SYSTEMATIC REVIEW article
Front. Neurol.
Sec. Neurological Biomarkers
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1640618
Diagnostic Utility of Neurogenic Biomarkers in Differentiating Sepsis with and without Associated Encephalopathy: A Systematic Review and Meta-Analytic Approach
Provisionally accepted
- The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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Background: Sepsis-associated encephalopathy (SAE) is a frequent complication of sepsis, manifesting as acute brain dysfunction and often resulting in persistent cognitive deficits, neurological impairment, and increased mortality. Timely and accurate diagnosis of SAE is essential to guide therapeutic decisions and improve clinical outcomes. In recent years, neurogenic biomarkers have emerged as potential serum-based indicators for the diagnosis and progression monitoring of SAE. Methods: A comprehensive search of PubMed/MEDLINE, Embase, the Cochrane Library, Web of Science, and Scopus was conducted from inception to April 30, 2025. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Results: Forty-seven studies (50 arms) were included. Random-effects analysis revealed a significant difference in serum NSE level between SAE and NE adult patients (WMD = 6.82; 95% CI: 5.43, 8.21; P < 0.001), S100β levels (WMD = 0.48; 95% CI: 0.37, 0.60; P < 0.001), GFAP level in the SAE group (WMD = 62.28; 95% CI: 45.42, 79.14; P < 0.001), TAU levels in the SAE individuals (WMD = 1.73; 95% CI: 0.95, 2.51; P < 0.001), UCH-L1 in SAE patients (WMD = 1.73; 95% CI: 0.95, 2.51; P < 0.001), APACHE II scores in the SAE group (WMD = 6.30; 95% CI: 4.61, 7.99; P < 0.001), and SOFA scores in SAE (WMD = 3.65; 95% CI: 2.96, 4.34; P < 0.001). Conclusion: Elevated levels of serum neurogenic biomarkers may serve as potential predictors of SAE and are associated with increased mortality in septic patients. These biomarkers show promise as reliable, minimally invasive tools for the diagnosis and longitudinal monitoring of SAE. However, the findings should be interpreted with caution due to substantial heterogeneity across the included studies.
Keywords: sepsis-associated encephalopathy, NSE, biomarker, S100β, Meta-analysis, systematic review
Received: 06 Jun 2025; Accepted: 22 Aug 2025.
Copyright: © 2025 Lin, Zhang, Ren, Cao, Wang and Chang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yumei Wang, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Cheng Chang, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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