Biomarkers of acute cerebral damage in complex diagnosis of sepsis-associated encephalopathy

Background. Sepsis-associated encephalopathy (SAE) is a common manifestation of sepsis that clearly influences outcomes and prognosis. To date, there are no modern serum biomarkers for diagnosis, treatment monitoring or prognosis of consequences in SAE. Objective. To identify the diagnostic and prognostic value of three cerebral biomarkers (astroglial protein S100B, neuron-specific enolase (NSE), antibodies to the NR2 subunit of NMDA glutamate receptor (NR2AT)) in patients with sepsis, as well as to evaluate their changes depending on clinical manifestations of SAE. Material and methods. A single-center prospective controlled clinical study included 33 critically ill patients with sepsis or septic shock (Sepsis-3) and extracranial focus of infection. Cerebral biomarkers were analyzed in 1, 7, 14, 21 and 28 days after diagnosis of sepsis. Patients with sepsis were examined daily using scales for assessing neurological disorders and multiple organ failure. To be able to diagnose SAE, we recruited the control group (33 patients) comparable in age, gender and concomitant diseases without infectious process. Results. There were significant differences between survivors and dead patients in serum S100B (106.55 (IQR 20.9—144.9) ng/l vs. 142.13 (IQR 41.275 — 165.57) ng/l, respectively, p<0.001) and NSE (4.90 (IQR 2.695—7.05) µg/l vs. 12.56 (IQR 4.115—8.76) µg/l, respectively, p<0.001). No correlation between NR2AT and outcomes was found. There was a correlation between SOFA and SAPS II scores with serum S100B and NSE. Serum NSE positively correlated with CRP (rho=0.736; p=0.002) and lactate (rho=0.644; p=0.033). According to ROC analysis, the most significant predictors of poor prognosis were S100B >126.4 ng/l (AUC 0.720; specificity 80% and sensitivity 70%) and NSE >4.85 µg/l (AUC 0.760; sensitivity 50% and specificity 100%). Conclusion. In patients with SAE, elevated S100B and NSE positively correlate with severity of sepsis and treatment outcomes.