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ABSTRACT
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.
Conclusion: 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.
GLOSSARY
- AIS=
- arterial ischemic stroke;
- AVM=
- arteriovenous malformation;
- CA=
- catheter arteriography;
- CEC=
- circulating endothelial cell;
- CI=
- confidence interval;
- EMP=
- endothelial microparticle;
- ETP=
- endogenous thrombin potential;
- FCA=
- focal cerebral arteriopathy;
- FITC=
- fluorescein isothiocyanate;
- FLAIR=
- fluid-attenuated inversion recovery;
- GOSH=
- Great Ormond Street Hospital;
- MP=
- microparticle;
- MPFP=
- microparticle-free plasma;
- MR=
- magnetic resonance;
- MRA=
- magnetic resonance angiography;
- OR=
- odds ratio;
- PACNS=
- primary angiitis of the CNS;
- PE=
- phycoerythrin;
- PPP=
- platelet-poor plasma;
- PSGL-1=
- P-selectin glycoprotein ligand 1;
- TF=
- tissue factor;
- TGA=
- thrombin generation assay;
- vWF=
- von Willebrand factor
Footnotes
Study funding: Supported by Action Medical Research and Arthritis Research UK.
Go to Neurology.org for full disclosures. Disclosures deemed relevant by the authors, if any, are provided at the end of this article.
Editorial, page 2084
Supplemental data at www.neurology.org
- Received February 18, 2012.
- Accepted June 21, 2012.
- © 2012 American Academy of Neurology
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