This systematic review and meta-analysis aimed to determine the prognostic value of S-100β protein to identify patients with post-concussion symptoms after a mild traumatic brain injury (mTBI). A search strategy was submitted to seven databases from their inception to October 2016. Individual patient data were requested. Cohort studies evaluating the association between S-100β protein level and post-concussion symptoms assessed at least seven days after the mTBI were considered. Outcomes were dichotomized as persistent (≥3 months) or early (≥7 days <3 months). Our search strategy yielded 23,298 citations of which 29 studies including between seven and 223 patients (n = 2505) were included. Post-concussion syndrome (PCS) (16 studies) and neuropsychological symptoms (9 studies) were the most frequently assessed outcomes. The odds of having persistent PCS (odds ratio [OR] 0.62, 95% confidence interval [CI]: 0.34–1.12, p = 0.11, I2 0% [n = five studies]) in patients with an elevated S-100β protein serum level were not significantly different from those of patients with normal values while the odds of having early PCS (OR 1.67, 95% CI: 0.98–2.85, p = 0.06, I2 38% [n = five studies]) were close to statistical significance. Similarly, having an elevated S-100β protein serum level was not associated with the odds of returning to work at six months (OR 2.31, 95% CI: 0.50–10.64, p = 0.28, I2 22% [n = two studies]). Overall risk of bias was considered moderate. Results suggest that the prognostic biomarker S-100β protein has a low clinical value to identify patients at risk of persistent post-concussion symptoms. Variability in injury to S-100ß protein sample time, mTBI populations, and outcomes assessed could potentially explain the lack of association and needs further evaluation.
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