Herpesvirus Infections and Childhood Arterial Ischemic Stroke

Abstract

Background Epidemiological studies demonstrate that childhood infections, including varicella zoster virus (VZV), are associated with an increased risk of arterial ischemic stroke (AIS). Other herpesviruses have been linked to childhood AIS in case reports. We sought to determine whether herpesvirus infections, which are potentially treatable, increase risk of childhood AIS. Methods and Results We enrolled 326 centrally-confirmed cases of AIS and 115 stroke-free controls with trauma (ages 29 days-18 years) with acute blood samples (≤3 weeks after stroke/trauma); cases had convalescent samples (7-28 days later) when feasible. Samples were tested by commercial ELISA kits for IgM/IgG antibodies to herpes simplex virus (HSV) 1 and 2, cytomegalovirus (CMV), Epstein Barr virus (EBV), and varicella zoster virus (VZV). An algorithm developed a priori classified serologic evidence of past and acute herpesvirus infection as dichotomous variables. Median (quartiles) age was 7.7 (3.1-14.3) years for cases and 10.7 (6.9-13.2) for controls (p=0.03). Serologic evidence of past infection did not differ between cases and controls. However, serologic evidence of acute herpesvirus infection doubled the odds of childhood AIS, even after adjusting for age, race, and socio-economic status (OR 2.2; 95% confidence interval, 1.2-4.0; p=0.007). Among 187 cases with acute and convalescent blood samples, 85 (45%) showed evidence of acute herpesvirus infection, with HSV-1 found most often. Most infections were asymptomatic. Conclusions Herpesviruses may act as a trigger for childhood AIS, even if the infection is subclinical. Antivirals like acyclovir might have a role in the prevention of recurrent stroke if further studies confirm a causal relationship.

Inflammatory Biomarkers in Childhood Arterial Ischemic Stroke

“…The VIPS study, and others, provide evidence that acute infection, such as the common cold or herpesviruses, act as triggers for childhood AIS. 7–10 Arterial wall imaging studies detecting enhancement in the wall of affected vessels in childhood arteriopathies may suggest an acute inflammatory process. 11, 12 Children whose arteriopathies progress after their index stroke have the highest risk of recurrent AIS.…”

Biological Plausibility of a Link Between Arterial Ischemic Stroke and Infection With Varicella-Zoster Virus or Herpes Simplex Virus

“…These same herpesviruses have evolved with humankind around the world since the great migration of modern humans across the Mandeb Strait out of Africa around 60 to 100 thousand years ago 1 . In the current report in this issue of Circulation , the authors sought to determine whether any of 5 herpesvirus infections—HSV1, HSV2, VZV, CMV or EBV—increased the risk of arterial ischemic stroke (AIS) in children 18 years of age or younger 2 . They conclude that HSV1 infection and to a lesser extent VZV infection may act as triggers for childhood AIS.…”

Parvovirus B19 Infection in Children With Arterial Ischemic Stroke

“…We combined these data with our previously published herpesvirus serologic data to identify combinations of infections. 2 …”

“…1 Serologic assays for herpesviruses demonstrated a high prevalence of acute, mostly subclinical herpes infections. 2 …”