Defining Acute Traumatic Encephalopathy: Methods of the "HEAD Injury Serum Markers and Multi-Modalities for Assessing Response to Trauma" (HeadSMART II) Study.

Despite an estimated 2.8 million annual ED visits, traumatic brain injury (TBI) is a syndromic diagnosis largely based on report of loss of consciousness, post-traumatic amnesia, and/or confusion, without readily available objective diagnostic tests at the time of presentation, nor an ability to identify a patient's prognosis at the time of injury. The recognition that "mild" forms of TBI and even sub-clinical impacts can result in persistent neuropsychiatric consequences, particularly when repetitive, highlights the need for objective assessments that can complement the clinical diagnosis and provide prognostic information about long-term outcomes. Biomarkers and neurocognitive testing can identify brain injured patients and those likely to have post-concussive symptoms, regardless of imaging testing results, thus providing a physiologic basis for a diagnosis of acute traumatic encephalopathy (ATE). The goal of the HeadSMART II (HEAD injury Serum markers and Multi-modalities for Assessing Response to Trauma) clinical study is to develop an in-vitro diagnostic test for ATE. The BRAINBox TBI Test will be developed in the current clinical study to serve as an aid in evaluation of patients with ATE by incorporating blood protein biomarkers, clinical assessments, and tools to measure, identify, and define associated pathologic evidence and neurocognitive impairments. This protocol proposes to collect data on TBI subjects by a multi-modality approach that includes serum biomarkers, clinical assessments, neurocognitive performance, and neuropsychological characteristics, to determine the accuracy of the BRAINBox TBI test as an aid to the diagnosis of ATE, defined herein, and to objectively determine a patient's risk of developing post-concussive symptoms.

Spatial regression analysis of MR diffusion reveals subject-specific white matter changes associated with repetitive head impacts in contact sports.

Repetitive head impacts (RHI) are a growing concern due to their possible neurocognitive effects, with research showing a season of RHI produce white matter (WM) changes seen on neuroimaging. We conducted a secondary analysis of diffusion tensor imaging (DTI) data for 28 contact athletes to compare WM changes. We collected pre-season and post-season DTI scans for each subject, approximately 3 months apart. We collected helmet data for the athletes, which we correlated with DTI data. We adapted the SPatial REgression Analysis of DTI (SPREAD) algorithm to conduct subject-specific longitudinal DTI analysis, and developed global inferential tools using functional norms and a novel robust p value combination test. At the individual level, most detected injured regions (93.3%) were associated with decreased FA values. Using meta-analysis techniques to combine injured regions across subjects, we found the combined injured region at the group level occupied the entire WM skeleton, suggesting the WM damage location is subject-specific. Several subject-specific functional summaries of SPREAD-detected WM change, e.g., the [Formula: see text] norm, significantly correlated with helmet impact measures, e.g. cumulative unweighted rotational acceleration (adjusted p = 0.0049), time between hits rotational acceleration (adjusted p value 0.0101), and time until DTI rotational acceleration (adjusted p = 0.0084), suggesting RHIs lead to WM changes.

Risk of female sexual dysfunction following concussion in women of reproductive age.

Objectives: Traumatic Brain Injury (TBI) has frequently been associated with changes in sexual functioning. The TBI and sexuality literature, however, has limited generalizability to concussed females, who often use the emergency department (ED) as their first line of care after head injury. Primary Objective: The primary objective of this study was to evaluate the impact of concussions on female sexual functioning. Secondary Objective: Secondarily, we evaluated if concussed women with sexual dysfunction also report more post-concussion symptoms (PCS) and/or mood changes. Research Design: This was a prospective cohort, with outcomes assessed at 6-10 weeks after ED enrollment. Methods and Procedures: Sexual dysfunction was defined as ≤ 45 on the Brain Injury Questionnaire on Sexuality (BIQS). The Rivermead Post-concussion Symptoms Questionnaire (RPQ) and the Hospital Anxiety and Depression Scale (HADS) assessed PCS and post-injury mood, respectively. Main Outcomes & Results: Eighty-nine eumenorrheic females (8-14 menstrual cycles/year) completed the study; 31(36%) had concussions, and 55(64%) were extremity injured. Concussed women had 70% increased risk of sexual dysfunction (adj.RR:1.70, 95% CI: 1.04,2.76; p = .03) versus extremity injured. Of clinical relevance, concussed women with sexual dysfunction also reported more PCS symptoms (adj.ß = 5.5, 95% CI: -6.7,18.2; p = .37) and mood scores (adj.ß = 8.0; 95% CI: -0.4, 16.4; p = .06). Conclusions: This study highlights the need for more research and interventions for one of the fastest growing subgroups within the TBI population.

Immediate Removal From Activity After Sport-Related Concussion Is Associated With Shorter Clinical Recovery and Less Severe Symptoms in Collegiate Student-Athletes.

