Diagnostic Value of Serum Neuron-Specific Enolase and S100 Calcium-Binding Protein B for Sepsis-Associated Encephalopathy: A Systematic Review and Meta-Analysis

Background: Sepsis-associated encephalopathy (SAE) is a frequent and serious complication of sepsis, but reliable diagnostic biomarkers remain limited.Objective To evaluate the diagnostic value of serum neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) in distinguishing SAE from sepsis without SAE.Methods A comprehensive literature search was conducted in PubMed, Embase and Web of Science between inception and January 2026. Studies comparing serum NSE and/or S100B levels between patients with SAE and patients with sepsis without SAE were included.Results Eight studies involving 722 participants (323 with SAE and 399 with sepsis but no SAE) were included. Both NSE and S100B levels were significantly elevated in the SAE group compared with the sepsis without SAE group. The pooled standardised mean difference (SMD) for NSE was 0.82 (95% confidence interval [CI]: 0.66–0.97, P < 0.001, I2 = 0.0%), indicating a large effect size with minimal heterogeneity. The pooled SMD for S100B was 0.94 (95% CI: 0.77–1.11, P < 0.001, I2 = 0.0%), also demonstrating a large effect size.Conclusions Serum NSE and S100B are significantly elevated in SAE and may help identify SAE early in patients with sepsis.