Evaluation of big endothelin–1 concentrations in serum and ventricular cerebrospinal fluid after early surgical compared with nonsurgical management of ruptured intracranial aneurysms

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>Whereas the removal of subarachnoid blood is possible during early-stage aneurysm surgery, this cannot be achieved in aneurysms treated by endovascular means. The levels of potential spasmogens in the cerebrospinal fluid (CSF) in patients receiving endovascular treatment might therefore be higher, with the potential for more severe post–subarachnoid hemorrhage (SAH) vasospasm.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Serum and CSF concentrations of big endothelin (ET)–1 were serially measured in patients with SAH receiving one of the following treatments: 1) early (within 72 hours of SAH) aneurysm surgical treatment (15 patients), 2) early endovascular treatment (17 patients), or 3) no intervention in the acute phase (12 patients). In patients suffering delayed infarctions higher levels of big ET–1 CSF were demonstrated than in those without infarctions (p = 0.01). In patients in whom surgery was performed in the acute phase lower big ET–1 CSF concentrations were demonstrated than in those who received embolization treatment or no treatment (p = 0.02). Subgroup analysis demonstrated that in patients receiving early endovascular treatment, higher big ET–1 CSF concentrations were revealed than in those undergoing early aneurysm surgery; this was true for patients with (microsurgery-treated, 1.84 ± 0.83 pg/ml; and embolization-treated 2.19 &amp; plusmn; 0.54 pg/ml) and without (microsurgery-treated 1.76 &amp; plusmn; 0.61 pg/ml; and embolization-treated 2.01 ± 0.48 pg/ml) delayed infarctions.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Among patients with SAH who received treatment during the acute phase, those undergoing early aneurysm surgery were shown to have lower big ET–1 CSF levels than those receiving embolization and no treatment (that is, the nonsurgical treatment groups). The clinical significance of this finding remains to be established in future clinical trials, because in the present study the trend toward lower levels of big ET–1 CSF in the microsurgically treated group was not paralleled by a lower delayed stroke rate or an improvement in neurological outcome.</jats:p></jats:sec>

The importance of early brain injury after subarachnoid hemorrhage

“…In aSAH patients, increase in CSF and plasma ET-1 is observed 24 hours from ictus (Kobayashi et al , 1995), and is associated with the occurrence of delayed vasospasm (Gruber et al , 2000a). Animal studies indicate that the increase in cerebral ET-1 after aSAH results from excessive release by astrocytes during the period of initial ischemia (Pluta et al , 1997a).…”

Precision medicine of aneurysmal subarachnoid hemorrhage, vasospasm and delayed cerebral ischemia

“…Patients with aSAH were found to have statistically significant elevations of sTNFR-1 in CSF when compared to patients with non-hemorrhagic hydrocephalus, and this elevation correlated with admission Hunt and Hess grade and neurologic outcome as measured by GOS [105]. In our own prospective study evaluating proteomic biomarkers in CSF of patients with aSAH, we found that mean and maximum CSF levels of sTNFR-1 had statistically significant correlation with clinical outcome, with elevated sTNFR-1 levels correlating with poor outcomes as measured by mRS [106].…”

To Look Beyond Vasospasm in Aneurysmal Subarachnoid Haemorrhage

“…Their elevation in serum, CSF, and microdialysis fluid is related to early and delayed ischemia and poor outcome [44, 57]. …”

“…Apoptosis is triggered by elevated ICP, ischemia, reperfusion, and acute vasospasm and by the neurotoxicity of blood breakdown components and oxidative stress [11, 44]. It involves neuronal, glial [87], and smooth muscle and endothelial cells, causing BBB disruption [88] and promoting vasospasm development.…”

“…An upregulation of its receptors is equally observed in the delayed phase; ET A receptor in particular is expressed predominantly on smooth muscle cells and is crucial in vasoconstriction and cell proliferation. ET-1 can produce long lasting vasoconstriction directly [ 44 ] and can induce morphological changes such as fibrosis or hyperplasia in the vascular wall [ 45 ]. Furthermore, a disequilibrium between NO and ET-1 level leads to unopposed vasoconstriction and promotes vasospasm development [ 46 ].…”