Endothelial injury in childhood stroke with cerebral arteriopathy: a cross-sectional study.
OBJECTIVE
Circulating endothelial cells (CECs) and microparticles (MPs) have been reported to reflect endothelial injury, cellular activation, and MP-mediated thrombin generation. We tested the hypothesis that these indices differ between children with cerebral arteriopathy and arterial ischemic stroke (AIS) recurrence, and those with a single event.


METHODS
This was a single-center cross-sectional study of 46 children with AIS and cerebral arteriopathy matched with pediatric controls. AIS recurrence was defined as new acute neurologic deficit with radiologic evidence of further cerebral infarction. CECs and MPs were identified with immunomagnetic bead extraction and flow cytometry, respectively. MP function as assessed by thrombin generation was determined using a fluorogenic assay.


RESULTS
Ten children had AIS recurrence while 36 had a single AIS event. CECs were raised in children with recurrent AIS, compared to those with no recurrence (p = 0.0001), and in controls (p = 0.0001). Total circulating annexin V+ MPs were significantly greater in children with recurrence than in those with no recurrence (p = 0.0020). These MPs were of endothelial or platelet origin, and a subpopulation expressed tissue factor. Finally, MP-mediated thrombin generation was enhanced in children with recurrent AIS compared to those with no recurrence (p = 0.0001), providing a link between inflammation, endothelial injury, and increased thrombotic tendency.


CONCLUSIONS
Despite the wide spectrum of clinical and radiologic presentation of childhood AIS, indices of endothelial injury and cellular activation are different in patients with single and recurrent events. This novel approach has potential for furthering understanding of AIS pathophysiology and prognosis.
Paediatric Rheumatology Department, Institute of Child Health and Great Ormond St Hospital for Children, London, UK. d.eleftheriou@ich.ucl.ac.uk
Despina
D
Eleftheriou
Vijeya
V
Ganesan
Ying
Y
Hong
Nigel J
NJ
Klein
Paul A
PA
Brogan
D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D055252:Cell-Derived Microparticles / Q000378:metabolism; D002539:Cerebral Arterial Diseases / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D020521:Stroke / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*
D015415:Biomarkers