Evidence map›Paper›PMID 26813104›Full record

ArticleCirculation2016

Herpesvirus Infections and Childhood Arterial Ischemic Stroke: Results of the VIPS Study.

Mitchell S V Elkind, Nancy K Hills, Carol A Glaser, Warren D Lo, Catherine Amlie-Lefond, Nomazulu Dlamini, Rachel Kneen, Eldad A Hod, Max Wintermark, Gabrielle A deVeber and 2 more

Registry-linked trialOpen access · bronzeAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06040255 (Focal Cerebral Arteriopathy Steroid Trial), which is not on this map. Cited by 45 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 2 pooled it
9.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06040255 phase4enrolling by invitationnot on this mapstarted 2023, after this paper: background citation

Focal Cerebral Arteriopathy Steroid Trial

TypeinterventionalSponsorUniversity of California, San FranciscoRan2023 to 2030Enrolled80ConditionsPediatric Stroke, Arteriopathy, Arterial Ischemic StrokeArmsmethylprednisolone, prednisolone, prednisone
3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.

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  11. Advances in the Diagnosis and Treatment of Pediatric Arterial Ischemic Stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Mitchell S V ElkindFrom Department of Neurology Columbia University, New York, NY (M.S.V.E.); Department of Epidemiology, Mailman School of Public Health, New York, NY (M.S.V.E.); Departments of Neurology (N.K.H., H.J.F.), Biostatistics & Epidemiology (N.K.H.), and Pediatrics (C.A.G., H.J.F.), University of California San Francisco, San Francisco, CA; Department of Pediatrics (Infectious Disease), Kaiser Permanente, Oakland, CA (C.A.G.); Departments of Pediatrics and Neurology, Ohio State University, Columbus OH (W.D.L.); Department of Neurology, University of Washington, Seattle, WA (C.A.-L,); Department of Neurology, Hospital for Sick Children, Toronto, Canada (N.D., G.A.deV.); Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, England (R.K.); Department of Pathology, Columbia University, New York, NY (E.A.H.); and Department of Radiology, Stanford University, Palo Alto, CA (M.W.).
Nancy K HillsFrom Department of Neurology Columbia University, New York, NY (M.S.V.E.); Department of Epidemiology, Mailman School of Public Health, New York, NY (M.S.V.E.); Departments of Neurology (N.K.H., H.J.F.), Biostatistics & Epidemiology (N.K.H.), and Pediatrics (C.A.G., H.J.F.), University of California San Francisco, San Francisco, CA; Department of Pediatrics (Infectious Disease), Kaiser Permanente, Oakland, CA (C.A.G.); Departments of Pediatrics and Neurology, Ohio State University, Columbus OH (W.D.L.); Department of Neurology, University of Washington, Seattle, WA (C.A.-L,); Department of Neurology, Hospital for Sick Children, Toronto, Canada (N.D., G.A.deV.); Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, England (R.K.); Department of Pathology, Columbia University, New York, NY (E.A.H.); and Department of Radiology, Stanford University, Palo Alto, CA (M.W.).
Carol A GlaserFrom Department of Neurology Columbia University, New York, NY (M.S.V.E.); Department of Epidemiology, Mailman School of Public Health, New York, NY (M.S.V.E.); Departments of Neurology (N.K.H., H.J.F.), Biostatistics & Epidemiology (N.K.H.), and Pediatrics (C.A.G., H.J.F.), University of California San Francisco, San Francisco, CA; Department of Pediatrics (Infectious Disease), Kaiser Permanente, Oakland, CA (C.A.G.); Departments of Pediatrics and Neurology, Ohio State University, Columbus OH (W.D.L.); Department of Neurology, University of Washington, Seattle, WA (C.A.-L,); Department of Neurology, Hospital for Sick Children, Toronto, Canada (N.D., G.A.deV.); Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, England (R.K.); Department of Pathology, Columbia University, New York, NY (E.A.H.); and Department of Radiology, Stanford University, Palo Alto, CA (M.W.).
Warren D LoFrom Department of Neurology Columbia University, New York, NY (M.S.V.E.); Department of Epidemiology, Mailman School of Public Health, New York, NY (M.S.V.E.); Departments of Neurology (N.K.H., H.J.F.), Biostatistics & Epidemiology (N.K.H.), and Pediatrics (C.A.G., H.J.F.), University of California San Francisco, San Francisco, CA; Department of Pediatrics (Infectious Disease), Kaiser Permanente, Oakland, CA (C.A.G.); Departments of Pediatrics and Neurology, Ohio State University, Columbus OH (W.D.L.); Department of Neurology, University of Washington, Seattle, WA (C.A.-L,); Department of Neurology, Hospital for Sick Children, Toronto, Canada (N.D., G.A.deV.); Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, England (R.K.); Department of Pathology, Columbia University, New York, NY (E.A.H.); and Department of Radiology, Stanford University, Palo Alto, CA (M.W.).
Catherine Amlie-LefondFrom Department of Neurology Columbia University, New York, NY (M.S.V.E.); Department of Epidemiology, Mailman School of Public Health, New York, NY (M.S.V.E.); Departments of Neurology (N.K.H., H.J.F.), Biostatistics & Epidemiology (N.K.H.), and Pediatrics (C.A.G., H.J.F.), University of California San Francisco, San Francisco, CA; Department of Pediatrics (Infectious Disease), Kaiser Permanente, Oakland, CA (C.A.G.); Departments of Pediatrics and Neurology, Ohio State University, Columbus OH (W.D.L.); Department of Neurology, University of Washington, Seattle, WA (C.A.-L,); Department of Neurology, Hospital for Sick Children, Toronto, Canada (N.D., G.A.deV.); Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, England (R.K.); Department of Pathology, Columbia University, New York, NY (E.A.H.); and Department of Radiology, Stanford University, Palo Alto, CA (M.W.).
