Circulating levels of neuropeptide proenkephalin A predict outcome in patients with aneurysmal subarachnoid hemorrhage

•Plasma proenkephalin A level is enhanced in aneurysmal subarachnoid hemorrhage.•Proenkephalin A is highly associated with severity of aneurysmal subarachnoid hemorrhage.•Proenkephalin A has predictive performance for clinical outcome of aneurysmal subarachnoid hemorrhage.

High plasma proenkephalin A level has been associated with ischemic stroke severity and clinical outcomes. This study aimed to assess the relationship between proenkephalin A and disease severity as well as to investigate its ability to predict long-term clinical outcome in patients with aneurysmal subarachnoid hemorrhage. Plasma proenkephalin A concentrations of one hundred and eighty patients and 180 sex- and age-matched healthy controls were measured by chemoluminescence sandwich immunoassay. Plasma proenkephalin A level was substantially higher in patients than in healthy controls (205.5 ± 41.6 pmol/L vs. 90.8 ± 21.1 pmol/L, P < 0.001), was highly associated with World Federation of Neurological Surgeons (WFNS) score (r = 0.470, P < 0.001) and Fisher score (r = 0.488, P < 0.001), was an independent predictor for 6-month mortality [odds ratio (OR), 1.183; 95% confidence interval (CI), 1.067–1.339; P = 0.004] and unfavorable outcome (Glasgow Outcome Scale score of 1–3) (OR, 1.119; 95% CI, 1.046–1.332; P = 0.005) using multivariate analysis, and had high area under receiver operating characteristic curve (AUC) for prediction of 6-month mortality (AUC, 0.831; 95% CI, 0.768–0.883) and unfavorable outcome (AUC, 0.821; 95% CI, 0.757–0.874). The predictive value of the plasma proenkephalin A concentration was also similar to those of WFNS score and Fisher score (both P > 0.05). In a combined logistic-regression model, proenkephalin A improved the AUCs of WFNS score and Fisher score, but the differences were not significant (both P > 0.05). Thus, proenkephalin A level may be a useful, complementary tool to predict mortality and functional outcome at 6 months after aneurysmal subarachnoid hemorrhage.