title: Infection, vaccination, and childhood arterial ischemic stroke: Results of the VIPS study.
abstract: OBJECTIVE
  Minor infection can trigger adult arterial ischemic stroke (AIS) and is common in childhood. We tested the hypotheses that infection transiently increases risk of AIS in children, regardless of stroke subtype, while vaccination against infection is protective.
  
  
  METHODS
  The Vascular Effects of Infection in Pediatric Stroke study is an international case-control study that prospectively enrolled 355 centrally confirmed cases of AIS (29 days-18 years old) and 354 stroke-free controls. To determine prior exposure to infections and vaccines, we conducted parental interviews and chart review.
  
  
  RESULTS
  Median (interquartile range) age was 7.6 years for cases and 9.3 for controls (p = 0.44). Infection in the week prior to stroke, or interview date for controls, was reported in 18% of cases, vs 3% of controls, conferring a 6.3-fold increased risk of AIS (p < 0.0001); upper respiratory infections were most common. Prevalence of preceding infection was similar across stroke subtypes: arteriopathic, cardioembolic, and idiopathic. Use of vasoactive cold medications was similarly low in both groups. Children with some/few/no routine vaccinations were at higher stroke risk than those receiving all or most (odds ratio [OR] 7.3, p = 0.0002). In an age-adjusted multivariate logistic regression model, independent risk factors for AIS included infection in the prior week (OR 6.3, p < 0.0001), undervaccination (OR 8.2, p = 0.0004), black race (compared to white; OR 1.9, p = 0.009), and rural residence (compared to urban; OR 3.0, p = 0.0003).
  
  
  CONCLUSIONS
  Infection may act as a trigger for childhood AIS, while routine vaccinations appear protective. Hence, efforts to reduce the spread of common infections might help prevent stroke in children.
authors.affiliation: From the Departments of Neurology (H.J.F., N.K.H., A.J.B.), Pediatrics (H.J.F., C.A.G., A.J.B.), Biostatistics and Epidemiology (N.K.H.), and Radiology (A.J.B.), University of California San Francisco; the Departments of Neurology and Epidemiology (M.S.V.E.), Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY; the Departments of Pediatrics and Neurology and Neurotherapeutics (M.M.D.), UT Southwestern Medical Center, Dallas, TX; the Department of Radiology (M.W.), Stanford University, Palo Alto, CA; the Division of Communicable Disease Control (C.A.G.), Center for Infectious Diseases, California Department of Public Health, Richmond; the Departments of Pediatrics and Neurosciences (M.T.), University of the Philippines-Philippine General Hospital, Manila, Philippines; the Departments of Neurology, Psychiatry, and Radiology (M.J.R.), Boston Children's Hospital, MA; the Pediatric Emergency Department (L.T.), Robert Debré Hospital, Paris Diderot University, Paris, France; and the Department of Neurology (G.A.d.), Hospital for Sick Children, Toronto, Canada. Heather.Fullerton@ucsf.edu.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Fullerton
authors.affiliation: From the Departments of Neurology (H.J.F., N.K.H., A.J.B.), Pediatrics (H.J.F., C.A.G., A.J.B.), Biostatistics and Epidemiology (N.K.H.), and Radiology (A.J.B.), University of California San Francisco; the Departments of Neurology and Epidemiology (M.S.V.E.), Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY; the Departments of Pediatrics and Neurology and Neurotherapeutics (M.M.D.), UT Southwestern Medical Center, Dallas, TX; the Department of Radiology (M.W.), Stanford University, Palo Alto, CA; the Division of Communicable Disease Control (C.A.G.), Center for Infectious Diseases, California Department of Public Health, Richmond; the Departments of Pediatrics and Neurosciences (M.T.), University of the Philippines-Philippine General Hospital, Manila, Philippines; the Departments of Neurology, Psychiatry, and Radiology (M.J.R.), Boston Children's Hospital, MA; the Pediatric Emergency Department (L.T.), Robert Debré Hospital, Paris Diderot University, Paris, France; and the Department of Neurology (G.A.d.), Hospital for Sick Children, Toronto, Canada.