Nomazulu DlaminiFrom Department of Neurology Columbia University, New York, NY (M.S.V.E.); Department of Epidemiology, Mailman School of Public Health, New York, NY (M.S.V.E.); Departments of Neurology (N.K.H., H.J.F.), Biostatistics & Epidemiology (N.K.H.), and Pediatrics (C.A.G., H.J.F.), University of California San Francisco, San Francisco, CA; Department of Pediatrics (Infectious Disease), Kaiser Permanente, Oakland, CA (C.A.G.); Departments of Pediatrics and Neurology, Ohio State University, Columbus OH (W.D.L.); Department of Neurology, University of Washington, Seattle, WA (C.A.-L,); Department of Neurology, Hospital for Sick Children, Toronto, Canada (N.D., G.A.deV.); Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, England (R.K.); Department of Pathology, Columbia University, New York, NY (E.A.H.); and Department of Radiology, Stanford University, Palo Alto, CA (M.W.).
Rachel KneenFrom Department of Neurology Columbia University, New York, NY (M.S.V.E.); Department of Epidemiology, Mailman School of Public Health, New York, NY (M.S.V.E.); Departments of Neurology (N.K.H., H.J.F.), Biostatistics & Epidemiology (N.K.H.), and Pediatrics (C.A.G., H.J.F.), University of California San Francisco, San Francisco, CA; Department of Pediatrics (Infectious Disease), Kaiser Permanente, Oakland, CA (C.A.G.); Departments of Pediatrics and Neurology, Ohio State University, Columbus OH (W.D.L.); Department of Neurology, University of Washington, Seattle, WA (C.A.-L,); Department of Neurology, Hospital for Sick Children, Toronto, Canada (N.D., G.A.deV.); Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, England (R.K.); Department of Pathology, Columbia University, New York, NY (E.A.H.); and Department of Radiology, Stanford University, Palo Alto, CA (M.W.).
Eldad A HodFrom Department of Neurology Columbia University, New York, NY (M.S.V.E.); Department of Epidemiology, Mailman School of Public Health, New York, NY (M.S.V.E.); Departments of Neurology (N.K.H., H.J.F.), Biostatistics & Epidemiology (N.K.H.), and Pediatrics (C.A.G., H.J.F.), University of California San Francisco, San Francisco, CA; Department of Pediatrics (Infectious Disease), Kaiser Permanente, Oakland, CA (C.A.G.); Departments of Pediatrics and Neurology, Ohio State University, Columbus OH (W.D.L.); Department of Neurology, University of Washington, Seattle, WA (C.A.-L,); Department of Neurology, Hospital for Sick Children, Toronto, Canada (N.D., G.A.deV.); Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, England (R.K.); Department of Pathology, Columbia University, New York, NY (E.A.H.); and Department of Radiology, Stanford University, Palo Alto, CA (M.W.).
Max WintermarkFrom Department of Neurology Columbia University, New York, NY (M.S.V.E.); Department of Epidemiology, Mailman School of Public Health, New York, NY (M.S.V.E.); Departments of Neurology (N.K.H., H.J.F.), Biostatistics & Epidemiology (N.K.H.), and Pediatrics (C.A.G., H.J.F.), University of California San Francisco, San Francisco, CA; Department of Pediatrics (Infectious Disease), Kaiser Permanente, Oakland, CA (C.A.G.); Departments of Pediatrics and Neurology, Ohio State University, Columbus OH (W.D.L.); Department of Neurology, University of Washington, Seattle, WA (C.A.-L,); Department of Neurology, Hospital for Sick Children, Toronto, Canada (N.D., G.A.deV.); Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, England (R.K.); Department of Pathology, Columbia University, New York, NY (E.A.H.); and Department of Radiology, Stanford University, Palo Alto, CA (M.W.).
Gabrielle A deVeberFrom Department of Neurology Columbia University, New York, NY (M.S.V.E.); Department of Epidemiology, Mailman School of Public Health, New York, NY (M.S.V.E.); Departments of Neurology (N.K.H., H.J.F.), Biostatistics & Epidemiology (N.K.H.), and Pediatrics (C.A.G., H.J.F.), University of California San Francisco, San Francisco, CA; Department of Pediatrics (Infectious Disease), Kaiser Permanente, Oakland, CA (C.A.G.); Departments of Pediatrics and Neurology, Ohio State University, Columbus OH (W.D.L.); Department of Neurology, University of Washington, Seattle, WA (C.A.-L,); Department of Neurology, Hospital for Sick Children, Toronto, Canada (N.D., G.A.deV.); Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, England (R.K.); Department of Pathology, Columbia University, New York, NY (E.A.H.); and Department of Radiology, Stanford University, Palo Alto, CA (M.W.).
Heather J FullertonFrom Department of Neurology Columbia University, New York, NY (M.S.V.E.); Department of Epidemiology, Mailman School of Public Health, New York, NY (M.S.V.E.); Departments of Neurology (N.K.H., H.J.F.), Biostatistics & Epidemiology (N.K.H.), and Pediatrics (C.A.G., H.J.F.), University of California San Francisco, San Francisco, CA; Department of Pediatrics (Infectious Disease), Kaiser Permanente, Oakland, CA (C.A.G.); Departments of Pediatrics and Neurology, Ohio State University, Columbus OH (W.D.L.); Department of Neurology, University of Washington, Seattle, WA (C.A.-L,); Department of Neurology, Hospital for Sick Children, Toronto, Canada (N.D., G.A.deV.); Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, England (R.K.); Department of Pathology, Columbia University, New York, NY (E.A.H.); and Department of Radiology, Stanford University, Palo Alto, CA (M.W.). Heather.Fullerton@ucsf.edu.
VIPS Investigators*
Hospital for Sick Children · CAKaiser Permanente · USThe Ohio State University · USAlder Hey Children's NHS Foundation Trust · GBStanford University · USUniversity of Washington · US

