Systematic review of clinical studies examining biomarkers of brain injury in athletes after sports-related concussion.

The aim of this study was to systematically review clinical studies examining biofluid biomarkers of brain injury for concussion in athletes. Data sources included PubMed, MEDLINE, and the Cochrane Database from 1966 to October 2013. Studies were included if they recruited athletes participating in organized sports who experienced concussion or head injury during a sports-related activity and had brain injury biomarkers measured. Acceptable research designs included experimental, observational, and case-control studies. Review articles, opinion papers, and editorials were excluded. After title and abstract screening of potential articles, full texts were independently reviewed to identify articles that met inclusion criteria. A composite evidentiary table was then constructed and documented the study title, design, population, methods, sample size, outcome measures, and results. The search identified 52 publications, of which 13 were selected and critically reviewed. All of the included studies were prospective and were published either in or after the year 2000. Sports included boxing (six studies), soccer (five studies), running/jogging (two studies), hockey (one study), basketball (one study), cycling (one study), and swimming (one study). The majority of studies (92%) had fewer than 100 patients. Three studies (23%) evaluated biomarkers in cerebrospinal fluid (CSF), one in both serum and CSF, and 10 (77%) in serum exclusively. There were 11 different biomarkers assessed, including S100ß, glial fibrillary acidic protein, neuron-specific enolase, tau, neurofilament light protein, amyloid beta, brain-derived neurotrophic factor, creatine kinase and heart-type fatty acid binding protein, prolactin, cortisol, and albumin. A handful of biomarkers showed a correlation with number of hits to the head (soccer), acceleration/deceleration forces (jumps, collisions, and falls), postconcussive symptoms, trauma to the body versus the head, and dynamics of different sports. Although there are no validated biomarkers for concussion as yet, there is potential for biomarkers to provide diagnostic, prognostic, and monitoring information postinjury. They could also be combined with neuroimaging to assess injury evolution and recovery.

Systematic review of clinical research on biomarkers for pediatric traumatic brain injury.

Abstract The objective was to systematically review the medical literature and comprehensively summarize clinical research performed on biomarkers for pediatric traumatic brain injury (TBI) and to summarize the studies that have assessed serum biomarkers acutely in determining intracranial lesions on CT in children with TBI. The search strategy included a literature search of PubMed,(®) MEDLINE,(®) and the Cochrane Database from 1966 to August 2011, as well as a review of reference lists of identified studies. Search terms used included pediatrics, children, traumatic brain injury, and biomarkers. Any article with biomarkers of traumatic brain injury as a primary focus and containing a pediatric population was included. The search initially identified 167 articles. Of these, 49 met inclusion and exclusion criteria and were critically reviewed. The median sample size was 58 (interquartile range 31-101). The majority of the articles exclusively studied children (36, 74%), and 13 (26%) were studies that included both children and adults in different proportions. There were 99 different biomarkers measured in these 49 studies, and the five most frequently examined biomarkers were S100B (27 studies), neuron-specific enolase (NSE) (15 studies), interleukin (IL)-6 (7 studies), myelin basic protein (MBP) (6 studies), and IL-8 (6 studies). There were six studies that assessed the relationship between serum markers and CT lesions. Two studies found that NSE levels ≥15 ng/mL within 24 h of TBI was associated with intracranial lesions. Four studies using serum S100B were conflicting: two studies found no association with intracranial lesions and two studies found a weak association. The flurry of research in the area over the last decade is encouraging but is limited by small sample sizes, variable practices in sample collection, inconsistent biomarker-related data elements, and disparate outcome measures. Future studies of biomarkers for pediatric TBI will require rigorous and more uniform research methodology, common data elements, and consistent performance measures.