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• W3129398995 abstract "HomeStrokeVol. 52, No. 3Moving Toward a New Horizon of Pediatric Stroke Intervention Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBMoving Toward a New Horizon of Pediatric Stroke Intervention Sarah Lee, MD Ryan J. FellingMD, PhD Sarah LeeSarah Lee Division of Child Neurology, Department of Neurology, Stanford University, Stanford, California (S.L.). Search for more papers by this author , Ryan J. FellingRyan J. Felling Correspondence to: Ryan J. Felling, MD, PhD, 200 N. Wolfe St, Suite 2158, Baltimore, MD 21287. Email E-mail Address: [email protected] https://orcid.org/0000-0002-0845-9356 Divisions of Child and Vascular Neurology, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD (R.J.F.). Search for more papers by this author Originally published22 Feb 2021https://doi.org/10.1161/STROKEAHA.120.033496Stroke. 2021;52:789–791This article is a commentary on the followingEndovascular Treatment for Acute Ischemic Stroke in ChildrenThis decade has witnessed significant scientific and technological advances that have transformed the hyperacute treatment of stroke due to large vessel occlusion (LVO). LVO represents 24% to 46% of arterial ischemic stroke in adults, but disproportionately affects stroke morbidity, more than doubling the risk of death or dependence as compared with non-LVO strokes.1,2 Unfortunately, similar epidemiological data regarding the relative impact of LVO in pediatric stroke is lacking. While the remarkable plasticity of young brains may serve to justify forgoing risky hyperacute therapies in favor of allowing natural recovery, there is countervailing evidence that many children sustain lasting motor and neurocognitive deficits poststroke, and that those with large territory or cortical+subcortical infarctions, as might be expected from a nonreperfused LVO, do significantly worse.3–5 Those of us who treat children with stroke long to translate the success that has been realized in adults to our own patients, to improve their functional outcomes and enhance their quality of life.See related article, p 781The new study by van Es et al6 is the first prospective pediatric endovascular thrombectomy (EVT) series yet published and adds support to a growing body of retrospective data establishing the feasibility and safety of EVT in children. From an ongoing prospective registry in the Netherlands, the investigators identified 9 children ranging in age from 13 months to 16 years with acute stroke due to LVO treated with EVT. Most patients had cardiac disease, including 4 requiring left ventricular assist device support who were therapeutically anticoagulated at the time of stroke. Procedural efficacy was excellent, with TICI 2b or 3 recanalization achieved in all but 1 patient after a median of 2 attempts. The authors note that smaller (3F) caliber sheaths were used for access in the younger patients in the series, but that all endovascular tools used were readily available and familiar to neurointerventionalists in adult stroke centers. The only periprocedural complication was a single femoral artery pseudoaneurysm. There were no intraprocedural intracranial complications reported, though one left ventricular assist device patient did suffer a severe intracranial hemorrhage 8 days after EVT.Early neurological recovery (defined by a substantial improvement in the PedNIHSS score within 24 hours of EVT) was seen in 6/9 children in this series, and long-term outcome at 6 months was favorable in all survivors, with modified Rankin Scale score indicating no or mild disability. Although most published case series, including the recent retrospective SaveChildS pediatric study, suggest excellent functional outcomes among children undergoing EVT, this cohort highlights the risk of poor outcome, particularly among children on left ventricular assist device support. Long-term mortality in this study was high (4/9 patients), but notably was restricted to the left ventricular assist device patients and reported as related to underlying cardiac disease rather than stroke or EVT complications in at least 3 of these patients. Indeed, optimizing blood pressure, sedation, and anticoagulation after stroke for a child in heart failure can be a tenuous balancing act. Working closely with pediatric cardiologists, surgeons, and intensivists to create consensus protocols for poststroke medical management of children on mechanical circulatory support may help improve survival in this at-risk population.Functional independence is a typical inclusion criterion for most adult stroke trials, allowing for a relatively homogenous baseline from which to