Infection, vaccination, and childhood arterial ischemic stroke

Fullerton, Heather J.; Hills, Nancy K.; Elkind, Mitchell S.V.; Dowling, Michael M.; Wintermark, Max; Glaser, Carol; Tan, Marilyn; Rivkin, Michael J.; Titomanlio, Luigi; Barkovich, A. James; deVeber, Gabrielle

doi:10.1212/wnl.0000000000002065

Cited by 112 publications

(95 citation statements)

References 32 publications

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“…In a prior analysis of the VIPS cohort, 39% of cases (versus 22% of controls, p<0.0001) had parental report of a clinical infection in the prior 4 weeks, and 18% of cases (3.4% of controls, p<0.0001) in the prior 1 week. 8 In a retrospective population-based study of children enrolled in Kaiser Permanente Northern California, 33% of 126 cases (versus 13% of controls) had a medical encounter for infection in the prior 4 weeks, 6 and 14% of cases (1.7% of controls) had an encounter in the prior 7 days. 5 The International Pediatric Stroke Study reported preceding infection in 24% of 676 AIS cases enrolled in 10 countries.…”

Section: Discussionmentioning

confidence: 99%

“…8, 28 They were asked whether the child had had a clinical infection in the 6 months preceding the stroke (cases) or enrollment (controls), and were asked detailed questions about the most recent infection including its location, clinical manifestations, and severity. They were also asked about prior vaccinations, including VZV, and markers of socioeconomic status (SES): residence (urban, suburban, rural), maternal education, and household income (converted to US dollars).…”

Section: Methodsmentioning

confidence: 99%

“…4–8 Infection could predispose to stroke through systemic inflammation causing a transient hypercoagulable state or endothelial injury. VZV, a member of the herpesvirus family, has been linked to AIS via a much more specific mechanism: by infecting the trigeminal nerve, which provides innervation to the cerebral vasculature, the virus may directly invade vessel walls and cause a focal arteriopathy (“post-varicella arteriopathy”).…”

Section: Introductionmentioning

confidence: 99%

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Herpesvirus Infections and Childhood Arterial Ischemic Stroke

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Herpesvirus Infections and Childhood Arterial Ischemic Stroke

et al. 2016

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“…The NIH-funded Vascular effects of Infection in Pediatric Stroke (VIPS) Study confirmed a robust association between infection in the prior week and childhood AIS; the most common pre-stroke infections were upper respiratory (present in 50%). 1 Serologic assays for herpesviruses demonstrated a high prevalence of acute, mostly subclinical herpes infections. 2 …”

Section: Introductionmentioning

confidence: 99%

Parvovirus B19 Infection in Children With Arterial Ischemic Stroke

Fullerton

Luna

Wintermark

et al. 2017

Stroke

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Background and Purpose Case-control studies suggest that acute infection transiently increases the risk of childhood arterial ischemic stroke (AIS). We hypothesized that an unbiased pathogen discovery approach utilizing MassTag polymerase chain reaction (PCR) would identify pathogens in the blood of childhood AIS cases. Methods The multi-center international “Vascular effects of Infection in Pediatric Stroke” study enrolled AIS cases, and stroke-free controls, aged 29 days through 18 years. Parental interview included questions on recent infections. In this pilot study, we used MassTag-PCR to test the plasma of the first 161 cases and 34 controls enrolled for a panel of 28 common bacterial and viral pathogens. Results Pathogen DNA was detected in no controls and 14 cases (8.7%): parvovirus B19 (n=10), herpesvirus 6 (n=2), adenovirus (n=1), and rhinovirus 6C (n=1). Parvovirus B19 infection was confirmed by serologies in all ten; infection was subclinical in eight. Four cases with parvovirus B19 had underlying congenital heart disease, while another five had a distinct arteriopathy involving a long-segment stenosis of the distal internal carotid and proximal middle cerebral arteries. Conclusion Using MassTag-PCR, we detected Parvovirus B19, a virus known to infect erythrocytes and endothelial cells, in some cases of childhood AIS. This approach can generate new, testable hypotheses about childhood stroke pathogenesis.

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“…This study by Fullerton and colleagues 4 involved children from several different countries. The researchers compared 355 children with stroke to 354 stroke-free children (the control group).…”

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confidence: 99%