Glial fibrillary acidic protein, ubiquitin c-terminal hydrolase-L1, S100 calcium binding protein B, alpha-II-spectrin breakdown product 150, interleukin 6, interleukin 1 receptor antagonist, and c-reactive protein were measured in serum. Linear models assessed changes in protein concentrations over time. Receiver operating curves quantified the discrimination of concussed athletes from controls. A Cox proportional hazard model determined whether proteins were associated with symptom recovery. RESULTS: All proteins except glial fibrillary acidic protein and c-reactive protein were significantly elevated at the early acute phase postinjury relative to baseline and both control groups and discriminated concussed athletes from controls with areas under the curve of 0.68 to 0.84. The candidate biomarkers also significantly improved the discrimination of concussed athletes from noncontact controls compared to symptom severity alone. Glial fibrillary acidic protein was elevated postinjury relative to baseline in concussed athletes with a loss of consciousness or amnesia. Finally, early acute levels of interleukin 1 receptor antagonist were associated with the number of days to symptom recovery. INTERPRETATION: Brain injury and inflammatory proteins show promise as objective diagnostic biomarkers for sport-related concussion, and inflammatory markers may provide prognostic value. ANN NEUROL 2020;87:907-920.

Understanding Traumatic Brain Injury in Females: A State-of-the-Art Summary and Future Directions.

In this report, we identify existing issues and challenges related to research on traumatic brain injury (TBI) in females and provide future directions for research. In 2017, the National Institutes of Health, in partnership with the Center for Neuroscience and Regenerative Medicine and the Defense and Veterans Brain Injury Center, hosted a workshop that focused on the unique challenges facing researchers, clinicians, patients, and other stakeholders regarding TBI in women. The goal of this "Understanding TBI in Women" workshop was to bring together researchers and clinicians to identify knowledge gaps, best practices, and target populations in research on females and/or sex differences within the field of TBI. The workshop, and the current literature, clearly highlighted that females have been underrepresented in TBI studies and clinical trials and have often been excluded (or ovariectomized) in preclinical studies. Such an absence in research on females has led to an incomplete, and perhaps inaccurate, understanding of TBI in females. The presentations and discussions centered on the existing knowledge regarding sex differences in TBI research and how these differences could be incorporated in preclinical and clinical efforts going forward. Now, a little over 2 years later, we summarize the issues and state of the science that emerged from the "Understanding TBI in Women" workshop while incorporating updates where they exist. Overall, despite some progress, there remains an abundance of research focused on males and relatively little explicitly on females.

Recommendations for the Emergency Department Prevention of Sport-Related Concussion.

Sport-related concussion refers to the subset of concussive injuries occurring during sport activities. Similar to concussion from nonsport mechanisms, sport-related concussion is associated with significant morbidity, including migrainous headaches, disruption in normal daily activities, and long-term depression and cognitive deficits. Unlike nonsport concussions, sport-related concussion may be uniquely amenable to prevention efforts to mitigate these problems. The emergency department (ED) visit for sport-related concussion represents an opportunity to reduce morbidity by timely diagnosis and management using best practices, and through education and counseling to prevent a subsequent sport-related concussion. This article provides recommendations to reduce sport-related concussion disability through primary, secondary, and tertiary preventive strategies enacted during the ED visit. Although many recommendations have a solid evidence base, several research gaps remain. The overarching goal of improving sport-related concussion outcome through enactment of ED-based prevention strategies needs to be explicitly studied.

S100B outperforms clinical decision rules for the identification of intracranial injury on head CT scan after mild traumatic brain injury.

Objective: To compare the classification accuracy of S100B to two clinical decision rules- Canadian CT Head Rule (CCHR) and New Orleans Criteria (NOC)-for predicting traumatic intracranial injuries (ICI) after mild traumatic brain injury (mild TBI).Methods: A secondary analysis of a prospective observational study of mild TBI patients was performed. The diagnostic performance of S100B for predicting ICI on head CT was compared to both the CHRR and NOC. Area under receiver operator characteristic (AUC) curves were used and multivariable analysis was used to create a new decision rule based on a combination of S100B and decision rule-related variables.Results: S100B had the highest negative predictive value (97.3%), positive predictive value (7.21%), specificity (33.6%) and positive likelihood ratio (1.3), and the lowest negative likelihood ratio (0.5). The proportion of mild TBI subjects with potentially avoidable head CT scans was highest using S100B (37.7%). The addition of S100B to both clinical decision rules significantly increased AUC. A novel decision rule adding S100B to three decision rule-related variables significantly improved prediction (p < 0.05).Conclusion: Serum S100B outperformed clinical decision rules for identifying mild TBI patients with ICI. Incorporating clinical variables with S100B maximized ICI prediction, but requires validation in an independent cohort.

