Relation of Serum TNF-α and TNF-α Genotype with Delayed Cerebral Ischemia and Outcome in Subarachnoid Hemorrhage

Abstract

The pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) remains obscure. The authors assessed the relationship of tumor necrosis factor alpha (TNF-α) and TNF-α gene polymorphisms with occurrence of DCI and poor outcome at 3months. Serum levels of TNF-α were measured every other day until discharge in 67 patients and the mean serum levels per patient during days 0-12 were dichotomized at the median value of the whole group. TNF-α genotyping was available in 31 patients and related to serum TNF-α by means of one-way ANOVA analysis. The authors calculated hazard ratio's (HR) with corresponding 95% confidence intervals (CI) for the association with DCI by means of Cox proportional hazard analysis and odds ratio's (OR) for the association with poor clinical outcome by means of logistic regression analysis. In both analyses the authors adjusted for sex, age, amount of blood, and clinical condition at admission. Leukocytes and CRP were investigated similarly for comparison. For high-serum TNF-α levels during days 0-12 adjusted HR was 0.6 (95%CI: 0.1-2.4) for DCI and adjusted OR 2.0 (95%CI: 0.4-9.0) for clinical outcome. Serum TNF-α levels were 11.4pg/ml for wildtype TNF-α genotype and 9.7pg/ml for the non-wildtype TNF-α genotype (P=0.15). For the non-wildtype TNF-α genotype the HR for DCI was 0.4 (95%CI: 0.1-2.6) and the OR for clinical outcome was 0.8 (95%CI: 0.1-4.0). It is unlikely that serum TNF-α or TNF-α genotype play an important role in the occurrence of DCI after SAH.