Increased Serum S100B Levels in Patients With Epilepsy: A Systematic Review and Meta-Analysis Study

Kai-Ge Liang, Rong-Zheng Mu, Yu Liu, Dan Jiang, Tian-Tian Jia, Yao-Jiang Huang, Kai-Ge Liang, Rong-Zheng Mu, Yu Liu, Dan Jiang, Tian-Tian Jia, Yao-Jiang Huang

Abstract

Importance: Accumulating evidence suggests that serum levels of S100B may play a role in epilepsy. Objective: We performed a meta-analysis to quantitatively summarize the serum S100B data available for patients with epilepsy. Data source: Two independent researchers conducted a systematic investigation of the Harvard Hollis+, Open Gray, Clinicaltrials, Wanfangdata, and CNKI databases through Dec 6, 2018, for all studies published in English and Chinese. The search terms included S100B and calcium-binding protein B in combination with epilepsy. Study selection: Original studies and reported data from these search terms are included. Studies where data overlapped with other studies were excluded. Data extraction and synthesis: investigators extracted, pooled and analyzed data from the included studies using a fixed-effects model in the Comprehensive Meta-Analysis3.3 and R software. Main outcomes and measures: Peripheral blood levels of S100B in patients with epilepsy compared with controls. Aberrations in peripheral blood levels of S100B were hypothesized to be related to epilepsy. Results: a fixed-effects meta-analysis of all 18 studies, including 1,057 unique participants, indicated that patients with epilepsy had significantly increased peripheral blood levels of S100B compared to controls (Hedges g = 1.568, 95% CI =1.431-1.706, P < 0.001). Sensitivity analysis showed that no single study significantly influenced the overall association of peripheral blood levels of S100B and epilepsy. Most of the subgroup analyses, including those of country, assay type and publication language, demonstrated a statistically significant association between peripheral blood levels of S100B and epilepsy. Meta-regression analyses indicated that gender (regression coefficient [SE], -0.2524 [0.0641]; 95%CI, -0.3781 to -0.1267; P = 0.0001) and mean age (regression coefficient [SE], -0.1224 [0.0426]; 95% CI, -0.2058 to -0.0390; P = 0.0040) might present serum S100B reductions, but sample size, years, assay type, publication language and country did not show moderating effects on the effect sizes. Furthermore, the trim-and-fill method used to adjust for funnel plot asymmetry in our meta-analysis confirmed that a positive outcome is unlikely to be due to publication bias. Conclusion and relevance: the results of this meta-analysis provide evidence for a significant increase in serum S100B levels in patients with epilepsy. Serum S100B is the most worthwhile biomarker of epilepsy, which is helpful for the clinical diagnosis and prognosis of epilepsy.

Keywords: S100B; epilepsy; level; meta-analysis; serum.

Figures

Figure 1
Figure 1
PRISMA flowchart. PRISMA flowchart for the literature search.
Figure 2
Figure 2
Forest plot for association between serum S100B levels and epilepsy. Square sizes are proportional to study weights. The diamond marker indicates pooled effect size.
Figure 3
Figure 3
Sensitivity analysis. No single study significantly influenced the overall association of S100B levels with epilepsy by sensitivity analysis.
Figure 4
Figure 4
Forest plot for subgroup analysis. Subgroup analysis by country.
Figure 5
Figure 5
Forest plot for subgroup analysis. Subgroup analysis by language.
Figure 6
Figure 6
Forest plot for subgroup analysis. Subgroup analysis by assay type.
Figure 7
Figure 7
Meta-regression in all studies. Association between mean age and effect size (Hedges g).
Figure 8
Figure 8
Meta-regression in all studies. Association between gender and effect size (Hedges g).
Figure 9
Figure 9
Funnel plots for assessment of publication bias. Funnel plots for assessment of publication bias.
Figure 10
Figure 10
Funnel plots for assessment of publication bias. The trim-and-fill method to adjust for funnel plot asymmetry in our meta-analysis.

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