MANAGEMENT OF ACUTE ISCHEMIC STROKE IN PEDIATRIC PATIENTS: CLINICAL METHODS AND OUTCOMES
Abstract
Background: Acute ischemic stroke (AIS) in the pediatric population is a rare condition. Despite its severe outcomes—including long-term neurological deficits and mortality— diagnosis of pediatric AIS is often delayed. In contrast to adult AIS, evidence-based guidelines for the pediatric population are limited, primarily due to the absence of data from multicenter randomized clinical trials.
Aim: This review aims to present a comprehensive overview of the treatment methods of AIS in children, focusing on thrombolysis, mechanical thrombectomy, and supportive neuroprotective strategies.
Material and Methods: An in-depth literature review was performed using PubMed, ScienceDirect, and Google Scholar, including keywords such as: “pediatric acute ischemic stroke”, “PAIS”, “acute ischemic stroke in children”, “acute ischemic stroke management”, “tenecteplase”, “thrombolysis in children”
Results: Intravenous thrombolysis with alteplase (0.9 mg/kg) may be considered in children ≥2 years of age within 4.5 hours of symptom onset, although data are still limited due to poor patient enrollment in the Thrombolysis in Pediatric Stroke Study (TIPS). Mechanical thrombectomy may be effective, even beyond the 6-hour window, particularly in cases involving large-vessel occlusion. Neuroprotective measures—such as glucose, temperature, and blood pressure control—may contribute to improved outcomes. For secondary prevention, antiplatelet or anticoagulant therapy is recommended.
Conclusions: Management of AIS in children still relies on extrapolated adult data. There is an urgent need for pediatric-specific clinical trials to establish evidence-based treatment protocols and guidelines. In the meantime, early diagnosis, reperfusion strategies, and supportive neuroprotective measures appear to be critical.
References
Abend, N. S., Beslow, L. A., Smith, S. E., Kessler, S. K., Vossough, A., Mason, S., Agner, S., Licht, D. J., & Ichord, R. N. (2011). Seizures as a presenting symptom of acute arterial ischemic stroke in childhood. J Pediatr, 159(3), 479–483. https://doi.org/10.1016/j.jpeds.2011.02.004
Adil, M. M., Beslow, L. A., Qureshi, A. I., Malik, A. A., & Jordan, L. C. (2016). Hypertension is Associated With Increased Mortality in Children Hospitalized With Arterial Ischemic Stroke. Pediatr Neurol, 56, 25–29. https://doi.org/10.1016/j.pediatrneurol.2015.11.002
Alexandrov, A. W., Tsivgoulis, G., Hill, M. D., Liebeskind, D. S., Schellinger, P., Ovbiagele, B., Arthur, A. S., Caso, V., Nogueira, R. G., Hemphill, J. C., 3rd, Grotta, J. C., Hacke, W., & Alexandrov, A. V. (2018). HeadPoST: Rightly positioned, or flat out wrong? Neurology, 90(19), 885–889. https://doi.org/10.1212/WNL.0000000000005481
Amlie-Lefond, C., & Wainwright, M. S. (2019). Organizing for Acute Arterial Ischemic Stroke in Children. Stroke, 50(12), 3662–3668. https://doi.org/10.1161/STROKEAHA.119.025497
Busto, R., Globus, M. Y., Neary, J. T., & Ginsberg, M. D. (1994). Regional alterations of protein kinase C activity following transient cerebral ischemia: effects of intraischemic brain temperature modulation. J Neurochem, 63(3), 1095–1103. https://doi.org/10.1046/j.1471-4159.1994.63031095.x
Capes, S. E., Hunt, D., Malmberg, K., Pathak, P., & Gerstein, H. C. (2001). Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke, 32(10), 2426–2432. https://doi.org/10.1161/hs1001.096194
