Biomarkers of Neurological Outcome After Aneurysmal Subarachnoid Hemorrhage as Early Predictors at Discharge from an Intensive Care Unit.

ABSTRACT

BACKGROUND: Subarachnoid bleeding is associated with brain injuries and ranges from almost negligible to acute and life threatening. The main objectives were to study changes in brain-specific biomarker levels in patients after an aneurysmal subarachnoid hemorrhage (aSAH) in relation to early clinical findings, severity scores, and intensive care unit (ICU) outcome. Analysis was done to identify specific biomarkers as predictors of a bad outcome in the acute treatment phase. METHODS: Analysis was performed for the proteins of neurofilament, neuron-specific enolase (NSE), microtubule-associated protein tau (MAPT), and for the proteins of glial cells, S100B, and glial fibrillary acidic protein (GFAP). Outcomes were assessed at discharge from the ICU and analyzed based on the grade in the Glasgow Outcome Scale (GOS). Patients were classified into two groups with a good outcome (Group 1 GOS IV-V, n = 24) and with a bad outcome (Group 2 GOS I-III, n = 31). Blood samples were taken upon admission to the ICU and afterward daily for up to 6 days. RESULTS: In Group 1, the level of S100B (1.0, 0.9, 0.7, 2.0, 1.0, 0.3 ng/mL) and NSE (1.5, 2.0, 1.6, 1.2, 16.6, 2.2 ng/mL) was significantly lower than in Group 2 (S100B 4.7, 4.8, 4.4, 4.5, 6.6, 6.8 ng/mL; NSE 4.0, 4.1, 4.3, 3.8, 4.4, 2.5 1.1 ng/mL) on day 1-6, respectively. MAPT was significantly lower only on the first and second day (83.2 ± 25.1, 132.7 ± 88.1 pg/mL in Group 1 vs. 625.0 ± 250.7, 616.4 ± 391.6 pg/mL in Group 2). GFAP was elevated in both groups from day 1 to 6. In the ROC analysis, S100B showed the highest ability to predict bad ICU outcome of the four biomarkers measured on admission [area under the curve (AUC) 0.81; 95% CI 0.67-0.94, p < 0.001]. NSE and MAPT also had significant predictive value (AUC 0.71; 95% CI 0.54-0.87, p = 0.01; AUC 0.74; 95% CI 0.55-0.92, p = 0.01, respectively). A strong negative correlation between the GOS and S100B and the GOS and NSE was recorded on days 1-5, and between the GOS and MAPT on day 1. CONCLUSION: Our findings provide evidence that brain biomarkers such as S100B, NSE, GFAP, and MAPT increase significantly in patients following aSAH. There is a direct relationship between the neurological outcome in the acute treatment phase and the levels of S100B, NSE, and MAPT. The detection of brain-specific biomarkers in conjunction with clinical data may constitute a valuable diagnostic and prognostic tool in the early phase of aSAH treatment.