Researchers at University of California at San Francisco (UCSF); Kaiser Permanente, Oakland, CA; and University of Utah, Salt Lake City performed a casecontrol study of recent exposure to trauma or infection in 126 childhood (<19 years old) cases of arterial ischemic stroke (AIS). Cases of AIS were identified from electronic records and confirmed by chart review in a cohort of 2.5 million children enrolled in a health care plan. Exposures to trauma and infection were determined from review of medical records prior to the stroke diagnosis. Twelve percent of cases of AIS (cf 1.6% of controls; p=0.001) had encountered a medical head or neck trauma as an independent risk factor for stroke within the prior 12 weeks. More severe head trauma, with loss of consciousness in 7 cases and hospital admission of 11 cases, was strongly associated with AIS. Median time trauma to stroke was 0.5 days (range 0-2 days).
A minor acute infection in the prior 4 weeks was also an independent risk factor in 33% of cases of AIS cf 13% of controls. Two cases were exposed to both trauma and infection. A medical encounter for minor acute infection increased a child's risk of AIS by >4-fold. Common infectious diagnoses included upper respiratory infections (33%), other viral syndromes (26%), acute otitis media (19%), and acute gastroenteritis (17%). Ten percent of cases, versus 0% of controls, had a recent major acute infection (sepsis or meningitis/encephalitis). No case of AIS had a recent history of chicken pox. AIS was associated with chronic autoimmune disease in 13 cases and with cardiac disease in 10. 
COMMENT. Previous prospective multicenter studies have established pediatric stroke risk factors and associations but have lacked adequate controls and determination of causation . The current study establishes arteriopathies related to infection and trauma as independent risk factors for AIS in children, but the mechanism of the thromboembolic event is unclear. Involvement of a prothrombotic pathway with infection is suggested.
Endothelial injury in childhood stroke with cerebral arteriopathy was studied at Great Ormond Street Hospital for Children, London, UK . Of 46 children with stroke (AIS), 10 had recurrence and 36 had a single AIS event. Levels of circulating endothelial cells (CECs) were significantly higher in children with AIS compared to healthy controls (p=0.03); they were higher in children with AIS recurrence compared to those with no recurrence (p=0.0001) and in controls (p=0.0001). Total circulating annexin V + microparticles (MPs) were significantly greater in children with AIS recurrence than in those with no recurrence (p=0020). CECs and MPs reflect endothelial injury, cellular activation, and MP-mediated thrombin generation. MP-mediated thrombin generation is enhanced in children with recurrent AIS compared to those with no recurrence (p=0.0001). These findings link inflammation, endothelial injury, and a tendency to thrombosis; they further the understanding of AIS pathophysiology.