BACKGROUND: Timely removal from activity after concussion symptoms remains problematic despite heightened awareness. Previous studies indicated potential adverse effects of continuing to participate in physical activity immediately after sustaining a concussion. Hypothesis/Purpose: The purpose was to determine the effect of timing of removal from play after concussion on clinical outcomes. It was hypothesized that immediate removal from activity after sport-related concussion (SRC) would be associated with less time missed from sport, a shorter symptomatic period, and better outcomes on acute clinical measures. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Data were reported from the National Collegiate Athletic Association and Department of Defense Grand Alliance: Concussion Awareness, Research, and Education (CARE) Consortium. Participants with 506 diagnosed SRCs from 18 sports and 25 institutions and military service academies were analyzed and classified as either immediate removal from activity (I-RFA) or delayed removal from activity (D-RFA). Outcomes of interest included time missed from sport attributed to their SRC, symptom duration, and clinical assessment scores. RESULTS: There were 322 participants (63.6%) characterized as D-RFA. I-RFA status was associated with significantly less time missed from sport ( R2 change = .022-.024, P < .001 to P = .001) and shorter symptom duration ( R2 change = .044-.046, P < .001 [all imputations]) while controlling for other SRC recovery modifiers. These athletes missed approximately 3 fewer days from sport participation. I-RFA athletes had significantly less severe acute SRC symptoms and were at lower risk of recovery taking ≥14 days (relative risk = .614, P < .001, small-medium effect size) and ≥21 days (relative risk = .534, P = .010, small effect size). CONCLUSION: I-RFA is a protective factor associated with less severe acute symptoms and shorter recovery after SRC. Conveying this message to athletes, coaches, and others involved in the care of athletes may promote timely injury reporting.

Age at First Concussion Influences the Number of Subsequent Concussions.

BACKGROUND: Individuals who sustain their first concussion during childhood may be at greater risk of sustaining multiple concussions throughout their lifetime because of a longer window of vulnerability. This article aims to estimate the association between age at first concussion and number of subsequent concussions. PATIENTS AND METHODS: A total of 23,582 collegiate athletes from 26 universities and military cadets from three military academies completed a concussion history questionnaire (65% males, age 19.9 ± 1.4 years). Participants self-reported concussions and age at time of each injury. Participants with a history of concussion (n = 3,647, 15.5%) were categorized as having sustained their first concussion during childhood (less than ten years old) or adolescence (≥10 and ≤18 years old). Poisson regression was used to model age group (childhood, adolescence) predicting the number of subsequent concussions (0, 1, 2+). A second Poisson regression was developed to determine whether age at first concussion predicted the number of subsequent concussions. RESULTS: Participants self-reporting their first concussion during childhood had an increased risk of subsequent concussions (rate ratio = 2.19, 95% confidence interval: 1.82, 2.64) compared with participants self-reporting their first concussion during adolescence. For every one-year increase in age at first concussion, we observed a 16% reduction in the risk of subsequent concussion (rate ratio = 0.84, 95% confidence interval: 0.82, 0.86). CONCLUSIONS: Individuals self-reporting a concussion at a young age sustained a higher number of concussions before age 18. Concussion prevention, recognition, and reporting strategies are of particular need at the youth level.

Validation of the Scandinavian guidelines for initial management of minimal, mild and moderate traumatic brain injury in adults.

BACKGROUND: Acute management of traumatic brain injury (TBI), in particular mild TBI, focuses on the detection of the 5-7 % who may be harboring potentially life-threatening intracranial hemorrhage (IH) using CT scanning. Guidelines intending to reduce unnecessary head CT scans using available clinical variables to detect those at high IH risk have shown varying results. Recently, the Scandinavian Neurotrauma Committee (SNC) derived a new set of high-IH risk variables for adults with TBI using an evidence-based literature review. Unlike previous guidelines, the SNC guideline incorporates serum values of the brain protein S100B with clinical variables. METHODS: We performed a nested cohort study of adults with mild TBI presenting to six emergency departments in New York and Pennsylvania within 6 h of injury. Patients were managed according to existing guidelines for CT selection. All patients underwent head CT scanning and serum S100B measurement, as well as prospective collection of clinical variables, as a requirement of the parent study. Using the SNC guidelines, S100B values and clinical variables were applied to these subjects, classifying each into one of five pre-defined severity categories, as well as predicting the need for head CT scanning to identify IH. This classification was then compared to actual head CT results to determine guideline sensitivity and specificity. RESULTS: In total, 662 adults (mean age 42 years, range 18-96; 258 females, 549 Caucasians) were available for analysis; 36 (5%) had IH on head CT scan. The SNC guidelines had a sensitivity of 97% (95% CI, 84-100%) and a specificity of 34% (95% CI, 30-37%) for the detection of IH on head CT. Application of the SNC guidelines would have resulted in a CT reduction of 32% (211/662 patients). One patient with low-risk mild TBI and a S100B level under 0.10 µg/L had a traumatic CT abnormality and would have been discharged with strict adherence to the guidelines. However, this patient did not need any intervention for the injury and had a good outcome. CONCLUSION: Using the SNC guideline could save approximately one third of CT scans in a pre-selected cohort of mild TBI patients with little or no impact on patient outcome.