The Use of an Electrophysiological Brain Function Index in the Evaluation of Concussed Athletes.

OBJECTIVE: To evaluate the effectiveness of the electroencephalographic (EEG) Brain Function Index (BFI) for characterizing sports-related concussive injury and recovery. PARTICIPANTS: Three hundred fifty-four (354) male contact sport high school and college athletes were prospectively recruited from multiple locations over 6 academic years of play (244 control baseline athletes and 110 athletes with a concussion). METHODS: Using 5 to 10 minutes of eyes closed resting EEG collected from frontal and frontotemporal regions, a BFI was computed for all subjects and sessions. Group comparisons were performed to test for the significance of the difference in the BFI score between the controls at baseline and athletes with a concussion at several time points. RESULTS: There was no significant difference in BFI between athletes with a concussion at baseline (ie, prior to injury) and controls at baseline (P = .4634). Athletes with a concussion, tested within 72 hours of injury, exhibited significant differences in BFI compared with controls (P = .0036). The significant differences in BFI were no longer observed at 45 days following injury (P = .19). CONCLUSION: Controls and athletes with a concussion exhibited equivalent BFI scores at preseason baseline. The concussive injury (measured within 72 hours) significantly affected brain function reflected in the BFI in the athletes with a concussion. The BFI of the athletes with a concussion returned to levels seen in controls by day 45, suggesting recovery. The BFI may provide an important objective marker of concussive injury and recovery.

Academic Dysfunction After a Concussion Among US High School and College Students.

OBJECTIVES: To determine whether concussed students experience greater academic dysfunction than students who sustain other injuries. METHODS: We conducted a prospective cohort study from September 2013 through January 2015 involving high school and college students who visited 3 emergency departments in the Rochester, New York, area. Using telephone surveys, we compared self-reported academic dysfunction between 70 students with concussions and a comparison group of 108 students with extremity injuries at 1 week and 1 month after injury. RESULTS: At 1 week after injury, academic dysfunction scores were approximately 16 points higher (b = 16.20; 95% confidence interval = 6.39, 26.00) on a 174-point scale in the concussed group than in the extremity injury group. Although there were no differences overall at 1-month after injury, female students in the concussion group and those with a history of 2 or more prior concussions were more likely to report academic dysfunction. CONCLUSIONS: Our results showed academic dysfunction among concussed students, especially female students and those with multiple prior concussions, 1 week after their injury. Such effects appeared to largely resolve after 1 month. Our findings support the need for academic adjustments for concussed students.

Sports-Related Concussion Results in Differential Expression of Nuclear Factor-κB Pathway Genes in Peripheral Blood During the Acute and Subacute Periods.

OBJECTIVE: To determine changes in global gene expression in peripheral leukocytes in the acute and subacute periods following a sports-related concussion in athletes. SETTING: Samples were collected at 2 universities in Rochester, New York. PARTICIPANTS: Fifteen contact sport athletes who experienced a sports-related concussion, and 16 nonconcussed teammates served as controls. DESIGN: Blood samples were collected at the start of the season (baseline), within 6 hours of injury (acute), and at 7 days (subacute) postinjury. Differential gene expression was measured using the GeneChip 3' in vitro transcription Expression kit and Affymetrix microarrays, and genes with fold difference of 2 or more were identified using Partek. MAIN MEASURES: Whole genome differential gene expression, and cognitive and balance measures to asses for clinical symptoms pre- and postinjury. RESULTS: In the concussed athletes, we observed 67 downregulated and 4 upregulated genes in the acute period and 63 downregulated and 2 upregulated genes in the subacute period compared with baseline. Of these, there were 28 genes from both time points involved in the inflammatory response. No significant differences in gene expression were detected in the control group. CONCLUSIONS: Our findings suggest that recovery from sports-related concussion relates to modulation of inflammation through cytokine and chemokine gene pathways, which can contribute to future development of personalized therapeutic agents.

Identification of a neurologic scale that optimizes EMS detection of older adult traumatic brain injury patients who require transport to a trauma center.