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Hills
authors.affiliation: From the Departments of Neurology (H.J.F., N.K.H., A.J.B.), Pediatrics (H.J.F., C.A.G., A.J.B.), Biostatistics and Epidemiology (N.K.H.), and Radiology (A.J.B.), University of California San Francisco; the Departments of Neurology and Epidemiology (M.S.V.E.), Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY; the Departments of Pediatrics and Neurology and Neurotherapeutics (M.M.D.), UT Southwestern Medical Center, Dallas, TX; the Department of Radiology (M.W.), Stanford University, Palo Alto, CA; the Division of Communicable Disease Control (C.A.G.), Center for Infectious Diseases, California Department of Public Health, Richmond; the Departments of Pediatrics and Neurosciences (M.T.), University of the Philippines-Philippine General Hospital, Manila, Philippines; the Departments of Neurology, Psychiatry, and Radiology (M.J.R.), Boston Children's Hospital, MA; the Pediatric Emergency Department (L.T.), Robert Debré Hospital, Paris Diderot University, Paris, France; and the Department of Neurology (G.A.d.), Hospital for Sick Children, Toronto, Canada.
authors.forename: Mitchell S V
authors.initials: MS
authors.lastname: Elkind
authors.affiliation: From the Departments of Neurology (H.J.F., N.K.H., A.J.B.), Pediatrics (H.J.F., C.A.G., A.J.B.), Biostatistics and Epidemiology (N.K.H.), and Radiology (A.J.B.), University of California San Francisco; the Departments of Neurology and Epidemiology (M.S.V.E.), Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY; the Departments of Pediatrics and Neurology and Neurotherapeutics (M.M.D.), UT Southwestern Medical Center, Dallas, TX; the Department of Radiology (M.W.), Stanford University, Palo Alto, CA; the Division of Communicable Disease Control (C.A.G.), Center for Infectious Diseases, California Department of Public Health, Richmond; the Departments of Pediatrics and Neurosciences (M.T.), University of the Philippines-Philippine General Hospital, Manila, Philippines; the Departments of Neurology, Psychiatry, and Radiology (M.J.R.), Boston Children's Hospital, MA; the Pediatric Emergency Department (L.T.), Robert Debré Hospital, Paris Diderot University, Paris, France; and the Department of Neurology (G.A.d.), Hospital for Sick Children, Toronto, Canada.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Dowling
authors.affiliation: From the Departments of Neurology (H.J.F., N.K.H., A.J.B.), Pediatrics (H.J.F., C.A.G., A.J.B.), Biostatistics and Epidemiology (N.K.H.), and Radiology (A.J.B.), University of California San Francisco; the Departments of Neurology and Epidemiology (M.S.V.E.), Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY; the Departments of Pediatrics and Neurology and Neurotherapeutics (M.M.D.), UT Southwestern Medical Center, Dallas, TX; the Department of Radiology (M.W.), Stanford University, Palo Alto, CA; the Division of Communicable Disease Control (C.A.G.), Center for Infectious Diseases, California Department of Public Health, Richmond; the Departments of Pediatrics and Neurosciences (M.T.), University of the Philippines-Philippine General Hospital, Manila, Philippines; the Departments of Neurology, Psychiatry, and Radiology (M.J.R.), Boston Children's Hospital, MA; the Pediatric Emergency Department (L.T.), Robert Debré Hospital, Paris Diderot University, Paris, France; and the Department of Neurology (G.A.d.), Hospital for Sick Children, Toronto, Canada.
