In pursuit of evidence-based treatments for paediatric stroke: the UK and Chest guidelines

Abstract

Arterial ischaemic stroke and cerebral sinovenous thrombosis are increasingly seen in infants and children. Incidence ranges from two to six per 100,000 children a year. Adverse outcome including death, neurological deficits, and reduced quality of life affect most children with stroke. Residual neurological deficits last many decades, for the rest of a patient's life. Of major concern is the risk of recurrent stroke, which affects up to 25% of children who have arterial ischaemic stroke after the newborn period. Children with ischaemic stroke are empirically treated with antithrombotics including antiplatelet (aspirin and clopidogrel) and anticoagulant (heparins and warfarin) drugs. No randomised controlled trials have been done besides those in patients with sickle-cell disease and adult trial data are not directly applicable to paediatric stroke due to maturational differences in coagulation and vascular systems as well as different stroke mechanisms. National and international networks of clinical and basic researchers focused on paediatric stroke are now developing. Recently published cohort and case-controlled studies are elucidating stroke mechanisms, outcomes, and treatment safety in children. Two sets of guidelines have been published in the past 6 months. These guidelines differ both in the scope of treatments and subgroups of patients with stroke they cover; however, both focus on ischaemic stroke beyond the newborn period. There are areas of agreement-for children with sickle-cell disease and stroke, both guidelines recommend initial and maintenance transfusion therapy to reduce the proportion of sickle-cell haemoglobin to less than 30%. For children with sinovenous thrombosis or arterial stroke due to dissection or cardiac embolism, both guidelines recommend anticoagulant therapy with warfarin or low molecular weight heparin for 3-6 months. However, the guidelines diverge in their recommendations for the initial treatment of non-haemorrhagic arterial ischaemic stroke, one recommending aspirin and the other 5-7 days of anticoagulants. The guidelines also differ in their recommendations for long-term treatment of children after arterial ischaemic stroke, one set recommending maintenance aspirin in all patients and the other only in children with vasculopathy. These differences arise from both a lack of sufficient evidence and the differing views of neurologists and haematologists in the treatment of paediatric cerebral thrombosis. WHERE NEXT?: Multicentre studies and networks provide increasingly precise data regarding mechanisms, outcomes, and treatment safety in paediatric stroke. These data and networks will enable clinical trials to address areas of divergent opinion and improve the outcome from childhood stroke in the near future.