Carlhan-Ledermann, A., Bartoli, A., Gebistorf, F., Beghetti, M., Sologashvili, T., Rebollo Polo, M., & Fluss, J. (2023). Decompressive hemicraniectomy in pediatric malignant arterial ischemic stroke: a case-based review. Childs Nerv Syst, 39(9), 2377–2389. https://doi.org/10.1007/s00381-023-06086-w
Castillo, J., Davalos, A., & Noya, M. (1999). Aggravation of acute ischemic stroke by hyperthermia is related to an excitotoxic mechanism. Cerebrovasc Dis, 9(1), 22–27. https://doi.org/10.1159/000015891
Chabrier, S., Ozanne, A., Naggara, O., Boulouis, G., Husson, B., & Kossorotoff, M. (2021). Hyperacute Recanalization Strategies and Childhood Stroke in the Evidence Age. Stroke, 52(1), 381–384. https://doi.org/10.1161/STROKEAHA.120.031133
Chadehumbe, M. A., Khatri, P., Khoury, J. C., Alwell, K., Szaflarski, J. P., Broderick, J. P., Kissela, B. M., & Kleindorfer, D. O. (2009). Seizures are common in the acute setting of childhood stroke: a population-based study. J Child Neurol, 24(1), 9–12. https://doi.org/10.1177/0883073808320756
Ferriero, D. M., Fullerton, H. J., Bernard, T. J., Billinghurst, L., Daniels, S. R., DeBaun, M. R., deVeber, G., Ichord, R. N., Jordan, L. C., Massicotte, P., Meldau, J., Roach, E. S., Smith, E. R., American Heart Association Stroke, C., Council on, C., & Stroke, N. (2019). Management of Stroke in Neonates and Children: A Scientific Statement From the American Heart Association/American Stroke Association. Stroke, 50(3), e51–e96. https://doi.org/10.1161/STR.0000000000000183
Fox, C. K., Glass, H. C., Sidney, S., Lowenstein, D. H., & Fullerton, H. J. (2013). Acute seizures predict epilepsy after childhood stroke. Ann Neurol, 74(2), 249–256. https://doi.org/10.1002/ana.23916
Fullerton, H. J., Chetkovich, D. M., Wu, Y. W., Smith, W. S., & Johnston, S. C. (2002). Deaths from stroke in US children, 1979 to 1998. Neurology, 59(1), 34–39. https://doi.org/10.1212/wnl.59.1.34
Fullerton, H. J., Wintermark, M., Hills, N. K., Dowling, M. M., Tan, M., Rafay, M. F., Elkind, M. S., Barkovich, A. J., deVeber, G. A., & Investigators, V. (2016). Risk of Recurrent Arterial Ischemic Stroke in Childhood: A Prospective International Study. Stroke, 47(1), 53–59. https://doi.org/10.1161/STROKEAHA.115.011173
Ganesan, V., Prengler, M., McShane, M. A., Wade, A. M., & Kirkham, F. J. (2003). Investigation of risk factors in children with arterial ischemic stroke. Ann Neurol, 53(2), 167–173. https://doi.org/10.1002/ana.10423
Globus, M. Y., Busto, R., Lin, B., Schnippering, H., & Ginsberg, M. D. (1995). Detection of free radical activity during transient global ischemia and recirculation: effects of intraischemic brain temperature modulation. J Neurochem, 65(3), 1250–1256. https://doi.org/10.1046/j.1471-4159.1995.65031250.x
He, L., Ladner, T. R., Pruthi, S., Day, M. A., Desai, A. A., Jordan, L. C., & Froehler, M. T. (2016). Rule of 5: angiographic diameters of cervicocerebral arteries in children and compatibility with adult neurointerventional devices. J Neurointerv Surg, 8(10), 1067–1071. https://doi.org/10.1136/neurintsurg-2015-012034
Hirtz, D., & Kirkham, F. J. (2019). Sickle Cell Disease and Stroke. Pediatr Neurol, 95, 34–41. https://doi.org/10.1016/j.pediatrneurol.2019.02.018
