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This prospective, controlled, observational cohort study assessed the performance of a novel panel of serum microRNA (miRNA) biomarkers relative to findings on cervical spinal cord magnetic resonance imaging (MRI) in collegiate football players. There were 44 participants included in the study: 30 non-athlete control subjects and 14 male collegiate football athletes participating in a Division I Football Bowl Subdivision of the National Collegiate Athletic Association. Diffuse tensor MRI and blood samples were acquired within the week before the athletic season began and within the week after the last game of the season. All miRNAs were significantly higher in athletes regardless of their fractional anisotropy (FA) values (p

The involvement of the central nervous system (CNS), specifically the white matter tracts in the cervical spinal cord, was examined with diffusion tensor imaging (DTI) following exposure to repetitive head acceleration events (HAEs) after a single season of collegiate football. Fifteen National Collegiate Athletic Association (NCAA) Division 1 football players underwent DTI of the cervical spinal cord (vertebral level C1–4) at pre-season (before any contact practices began) and post-season (within 1 week of the last regular season game) intervals. Helmet accelerometer data were also collected in parallel throughout the season. From pre-season to post-season, a significant decrease (p

In adults, glial fibrillary acidic protein (GFAP) has been shown to out-perform S100β in detecting intracranial lesions on computed tomography (CT) in mild traumatic brain injury (TBI). This study examined the ability of GFAP and S100β to detect intracranial lesions on CT in children and youth involved in trauma. This prospective cohort study enrolled a convenience sample of children and youth at two pediatric and one adult Level 1 trauma centers following trauma, including both those with and without head trauma. Serum samples were obtained within 6 h of injury. The primary outcome was the presence of traumatic intracranial lesions on CT scan. There were 155 pediatric trauma patients enrolled, 114 (74%) had head trauma and 41 (26%) had no head trauma. Out of the 92 patients who had a head CT, eight (9%) had intracranial lesions. The area under the receiver operating characteristic curve (AUC) for distinguishing head trauma from no head trauma for GFAP was 0.84 (0.77-0.91) and for S100β was 0.64 (0.55-0.74; p

Midline shift following severe traumatic brain injury (sTBI) detected on computed tomography (CT) scans is an established predictor of poor outcome. We hypothesized that lateral ventricular volume (LVV) asymmetry is an earlier sign of developing asymmetric intracranial pathology than midline shift. This retrospective analysis was performed on data from 84 adults with blunt sTBI requiring a ventriculostomy who presented to a Level I trauma center. Seventy-six patients underwent serial CTs within 3 h and an average of three scans within the first 10 d of sTBI. Left and right LVVs were quantified by computer-assisted manual volumetric measurements. LVV ratios (LVR) were determined on the admission CT to evaluate ventricular asymmetry. The relationship between the admission LVR value and subsequent midline shift development was tested using receiver operating characteristic (ROC) analysis, and odds ratio (OR) and relative risk tests. Sixty patients had no >5 mm midline shift on the initial admission scan. Of these, 15 patients developed it subsequently (16 patients already had >5 mm midline shift on admission scans). For >5 mm midline shift development, admission LVR of >1.67 was shown to have a sensitivity of 73.3% and a specificity of 73.3% (area under the curve=0.782; p1.67 as exposure yielded an OR of 7.56 (p

Biomarkers are important for accurate diagnosis of complex disorders such as traumatic brain injury (TBI). For a complex and multifaceted condition such as TBI, it is likely that a single biomarker will not reflect the full spectrum of the response of brain tissue to injury. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are among of the most widely studied biomarkers for TBI. Because UCH-L1 and GFAP measure distinct molecular events, we hypothesized that analysis of both biomarkers would be superior to analysis of each alone for the diagnosis and prognosis of TBI. Serum levels of UCH-L1 and GFAP were measured in a cohort of 206 patients with TBI enrolled in a multicenter observational study (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI]). Levels of the two biomarkers were weakly correlated to each other (r=0.364). Each biomarker in isolation had good sensitivity and sensitivity for discriminating between TBI patients and healthy controls (area under the curve [AUC] 0.87 and 0.91 for UCH-L1 and GFAP, respectively). When biomarkers were combined, superior sensitivity and specificity for diagnosing TBI was obtained (AUC 0.94). Both biomarkers discriminated between TBI patients with intracranial lesions on CT scan and those without such lesions, but GFAP measures were significantly more sensitive and specific (AUC 0.88 vs. 0.71 for UCH-L1). For association with outcome 3 months after injury, neither biomarker had adequate sensitivity and specificity (AUC 0.65-0.74, for GFAP, and 0.59-0.80 for UCH-L1, depending upon Glasgow Outcome Scale Extended [GOS-E] threshold used). Our results support a role for multiple biomarker measurements in TBI research. (ClinicalTrials.gov Identifier NCT01565551)

Biospecimens represent a critically important resource in pediatric brain injury research. Data from these specimens can be used to identify and classify injury, understand the molecular mechanisms underlying different types of brain injury, and ultimately identify therapeutic targets to tailor treatments for individual patient needs. To realize the full potential of biospecimens in pediatric traumatic brain injury (TBI), standardization and adoption of best practice guidelines are needed to ensure the quality and consistency of specimens. Multiple groups, including the National Cancer Institute (NCI), the International Society for Biological and Environmental Repositories (ISBER), and the Organisation for Economic Co-operation and Development (OECD), have previously published best practice guidelines for biospecimen resources. Recommendations have also been provided by the Biospecimens and Biomarkers Workgroup of the interagency TBI Common Data Elements (CDE) initiative. The recommendations from all of these sources, however, focus exclusively on adult biospecimen collection. There are no published pediatric-specific biospecimen collection guidelines. An additional workgroup was formed to specifically address this gap. The aim of the Pediatric TBI CDE Biospecimens and Biomarkers Workgroup was to provide recommendations for best practice guidelines to standardize the quality and accessibility of biospecimens for pediatric brain injury research in general, and for pediatric TBI research in particular. Consensus recommendations were developed by review of previously published adult-specific recommendations, including the recommendations of the original TBI Common Data Elements Biospecimens and Biomarkers Workgroup, and by participation in the interagency workshop "Common Data Elements for TBI Research: Pediatric Considerations," held in Houston, Texas in March of 2010. These recommendations represent expert opinion on this subject. The authors of this article were members of the Biospecimens Workgroup. We hope that with adoption of these best practices, future investigators will be able to obtain biospecimens in a consistent way that meets the needs of pediatric patients, and helps to accelerate acquisition of pediatric-specific biomarker data.