OBJECTIVE: We sought to identify a scale or components of a scale that optimize detection of older adult traumatic brain injury (TBI) patients who require transport to a trauma center, regardless of mechanism. METHODS: We assembled a consensus panel consisting of nine experts in geriatric emergency medicine, prehospital medicine, trauma surgery, geriatric medicine, and TBI, as well as prehospital providers, to evaluate the existing scales used to identify TBI. We reviewed the relevant literature and solicited group feedback to create a list of candidate scales and criteria for evaluation. Using the nominal group technique, scales were evaluated by the expert panel through an iterative process until consensus was achieved. RESULTS: We identified 15 scales for evaluation. The panel's criteria for rating the scales included ease of administration, prehospital familiarity with scale components, feasibility of use with older adults, time to administer, and strength of evidence for their performance in the prehospital setting. After review and discussion of aggregated ratings, the panel identified the Simplified Motor Scale, GCS-Motor Component, and AVPU (alert, voice, pain, unresponsive) as the strongest scales, but determined that none meet all EMS provider and patient needs due to poor usability and lack of supportive evidence. The panel proposed that a dichotomized decision scheme that includes domains of the top-rated scales -level of alertness (alert vs. not alert) and motor function (obeys commands vs. does not obey) -may be more effective in identifying older adult TBI patients who require transport to a trauma center in the prehospital setting. CONCLUSIONS: Existing scales to identify TBI are inadequate to detect older adult TBI patients who require transport to a trauma center. A new algorithm, derived from elements of previously established scales, has the potential to guide prehospital providers in improving the triage of older adult TBI patients, but needs further evaluation prior to use.

Menstrual phase as predictor of outcome after mild traumatic brain injury in women.

OBJECTIVE: To determine whether menstrual cycle phase in women at the time of mild traumatic brain injury (mTBI) predicts 1-month outcomes. SETTING: Six emergency departments; 5 in Upstate New York, and 1 in Pennsylvania. PARTICIPANTS: One hundred forty-four female participants (age, 16-60) who presented to participating emergency departments within 4 hours of mTBI. DESIGN: Nested cohort study with neurologic and quality-of-life outcome assessment, 1 month after enrollment. Female subjects aged 16 to 60 enrolled in the parent cohort study, with 1-month neurological determination data available, were classified into menstrual cycle groups by serum progesterone concentration and self-reported contraceptive use. MAIN MEASURES: Rivermead Post Concussion Questionnaire and EuroQoL/EQ5D. RESULTS: Women injured during the luteal phase of their menstrual cycle, when progesterone concentration is high, had significantly lower EuroQoL General Health Ratings and Index Scores than women injured during the follicular phase of their cycle or women taking oral contraceptives. Multivariate analysis confirmed a significant independent effect of menstrual cycle phase on EuroQoL Index Score and the Rivermead Post Concussion Questionnaire Somatic Subscore. CONCLUSION: Menstrual cycle phase and progesterone concentration at the time of mTBI affect 1-month quality-of-life and neurologic outcomes. This association has important implications for treatment and prognosis after mTBI.

Identification of Concussion Subtypes Based on Intrinsic Brain Activity.

Importance: The identification of brain activity-based concussion subtypes at time of injury has the potential to advance the understanding of concussion pathophysiology and to optimize treatment planning and outcomes. Objective: To investigate the presence of intrinsic brain activity-based concussion subtypes, defined as distinct resting state quantitative electroencephalography (qEEG) profiles, at the time of injury. Design, Setting, and Participants: In this retrospective, multicenter (9 US universities and high schools and 4 US clinical sites) cohort study, participants aged 13 to 70 years with mild head injuries were included in longitudinal cohort studies from 2017 to 2022. Patients had a clinical diagnosis of concussion and were restrained from activity by site guidelines for more than 5 days, with an initial Glasgow Coma Scale score of 14 to 15. Participants were excluded for known neurological disease or history of traumatic brain injury within the last year. Patients were assessed with 2 minutes of artifact-free EEG acquired from frontal and frontotemporal regions within 120 hours of head injury. Data analysis was performed from July 2021 to June 2023. Main Outcomes and Measures: Quantitative features characterizing the EEG signal were extracted from a 1- to 2-minute artifact-free EEG data for each participant, within 120 hours of injury. Symptom inventories and days to return to activity were also acquired. Results: From the 771 participants (mean [SD] age, 20.16 [5.75] years; 432 male [56.03%]), 600 were randomly selected for cluster analysis according to 471 qEEG features. Participants and features were simultaneously grouped into 5 disjoint subtypes by a bootstrapped coclustering algorithm with an overall agreement of 98.87% over 100 restarts. Subtypes were characterized by distinctive profiles of qEEG measure sets, including power, connectivity, and complexity, and were validated in the independent test set. Subtype membership showed a statistically significant association with time to return to activity. Conclusions and Relevance: In this cohort study, distinct subtypes based on resting state qEEG activity were identified within the concussed population at the time of injury. The existence of such physiological subtypes supports different underlying pathophysiology and could aid in personalized prognosis and optimization of care path.

