Abstract
Stroke in children is a heterogeneous disorder. Over 100 risk factors for stroke have been reported and genetic predisposition to stroke has been established. The most frequently reported risk factors are congenital heart malformations, hemolytic anemias, collagen vascular diseases, some rare inborn metabolic disorders, trauma, infection and thrombophilia. The aim of this article is to provide an overview of investigated inherited prothrombotic risk factors in children with first ischemic stroke. Various prothrombotic risk factors have been investigated in pediatric stroke including elevated homocysteine and lipoprotein (a), antithrombin, protein C and protein S deficiency, Factor V Leiden, Factor II G20210A and plasminogen activator inhibitor-1 4G/5G polymorphism. Despite similar criteria for inclusion of different studies in meta-analyses investigating first ischemic stroke in children, the obtained results were not consistent for all prothrombotic risk factors. The discrepancies found could be explained by methodological issues like different sample sizes, patient populations included and lack of controls. In order to provide the necessary power for randomized control trials, multi-center, multi-national approaches like International Pediatric Stroke Study have been initiated with the aim to describe risk factors for childhood stroke and explore their relationship with presentation, age, geography, and infarct characteristics. Although it is evident from numerous studies that the frequency of inherited prothrombotic factors is increased in pediatric stroke, single thrombophilia does not fully explain stroke in a child as it represents only a mild risk factor. Further studies are needed, as improved understanding of underlying mechanisms will improve primary and secondary prevention of childhood stroke.
Highlights
Stroke is defined by the World Health Organization as rapidly developing signs of focal disturbance of cerebral function with symptoms lasting at least 24 hours or leading to death with no apparent cause other than of vascular origin (1)
Pediatric stroke is divided into ischemic and hemorrhagic stroke with subdivision of ischemic stroke according to the time of onset to childhood ischemic stroke and ischemic perinatal stroke (IPS)
PRESUMED PERINATAL ischemic stroke fetal ischemic stroke diagnosed before birth by using fetal imaging methods; (ii) neonatal ischemic stroke diagnosed after birth and before 28th postnatal day including preterm; (iii) presumed perinatal ischemic stroke, diagnosed in infants after the 28th postnatal day in whom it is presumed that the event occurred between the 20th week of fetal life through the 28th postnatal day
Summary
Stroke is defined by the World Health Organization as rapidly developing signs of focal disturbance of cerebral function with symptoms lasting at least 24 hours or leading to death with no apparent cause other than of vascular origin (1). This definition is far from ideal for children, because children with symptoms compatible with transient ischemic attack can have brain infarction shown by brain imaging despite the transient nature of their symptoms. IPS is defined as a group of heterogeneous conditions characterized by focal disruption of cerebral blood flow secondary to arterial or cerebral venous thrombosis or embolization between 20 weeks of fetal life through the 28th postnatal day, confirmed by neuroimaging or neuropathological studies (4).
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