Recurrent stroke: the role of thrombophilia in a large international pediatric stroke population

Abstract

Risk factors for arterial ischemic stroke in children include vasculopathy and prothrombotic risk factors but their relative importance to recurrent stroke is uncertain. Data on recurrent stroke from databases held in Canada (Toronto), Germany (Kiel-Lübeck/Münster), and the UK (London/Southampton) were pooled. Data were available from 894 patients aged 1 month to 18 years at first stroke (median age, 6 years) with a median follow-up of 35 months. Among these 894 patients, 160 (17.9%) had a recurrence between 1 day and 136 months after the first stroke (median, 3.1 months). Among 288 children with vasculopathy, recurrence was significantly more common [hazard ratio (HR) 2.5, 95% confidence interval (95% CI) 1.92-3.5] compared to the rate in children without vasculopathy. Adjusting for vasculopathy, isolated antithrombin deficiency (HR 3.9; 95% CI: 1.4-10.9), isolated elevated lipoprotein (a) (HR 2.3; 95% CI: 1.3-4.1), and the presence of more than one prothrombotic risk factor (HR 1.9; 95% CI: 1.12-3.2) were independently associated with an increased risk of recurrence. Recurrence rates calculated per 100 person-years were 10 (95% CI: 3-24) for antithrombin deficiency, 6 (95% CI: 4-9) for elevated lipoprotein (a), and 13 (95% CI: 7-20) for the presence of more than one prothrombotic risk factor. Identifying children at increased risk of a second stroke is important in order to intensify measures aimed at preventing such recurrences.

Risk Factors for Recurrent Arterial Ischemic Stroke in Children and Young Adults

“…Almost 91% of these patients experienced recurrence within the first 6 months after AIS, whereas 45.5% of cases recurred within the first month [36]. A higher prevalence of recurrent stroke was noted by deVeber et al [29] and Sfaihi et al [37], namely 17.9% and 18% from 1 day to 136 months after the first stroke, respectively. In a group of 84 AIS children [38], the median interval to recurrence was 2.3 months and in most observed patients (77%), recurrence occurred within the first 6 months after stroke.…”

“…According to an international study by deVeber at al. [29], the following prothrombotic risk factors, i.e., antithrombin deficiency, elevated lipoprotein (a), and the co-existence of more than one prothrombotic factor, were associated with the increase in AIS recurrence risk when adjusting for vasculopathy. The authors observed a single prothrombotic disorder in 269 children with AIS, whereas in 88 patients, more than one prothrombotic risk factor was detected.…”

“…Until now, one of the confirmed risk factors for recurrent stroke in children has been the presence of vasculopathy, even when Moyamoya is excluded. In a study by deVeber et al [29], AIS recurrence was significantly more common among children with vasculopathy than in children without vasculopathy (HR = 2.5).…”

“…In turn, the etiologic factors for AIS in young adults include, among others, cardiac embolism, cervical artery dissection, atherothrombosis, and small vessel disease, whereas in almost 30% of cases, the cause of stroke is undetermined [28].Despite this, the neurological consequences of AIS, including post-stroke seizures, motor disability, and recurrence of the disease, are detrimental for both age populations. Additionally, they involve huge costs related to many years of care, rehabilitation, and treatment.According to the latest definition provided by deVeber et al [29], recurrent stroke is defined as clinically symptomatic AIS events manifested as acute focal neurological deficits with infarction in a vascular distribution in neuroimaging, which began more than 24 h following the onset of the first stroke. The recurrence of stroke was demonstrated as a factor increasing the risk of mortality in patients.…”

“…According to the latest definition provided by deVeber et al [29], recurrent stroke is defined as clinically symptomatic AIS events manifested as acute focal neurological deficits with infarction in a vascular distribution in neuroimaging, which began more than 24 h following the onset of the first stroke. The recurrence of stroke was demonstrated as a factor increasing the risk of mortality in patients.…”