Abstract 38: Herpes Viruses in Childhood Arterial Ischemic Stroke: Interim Results of the VIPS Study

Abstract

Background: Varicella zoster virus (VZV) is a known cause of cerebral arteriopathy and arterial ischemic stroke (AIS) in children, and scant evidence suggests other herpes viruses may also play a role. An objective of the Vascular effects of Infection in Pediatric Stroke (VIPS) study was to determine whether recent infection with herpes viruses_as measured by serologies_is associated with childhood AIS. Methods: VIPS is an international prospective 35-center case-control study enrolling 350 children (28 days-18 years) with AIS and 120 unmatched trauma controls. Case confirmation and vascular imaging review are performed centrally. Acute blood samples are collected ≤3 weeks after stroke/trauma; convalescent samples 7-28 days after the acute draw in cases only. Samples were tested for IgG and IgM antibodies to herpes simplex virus (HSV) 1 and 2, cytomegalovirus (CMV), Epstein Barr virus (EBV), and VZV. An algorithm developed a priori by a pediatric infectious disease expert (C.A.G.) classified acute infection as a dichotomous variable. Results: Of 310 cases enrolled thus far, 141 cases with paired samples and 44 controls underwent serologic analysis. Median age (IQR) was 7.0 years (2.9, 14.3) for cases and 8.3 (3.3, 13.3) for controls (P=0.90). Evidence of an acute herpes infection was found in 41% of cases versus 9% of controls (P<0.0001; Table). The most commonly identified virus was HSV-1. After adjusting for age in a multivariable logistic regression analysis, herpes exposure remained a significant predictor of AIS (OR 9.0, 95% CI 3.1, 38.7; P=0.0004). Of the 58 cases positive for herpes, 36% had a definite arteriopathy, and 33% a possible arteriopathy, compared to 34% and 24%, respectively, of 83 negative cases. Conclusions: In this interim analysis, acute exposure to a herpes virus appears associated with childhood AIS, present in 41% of cases that were tested.