Evidence of Varicella Zoster Virus Reactivation in Children With Arterial Ischemic Stroke: Results of the VIPS II Study

Heather J Fullerton; Nancy K Hills; Max Wintermark; Nomazulu Dlamini; Catherine Amlie-Lefond; Michael M Dowling; Lori C Jordan; Neil R Friedman; Mitchell S V Elkind; Charles Grose; VIPS II Investigators

doi:10.1161/JAHA.124.039184

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Evidence of Varicella Zoster Virus Reactivation in Children With Arterial Ischemic Stroke: Results of the VIPS II Study

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Evidence of Varicella Zoster Virus Reactivation in Children With Arterial Ischemic Stroke: Results of the VIPS II Study

Heather J Fullerton, Nancy K Hills, Max Wintermark, Nomazulu Dlamini, Catherine Amlie-Lefond, Michael M Dowling, Lori C Jordan, Neil R Friedman, Mitchell S V Elkind, Charles Grose, …

Journal of the American Heart Association, Vol.14(6), e039184

03/18/2025

DOI: 10.1161/JAHA.124.039184

PMCID: PMC12132736

PMID: 40099546

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Abstract

Varicella zoster virus (VZV) has historically been associated with focal cerebral arteriopathy and arterial ischemic stroke (AIS) in children, and risk of AIS and myocardial infarction in adults. The VIPS (Vascular Effects of Infection in Pediatric Stroke) II study aimed to determine whether VZV remains a pediatric stroke trigger in an era of routine VZV vaccination. This 22-center prospective cohort study enrolled 205 patients (28 days to 18 years; median, 11.6 years) with spontaneous AIS (December 2016 to January 2022) in North America and Australia, performed parental interviews, and collected baseline (hyperacute [≤72 hours; n=194] and acute [4-6 days; n=181]) and convalescent (1-6 weeks; n=74) serum samples. A virology research laboratory measured VZV IgM and IgG titers by an in-house ELISA in patients with AIS and 95 unmatched well control children. Baseline serologies indicated prior VZV exposure in 198 patients (97%). Parents recalled prior VZV vaccination in 160 (78%) and remote chickenpox in 3 (1.4%). Twenty patients (9.8%) had serologic evidence of recent VZV reactivation at the time of their stroke; all were asymptomatic. All had remote VZV exposure with VZV vaccination (median) 6.1 years prior. We observed recent VZV reactivation in patients with focal cerebral arteriopathy (4/32 [12.5%]) but not with arterial dissection or moyamoya. All 95 controls had serologic evidence of prior VZV exposure and 3 (3.1%) had recent VZV reactivation. One in 10 patients with childhood AIS had recent, asymptomatic VZV reactivation. In a vaccinated population, VZV may continue to play a modest role in childhood stroke pathogenesis.

Adolescent

Antibodies, Viral - blood

Australia - epidemiology

Child

Child, Preschool

Female

Herpesvirus 3, Human - immunology

Humans

Infant

Infant, Newborn

Ischemic Stroke - diagnosis

Ischemic Stroke - epidemiology

Ischemic Stroke - immunology

Ischemic Stroke - virology

Male

Prospective Studies

Varicella Zoster Virus Infection - complications

Varicella Zoster Virus Infection - diagnosis

Varicella Zoster Virus Infection - epidemiology

Virus Activation

Details

Title: Subtitle: Evidence of Varicella Zoster Virus Reactivation in Children With Arterial Ischemic Stroke: Results of the VIPS II Study
Creators: Heather J Fullerton - University of California, San Francisco
Nancy K Hills - University of California, San Francisco
Max Wintermark - Department of Radiology MD Anderson Cancer Center Houston TX USA
Nomazulu Dlamini - Hospital for Sick Children
Catherine Amlie-Lefond - Seattle Children's Hospital
Michael M Dowling - The University of Texas Southwestern Medical Center
Lori C Jordan - Vanderbilt University Medical Center
Neil R Friedman - Phoenix (United States)
Mitchell S V Elkind - Columbia University
Charles Grose - Department of Pediatrics, Division of Infectious Diseases/Virology University of Iowa Iowa City IA USA
VIPS II Investigators
Resource Type: Journal article
Publication Details: Journal of the American Heart Association, Vol.14(6), e039184
DOI: 10.1161/JAHA.124.039184
PMID: 40099546
PMCID: PMC12132736
NLM abbreviation: J Am Heart Assoc
ISSN: 2047-9980
eISSN: 2047-9980
Publisher: WILEY
Grant note: National Institutes of Health: R01 NS104094 Marc and Lynne Benioff philanthropic gift
This work was supported by National Institutes of Health R01 NS104094 (Fullerton) and Marc and Lynne Benioff philanthropic gift. All authors receive National Institutes of Health funding for this project.
Language: English
Date published: 03/18/2025
Academic Unit: Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
Record Identifier: 9984801890902771

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