Early Detection of Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage Using Serum and Cerebrospinal Fluid Biomarkers

TL;DR

This study shows that blood and spinal fluid markers like IL-6 and ET-1 can detect brain artery narrowing early in patients with a type of brain bleed, potentially improving treatment timing.

Contribution

The study identifies IL-6 and ET-1 as early predictive biomarkers for cerebral vasospasm in aneurysmal subarachnoid hemorrhage patients.

Findings

Elevated IL-6 and ET-1 levels on day 3 were significantly associated with cerebral vasospasm.

Higher IL-6 and ET-1 levels predicted poor clinical outcomes at discharge.

Biomarker elevation occurred before radiological confirmation of vasospasm.

Abstract

Background/introduction

The aim of this study was to understand the effectiveness of particular serum and cerebrospinal fluid (CSF) biomarkers for the early diagnosis of cerebral vasospasm (CV) in patients with aneurysmal subarachnoid hemorrhage (aSAH) and to document any correlation with clinical and radiological outcomes. aSAH carries a high risk of CV and delayed cerebral ischemia, which are leading causes of disability and death. Current diagnostic tools like transcranial Doppler and angiography often detect vasospasm only after clinical manifestation, highlighting the need for early predictive biomarkers. This study investigates the potential of serum and CSF biomarkers, specifically IL-6, ET-1, and S100B, to enable early diagnosis of CV and improve correlation with clinical and radiological outcomes.

Materials and methods

The data were obtained from the Department of Neurosurgery in Mardan Medical Complex Hospital in Mardan, Pakistan, from July 2019 to July 2024. The study included 60 patients aged 18 to 80 years with a diagnosis of aSAH who were admitted within 48 hours of the onset of the disease. Blood and CSF were obtained on days 1, 3, and 7 after ictus. The analyzed biomarkers were interleukin-6 (IL-6), S100 calcium-binding protein B (S100B protein), and endothelin-1 (ET-1). Transcranial Doppler ultrasonography was used to evaluate vasospasm, and computed tomography angiography was used when necessary. SPSS software was used to analyze data, with statistical significance set at p < 0.05. Logistic regression analysis was performed to understand the relationship between biomarker levels and the occurrence of vasospasm.

Results

Radiology confirmed the diagnosis of vasospasm in 35 (58.3%) of the 60 patients with a mean age of 55.4 ± 12.1 years. On day 3, the levels of IL-6 and endothelin-1 were significantly higher in the vasospasm group than in the non-vasospasm group (p = 0.003 and p = 0.012, respectively), while S100B findings were inconsistent. The risk of vasospasm was 2.5 times higher in patients with increased IL-6 values. Early elevation of biomarkers was associated with poor Glasgow Outcome Scale scores at discharge (p = 0.016). Elevated serum IL-6 (>100 pg/mL) and CSF ET-1 (>10 pg/mL) on day 3 were significant predictors of poor outcome, with odds ratios of 3.2 (95% CI 1.4-7.4; p = 0.005) and 2.8 (95% CI 1.2-6.6; p = 0.015), respectively.

Conclusion

Serum and CSF biomarkers, particularly IL-6 and endothelin-1, may help identify CV early after aSAH, even without radiological signs. Incorporating these biomarkers into care could enable earlier treatment and improve outcomes, though multicenter studies are needed to establish standardized protocols.

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