Stroke is an increasingly recognized cause of childhood disability, occurring in as many as 13 per 100,000 children per year. Despite improved recognition, our understanding of the pathophysiology of this disease remains limited. A better understanding could improve our care of these children, and also shed light on non-atherosclerotic mechanisms of stroke applicable to both children and adults. Infection may be an important risk factor for childhood stroke, either due to systemic effects of inflammatory mediators causing a relatively pro-thrombotic state, or by direct or indirect effects on blood vessels through a variety of mechanisms. The overall goal of this project is explore the role of infection in childhood stroke, and thereby improve our understanding of the mechanisms underlying this disease.
The Specific Aims of the study are: 1) to determine whether infections (recent febrile infection, severe acute infections such as meningitis and remote chicken pox) are risk factors for first childhood stroke;2) to determine whether a history of infection prior to a first stroke predicts stroke recurrence, and 3) to determine whether vaccinations against varicella-zoster virus, influenza virus and bacterial etiologies of meningitis are protective against childhood stroke. We propose a case-control study within the well-defined population of approximately 1 million children enrolled in Kaiser Permanente Medical Care Program (KPMCP), a health maintenance organization including 16 hospitals and 36 out-patient facilities in Northern California. We will include as cases all children with stroke over a 17 year time period (1993 to 2009);controls will be randomly selected from the KPMCP population and matched for age. Exposure history will be measured through review of electronic and traditional medical records, and by telephone interview of subjects or their surrogates. Public Health Relevance: This study will improve our understanding of why children have strokes, an important cause of life-long physical and mental disability that tends to occur in the very youngest of children, those in the first year of life. Understanding why strokes occur in children is the first step towards designing effective methods of preventing stroke.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02NS053883-05
Application #
7840433
Study Section
NST-2 Subcommittee (NST)
Program Officer
Hicks, Ramona R
Project Start
2006-06-08
Project End
2011-08-31
Budget Start
2010-06-01
Budget End
2011-08-31
Support Year
5
Fiscal Year
2010
Total Cost
$171,518
Indirect Cost
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Fox, Christine K; Sidney, Stephen; Fullerton, Heather J (2015) Community-based case-control study of childhood stroke risk associated with congenital heart disease. Stroke 46:336-40
Hills, Nancy K; Sidney, Stephen; Fullerton, Heather J (2014) Timing and number of minor infections as risk factors for childhood arterial ischemic stroke. Neurology 83:890-7
Mueller, Sabine; Fullerton, Heather J; Stratton, Kayla et al. (2013) Radiation, atherosclerotic risk factors, and stroke risk in survivors of pediatric cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys 86:649-55
Mueller, Sabine; Sear, Katherine; Hills, Nancy K et al. (2013) Risk of first and recurrent stroke in childhood cancer survivors treated with cranial and cervical radiation therapy. Int J Radiat Oncol Biol Phys 86:643-8
Fox, Christine K; Glass, Hannah C; Sidney, Stephen et al. (2013) Acute seizures predict epilepsy after childhood stroke. Ann Neurol 74:249-56
Singhal, Nilika Shah; Hills, Nancy K; Sidney, Stephen et al. (2013) Role of trauma and infection in childhood hemorrhagic stroke due to vascular lesions. Neurology 81:581-4
Fox, Christine K; Johnston, S Claiborne; Sidney, Stephen et al. (2012) High critical care usage due to pediatric stroke: results of a population-based study. Neurology 79:420-7
Hills, Nancy K; Johnston, S Claiborne; Sidney, Stephen et al. (2012) Recent trauma and acute infection as risk factors for childhood arterial ischemic stroke. Ann Neurol 72:850-8
Ichord, Rebecca N; Bastian, Rachel; Abraham, Lisa et al. (2011) Interrater reliability of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) in a multicenter study. Stroke 42:613-7

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