Recurrent arterial ischemic stroke in childhood: the role of prothrombotic disorders and underlying conditions

Background: Recurrence after childhood stroke remains a significant problem, but there are few large studies looking for the risk factors of recurrence.

Methods: On the basis of prospective patient enrollment, data on recurrent ischemic stroke (defined as a further clinical focal neurological event associated with new infarction) from the German collaborative study and the Registries at Great Ormond Street Hospital and at the Hospital for Sick Children were pooled. Using logistic regression, the effect on the risk of recurrent stroke of underlying conditions (cardiac disorder, vasculopathy) and hypercoagulable states was examined: protein C, protein S, and antithrombin deficiency, anticardiolipin antibodies, elevation of lipoprotein (a), fibrinogen and homocysteine, as well as genetic polymorphisms (e.g. factor V G1691A mutation, factor II G20210A mutation, MTHFR 677TT variant).

Results: Data were available from 672 patients (55% male) with a median age at first stroke of 6 years (range: 1 month –21 years). 74 (11%) had recurrent stroke. In univariate analysis the risk of recurrent stroke is significantly increased in patients with multiple (>1) prothrombotic risk factors, and with respect to single prothrombotic factors significant results were found for elevated Lp(a), homocysteine and fibrinogen. Multivariate analysis shows a trend for an increase risk of recurrence in patients with an underlying vasculopathy (Hazard ratio (HR) 1.8, confidence interval (CI) 1.0–3.8, p-value 0.04). Significant results were found for the presence of more than one prothrombotic risk factor (HR 2.5, CI 1.2–5.1, p-value 0.01).

Conclusion: Individually, the presence of prothrombotic disorders independently increases risk of recurrence. Prothrombotic testing should be considered in children with stroke. There is an urgent need for international collaborative studies to examine the risk factors for first ischemic stroke and recurrence, which hopefully lead to controlled trials of management.

Keywords: ischemic stroke, recurrence, thrombophilia, vasculopathies