Effectiveness of biomedical interventions on the chronic stage of traumatic brain injury: a systematic review of randomized controlled trials.

Traumatic brain injury (TBI), in any form and severity, can pose risks for developing chronic symptoms that can profoundly hinder patients' work/academic, social, and personal lives. In the past 3 decades, a multitude of pharmacological, stimulation, and exercise-based interventions have been proposed to ameliorate symptoms, memory impairment, mental fatigue, and/or sleep disturbances. However, most research is preliminary, thus limited influence on clinical practice. This review aims to systematically appraise the evidence derived from randomized controlled trials (RCT) regarding the effectiveness of pharmacological, stimulation, and exercise-based interventions in treating chronic symptoms due to TBI. Our search results indicate that despite the largest volume of literature, pharmacological interventions, especially using neurostimulant medications to treat physical, cognitive, and mental fatigue, as well as daytime sleepiness, have yielded inconsistent results, such that some studies found improvements in fatigue (e.g., Modafinil, Armodafinil) while others failed to yield the improvements after the intervention. Conversely, brain stimulation techniques (e.g., transcranial magnetic stimulation, blue light therapy) and exercise interventions were effective in ameliorating mental health symptoms and cognition. However, given that most RCTs are equipped with small sample sizes, more high-quality, larger-scale RCTs is needed.

A Pilot Study Investigating the Use of Serum Glial Fibrillary Acidic Protein to Monitor Changes in Brain White Matter Integrity After Repetitive Head Hits During a Single Collegiate Football Game.

Repetitive head hits (RHHs) in sports and military settings are increasingly recognized as a risk factor for adverse neurological outcomes, but they are not currently tracked. Blood-based biomarkers of concussion have recently been shown to increase after nonconcussive RHHs during a single sporting contest, raising the possibility that they could be used in real time to monitor the brain's early response to repeated asymptomatic head hits. To test this hypothesis, we measured GFAP in serum immediately before (T0), immediately after (T1) and 45 min (T2) after a single collegiate football game in 30 athletes. Glial fibrillary acidic protein (GFAP) changes were correlated with three measures of head impact exposure (number of hits, total linear acceleration, and total rotational acceleration captured by helmet impact sensors) and to changes in brain white matter (WM) integrity, estimated by regional changes in fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging from 24 h before (T1) to 48 h after (T3) the game. To account for the potentially confounding effects of physical exertion on GFAP, correlations were adjusted for kilocalories of energy expended during the game measured by wearable body sensors. All 30 participants were male with a mean age of 19.5 ± 1.2 years. No participant had a concussion during the index game. We observed a significant increase in GFAP from T0 to T1 (mean 79.69 vs. 91.95 pg/mL, p = 0.008) and from T0 to T2 (mean 79.69 vs. 99.21 pg/mL, p < 0.001). WM integrity decreased in multiple WM regions but was statistically significant in the right fornix (mean % FA change -1.43, 95% confidence interval [CI]: -2.20, -0.66). T0 to T2 increases in GFAP correlated with reduced FA in the left fornix, right fornix, and right medical meniscus and with increased MD in the right fornix (r-values ranged from 0.59 to 0.61). Adjustment for exertion had minimal effect on these correlations. GFAP changes did not correlate to head hit exposure, but after adjustment for exertion, T0 to T2 increases correlated with all three hit metrics (r-values ranged from 0.69 to 0.74). Thus, acute elevations in GFAP after a single collegiate football game of RHHs correlated with in-game head hit exposure and with reduced WM integrity 2 days later. These results suggest that GFAP may be a biologically relevant indicator of the brain's early response to RHHs during a single sporting event. Developing tools to measure the neurological response to RHHs on an individual level has the potential to provide insight into the heterogeneity in adverse outcomes after RHH exposure and for developing effective and personalized countermeasures. Owing to the small sample size, these findings should be considered preliminary; validation in a larger, independent cohort is necessary.

The Interval Between Concussions Does Not Influence Time to Asymptomatic or Return to Play: A CARE Consortium Study.

