Characteristics of patients included and enrolled in studies on the prognostic value of serum biomarkers for prediction of postconcussion symptoms following a mild traumatic brain injury: a systematic review

OBJECTIVE: Mild traumatic brain injury (mTBI) has been insufficiently researched, and its definition remains elusive. Investigators are confronted by heterogeneity in patients, mechanism of injury and outcomes. Findings are thus often limited in generalisability and clinical application. Serum protein biomarkers are increasingly assessed to enhance prognostication of outcomes, but their translation into clinical practice has yet to be achieved. A systematic review was performed to describe the adult populations included and enrolled in studies that evaluated the prognostic value of protein biomarkers to predict postconcussion symptoms following an mTBI. DATA SOURCES: Searches of MEDLINE, Embase, CENTRAL, CINAHL, Web of Science, PsycBITE and PsycINFO up to October 2016. DATA SELECTION AND EXTRACTION: Two reviewers independently screened for potentially eligible studies, extracted data and assessed the overall quality of evidence by outcome using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: A total of 23 298 citations were obtained from which 166 manuscripts were reviewed. Thirty-six cohort studies (2812 patients) having enrolled between 7 and 311 patients (median 89) fulfilled our inclusion criteria. Most studies excluded patients based on advanced age (n=10 (28%)), neurological disorders (n=20 (56%)), psychiatric disorders (n=17 (47%)), substance abuse disorders (n=13 (36%)) or previous traumatic brain injury (n=10 (28%)). Twenty-one studies (58%) used at least two of these exclusion criteria. The pooled mean age of included patients was 39.3 (SD 4.6) years old (34 studies). The criteria used to define a mTBI were inconsistent. The most frequently reported outcome was postconcussion syndrome using the Rivermead Post-Concussion Symptoms Questionnaire (n=18 (50%)) with follow-ups ranging from 7 days to 5 years after the mTBI. CONCLUSIONS: Most studies have recruited samples that are not representative and generalisable to the mTBI population. These exclusion criteria limit the potential use and translation of promising serum protein biomarkers to predict postconcussion symptoms.