Novel Biomarkers for DCI after SAH: Microparticles Revisited

Spontaneous subarachnoid hemorrhage from a ruptured intracranial aneurysm accounts for approximately 5% of all cases of stroke. Although initial mortality has been constantly declining over the past two decades, long-term clinical outcomes still remain disappointing because of numerous delayed adverse sequelae. Delayed cerebral ischemia is such a common complication in the course of subarachnoid hemorrhage and occurs in approximately 2040% of patients and may progress to cerebral infarction with increased risk of unfavorable outcome. Despite extensive experimental and clinical research up to date the causes of this serious complication remain poorly understood. While traditionally attributed to large-vessel vasospasm, contemporary research has indicated that delayed cerebral ischemia may rather result from a multifactorial vasculopathy exacerbated by microthrombosis, inflammation, and endothelial dysfunction. Recently, small membrane fragments, so-called microparticles, shed from endothelium and surfaces of circulating blood cells, have been implicated in exact these mechanisms, and elevated microparticle levels are found in thromboembolic diseases. Importantly, in a pilot-study our research group was able to detect increased microparticle release into the systemic circulation in patients with subarachnoid hemorrhage. Further, we found a strong correlation with the occurrence of delayed ischemic complications. Our findings have been corroborated by another study suggesting that an increase in microparticle load may allow early prediction of delayed cerebral ischemia. We hypothesize that the generation of cellular microparticles is a consequence of the microvascular dysfunction after subarachnoid hemorrhage, and has an impact on the occurrence of delayed cerebral ischemia. Further, we hypothesize that changes in microparticle burden precede the emergence of delayed cerebral ischemia and detection of these abnormalities can help to identify patients at risk. These hypotheses form the basis of a prospective observational study enrolling 70 patients suffering from subarachnoid hemorrhage and 32 controls who will be followed prospectively over a period of 3 month. In this study we will examine the temporal evolution of changes in microparticle load by flow cytometry in the systemic circulation. Our study will be the first to detect microparticles in this patient cohort in the cerebral circulation by blood withdrawals from the internal jugular vein and intracranial arteries during catheter angiography. In addition, we will analyze microparticles in the cerebrospinal fluid drawn from external ventricular drain catheters. We will correlate the potential qualitative and quantitative microparticle alterations with angiographic vasospasm and delayed cerebral ischemia assessed by magnetic resonance imaging according to a standardized protocol, as well as with functional outcome assessed 3 month after the ictus. The characterization of potential novel biomarkers that will allow earlier identification of patients at risk may guide treatment decisions in this vulnerable patient population.