Abstract
Introduction: Ischemic stroke represents a major public health challenge due to its high burden of disability and mortality. Advances in neuroimaging and reperfusion therapies have transformed its management in the acute phase.
Materials and methods: A literature search was conducted in databases (PubMed, EMBASE, LILACS, SCOPUS) from 2008 to November of 2025. Sources addressing advanced neuroimaging and new indications for reperfusion therapies in the extended window were selected, aiming to synthesize the information for easy reading and to provide an updated review based on the latest available evidence.
Results: Advanced neuroimaging enables individualized therapeutic decisions by focusing on tissue time rather than chronological time. Increasingly broader criteria are being proposed for selecting candidates for reperfusion therapies.
Discussion: The latest evidence is shifting the paradigm of acute stroke treatment, allowing for an extended therapeutic window and increasing the number of patients who can benefit from intervention, with the goal of reducing mortality and disability associated with this condition.
Conclusions: The management of acute ischemic stroke has evolved significantly in recent years. New pharmacological and endovascular therapies are offering improved outcomes, even in patients with large infarcts and longer time windows.
References
Ministerio de Salud y Protección Social. Mujeres: las más afectadas por accidente cerebrovascular ACV en Colombia, según cifras del Ministerio de Salud y Protección Social [internet]. Colombia: Minsalud; 2024. [citado 2025 Jun 29]. https://www.minsalud.gov.co/Paginas/mujeres-las-mas-afectadas-por-accidente-cerebrovascular-en-colombia.aspx
García Alfonso C, Martínez Reyes AE, García V, Ricaurte-Fajardo A, Torres I, Coral J. Actualización en diagnóstico y tratamiento del ataque cerebrovascular isquémico agudo. Univ Med. 2019;60(3). http://dx.doi.org/10.11144/javeriana.umed60-3.actu
Khawar H, McFarlane S, Libman RB. Stroke mimics at 30 years: where we have been, where we are now, and where we are going. Stroke. 2025;56(4):1061-8. https://doi.org/10.1161/strokeaha.124.048067
Vilela P, Rowley HA. Brain ischemia: CT and MRI techniques in acute ischemic stroke. Eur J Radiol. 2017;96:162-72. https://doi.org/10.1016/j.ejrad.2017.08.014
Shulman JG, Abdalkader M. Imaging of central nervous system ischemia. Continuum. 2023;29(1):54-72. https://doi.org/10.1212/con.0000000000001185
van Poppel LM, Majoie CBLM, Marquering HA, Emmer BJ. Associations between early ischemic signs on non-contrast CT and time since acute ischemic stroke onset: a scoping review. Eur J Radiol. 2022;155:110455. https://doi.org/10.1016/j.ejrad.2022.110455
Barber PA, Demchuk AM, Zhang J, Buchan AM. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. Lancet. 2000;355(9216):1670-4. https://doi.org/10.1016/s0140-6736(00)02237-6
Hill MD, Rowley HA, Adler F, Eliasziw M, Furlan A, Higashida RT, et al. Selection of acute ischemic stroke patients for intra-arterial thrombolysis with pro-urokinase by using ASPECTS. Stroke. 2003;34(8):1925-31. https://doi.org/10.1161/01.str.0000082483.37127.d0
Schellinger PD, Bryan RN, Caplan LR, Detre JA, Edelman RR, Jaigobin C, et al. Evidence-based guideline: the role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2010;75(2):177-85. https://doi.org/10.1212/wnl.0b013e3181e7c9dd
Makin SD, Doubal FN, Dennis MS, Wardlaw JM. Clinically confirmed stroke with negative diffusion-weighted imaging magnetic resonance imaging: Longitudinal study of clinical outcomes, stroke recurrence, and systematic review. Stroke. 2015;46(11):3142-8. https://doi.org/10.1161/STROKEAHA.115.010665
Allen LM, Hasso AN, Handwerker J, Farid H. Sequence-specific MR imaging findings that are useful in dating ischemic stroke. Radiographics. 2012;32(5):1285-97. https://doi.org/10.1148/rg.325115760
