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September 02, 2014; 83 (10) Article

Timing and number of minor infections as risk factors for childhood arterial ischemic stroke

Nancy K. Hills, Stephen Sidney, Heather J. Fullerton
First published August 20, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000752
Nancy K. Hills
From the Departments of Neurology (N.K.H., H.J.F.), Epidemiology and Biostatistics (N.K.H.), and Pediatrics (H.J.F.), University of California, San Francisco; and the Division of Research (S.S.), Kaiser Permanente Northern California, Oakland.
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Stephen Sidney
From the Departments of Neurology (N.K.H., H.J.F.), Epidemiology and Biostatistics (N.K.H.), and Pediatrics (H.J.F.), University of California, San Francisco; and the Division of Research (S.S.), Kaiser Permanente Northern California, Oakland.
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Heather J. Fullerton
From the Departments of Neurology (N.K.H., H.J.F.), Epidemiology and Biostatistics (N.K.H.), and Pediatrics (H.J.F.), University of California, San Francisco; and the Division of Research (S.S.), Kaiser Permanente Northern California, Oakland.
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Citation
Timing and number of minor infections as risk factors for childhood arterial ischemic stroke
Nancy K. Hills, Stephen Sidney, Heather J. Fullerton
Neurology Sep 2014, 83 (10) 890-897; DOI: 10.1212/WNL.0000000000000752

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Abstract

Objective: In a population-based case-control study, we examined whether the timing and number of minor infections increased risk of childhood arterial ischemic stroke (AIS).

Methods: Among 102 children with AIS and 306 age-matched controls identified from a cohort of 2.5 million children in a large integrated health care plan (1993–2007), we abstracted data on all medical visits for minor infection within the 2 years prior to AIS or index date for pairwise age-matched controls. We excluded cases of AIS with severe infection (e.g., sepsis, meningitis). Using conditional logistic regression, we examined the effect of timing and total number of minor infections on stroke risk.

Results: After adjusting for known pediatric stroke risk factors, the strongest association between infection and AIS was observed for infectious visits ≤3 days prior to stroke (odds ratio [OR] 12.1, 95% confidence interval [CI] 2.5, 57, p = 0.002). Respiratory infections represented 80% of case infections in that time period. Cases had more infectious visits, but not significantly so, for all time periods ≥4 days prior to the stroke. A greater cumulative number of infectious visits over 2 years did not increase risk of AIS.

Conclusions: Minor infections appear to have a strong but short-lived effect on pediatric stroke risk, while cumulative burden of infection had no effect. Proposed mechanisms for the link between minor infection and stroke in adults include an inflammatory-mediated prothrombotic state and chronic endothelial injury. The transient effect of infection in children may suggest a greater role for a prothrombotic mechanism.

GLOSSARY

AIS=
arterial ischemic stroke;
CI=
confidence interval;
ICD-9=
International Classification of Diseases, 9th revision;
KPNC=
Kaiser Permanente Northern California;
KPSS=
Kaiser Pediatric Stroke Study;
OR=
odds ratio

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 872

  • Received January 9, 2014.
  • Accepted in final form May 14, 2014.
  • © 2014 American Academy of Neurology
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