Cerebrospinal fluid 20-HETE is associated with delayed cerebral ischemia and poor outcomes after aneurysmal subarachnoid hemorrhage

Stroke. 2011 Jul;42(7):1872-7. doi: 10.1161/STROKEAHA.110.605816. Epub 2011 May 26.


Background and purpose: Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (aSAH); it is manifested by changes in cerebral blood flow accompanied by neurological decline, and it results in long-term functional and neuropsychological impairment. Preclinical evidence has demonstrated that the arachidonic acid metabolite, 20-hydroxyeicosatetraenoic acid (20-HETE), affects cerebral microvascular tone and cerebral blood flow after aSAH. The purpose of this study was to determine whether cerebrospinal fluid 20-HETE levels were associated with DCI and long-term neuropsychological outcomes in aSAH patients.

Methods: Cerebrospinal fluid samples were collected twice daily through 14 days after hemorrhage on 108 acute, adult, aSAH patients. Samples were analyzed for 20-HETE via HPLC MSQ single quadrupole mass spectrometry. DCI was defined as the presence of impaired cerebral blood flow (angiographic vasospasm, elevated transcranial Dopplers, abnormal computed tomography or magnetic resonance perfusion scans) accompanied by neurological deterioration. Outcomes, including death and neuropsychological testing, were completed at 3 months after hemorrhage.

Results: Detectable 20-HETE levels were observed in 31% of patient samples and were associated with severity of hemorrhage (Hunt & Hess [HH], P=0.04; Fisher, P=0.05). Detection of 20-HETE was not associated with angiographic vasospasm (P=0.34); however, detectable 20-HETE was significantly associated with DCI (P=0.016). Our data also suggest that detectable 20-HETE was associated with decreased performance in 5 neuropsychological domains.

Conclusions: These results provide the first clinical evidence that cerebrospinal fluid 20-HETE concentrations are associated with DCI and poor outcomes, and this provides impetus for future studies to elucidate the clinical utility of inhibiting 20-HETE formation as a novel therapeutic intervention in patients with aSAH.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain Ischemia / cerebrospinal fluid*
  • Cerebrovascular Circulation
  • Female
  • Humans
  • Hydroxyeicosatetraenoic Acids / cerebrospinal fluid*
  • Male
  • Microcirculation
  • Middle Aged
  • Neuropsychological Tests
  • Subarachnoid Hemorrhage / cerebrospinal fluid*
  • Subarachnoid Hemorrhage / therapy
  • Treatment Outcome
  • Ultrasonography, Doppler / methods


  • Hydroxyeicosatetraenoic Acids
  • 20-hydroxy-5,8,11,14-eicosatetraenoic acid