Heather J Fullerton1, Nancy K Hills2, Mitchell S V Elkind2, Michael M Dowling2, Max Wintermark2, Carol A Glaser2, Marilyn Tan2, Michael J Rivkin2, Luigi Titomanlio2, A James Barkovich2, Gabrielle A deVeber2. 1. 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. 2. 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.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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: Kristin L Nichol; James Nordin; John Mullooly; Richard Lask; Kelly Fillbrandt; Marika Iwane Journal: N Engl J Med Date: 2003-04-03 Impact factor: 91.245
Authors: Max Wintermark; Nancy K Hills; Gabrielle A deVeber; A James Barkovich; Mitchell S V Elkind; Katherine Sear; Guangming Zhu; Carlos Leiva-Salinas; Qinghua Hou; Michael M Dowling; Timothy J Bernard; Neil R Friedman; Rebecca N Ichord; Heather J Fullerton Journal: Stroke Date: 2014-11-11 Impact factor: 7.914
Authors: Carlos Cantu; Antonio Arauz; Luis M Murillo-Bonilla; Mario López; Fernando Barinagarrementeria Journal: Stroke Date: 2003-06-05 Impact factor: 7.914
Authors: A J Grau; F Buggle; S Heindl; C Steichen-Wiehn; T Banerjee; M Maiwald; M Rohlfs; H Suhr; W Fiehn; H Becher Journal: Stroke Date: 1995-03 Impact factor: 7.914
Authors: Heather J Fullerton; Gabrielle A deVeber; Nancy K Hills; Michael M Dowling; Christine K Fox; Mark T Mackay; Adam Kirton; Jerome Y Yager; Timothy J Bernard; Eldad A Hod; Max Wintermark; Mitchell S V Elkind Journal: Stroke Date: 2016-08-04 Impact factor: 7.914
Authors: Lori C Jordan; Nancy K Hills; Christine K Fox; Rebecca N Ichord; Paola Pergami; Gabrielle A deVeber; Heather J Fullerton; Warren Lo Journal: Neurology Date: 2018-07-06 Impact factor: 9.910
Authors: Eliza C Miller; Marisa Gallo; Erin R Kulick; Alexander M Friedman; Mitchell S V Elkind; Amelia K Boehme Journal: Stroke Date: 2018-05 Impact factor: 7.914
Authors: L Gerstl; M V Bonfert; T Nicolai; M Dieterich; C Adamczyk; F Heinen; M Olivieri; M Steinlin Journal: Nervenarzt Date: 2017-12 Impact factor: 1.214
Authors: Eliza C Miller; Hajere J Gatollari; Gloria Too; Amelia K Boehme; Lisa Leffert; Randolph S Marshall; Mitchell S V Elkind; Joshua Z Willey Journal: Stroke Date: 2017-05-25 Impact factor: 7.914
Authors: Heather J Fullerton; Jorge M Luna; Max Wintermark; Nancy K Hills; Rafal Tokarz; Ying Li; Carol Glaser; Gabrielle A DeVeber; W Ian Lipkin; Mitchell S V Elkind Journal: Stroke Date: 2017-09-01 Impact factor: 7.914
Authors: Melissa G Chung; Kristin P Guilliams; Jenny L Wilson; Lauren A Beslow; Michael M Dowling; Neil R Friedman; Sahar M A Hassanein; Rebecca Ichord; Lori C Jordan; Mark T Mackay; Mubeen F Rafay; Michael Rivkin; Marcela Torres; Dimitrios Zafeiriou; Gabrielle deVeber; Christine K Fox Journal: Pediatr Neurol Date: 2019-06-27 Impact factor: 3.372
Authors: Heather J Fullerton; Nicholas Stence; Nancy K Hills; Bin Jiang; Catherine Amlie-Lefond; Timothy J Bernard; Neil R Friedman; Rebecca Ichord; Mark T Mackay; Mubeen F Rafay; Stéphane Chabrier; Maja Steinlin; Mitchell S V Elkind; Gabrielle A deVeber; Max Wintermark Journal: Stroke Date: 2018-11 Impact factor: 7.914
Authors: 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; Heather J Fullerton Journal: Circulation Date: 2016-01-26 Impact factor: 29.690