authors.forename: Max
authors.initials: M
authors.lastname: Wintermark
authors.affiliation: From the Departments of Neurology (H.J.F., N.K.H., A.J.B.), Pediatrics (H.J.F., C.A.G., A.J.B.), Biostatistics and Epidemiology (N.K.H.), and Radiology (A.J.B.), University of California San Francisco; the Departments of Neurology and Epidemiology (M.S.V.E.), Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY; the Departments of Pediatrics and Neurology and Neurotherapeutics (M.M.D.), UT Southwestern Medical Center, Dallas, TX; the Department of Radiology (M.W.), Stanford University, Palo Alto, CA; the Division of Communicable Disease Control (C.A.G.), Center for Infectious Diseases, California Department of Public Health, Richmond; the Departments of Pediatrics and Neurosciences (M.T.), University of the Philippines-Philippine General Hospital, Manila, Philippines; the Departments of Neurology, Psychiatry, and Radiology (M.J.R.), Boston Children's Hospital, MA; the Pediatric Emergency Department (L.T.), Robert Debré Hospital, Paris Diderot University, Paris, France; and the Department of Neurology (G.A.d.), Hospital for Sick Children, Toronto, Canada.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Glaser
authors.affiliation: From the Departments of Neurology (H.J.F., N.K.H., A.J.B.), Pediatrics (H.J.F., C.A.G., A.J.B.), Biostatistics and Epidemiology (N.K.H.), and Radiology (A.J.B.), University of California San Francisco; the Departments of Neurology and Epidemiology (M.S.V.E.), Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY; the Departments of Pediatrics and Neurology and Neurotherapeutics (M.M.D.), UT Southwestern Medical Center, Dallas, TX; the Department of Radiology (M.W.), Stanford University, Palo Alto, CA; the Division of Communicable Disease Control (C.A.G.), Center for Infectious Diseases, California Department of Public Health, Richmond; the Departments of Pediatrics and Neurosciences (M.T.), University of the Philippines-Philippine General Hospital, Manila, Philippines; the Departments of Neurology, Psychiatry, and Radiology (M.J.R.), Boston Children's Hospital, MA; the Pediatric Emergency Department (L.T.), Robert Debré Hospital, Paris Diderot University, Paris, France; and the Department of Neurology (G.A.d.), Hospital for Sick Children, Toronto, Canada.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Tan
authors.affiliation: From the Departments of Neurology (H.J.F., N.K.H., A.J.B.), Pediatrics (H.J.F., C.A.G., A.J.B.), Biostatistics and Epidemiology (N.K.H.), and Radiology (A.J.B.), University of California San Francisco; the Departments of Neurology and Epidemiology (M.S.V.E.), Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY; the Departments of Pediatrics and Neurology and Neurotherapeutics (M.M.D.), UT Southwestern Medical Center, Dallas, TX; the Department of Radiology (M.W.), Stanford University, Palo Alto, CA; the Division of Communicable Disease Control (C.A.G.), Center for Infectious Diseases, California Department of Public Health, Richmond; the Departments of Pediatrics and Neurosciences (M.T.), University of the Philippines-Philippine General Hospital, Manila, Philippines; the Departments of Neurology, Psychiatry, and Radiology (M.J.R.), Boston Children's Hospital, MA; the Pediatric Emergency Department (L.T.), Robert Debré Hospital, Paris Diderot University, Paris, France; and the Department of Neurology (G.A.d.), Hospital for Sick Children, Toronto, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rivkin
authors.affiliation: From the Departments of Neurology (H.J.F., N.K.H., A.J.B.), Pediatrics (H.J.F., C.A.G., A.J.B.), Biostatistics and Epidemiology (N.K.H.), and Radiology (A.J.B.), University of California San Francisco; the Departments of Neurology and Epidemiology (M.S.V.E.), Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY; the Departments of Pediatrics and Neurology and Neurotherapeutics (M.M.D.), UT Southwestern Medical Center, Dallas, TX; the Department of Radiology (M.W.), Stanford University, Palo Alto, CA; the Division of Communicable Disease Control (C.A.G.), Center for Infectious Diseases, California Department of Public Health, Richmond; the Departments of Pediatrics and Neurosciences (M.T.), University of the Philippines-Philippine General Hospital, Manila, Philippines; the Departments of Neurology, Psychiatry, and Radiology (M.J.R.), Boston Children's Hospital, MA; the Pediatric Emergency Department (L.T.), Robert Debré Hospital, Paris Diderot University, Paris, France; and the Department of Neurology (G.A.d.), Hospital for Sick Children, Toronto, Canada.
