Serum NSE and S100B Rise in Sepsis-Associated EncephalopathyNSE and S100B Proteins May Help Identify Sepsis Brain Injury
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicalsPublished November 4, 2026Study authors: Li Zhang, Zhong Shuyu, Chen Minjing, Chen HuanPubMed ↗DOI ↗Editorial oversight: Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic
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Key Takeaway
NSE and S100B are significantly elevated in sepsis-associated encephalopathy, supporting their potential for earlier detection.
A meta-analysis pooled data from 722 patients to assess whether two serum biomarkers, neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B), can distinguish sepsis-associated encephalopathy (SAE) from sepsis without encephalopathy.
Both markers were significantly higher in patients with SAE. NSE showed a standardized mean difference of 0.82 (95% CI 0.66-0.97, P < 0.001), and S100B showed a standardized mean difference of 0.94 (95% CI 0.77-1.11, P < 0.001).
The findings suggest these biomarkers may support earlier identification of SAE in patients with sepsis, a complication that can be difficult to detect clinically.
The analysis draws on observational and diagnostic data, so the results reflect association rather than proven causality. Certainty of evidence was not reported, and the included studies' settings, follow-up, and absolute biomarker values were not described. No safety, funding, or conflict-of-interest information was provided.
Larger prospective studies with standardized thresholds are needed before NSE and S100B can be adopted into routine clinical decision-making for SAE.
How this fits prior evidence
This meta-analysis extends prior coverage of sepsis-related organ dysfunction and prognostic markers. Previous items highlighted echocardiographic myocardial dysfunction in sepsis, dendritic cell dysfunction in immunoparalysis, and malignancy as a mortality risk factor. It also adds to the biomarker literature, where high THBS1 expression was linked to poorer outcomes. Unlike those, this review focuses on neurological injury, showing that NSE and S100B are elevated in SAE with moderate effect sizes (SMD 0.82 and 0.94). These findings align with the broader theme of identifying organ-specific dysfunction in sepsis, but the observational nature limits causal inference.
Researchers analyzed data from 722 patients to see if certain proteins in the blood could help identify sepsis-associated encephalopathy (SAE). SAE is a type of brain dysfunction that can occur in patients with a severe infection called sepsis. The study looked specifically at two proteins: serum neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B).
The results showed that both NSE and S100B levels were significantly higher in patients who had brain complications compared to those with sepsis who did not have those complications. Because these levels were notably different, these proteins may serve as useful markers for doctors to identify brain issues early.
While these findings are promising for identifying complications, it is important to note that this was a meta-analysis of observational data. This means the study shows a link between these proteins and brain injury, but it does not prove that the proteins cause the condition. These markers are currently tools for identification rather than a replacement for standard medical care.
What this means for you:
Higher levels of NSE and S100B proteins in the blood may help identify brain complications in sepsis patients.
Common questions
What are NSE and S100B?
NSE and S100B are specific proteins found in the blood. This study looked at these proteins to see if they could help doctors distinguish between patients with sepsis who have brain complications and those who do not. The study found that both proteins were significantly higher in patients with brain complications.
Can these proteins help find brain issues in sepsis patients?
The study suggests that these proteins may help identify sepsis-associated encephalopathy early. Because levels of NSE and S100B were significantly elevated in patients with brain complications, they could serve as useful markers for doctors to monitor patients during treatment.
Is this a new treatment for sepsis?
No, these proteins are not a treatment. They are markers used to identify complications. The study shows a link between higher protein levels and brain issues, but it does not provide a new medicine or therapy for patients.
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 standardized mean difference (SMD) for NSE was 0.82 (95% confidence interval [CI]: 0.66-0.97, P < 0.001, I = 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, I = 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.
