Cryptogenic Pediatric Ischemic Stroke: What's the Hole Story?

Stroke is an underrecognized cause of morbidity and mortality in children. When the reason for stroke remains undetermined (cryptogenic), implementation of appropriate secondary prevention strategies is hindered, potentially leaving the child vulnerable to future ischemic events and related disability. Unfortunately, approximately one-third of childhood strokes are cryptogenic, a higher proportion than in young adults.1 The contribution of patent foramen ovale (PFO) to cryptogenic stroke, as well as the role of PFO closure in stroke secondary prevention, has long been a controversial topic, with a recent review summarizing key adult literature.2 Multiple randomized, open-label trials demonstrated that PFO closure reduces recurrent stroke risk in a subset of young adults with cryptogenic strokes compared with antiplatelet therapy alone.3-5 These trials underpin the 2020 American Academy of Neurology practice advisory stating that clinicians may recommend PFO closure for patients <60 years of age with a PFO and embolic-appearing infarct when no other mechanisms of stroke are identified.6 The Risk of Paradoxical Embolism score, validated in patients ≥18 years of age, can be used to identify patients whose cryptogenic strokes are likely causally linked to their PFO.7 The score is weighted to assign more points to younger patients, implicating PFO in stroke pathogenesis more often in the young, especially those without other vascular risk factors. These advances in our understanding of the role of PFO in cryptogenic stroke in adults, especially in younger adults, makes this area ripe for investigation in children and begs the question: does PFO play a pathogenic role in childhood stroke?

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