compare outcomes. As shown in this study, a significant proportion of children with LVO may be critically ill, on mechanical circulatory support, with guarded overall prognoses from underlying cardiac disease prestroke and susceptible to unique complications poststroke. Excluding these children for the sake of homogeneity would be unwise, as it is this subpopulation that is perhaps at highest risk for developing LVO; furthermore, neurological morbidity is an important contributor to functional outcome in this population. Rather than considering the heterogeneity of pediatric stroke as a liability, harnessing real-world variability in current practice and employing within-group comparisons to determine who may benefit from these promising therapies prospectively would further the field significantly, and hopefully provide a framework for the establishment of pediatric-specific EVT guidelines.While the results presented in this study are encouraging and add additional support for the feasibility and safety of EVT in children with arterial ischemic stroke, significant limitations must be acknowledged. First, this was a very small series of children, most of whom had stroke due to cardioembolism. Many children with stroke will have other causes such as arteriopathy, and safety and efficacy of EVT in this substantial subset of patients remain unknown. Second, most patients in this series were treated within relatively early time windows (≤6 hours from onset). Early-window adult EVT trials like MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) required presentation within 6 hours to qualify, while recent late-window trials such as DAWN (The DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With the Trevo)7 and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke)8 have moved the field away from a time-based approach to a more individualized tissue-based approach by assessing the degree of mismatch between core (irreversibly infarcted tissue) and penumbra (critically hypoperfused tissue destined to infarct if not reperfused in time). As the authors point out, the role of delayed treatment is particularly important in children, as presentation typically occurs in later (>6 hours) time windows.9,10 Additionally, critically ill children requiring sedation and paralysis may not have a clear last known well time. However, consensus criteria for what constitutes a relevant mismatch in children, and within what timeframe, still need to be established; despite increasing utilization in late time windows, tremendous variability still exists in current practice with regard to qualifying age, National Institutes of Health Stroke Scale, and imaging parameters for pediatric EVT eligibility.11 Finally, sufficient data regarding the natural history of nonreperfused LVO in children under noninterventional management is sorely lacking. Without a control group or, at the very least, good historical comparisons, the question of clinical efficacy cannot be definitively answered. A prospective comparison of nonreperfused and reperfused LVO in children could settle this debate, though ensuring a matched cohort will be increasingly difficult as EVT in children becomes more accepted as standard-of-care.The authors remark that completing a randomized controlled EVT trial in the pediatric population is unlikely, citing the TIPS study (Thrombolysis in Pediatric Stroke), which was closed early due to lack of accrual. However, TIPS paved the way for the development of pediatric stroke centers worldwide—sites that now have the infrastructure in place to participate in prospective hyperacute stroke studies. The extended time window for endovascular treatment also makes a prospective pediatric research study more feasible. Beyond an observational registry, validating biomarkers able to identify children who stand to benefit from reperfusion could potentially change current practice; however, inherent differences not only between adults and children, but also between children of different ages and baseline comorbidities, must be carefully considered in study design and interpretation. For example, a clinical-core approach must acknowledge that National Institutes of Health in children younger than 2 years may be unreliable; that seizure and fluctuating symptoms at stroke onset are more common in children; and that those at particular risk for embolic stroke may be paralyzed or sedated, confounding an accurate neurological exam. A neuroimaging-based core-penumbra approach must recognize that a subset of children (such as those on mechanical circulatory support) are unable to undergo magnetic resonance imaging, and that the cerebral perfusion