Soluble Fms-Like Tyrosine Kinase 1 (sFlt-1) and Risk of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

World Neurosurg. 2017 Dec:108:84-89. doi: 10.1016/j.wneu.2017.08.128. Epub 2017 Sep 1.

Abstract

Background: The molecular mechanisms underlying cerebral vasospasm and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) are incompletely understood. We hypothesized that circulating antiangiogenic factors, such as soluble Fms-like tyrosine kinase 1 (sFlt-1) and soluble transforming growth factor β coreceptor, soluble endoglin (sEng), are important markers of their pathophysiology.

Methods: We performed a prospective study in patients with aSAH and measured cerebrospinal fluid and serum levels of sFlt-1 and sEng on postbleed day 1 and 6 and correlated levels with incidence and severity of cerebral vasospasm and DCI.

Results: Twenty-seven patients with aSAH were enrolled in the study. Severe angiographic vasospasm was present in 14.8% of patients and DCI occurred in 33.3%. Serum sFlt1 levels were increased on postbleed day 6 in patients who developed vasospasm. However, on postbleed day 1, there were no differences in patients who developed vasospasm. Increased serum sFlt-1 levels on postbleed day 1 were found to predict the development of severe angiographic vasospasm with an area under the curve of 0.818 with an optimal cutoff value of 95 pg/mL. Alterations in sFlt1 were not associated with DCI. Serum and cerebrospinal fluid sEng levels did not correlate with vasospasm or DCI.

Conclusions: Serum levels of sFlt-1 are increased in patients with aSAH who are at risk for severe vasospasm. Further studies with larger sample sizes are needed to evaluate whether sFlt-1 levels may predict onset of severe vasospasm and DCI.

Keywords: Aneurysm; Angiogenesis; Cerebral ischemia; Outcome; Subarachnoid hemorrhage; Vasospasm.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging
  • Cerebral Angiography
  • Endoglin / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Subarachnoid Hemorrhage / complications*
  • Subarachnoid Hemorrhage / epidemiology
  • Subarachnoid Hemorrhage / metabolism*
  • Subarachnoid Hemorrhage / therapy
  • Treatment Outcome
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*
  • Vasospasm, Intracranial / epidemiology
  • Vasospasm, Intracranial / etiology*
  • Vasospasm, Intracranial / metabolism*
  • Vasospasm, Intracranial / therapy
  • Young Adult

Substances

  • Biomarkers
  • ENG protein, human
  • Endoglin
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1