INTRODUCTION: The purpose of this study was to determine if the time interval between two concussive events influences the number of days to asymptomatic status, days to return to play, or performance on common post-concussion assessments following the second concussion. METHODS: Data from 448 collegiate athletes and service academy cadets with two concussions (time between concussions: median 295.0 days [interquartile range: 125.0-438.2]), 40.0% female) were analyzed from Concussion Assessment Research and Education (CARE) Consortium institutions between 2014 and 2020. Days between concussions was the primary predictor variable. Primary outcome measures included time to asymptomatic and time to return to play following the second concussion. Secondary outcome measures included total number of symptoms, total symptom severity, Balance Error Scoring System total score, and Standardized Assessment of Concussion total score within 48 h of their second concussion. RESULTS: Time between concussions did not significantly contribute to the multivariate time to asymptomatic (p = 0.390), time to return to play (p = 0.859), or the secondary outcomes (p-range = 0.165-0.477) models. Time to asymptomatic (p = 0.619) or return to play (p = 0.524) did not differ between same-season and different-season concussions. Sex significantly contributed to the return to play (p = 0.005) multivariate model. Delayed symptom onset and immediate removal from play/competition significantly contributed to the total number of symptoms (p = 0.001, p = 0.014) and symptom severity (p = 0.011, p = 0.022) multivariate models. CONCLUSION: These results suggest that in a population with a large period between injuries, the time between concussions may not be relevant to clinical recovery.

The relation between posttraumatic stress disorder and mild traumatic brain injury acquired during Operations Enduring Freedom and Iraqi Freedom.

OBJECTIVE: To understand the relations of mild traumatic brain injury (TBI), blast exposure, and brain white matter structure to severity of posttraumatic stress disorder (PTSD). DESIGN: Nested cohort study using multivariate analyses. PARTICIPANTS: Fifty-two OEF/OIF veterans who served in combat areas between 2001 and 2008 were studied approximately 4 years after the last tour of duty. MAIN MEASURES: PTSD Checklist-Military; Combat Experiences Survey, interview questions concerning blast exposure and TBI symptoms; anatomical magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI) scanning of the brain. RESULTS: PTSD severity was associated with higher 1st percentile values of mean diffusivity on DTI (regression coefficient [r] = 4.2, P = .039), abnormal MRI (r = 13.3, P = .046), and the severity of exposure to combat events (r = 5.4, P = .007). Mild TBI was not significantly associated with PTSD severity. Blast exposure was associated with lower 1st percentile values of fractional anisotropy on DTI (odds ratio [OR] = 0.38 per SD; 95% confidence interval [CI], 0.15-0.92), normal MRI (OR = 0.00, 95% likelihood ratio test CI, 0.00-0.09), and the severity of exposure to traumatic events (OR = 3.64 per SD; 95% CI, 1.40-9.43). CONCLUSIONS: PTSD severity is related to both the severity of combat stress and underlying structural brain changes on MRI and DTI but not to a clinical diagnosis of mild TBI. The observed relation between blast exposure and abnormal DTI suggests that subclinical TBI may play a role in the genesis of PTSD in a combat environment.

Inability of S100B to predict postconcussion syndrome in children who present to the emergency department with mild traumatic brain injury: a brief report.

OBJECTIVE: This study aimed to explore the ability of the serum marker S100B to predict the development and severity of postconcussion syndrome (PCS) at 3 months in children after mild traumatic brain injury (mTBI). METHODS: This is a retrospective analysis of a prospective observational study conducted in a pediatric emergency department (ED). Children were eligible for the study if they were between the ages 5 and 18 years, presented within 6 hours of injury, met the case definition of mTBI from American Congress of Rehabilitation Medicine, had a Glasgow Coma Scale score of greater than 13, consented to have blood drawn for S100B levels, and completed the 3-month telephone follow-up. At the follow-up, the Rivermead Postconcussion Questionnaire was conducted to determine the development and severity of PCS. RESULTS: A total of 76 children were included in this cohort. The children had a mean (SD) age of 14.0 (3.1) years, 60.5% were male, and 89.5% had a Glasgow Coma Scale of 15. Twenty-eight (36.8%) developed PCS. For the children who developed PCS, the mean (SD) S100B level was 0.092 (0.376) µg/L. For children who did not develop PCS (n = 48), the mean (SD) S100B level was 0.022 (0.031) µg/L. The analyses did not support an association between initial S100B levels measured in the ED and development of PCS or severity of PCS symptoms. CONCLUSIONS: In this small sample, S100B, measured immediately after injury in the ED, did not seem to predict those children with mTBI who will go on to develop PCS.