Ichord, R. N., Bastian, R., Abraham, L., Askalan, R., Benedict, S., Bernard, T. J., Beslow, L., Deveber, G., Dowling, M., Friedman, N., Fullerton, H., Jordan, L., Kan, L., Kirton, A., Amlie-Lefond, C., Licht, D., Lo, W., McClure, C., Pavlakis, S.,…Jawad, A. F. (2011). Interrater reliability of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) in a multicenter study. Stroke, 42(3), 613–617. https://doi.org/10.1161/STROKEAHA.110.607192
Ignjatovic, V., Pelkmans, L., Kelchtermans, H., Al Dieri, R., Hemker, C., Kremers, R., Bloemen, S., Karlaftis, V., Attard, C., de Laat, B., & Monagle, P. (2015). Differences in the mechanism of blood clot formation and nanostructure in infants and children compared with adults. Thromb Res, 136(6), 1303–1309. https://doi.org/10.1016/j.thromres.2015.10.034
Krishnamurthi, R. V., deVeber, G., Feigin, V. L., Barker-Collo, S., Fullerton, H., Mackay, M. T., O'Callahan, F., Lindsay, M. P., Kolk, A., Lo, W., Shah, P., Linds, A., Jones, K., Parmar, P., Taylor, S., Norrving, B., Mensah, G. A., Moran, A. E., Naghavi, M.,…Group, G. B. D. S. P. E. (2015). Stroke Prevalence, Mortality and Disability-Adjusted Life Years in Children and Youth Aged 0-19 Years: Data from the Global and Regional Burden of Stroke 2013. Neuroepidemiology, 45(3), 177–189. https://doi.org/10.1159/000441087
Laptook, A. R., & Corbett, R. J. (2002). The effects of temperature on hypoxic-ischemic brain injury. Clin Perinatol, 29(4), 623–649, vi. https://doi.org/10.1016/s0095-5108(02)00057-x
Lopez Alvarez, J. M., Perez Quevedo, O., Santana Cabrera, L., Escot, C. R., Loro Ferrer, J. F., Lorenzo, T. R., & Liminana Canal, J. M. (2017). Vascular ultrasound in pediatrics: estimation of depth and diameter of jugular and femoral vessels. J Ultrasound, 20(4), 285–292. https://doi.org/10.1007/s40477-017-0272-3
Mallick, A. A., Ganesan, V., Kirkham, F. J., Fallon, P., Hedderly, T., McShane, T., Parker, A. P., Wassmer, E., Wraige, E., Amin, S., Edwards, H. B., Tilling, K., & O'Callaghan, F. J. (2014). Childhood arterial ischaemic stroke incidence, presenting features, and risk factors: a prospective population-based study. Lancet Neurol, 13(1), 35–43. https://doi.org/10.1016/S1474-4422(13)70290-4
Martini, S. R., & Kent, T. A. (2007). Hyperglycemia in acute ischemic stroke: a vascular perspective. J Cereb Blood Flow Metab, 27(3), 435–451. https://doi.org/10.1038/sj.jcbfm.9600355
Mastrangelo, M., Giordo, L., Ricciardi, G., De Michele, M., Toni, D., & Leuzzi, V. (2022). Acute ischemic stroke in childhood: a comprehensive review. Eur J Pediatr, 181(1), 45–58. https://doi.org/10.1007/s00431-021-04212-x
Mazdeh, M., Abolfathi, P., Sabetghadam, M., Mohammadi, Y., & Mehrpooya, M. (2022). Clinical Evidence of Acetyl-L-Carnitine Efficacy in the Treatment of Acute Ischemic Stroke: A Pilot Clinical Trial. Oxid Med Cell Longev, 2022, 2493053. https://doi.org/10.1155/2022/2493053
Medley, T. L., Miteff, C., Andrews, I., Ware, T., Cheung, M., Monagle, P., Mandelstam, S., Wray, A., Pridmore, C., Troedson, C., Dale, R. C., Fahey, M., Sinclair, A., Walsh, P., Stojanovski, B., & Mackay, M. T. (2019). Australian Clinical Consensus Guideline: The diagnosis and acute management of childhood stroke. Int J Stroke, 14(1), 94–106. https://doi.org/10.1177/1747493018799958
Morimoto, T., Ginsberg, M. D., Dietrich, W. D., & Zhao, W. (1997). Hyperthermia enhances spectrin breakdown in transient focal cerebral ischemia. Brain Res, 746(1-2), 43–51. https://doi.org/10.1016/s0006-8993(96)01154-7
Parmar, N., Albisetti, M., Berry, L. R., & Chan, A. K. (2006). The fibrinolytic system in newborns and children. Clin Lab, 52(3-4), 115–124.
