S100B, GFAP, UCH-L1 and NSE as predictors of abnormalities on CT imaging following mild traumatic brain injury: a systematic review and meta-analysis of diagnostic test accuracy

Neurosurg Rev. 2022 Apr;45(2):1171-1193. doi: 10.1007/s10143-021-01678-z. Epub 2021 Oct 28.

Abstract

Biomarkers such as calcium channel binding protein S100 subunit beta (S100B), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1) and neuron-specific enolase (NSE) have been proposed to aid in screening patients presenting with mild traumatic brain injury (mTBI). As such, we aimed to characterise their accuracy at various thresholds. MEDLINE, SCOPUS and EMBASE were searched, and articles reporting the diagnostic performance of included biomarkers were eligible for inclusion. Risk of bias was assessed using the QUADAS-II criteria. A meta-analysis was performed to assess the predictive value of biomarkers for imaging abnormalities on CT. A total of 2939 citations were identified, and 38 studies were included. Thirty-two studies reported data for S100B. At its conventional threshold of 0.1 μg/L, S100B had a pooled sensitivity of 91% (95%CI 87-94) and a specificity of 30% (95%CI 26-34). The optimal threshold for S100B was 0.72 μg/L, with a sensitivity of 61% (95% CI 50-72) and a specificity of 69% (95% CI 64-74). Nine studies reported data for GFAP. The optimal threshold for GFAP was 626 pg/mL, at which the sensitivity was 71% (95%CI 41-91) and specificity was 71% (95%CI 43-90). Sensitivity of GFAP was maximised at a threshold of 22 pg/mL, which had a sensitivity of 93% (95%CI 73-99) and a specificity of 36% (95%CI 12-68%). Three studies reported data for NSE and two studies for UCH-L1, which precluded meta-analysis. There is evidence to support the use of S100B as a screening tool in mild TBI, and potential advantages to the use of GFAP, which requires further investigation.

Keywords: Biomarker; Computed tomography; GFAP; S100b; Traumatic brain injury.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Biomarkers
  • Brain Concussion* / diagnostic imaging
  • Brain Injuries, Traumatic* / diagnostic imaging
  • Diagnostic Tests, Routine
  • Glial Fibrillary Acidic Protein
  • Humans
  • Phosphopyruvate Hydratase
  • S100 Calcium Binding Protein beta Subunit
  • Tomography, X-Ray Computed
  • Ubiquitin Thiolesterase

Substances

  • Biomarkers
  • Glial Fibrillary Acidic Protein
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • Ubiquitin Thiolesterase
  • Phosphopyruvate Hydratase