thresholds defining ischemic core and penumbra in adults may not apply to children due to differences in cerebrovascular collateral circulation. While a randomized EVT trial in children would be challenging due to low numbers and growing lack of equipoise, large international, multi-center networks such as the International Pediatric Stroke Study and the International Pediatric Stroke Organization, and expanded time windows for intervention will facilitate prospective pediatric research. Now may be an ideal opportunity to move beyond the limitations inherent in retrospective and registry-based studies and toward the development of targeted studies of hyperacute therapies for children with stroke, aiming for the same level of standardized stroke care that has been transformative for adults.Sources of FundingNone.Disclosures None.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Sources of Funding and Disclosures, see page 791.Correspondence to: Ryan J. Felling, MD, PhD, 200 N. Wolfe St, Suite 2158, Baltimore, MD 21287. Email [email protected]eduReferences1. Rennert RC, Wali AR, Steinberg JA, Santiago-Dieppa DR, Olson SE, Pannell JS, Khalessi AA. Epidemiology, natural history, and clinical presentation of large vessel ischemic stroke.Neurosurgery. 2019; 85(suppl_1):S4–S8. doi: 10.1093/neuros/nyz042Google Scholar2. Malhotra K, Gornbein J, Saver JL. Ischemic strokes due to large-vessel occlusions contribute disproportionately to stroke-related dependence and death: a review.Front Neurol. 2017; 8:651. doi: 10.3389/fneur.2017.00651CrossrefMedlineGoogle Scholar3. Vázquez López M, de Castro de Castro P, Barredo Valderrama E, Miranda Herrero MC, Gil Villanueva N, Alcaraz Romero AJ, Pascual Pascual SI. Outcome of arterial ischemic stroke in children with heart disease.Eur J Paediatr Neurol. 2017; 21:730–737. doi: 10.1016/j.ejpn.2017.05.007Google Scholar4. Felling RJ, Rafay MF, Bernard TJ, Carpenter JL, Dlamini N, Hassanein SMA, Jordan LC, Noetzel MJ, Rivkin MJ, Shapiro KA, et al.; International Pediatric Stroke Study Group. Predicting recovery and outcome after pediatric stroke: results from the International Pediatric Stroke Study.Ann Neurol. 2020; 87:840–852. doi: 10.1002/ana.25718Google Scholar5. deVeber GA, Kirton A, Booth FA, Yager JY, Wirrell EC, Wood E, Shevell M, Surmava AM, McCusker P, Massicotte MP, et al.. Epidemiology and outcomes of arterial ischemic stroke in children: the Canadian Pediatric Ischemic Stroke Registry.Pediatr Neurol. 2017; 69:58–70. doi: 10.1016/j.pediatrneurol.2017.01.016CrossrefMedlineGoogle Scholar6. van Es A, Hunfeld M, van den Wijngaard I, Kraemer U, Engelen M, van Hasselt B, Fransen P, Dippel D, Majoie C, van der Lugt A, et al.. Endovascular treatement for acute ischemic stroke in children: experience from the MR CLEAN Registry.Stroke. 2020; 52:781–788. doi: 10.1161/STROKEAHA.120.030210Google Scholar7. Desai SM, Haussen DC, Aghaebrahim A, Al-Bayati AR, Santos R, Nogueira RG, Jovin TG, Jadhav AP. Thrombectomy 24 hours after stroke: beyond DAWN.J Neurointerv Surg. 2018; 10:1039–1042. doi: 10.1136/neurintsurg-2018-013923Google Scholar8. Albers GW, Lansberg MG, Kemp S, Tsai JP, Lavori P, Christensen S, Mlynash M, Kim S, Hamilton S, Yeatts SD, et al.. A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3).Int J Stroke. 2017; 12:896–905. doi: 10.1177/1747493017701147CrossrefMedlineGoogle Scholar9. Rafay MF, Pontigon AM, Chiang J, Adams M, Jarvis DA, Silver F, Macgregor D, Deveber GA. Delay to diagnosis in acute pediatric arterial ischemic stroke.Stroke. 2009; 40:58–64. doi: 10.1161/STROKEAHA.108.519066LinkGoogle Scholar10. Srinivasan J, Miller SP, Phan TG, Mackay MT. Delayed recognition of initial stroke in children: need for increased awareness.Pediatrics. 2009; 124:e227–e234. doi: 10.1542/peds.2008-3544CrossrefMedlineGoogle Scholar11. Wilson JL, Amlie-Lefond C, Abruzzo T, Orbach DB, Rivkin MJ, deVeber GA, Pergami P. Survey of practice patterns and preparedness for endovascular therapy in acute pediatric stroke.Childs Nerv Syst. 2019; 35:2371–2378. doi: 10.1007/s00381-019-04358-yGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesEndovascular Treatment for Acute Ischemic Stroke in ChildrenAdriaan C.G.M. van Es, et al. Stroke. 2021;52:781-788 March 2021Vol 52, Issue 3Article InformationMetrics Download: 1,058 © 2021 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.120.033496PMID: 33617342 Originally publishedFebruary 22, 2021 Keywordsthrombectomyfemoral arteryintracranial hemorrhagemorbidityischemic strokeEditorialsPDF download SubjectsCerebrovascular Disease/StrokeCerebrovascular ProceduresRevascularizationIschemic Stroke" @default.
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