Funding

VIPS: Vascular Effects of Infection in Pediatric StrokeR01NS062820 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DEVEBER, GABRIELLE ALINE, FULLERTON, HEATHER J · 2009 to 2013
$6.6M
NINDS NIH HHS R01 NS062820
6 · The paper itself

Abstract

backgroundEpidemiological studies demonstrate that childhood infections, including varicella zoster virus, 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 the risk of childhood AIS. METHODS AND

resultsWe enrolled 326 centrally confirmed cases of AIS and 115 stroke-free controls with trauma (29 days to 18 years of age) with acute blood samples (≤3 weeks after stroke/trauma); cases had convalescent samples (7-28 days later) when feasible. Samples were tested by commercial enzyme-linked immunosorbent assay kits for immunoglobulin M/immunoglobulin G antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, and varicella zoster virus. An algorithm developed a priori classified serological evidence of past and acute herpesvirus infection as dichotomous variables. The median (quartiles) age was 7.7 (3.1-14.3) years for cases and 10.7 (6.9-13.2) years for controls (P=0.03). Serological evidence of past infection did not differ between cases and controls. However, serological evidence of acute herpesvirus infection doubled the odds of childhood AIS, even after adjusting for age, race, and socioeconomic status (odds ratio, 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; herpes simplex virus 1 was found most often. Most infections were asymptomatic.

conclusionsHerpesviruses 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.

Indexed as

AdolescentBrain IschemiaCase-Control StudiesChildChild, PreschoolFemaleHerpesviridae InfectionsHumansInfantInfant, NewbornInternationalityMaleProspective StudiesStrokechildherpesviridae infectionsinfectionpediatricsstroke

Identifiers

PMID26813104
PMCPMC4766042
OpenAlexW2267911158

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.