Predictive value of S-100β protein for prognosis in patients with moderate and severe traumatic brain injury: systematic review and meta-analysis

BMJ. 2013 Apr 4;346:f1757. doi: 10.1136/bmj.f1757.


Objectives: To determine the ability and accuracy of the S-100β protein in predicting prognosis after a moderate or severe traumatic brain injury.

Design: Systematic review and meta-analysis of randomised controlled trials and observational studies.

Data sources: Medline, Embase, Cochrane Central Register of Controlled Trials, BIOSIS (from their inception to April 2012), conference abstracts, bibliographies of eligible articles, and relevant narrative reviews.

Study selection: Two reviewers independently reviewed citations and selected eligible studies, defined as cohort studies or randomised control trials including patients with moderate or severe traumatic brain injury and evaluating the prognostic value of S-100β protein. Outcomes evaluated were mortality, score on the Glasgow outcome scale, or brain death.

Data extraction: Two independent reviewers extracted data using a standardised form and evaluated the methodological quality of included studies. Pooled results were presented with geometric means ratios and analysed with random effect models. Prespecified sensitivity analyses were performed to explain heterogeneity.

Results: The search strategy yielded 9228 citations. Two randomised controlled trials and 39 cohort studies were considered eligible (1862 patients). Most studies (n=23) considered Glasgow outcome score ≤ 3 as an unfavourable outcome. All studies reported at least one measurement of S-100β within 24 hours after traumatic brain injury. There was a significant positive association between S-100β protein concentrations and mortality (12 studies: geometric mean ratio 2.55, 95% confidence interval 2.02 to 3.21, I(2)=56%) and score ≤ 3 (18 studies: 2.62, 2.01 to 3.42, I(2)=79%). Sensitivity analysis based on sampling time, sampling type, blinding of outcome assessors, and timing of outcome assessment yielded similar results. Thresholds for serum S-100β protein values with 100% specificity ranged from 1.38 to 10.50 µg/L for mortality (six studies) and from 2.16 to 14.00 µg/L for unfavourable neurological prognosis as defined by the Glasgow outcome score.

Conclusions: After moderate or severe traumatic brain injury, serum S-100β protein concentrations are significantly associated with unfavourable prognosis in the short, mid, or long term. Optimal thresholds for discrimination remain unclear. Measuring the S-100β protein could be useful in evaluating the severity of traumatic brain injury and in the determination of long term prognosis in patients with moderate and severe injury.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Biomarkers / blood
  • Brain Injuries / blood*
  • Brain Injuries / mortality
  • Female
  • Glasgow Outcome Scale
  • Humans
  • Injury Severity Score
  • Male
  • Nerve Growth Factors / blood*
  • Predictive Value of Tests
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Reproducibility of Results
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins / blood*
  • Sensitivity and Specificity
  • Survival Analysis


  • Biomarkers
  • Nerve Growth Factors
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins