Prevalence of patent foramen ovale in a cohort of children with cryptogenic ischemic stroke

Shih EK, Beslow LA, Natarajan SS, Falkensammer CB, Messé SR, Ichord RN. Prevalence of Patent Foramen Ovale in a Cohort of Children With Cryptogenic Ischemic Stroke. Neurology. 2021 Nov 23;97(21):e2096-e2102. doi: 10.1212/WNL.0000000000012892. Epub 2021 Oct 14. PMID: 34649876.

Abstract

Background and objectives: To determine the significance of patent foramen ovale (PFO) in childhood stroke, we compared PFO prevalence, PFO features, and stroke recurrence risk in 25 children with cryptogenic arterial ischemic stroke (AIS), 54 children with AIS from a known etiology, and 209 healthy controls.

Methods: We performed a case-control analysis of a 14-year prospectively enrolled single-center cohort of children with AIS who underwent transthoracic echocardiogram (TTE) and compared them to TTEs of otherwise healthy children evaluated for benign cardiac concerns. Stroke patients 29 days to 18 years of age at stroke ictus with confirmed acute AIS on imaging, availability of complete diagnostic studies of stroke risk factors, including TTE images available for central review, and at least 1 follow-up evaluation after index stroke were included. Presence of PFO and high-risk PFO features were assessed by 2 independent, blinded reviewers and compared between groups with the Fisher exact test. Stroke/TIA recurrence risk was determined from Cox proportional hazards models.

Results: Of 154 children with first-ever AIS, 79 were eligible; 25 had cryptogenic AIS, and 54 had a known cause. PFO prevalence was higher in the cryptogenic group (7, 28%) compared to both the known stroke etiology group (3, 5.6%, p = 0.009) and controls without stroke (24, 11.5%, p = 0.03). There were no significant differences in presence of right-to-left shunt and atrial septal aneurysm. Median follow-up time for entire stroke cohort was 20.9 months. Stroke-free recurrence at 2-years did not differ between children with and without PFO (HR 2.0, 95% CI 0.4-9.3, p = 0.39).

Discussion: PFO prevalence was higher in children with cryptogenic stroke compared to patients with AIS with known etiology and healthy controls. PFO was not associated with increased recurrence risk. Optimal secondary preventive treatment in children with cryptogenic stroke and PFO remains uncertain and requires further study.

Classification of evidence: This study provides Class III evidence that children with cryptogenic ischemic stroke have an increased frequency of PFO compared to children with ischemic stroke of known etiology and healthy controls.