Abstract 149: Elevated mir-9 in Cerebrospinal Fluid is Associated With Poor Functional Outcome After Subarachnoid Hemorrhage

Abstract

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) has a lower incidence than ischemic stroke but affects younger individuals with a high mortality and a high frequency of complications in survivors. The underlying pathways that contribute to poor functional outcome are poorly understood. Hypothesis: MicroRNA (miRNA) changes in cerebrospinal fluid (CSF) are associated with the occurrence of delayed cerebral ischemia and poor functional outcome after SAH. Methods: Using real-time polymerase quantification chain reaction (RT-qPCR), 43 selected miRNAs were measured in daily CSF samples from a discovery cohort of SAH patients admitted to Rigshospitalet, Copenhagen, Denmark, and compared to neurologically healthy patients. Findings were validated in CSF from a replication cohort of SAH patients admitted to Massachusetts General Hospital, Boston, Massachusetts. Outcome measures were delayed cerebral ischemia (DCI), as well as functional outcome three months after ictus measured by the modified Rankin Scale score. Results: MiRNAs were quantified and passed RT-qPCR quality control in 427 CSF samples from 63 SAH patients in the discovery cohort, in 104 CSF samples from 63 SAH patients in the replication cohort and in 11 CSF samples from 11 neurologically healthy patients. Elevated miR-9-3p was associated with a poor functional outcome in both the discovery cohort (p < 0.0001) after correction for multiple testing (q < 0.01) and in the replication cohort (p < 0.01). Furthermore, elevated miR-9-5p was associated with a poor functional outcome in the discovery cohort (p < 0.01) after correction for multiple testing (q < 0.05). No miRNA was associated with DCI in both cohorts. Conclusions: Mir-9-3p is elevated in the CSF following SAH and this elevation is associated with a poor functional outcome.