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

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.

Time-Dependent Changes in the Biofluid Levels of Neural Injury Markers in Severe Traumatic Brain Injury Patients–Cerebrospinal Fluid and Cerebral Microdialysates: A Longitudinal Prospective Pilot Study

“…We also detected a similar temporal pattern in matching bECF samples. S100B is one of the best-characterized protein markers in TBI (for review, see past works 18 , 34 ), and its very short half-life (∼0.5 h) 35 makes it ideal as a marker of de novo release. Serum S100B levels have been established as part of the Scandinavian TBI management guidelines.…”

“…The protein biomarkers S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), Tau, and phosphorylated Tau (p-Tau) have been extensively studied in TBI, 17 , 18 and their elevated serum and CSF levels have been shown to indicate the extent of neuronal, glial, and axonal damage as well as correlate with injury severity and outcome. 19–24 In this pilot study, we used microcapillary electrophoresis-coupled western analysis (WES) to determine the qualitative, quantitative, and temporal relationships between CSF and bECF levels of S100B, NSE, Tau, and p-Tau.…”

Glial fibrillary acidic protein level on admission can predict severe traumatic brain injury in patients with severe multiple trauma: A single-center retrospective observational study

“…Furthermore, an elevation in the GFAP level was associated with only head/neck AIS score, and as the GFAP level increased, TBI severity increased. Recent meta-analyses show that S100β levels are a more suitable screening tool than GFAP for the detection of TBI in mild to moderate ( Amoo et al, 2022 ) and moderate to severe ( Mondello et al, 2021 ) patients with TBI in the emergency room. In contrast, a cohort shows that GFAP levels have higher accuracy for predicting non-severe and severe TBI (ICU and general word), but this is not the case for S100β ( Czeiter et al, 2020 ).…”

The effects of early exercise in traumatic brain-injured rats with changes in motor ability, brain tissue, and biomarkers

“…A previous study showed that various biomarkers, such as GFAP, NSE, PDP9.5, HSP70, and S100β, rapidly increased after brain blood-barrier disruption in patients with TBI (18,19). Hence, we hypothesized that early exercise therapy may inhibit injury-related proteins in the tissues affected by TBI, and thus improve the behavioral function in TBI in animals.…”