1265 A Metabolomics-Based Approach to Predict Outcomes and Complications From Aneurysmal Subarachnoid Hemorrhage

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) results in significant morbidity and mortality with delayed cerebral ischemia (DCI) contributing to poor outcomes. Pathophysiological mechanisms leading to the subacute complication and eventual functional deficits are poorly understood. METHODS: Adult subjects with aSAH were included. Control subjects consisted of healthy controls from an outpatient clinic and hospitalized individuals admitted to an intensive care unit (ICU). Plasma samples were analyzed within 24-hours (T1) and 7-days after aSAH (T2). Untargeted metabolomics was performed one each sample with a total of 1,370 metabolites detected. Partial least squared discriminant analysis (PLS-DA) was used to determine differential metabolites, enrichment analysis was done for functional interpretation, and hierarchical clustering was used to build a hierarchy of clusters of metabolites distinguishing control from aSAH subjects. RESULTS: A total of 70 aSAH subjects were including along with 30 healthy controls and 17 hospitalized controls. Metabolites readily distinguished aSAH from control subjects. Enrichment analysis revealed increases in amino acid and fatty acid metabolism in aSAH compared with control subjects. Paired analysis revealed ongoing shifts in amino acid and lipid metabolism from T1 to T2. Long chain saturated fatty acids (LCSFA), polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA), monoacylglycerols (MAG), diacylglycerols (DAG), and ceramides (CM) were significantly higher in aSAH than control subjects. Acyl-carnitines (AC) and ticarboxylic acid (TCA) cycle metabolites were higher in control subjects and lower in aSAH subjects. Sphingosine and sphinganine were significantly higher in aSAH who developed DCI. Lysophospholipids and acylcarnitines were significantly increased in subjects with good 3-month functional outcomes. In multivariable models after correction for confounding variables, sphingosine and sphinganine were associated with DCI. CONCLUSIONS: Lipid metabolites including sphingolipids and lysophospholipids are potential biomarkers of DCI and outcomes after aSAH.