✓ Plasma and cerebrospinal fluid (CSF) concentrations of endothelin (ET)-1, ET-3, and big ET-1 in patients with aneurysmal rupture were measured serially for 2 weeks after the onset of aneurysmal subarachnoid hemorrhage (SAH) and compared with levels of ETs in patients without SAH and the plasma concentrations of ETs in normal volunteers. Big ET-1 was the predominant peptide present in the CSF of SAH patients. The CSF concentrations of big ET-1, ET-1, and ET-3 were significantly higher in older patients than in younger patients. In SAH patients with cerebral vasospasm (CVS) documented by transcranial Doppler sonography and clinical signs, postoperative concentrations of ETs in the CSF remained at or were increased above levels measured before surgery. In SAH patients without CVS, the concentrations of ETs in the CSF decreased with time, whereas the time course of CVS coincided with the increase in concentrations of big ET-1 and ET-1. The temporal dependence of concentrations of big ET-1 and ET-1 in SAH patients with and without CVS were significantly different. The volume of hematoma in the basal cisterns as detected by computerized tomography was predictive of the concentrations of ETs in the CSF. Plasma concentrations of ETs were not correlated wtih CVS. The possible role of ETs in the pathogenesis of CVS associated with SAH and the controversial data reported to date are discussed.
Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma
Volker Seifert, Bernd-Michael Löffler, Michael Zimmermann, Sébastiên Roux and Dietmar Stolke
E. François Aldrich, Randall Higashida, Abdel Hmissi, Elizabeth J. Le, R. Loch Macdonald, Angelina Marr, Stephan A. Mayer, Sébastien Roux and Nicolas Bruder
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant morbidity and mortality. The presence of thick, diffuse subarachnoid blood may portend a worse clinical course and outcome, independently of other known prognostic factors such as age, aneurysm size, and initial clinical grade.
In this post hoc analysis, patients with aSAH undergoing surgical clipping (n = 383) or endovascular coiling (n = 189) were pooled from the placebo arms of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS)–2 and CONSCIOUS-3 randomized, double-blind, placebo-controlled phase 3 studies, respectively. Patients without and with thick, diffuse SAH (≥ 4 mm thick and involving ≥ 3 basal cisterns) on admission CT scans were compared. Clot size was centrally adjudicated. All-cause mortality and vasospasm-related morbidity at 6 weeks and Glasgow Outcome Scale–Extended (GOSE) scores at 12 weeks after aSAH were assessed. The effect of the thick and diffuse cisternal aSAH on vasospasm-related morbidity and mortality, and on poor clinical outcome at 12 weeks, was evaluated using logistic regression models.
Overall, 294 patients (51.4%) had thick and diffuse aSAH. Compared to patients with less hemorrhage burden, these patients were older (median age 55 vs 50 years) and more often had World Federation of Neurosurgical Societies (WFNS) grade III–V SAH at admission (24.1% vs 16.5%). At 6 weeks, all-cause mortality and vasospasm-related morbidity occurred in 36.1% (95% CI 30.6%–41.8%) of patients with thick, diffuse SAH and in 14.7% (95% CI 10.8%–19.5%) of those without thick, diffuse SAH. Individual event rates were 7.5% versus 2.5% for all-cause death, 19.4% versus 6.8% for new cerebral infarct, 28.2% versus 9.4% for delayed ischemic neurological deficit, and 24.8% versus 10.8% for rescue therapy due to cerebral vasospasm, respectively. Poor clinical outcome (GOSE score ≥ 4) was observed in 32.7% (95% CI 27.3%–38.3%) and 16.2% (95% CI 12.1%–21.1%) of patients with and without thick, diffuse SAH, respectively.
In a large, centrally adjudicated population of patients with aSAH, WFNS grade at admission and thick, diffuse SAH independently predicted vasospasm-related morbidity and poor 12-week clinical outcome. Patients with thick, diffuse cisternal SAH may be an important cohort to target in future clinical trials of treatment for vasospasm.