Abstract
Introduction: Brain arteriovenous malformations (bAVMs) are the leading cause of pediatric hemorrhagic stroke. Prior studies have implicated inflammation as a major contributor to bAVM pathogenesis, with increased inflammatory cell infiltration and IL-6 protein levels reported in bAVM tissue. However, few studies have evaluated circulating inflammatory proteins as biomarkers for bAVM or intracranial hemorrhage (ICH).
Hypothesis: We hypothesized that higher plasma levels of interleukin (IL)-1B and IL-6 would be associated with bAVM ICH at initial presentation.
Methods: Pediatric bAVM cases (<19 years) evaluated at our institution between 2005 and 2022 were enrolled into an ongoing cohort study. Plasma samples (n=119) were collected and analyzed using the OLINK Explore 384 Inflammation panel. Protein levels were quantified based on log-log standard curves, and log2-transformed for analysis. Multivariable regression analysis compared plasma protein levels between cases with and without ICH presentation, adjusting for sex, race, ethnicity, age, and time between initial presentation and first plasma collection. Exponentiated coefficients are presented as proportional increase (PI).
Results: Samples were collected a median of 23.5 days after presentation in the ICH group and 140 days in the non-ICH group. Plasma levels of IL-6 were higher in bAVM patients with ICH vs. those without ICH (PI=3.22, 95% CI=1.32-7.85, p=0.011), adjusting for age, sex, race and Hispanic ethnicity. After further adjustment for time to sample collection, the association between IL-6 levels and ICH was no longer significant. (PI =1.36, CI=0.57-3.29, p=0.478). There was no difference in plasma levels of IL-1B between groups (PI=0.85, 95% CI=0.65-1.12, p=0.26).
Conclusion: Plasma levels of IL-6 were associated with ICH presentation in this pediatric bAVM cohort; however, this association may reflect downstream effects of the hemorrhage. Further studies are needed to help clarify whether plasma IL-6 levels can be used to predict hemorrhage risk in patients with unruptured bAVMs.