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. [1]

COMMENT. Previous prospective multicenter studies have established pediatric stroke risk factors and associations but have lacked adequate controls and determination of causation [2]. 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 [3]. 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.