Endovascular hyperacute stroke therapies - what do recent trials mean for children?

Abstract

Intravenous tissue plasminogen activator (IV tPA) for hyperacute arterial ischaemic stroke (AIS) was a game-changer in adults. Although only a minority of patients are eligible, improvement in outcomes drove investment in complex treatment pathways. In 2015, five trials demonstrated the superiority of endovascular therapy (thrombectomy/intra-arterial thrombolysis) over IV tPA alone in adults with intracranial large vessel occlusion, treated within 6 hours.1 What does this mean for children? A trial of hyperacute IV tPA in paediatric AIS (TIPS) was closed due to non-recruitment.2 Major issues for children are prompt recognition and access to diagnostic imaging.3 However, centres that opened to recruitment to TIPS underwent a culture change, where possible stroke was treated as an emergency with institutional protocols for rapid assessment, diagnosis, and treatment.4 This should now be the standard of care in tertiary centres, but the major road-blocks to any hyperacute therapy (namely delays in recognition, transfer, investigation, and frequent comorbidities) span the entire pathway from pre-hospital to specialist centre. The challenge of suitable devices and skills to instrument intracranial arteries in small children cannot be understated. While delivering a sick child to an interventional neuroradiologist with paediatric experience is challenging, this could be both achievable and appropriate in specific populations, for example in children with cardioembolic stroke on cardiac support devices. Ultimately, as with adults, only a minority of children with AIS will have intracranial large artery occlusion, prompting consideration of endovascular therapy. Thus, even in adults endovascular therapy will only be the tip of the iceberg of acute stroke diagnosis and care. Given the history of TIPS, funding for any future hyperacute treatment trial in paediatric AIS will be challenging and, given the diversity of aetiologies in paediatric AIS, it is unlikely that a single treatment will be suitable for all. It is perhaps unfashionable in this era of evidence and protocol-driven medicine to propose that the clinical approach to paediatric AIS needs to be individualized. Investment in educating the pre-hospital sector of the potential significance of acute focal neurological symptoms in children can only improve care for all children with ‘brain attacks’. Once in hospital, institutional infrastructure should be developed to fast-track access to diagnostic imaging and critical investigations – ‘stroke mimics’ are frequently emergencies in themselves and merit rapid diagnosis and treatment. Most children who die as a consequence of AIS do so from potentially remediable sequelae, namely haemorrhage, brain swelling, or secondary hydrocephalus. Recognition, and early and aggressive management of these conditions, is an achievable immediate goal. Developing multidisciplinary stroke teams in paediatric neurology centres will skill-up and empower professionals to develop local protocols and procedures and to make complex case-by-case decisions, arguably a more intelligent approach than treating every child with AIS in the same way. There will be a few children who may benefit from interventions such as endovascular therapies and it is likely that developments in adult AIS treatment will improve access. Deciding whether or not to proceed with this or other complex interventions will require experience and skill and can only happen effectively if scenarios are rehearsed many more times than they are enacted. In the absence of trial evidence, clinical guidelines can only provide a limited amount of direction. However, having a more urgent and individualized approach to the care of children with acute stroke is likely to have wider and more immediate benefits for a larger number of children than those who could benefit from endovascular therapies alone.