Admission serum high mobility group box 1 (HMGB1) protein predicts delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage

Abstract

High mobility group box 1 protein (HMGB1) is a prototypical damage associated particle and acts as a key player in aseptic infammation. HMGB1 appears critical for the crosstalk of a prothrombotic and proinfammatory state that is implicated in mediating and exacerbating ischemic brain injury. The role of HMGB1 in aneurysmal subarachnoid hemorrhage (aSAH) remains to be elucidated. A prospective, single blinded observational study was designed to investigate the role of HMGB1 in aSAH. Serial serum HMGB1 level quantifcation on admission day 0, 4, 8, and 12 was performed. Primary outcome measures were delayed cerebral ischemia (DCI — new infarction on CT) and poor functional outcome (90-day modifed Rankin Scale 4–6). The role of HMGB1 levels for DCI, functional outcome and radiological vasospasm prediction was analyzed. Collectively, 83 aSAH patients were enrolled. Five patients died within 48 h. In 29/78 patients (37.2%), DCI was identifed. In multivariable analysis, radiological vasospasm and admission HMGB1 were independent predictors for DCI. Younger age and higher white blood cell count, but not insult burden (World Federation of Neurosurgical Societies scale, modifed Fisher scale, intraparenchymal or intraventricular hematoma existence) correlated with admission HMGB1 levels. Serial HMGB1 levels did not difer between patients with or without DCI, poor functional outcome or radiological vasospasm development. Admission serum HMGB1 does not refect initial insult burden but serves as an independent biomarker predictive of DCI. Further studies are warranted to disentangle the role of HMGB1 surrounding the sequelae of aSAH.