authors.forename: Luigi
authors.initials: L
authors.lastname: Titomanlio
authors.affiliation: From the Departments of Neurology (H.J.F., N.K.H., A.J.B.), Pediatrics (H.J.F., C.A.G., A.J.B.), Biostatistics and Epidemiology (N.K.H.), and Radiology (A.J.B.), University of California San Francisco; the Departments of Neurology and Epidemiology (M.S.V.E.), Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY; the Departments of Pediatrics and Neurology and Neurotherapeutics (M.M.D.), UT Southwestern Medical Center, Dallas, TX; the Department of Radiology (M.W.), Stanford University, Palo Alto, CA; the Division of Communicable Disease Control (C.A.G.), Center for Infectious Diseases, California Department of Public Health, Richmond; the Departments of Pediatrics and Neurosciences (M.T.), University of the Philippines-Philippine General Hospital, Manila, Philippines; the Departments of Neurology, Psychiatry, and Radiology (M.J.R.), Boston Children's Hospital, MA; the Pediatric Emergency Department (L.T.), Robert Debré Hospital, Paris Diderot University, Paris, France; and the Department of Neurology (G.A.d.), Hospital for Sick Children, Toronto, Canada.
authors.forename: A James
authors.initials: AJ
authors.lastname: Barkovich
authors.affiliation: From the Departments of Neurology (H.J.F., N.K.H., A.J.B.), Pediatrics (H.J.F., C.A.G., A.J.B.), Biostatistics and Epidemiology (N.K.H.), and Radiology (A.J.B.), University of California San Francisco; the Departments of Neurology and Epidemiology (M.S.V.E.), Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY; the Departments of Pediatrics and Neurology and Neurotherapeutics (M.M.D.), UT Southwestern Medical Center, Dallas, TX; the Department of Radiology (M.W.), Stanford University, Palo Alto, CA; the Division of Communicable Disease Control (C.A.G.), Center for Infectious Diseases, California Department of Public Health, Richmond; the Departments of Pediatrics and Neurosciences (M.T.), University of the Philippines-Philippine General Hospital, Manila, Philippines; the Departments of Neurology, Psychiatry, and Radiology (M.J.R.), Boston Children's Hospital, MA; the Pediatric Emergency Department (L.T.), Robert Debré Hospital, Paris Diderot University, Paris, France; and the Department of Neurology (G.A.d.), Hospital for Sick Children, Toronto, Canada.
authors.forename: Gabrielle A
authors.initials: GA
authors.lastname: deVeber
mesh_terms: D000293:Adolescent; D016470:Bacteremia / Q000453:epidemiology; D002545:Brain Ischemia / Q000150:complications / Q000453:epidemiology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005334:Fever / Q000453:epidemiology; D005759:Gastroenteritis / Q000453:epidemiology; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D007231:Infant, Newborn; D007239:Infections / Q000453:epidemiology*; D000069544:Infectious Encephalitis / Q000453:epidemiology; D007251:Influenza, Human / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008581:Meningitis / Q000453:epidemiology; D015999:Multivariate Analysis; D014663:Nasal Decongestants / Q000627:therapeutic use; D016017:Odds Ratio; D010033:Otitis Media / Q000453:epidemiology; D011014:Pneumonia / Q000453:epidemiology; D015995:Prevalence; D011446:Prospective Studies; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000453:epidemiology; D012307:Risk Factors; D018805:Sepsis / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology; D014481:United States / Q000453:epidemiology; D014611:Vaccination / Q000706:statistics & numerical data*; D014612:Vaccines / Q000627:therapeutic use
chemical_list: D014663:Nasal Decongestants; D014612:Vaccines