Pero, G., Ruggieri, F., Macera, A., Piano, M., Gladin, C. R., Motto, C., Cervo, A., & Chieregato, A. (2023). Endovascular treatment of acute ischemic stroke in childhood: A comprehensive literature review based on the experience of a single center. Eur J Radiol Open, 11, 100528. https://doi.org/10.1016/j.ejro.2023.100528
Pilarska, E., Kopyta, I., Szurowska, E., Radon-Proskura, J., Irga-Jaworska, N., Kozera, G., Sabiniewicz, R., Emich-Widera, E., & Wojczal, J. (2023). Polish recommendations for diagnosis and therapy of paediatric stroke. Neurol Neurochir Pol, 57(3), 243–260. https://doi.org/10.5603/PJNNS.a2023.0034
Rivkin, M. J., Bernard, T. J., Dowling, M. M., & Amlie-Lefond, C. (2016). Guidelines for Urgent Management of Stroke in Children. Pediatr Neurol, 56, 8–17. https://doi.org/10.1016/j.pediatrneurol.2016.01.016
Rivkin, M. J., deVeber, G., Ichord, R. N., Kirton, A., Chan, A. K., Hovinga, C. A., Gill, J. C., Szabo, A., Hill, M. D., Scholz, K., & Amlie-Lefond, C. (2015). Thrombolysis in pediatric stroke study. Stroke, 46(3), 880–885. https://doi.org/10.1161/STROKEAHA.114.008210
Saini, M., Saqqur, M., Kamruzzaman, A., Lees, K. R., Shuaib, A., & Investigators, V. (2009). Effect of hyperthermia on prognosis after acute ischemic stroke. Stroke, 40(9), 3051–3059. https://doi.org/10.1161/STROKEAHA.109.556134
Sporns, P. B., Bhatia, K., Abruzzo, T., Pabst, L., Fraser, S., Chung, M. G., Lo, W., Othman, A., Steinmetz, S., Jensen-Kondering, U., Schob, S., Kaiser, D. P. O., Marik, W., Wendl, C., Kleffner, I., Henkes, H., Kraehling, H., Nguyen-Kim, T. D. L., Chapot, R.,…Wildgruber, M. (2024). Endovascular thrombectomy for childhood stroke (Save ChildS Pro): an international, multicentre, prospective registry study. Lancet Child Adolesc Health, 8(12), 882–890. https://doi.org/10.1016/S2352-4642(24)00233-5
Sporns, P. B., Fullerton, H. J., Lee, S., Kirton, A., & Wildgruber, M. (2021). Current treatment for childhood arterial ischaemic stroke. Lancet Child Adolesc Health, 5(11), 825–836. https://doi.org/10.1016/S2352-4642(21)00167-X
Sporns, P. B., Psychogios, M. N., Straeter, R., Hanning, U., Minnerup, J., Chapot, R., Henkes, H., Henkes, E., Grams, A., Dorn, F., Nikoubashman, O., Wiesmann, M., Bier, G., Weber, A., Broocks, G., Fiehler, J., Brehm, A., Kaiser, D., Yilmaz, U.,…Save Child, S. I. (2021). Clinical Diffusion Mismatch to Select Pediatric Patients for Embolectomy 6 to 24 Hours After Stroke: An Analysis of the Save ChildS Study. Neurology, 96(3), e343–e351. https://doi.org/10.1212/WNL.0000000000011107
Sporns, P. B., Straeter, R., Minnerup, J., Wiendl, H., Hanning, U., Chapot, R., Henkes, H., Henkes, E., Grams, A., Dorn, F., Nikoubashman, O., Wiesmann, M., Bier, G., Weber, A., Broocks, G., Fiehler, J., Brehm, A., Psychogios, M., Kaiser, D.,…Save Child, S. I. (2020). Does Device Selection Impact Recanalization Rate and Neurological Outcome?: An Analysis of the Save ChildS Study. Stroke, 51(4), 1182–1189. https://doi.org/10.1161/STROKEAHA.119.028221
