Increased serum pannexin-1 concentrations reflect illness severity and predict a poor prognosis after acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study

Abstract

Background: Pannexin-1 is a nonselective, large pore and voltage gated channel protein, whose activation may aggravate acute brain injury. We ascertained the clinical significance of serum pannexin-1 as a prognostic biomarker of acute intracerebral hemorrhage (ICH).

Methods: In this prospective, observational study of 124 acute supratentorial ICH patients and 124 healthy controls, serum pannexin-1 concentrations were determined. Admission National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume were used for assessment of hemorrhagic severity, post-stroke 6-month modified Rankin scale (mRS) score was registered to reflect clinical outcome and early neurologic deterioration (END) and 6-month poor outcome (mRS score of 3-6) were regarded as the 2 prognostic parameters. Their associations with serum pannexin-1 concentrations were investigated using multivariate analysis. The predictive performance was evaluated in terms of area under receiver operating characteristic curve (AUC).

Results: In comparison to controls, significantly increased serum pannexin-1 concentrations after ICH (median, 6.8 vs. 2.7 mg/ml) were independently correlative with NIHSS score (β, 0.193; 95% CI: 0.086-0.300), hematoma volume (β, 0.641; 95% CI: 0.423-0.859) and mRS score (β, 0.199; 95% CI: 0.065-0.174), were independently predictive of END (OR, 1.176; 95% CI: 1.081-1.280) and poor outcome (odds ratio, 1.218; 95% CI: 1.059-1.400), as well as were efficiently discriminative of END (AUC, 0.764; 95% CI: 0.663-0.864) and poor 6-month outcome (AUC, 0.790; 95% CI: 0.711-0.870). Serum pannexin-1 combined with NIHSS score and hematoma volume (AUC, 0.908; 95% CI: 0.857-0.960) displayed significantly higher predictive ability for poor 6-month outcome than NIHSS score and hematoma volume alone (both P < 0.05).

Conclusion: Rising serum pannexin-1 concentrations following ICH, in strong correlation with hemorrhagic severity, independently distinguish the risk of END and 90-day poor outcome. Assumably, serum pannexin-1 may represent a valuable prognostic biomarker of ICH.

Keywords: Biomarkers; Early neurologic deterioration; Intracerebral hemorrhage; Outcome; Pannexin-1; Prognosis; Severity.