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((R)), MEDLINE (R), 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 S100 beta, 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.