Childhood Stroke: Thinking Locally, Acting Globally?

Abstract

HomeStrokeVol. 52, No. 1Childhood Stroke Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBChildhood StrokeThinking Locally, Acting Globally? Catherine Amlie-Lefond, MD and Mark S. Wainwright, MD, PhD Catherine Amlie-LefondCatherine Amlie-Lefond Correspondence to: Catherine Amlie-Lefond, MD, Seattle Children’s Hospital, 4800 Sand Point Way NE, Seattle, WA 98105. Email E-mail Address: [email protected] Division of Neurology, Seattle Children’s Hospital, University of Washington. Search for more papers by this author and Mark S. WainwrightMark S. Wainwright Division of Neurology, Seattle Children’s Hospital, University of Washington. Search for more papers by this author Originally published7 Dec 2020https://doi.org/10.1161/STROKEAHA.120.032854Stroke. 2021;52:162–163This article is a commentary on the followingImaging Predictors of Neurologic Outcome After Pediatric Arterial Ischemic StrokeOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 7, 2020: Ahead of Print The causes of arterial ischemic stroke (AIS) in children differ from adults, and outcome is highly variable. Accordingly, decisions about risks and benefits of thrombolysis or thrombectomy in childhood AIS must be made in the absence of reliable predictors of outcome.See related article, p 152In the current issue of Stroke, Jiang et al1 report on the predictive value of initial neuroimaging for neurological outcome at 1 year following childhood AIS. In this study, the authors performed a secondary analysis of imaging collected as part of the prospective VIPS study (Vascular Effects of Infection in Pediatric Stroke) cohort.2 This cohort includes children aged 29 days to 18 years at 37 international sites, and vascular imaging was required for inclusion. Of the 355 subjects in the original study, 288 were included in this analysis. The size of this cohort, prospective data collection, and international scope are strengths of the present study. Similar to prior studies, Jiang et al found that larger stroke volume and younger age are associated with a worse outcome. Notably, the association of poor outcome with injury to some locations (eg, uncinate fasciculus and angular gyrus) remained significant at any age. For others (insular cortex), this risk was present only for AIS occurring before the age of 2 years.Previous studies have also shown that younger children tend to have a worse outcome, particularly children who experience stroke during the first year of life,3 although as the authors of this report point out, other studies have not found this association. This discrepancy may reflect the heterogeneity of etiologies in childhood stroke. For example, children with morbidities such as congenital heart disease where brain injury can begin in the prenatal period and continue throughout life may contribute disproportionately in series from academic settings. Consistent with previous studies, the combined involvement of cortex, subcortical white matter, and subcortical nuclei may predict greater risk for long-term impairment, although as the authors point out, it is not clear if the effect is due to stroke size or disrupted connectivity. Loss of connectivity is the acute result of stroke, but the formation of aberrant connectivity may also impair stroke outcome.As previously shown in this large, carefully characterized cohort,4 standardized and carefully interpreted neuroimaging can inform our understanding of childhood stroke etiology and pathophysiology. There is a need for robust early predictors of outcome following childhood stroke to counsel families and to develop evidence-based strategies for reperfusion and neuroprotection. In adults, early National Institutes of Health Stroke Scale is a robust predictor of outcome, but obtaining accurate National Institutes of Health Stroke Scale is limited in the very young child and often confounded by critical illness, sedation, and lack of cooperation. The current study may inform future studies that will identify subsets of patients whose particular imaging features will more strongly predict poor outcome and who may be more likely to benefit from acute interventions. Nevertheless, this well-done study suggests that neuroimaging will not be adequately predictive. The meticulous volumetric analyses of the magnetic resonance imaging in this study is a strength of this article but also limits any future clinical application in which imaging findings of stroke location and size could be used to inform hyperacute decisions about risks and benefits of neuroprotective interventions. In the developing brain, structure—stroke size and location—may not adequately predict function.Acute neuroprotective care may focus on mitigating regional neuronal and glial injury, but ultimately improving recovery following childhood stroke will require understanding of the impact of comorbidities of childhood AIS and the contribution of therapies that promote the recovery of the networks that connect these regions. In highlighting the equivocal relationship between infarct volume and outcome after AIS in the developing brain, Jiang et al have strengthened the argument for the focus of future research on the impact of AIS on network connectivity and the potential of these pathways as tractable targets for neuroprotection in childhood AIS. In doing so, they have indirectly raised the exciting possibility that the window for neuroprotection in the developing brain may extend long after the brief time window for the use of thrombolysis or thrombectomy.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Disclosures, see page 163.Correspondence to: Catherine Amlie-Lefond, MD, Seattle Children’s Hospital, 4800 Sand Point Way NE, Seattle, WA 98105. Email [email protected]org