Qualitative Metabolomics Analysis of Cerebral Spinal Fluid in Aneurysmal Subarachnoid Hemorrhage (SAH) Patients

摘要

Background: Aneurysmal Subarachnoid Hemorrhage (SAH) is caused by a ruptured intracranial brain aneurysm and is one of the deadliest stroke subtypes. SAH is a common stroke subtype and is the 2nd leading cause of death worldwide and the 4th leading cause of death in the United States. About 66% of SAH patients develop delayed arterial narrowing called vasospasm (VSP). About 33% of SAH patients develop delayed ischemic neurology deficits (DIND) despite maximal medical therapy. Currently only nimodipine, FDA-approved since the 1980s, has been proven to reduce VSP and DIND. Despite this medication, when patients develop progressive VSP and DIND interventricular nicardipine (IVN) were given as rescue therapy. Prediction of which SAH patients ultimately develop severe VSP and DIND remains problematic, since symptoms may occur suddenly and without warning, leaving little time for therapeutic intervention. An individualized medicine approach utilizing a molecular profile that predicts the nature of the disease could guide therapeutic interventions and lead to a better understanding of the pathogenesis of VSP/DIND. Objective: 1. To determine metabolomics profile of CSF of SAH patients before and after Vasospasm and whether CSF metabolome can predict SAH patients who may develop VSP and DIND in future. 2. To find out CSF drug dose response in SAH patients Methods: 1. UPLC-ToF-MS based untargeted metabolomics profiling of CSF of SAH patients was performed for prediction of SAH patients who may develop VSP and DIND in future. 2. Quantitative measurements of nimodipine and nicardipine drugs in CSF were done using LC MS/MS.