Sun, L. R., & Lynch, J. K. (2023). Advances in the Diagnosis and Treatment of Pediatric Arterial Ischemic Stroke. Neurotherapeutics, 20(3), 633–654. https://doi.org/10.1007/s13311-023-01373-5
Sun, L. R., Wilson, J. L., Waak, M., Kiskaddon, A., Goldenberg, N. A., Jordan, L. C., & Barry, M. (2023). Tenecteplase in Acute Stroke: What About the Children? Stroke, 54(7), 1950–1953. https://doi.org/10.1161/STROKEAHA.123.042951
Sund-Levander, M., Forsberg, C., & Wahren, L. K. (2002). Normal oral, rectal, tympanic and axillary body temperature in adult men and women: a systematic literature review. Scand J Caring Sci, 16(2), 122–128. https://doi.org/10.1046/j.1471-6712.2002.00069.x
Tsze, D. S., & Valente, J. H. (2011). Pediatric stroke: a review. Emerg Med Int, 2011, 734506. https://doi.org/10.1155/2011/734506
Uohara, M. Y., Beslow, L. A., Billinghurst, L., Jones, B. M., Kessler, S. K., Licht, D. J., & Ichord, R. N. (2017). Incidence of Recurrence in Posterior Circulation Childhood Arterial Ischemic Stroke. JAMA Neurol, 74(3), 316–323. https://doi.org/10.1001/jamaneurol.2016.5166
Vinayan, K. P., Nambiar, V., & Anand, V. (2022). Acute Ischemic Stroke in Children - Should We Thrombolyze? Ann Indian Acad Neurol, 25(1), 21–25. https://doi.org/10.4103/aian.aian_527_21
Wang, L., Hao, M., Wu, N., Wu, S., Fisher, M., & Xiong, Y. (2024). Comprehensive Review of Tenecteplase for Thrombolysis in Acute Ischemic Stroke. J Am Heart Assoc, 13(9), e031692. https://doi.org/10.1161/JAHA.123.031692
Wintermark, M., Hills, N. K., DeVeber, G. A., Barkovich, A. J., Bernard, T. J., Friedman, N. R., Mackay, M. T., Kirton, A., Zhu, G., Leiva-Salinas, C., Hou, Q., Fullerton, H. J., & Investigators, V. (2017). Clinical and Imaging Characteristics of Arteriopathy Subtypes in Children with Arterial Ischemic Stroke: Results of the VIPS Study. AJNR Am J Neuroradiol, 38(11), 2172–2179. https://doi.org/10.3174/ajnr.A5376
Yock-Corrales, A., Mackay, M. T., Mosley, I., Maixner, W., & Babl, F. E. (2011). Acute childhood arterial ischemic and hemorrhagic stroke in the emergency department. Ann Emerg Med, 58(2), 156–163. https://doi.org/10.1016/j.annemergmed.2010.10.013
Zimmer, J. A., Garg, B. P., Williams, L. S., & Golomb, M. R. (2007). Age-related variation in presenting signs of childhood arterial ischemic stroke. Pediatr Neurol, 37(3), 171–175. https://doi.org/10.1016/j.pediatrneurol.2007.05.010
Views:
69
Downloads:
18
Copyright (c) 2025 Edyta Szymańska, Adrianna Maria Mikołajczyk, Patryk Pustuła, Anna Maria Pietrzak, Julia Prabucka-Marciniak, Joanna Kaszczewska, Zuzanna Natalia Burkacka, Kacper Konrad Kmieć, Zofia Szypuła, Wiktoria Garbacz, Hanna Eve Feder
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
