Abstract Body: Introduction: The immune response within the central nervous system (CNS) is heightened after hemorrhagic stroke, yet the association between inflammation and outcome is unclear. Analysis of cerebrospinal fluid (CSF) from patients with external ventricular drains (EVDs) enables analysis of the CNS inflammatory profile. We hypothesize that hemorrhagic stroke patients with a more proinflammatory CSF profile will have worse outcomes at discharge.

Methods: Using cytometric bead array, we measured a panel of cytokines in CSF and blood samples collected from hemorrhagic stroke patients between day 0 and 7 after symptom onset. Ventricular CSF was collected from control patients undergoing shunt placement for normal pressure hydrocephalus. C-C motif chemokine ligand 2 (CCL2), interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-colony stimulating factor (G-CSF), and vascular endothelial growth factor (VEGF) were all detectable within the CSF at this time point. All cytokine concentrations were log transformed given non-normal distributions. Using univariate and multivariate analyses, we examined the relationship between discharge outcomes using Modified Rankin Score (mRS) and CSF cytokine levels.

Results: CSF was collected from 25 intracerebral hemorrhage (ICH) patients, 54 subarachnoid hemorrhage (SAH) patients, and 25 controls. Hemorrhagic stroke patients showed higher IL-8, IL-6, CCL2, and G-CSF compared to plasma samples and control CSF (all p< 0.01). In ICH patients, higher CSF VEGF was associated with a worse discharge mRS (mRS 5-6 vs 0-4) (p=0.029). In SAH patients, there was a trend towards an association between higher CSF IL-6, IL-8, and G-CSF and worse discharge mRS (p= 0.056, 0.087, and 0.071 respectively). In multivariate analyses looking at each cytokine with discharge mRS, adjusted for age, sex, and ICH volume, log IL-8 in CSF was associated with higher discharge mRS in ICH patients (p=0.012).

Conclusion: Our data show that CSF cytokine levels are higher in the first 7 days post-hemorrhagic stroke than in controls or plasma. In ICH, elevated CSF VEGF and IL-8 are both associated with worse outcome at discharge. These findings provide the rationale for investigation into the relationship between CSF cytokines and outcome in hemorrhagic stroke, which can lead to discovery of therapeutic targets for improving outcome in this devastating condition.