Abstract
BACKGROUND: The mechanism of development of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. Inflammatory processes are implicated in the development of ischemic stroke and may also predispose to the development of DCI following SAH. The objective of this study was to test whether concentrations of circulating inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin 1 receptor antagonist (IL-1Ra)) were predictive for DCI following SAH. Secondary analyses considered white cell count (WCC) and erythrocyte sedimentation rate (ESR). METHODS: This was a single-center case-control study nested within a prospective cohort. Plasma inflammatory markers were measured in patients up to 15 days after SAH (initial, peak, average, final and rate of change to final). Cases were defined as those developing DCI. Inflammatory markers were compared between cases and randomly selected matched controls. RESULTS: Among the 179 participants there were 46 cases of DCI (26%). In primary analyses the rate of change of IL-6 was associated with DCI (OR 2.3 (95% CI 1.1 to 5.0); p=0.03). The final value and rate of change of WCC were associated with DCI (OR 1.2 (95% CI 1.0 to 1.3) and OR 1.3 (95% CI 1.0 to 1.6), respectively). High values of ESR were associated with DCI (OR 2.4 (95% CI 1.3 to 4.6) initial; OR 2.3 (95% CI 1.3 to 4.2) average; OR 2.1 (95% CI 1.1 to 3.9) peak; and OR 2.0 (95% CI 1.2 to 3.3) final value). CONCLUSIONS: Leucocytosis and change in IL-6 prior to DCI reflect impending cerebral ischemia. The time-independent association of ESR with DCI after SAH may identify this as a risk factor. These data suggest that systemic inflammatory mechanisms may increase the susceptibility to the development of DCI after SAH.