Alkhiri A, Alturki F, Alansari NM, Almaghrabi AA, Alghamdi BA, Alamri AF, et al. Prognosis and distribution of ischemic stroke with negative diffusion-weighted imaging: a systematic review and meta-analysis. Front Neurol. 2024;15:1376439. https://doi.org/10.3389/fneur.2024.1376439
Dundamadappa S, Iyer K, Agrawal A, Choi DJ. Multiphase CT angiography: a useful technique in acute stroke imaging-collaterals and beyond. AJNR Am J Neuroradiol. 2021;42(2):221-7. https://doi.org/10.3174/ajnr.a6889
García-Tornel A, Carvalho V, Boned S, Flores A, Rodríguez-Luna D, Pagola J, et al. Improving the evaluation of collateral circulation by multiphase computed tomography angiography in acute stroke patients treated with endovascular reperfusion therapies. Interv Neurol. 2016;5(3-4):209-17. https://doi.org/10.1159/000448525
Campbell BCV, Weir L, Desmond PM, Tu HTH, Hand PJ, Yan B, et al. CT perfusion improves diagnostic accuracy and confidence in acute ischaemic stroke. J Neurol Neurosurg Psychiatry. 2013;84(6):613-8. https://doi.org/10.1136/jnnp-2012-303752
Demeestere J, Wouters A, Christensen S, Lemmens R, Lansberg MG. Review of perfusion imaging in acute ischemic stroke: from time to tissue. Stroke. 2020;51(3):1017-24. https://doi.org/10.1161/strokeaha.119.028337
Christensen S, Lansberg MG. CT perfusion in acute stroke: practical guidance for implementation in clinical practice. J Cereb Blood Flow Metab. 2019;39(9):1664-8. https://doi.org/10.1177/0271678x18805590
Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-29. https://doi.org/10.1056/nejmoa0804656
Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med. 2019;380(19):1795-803. https://doi.org/10.1056/nejmoa1813046
Campbell BCV, Ma H, Ringleb PA, Parsons MW, Churilov L, Bendszus M, et al. Extending thrombolysis to 4·5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data. Lancet. 2019;394(10193):139-47. https://doi.org/10.1016/s0140-6736(19)31053-0
Zhou Y, He Y, Campbell BCV, Liebeskind DS, Yuan C, Chen H, et al. Alteplase for acute ischemic stroke at 4.5 to 24 hours: the HOPE randomized clinical trial. JAMA 2025;334:788-97. https://doi.org/10.1001/jama.2025.12063
Menon BK, Buck BH, Singh N, Deschaintre Y, Almekhlafi MA, Coutts SB, et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. Lancet. 2022;400(10347):161-9. https://doi.org/10.1016/s0140-6736(22)01054-6
Wang Y, Li S, Pan Y, Li H, Parsons MW, Campbell BCV, et al. Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial. Lancet. 2023;401(10377):645-54. https://doi.org/10.1016/s0140-6736(22)02600-9
Muir KW, Ford GA, Ford I, Wardlaw JM, McConnachie A, Greenlaw N, et al. Tenecteplase versus alteplase for acute stroke within 4·5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial. Lancet Neurol. 2024;23(11):1087-96. https://doi.org/10.1016/s1474-4422(24)00377-6
Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2018;378(17):1573-82. https://doi.org/10.1056/nejmoa1716405
Gerschenfeld G, Liegey JS, Laborne FX, Yger M, Lyon V, Checkouri T, et al. Treatment times, functional outcome, and hemorrhage rates after switching to tenecteplase for stroke thrombolysis: Insights from the TETRIS registry. Eur Stroke J 2022;7(4):358-64. https://doi.org/10.1177/23969873221113729
Qiu Z, Li F, Sang H, Yuan G, Xie D, Zhou K, et al. Intravenous tenecteplase before thrombectomy in stroke. N Engl J Med. 2025;393(2):139-50. https://doi.org/10.1056/nejmoa2503867
Yogendrakumar V, Campbell BCV, Churilov L, Garcia-Esperon C, Choi PMC, Cordato DJ, et al. Efficacy of tenecteplase in large vessel occlusion stroke within 24 hours of symptom onset: the ETERNAL-LVO randomized controlled trial. Stroke 2025;56(12):3332-41. https://doi.org/10.1161/strokeaha.125.052511
Albers GW, Jumaa M, Purdon B, Zaidi SF, Streib C, Shuaib A, et al. TIMELESS Investigators. Tenecteplase for stroke at 4.5 to 24 hours with perfusion-imaging selection. N Engl J Med. 2024;390(8):701-11. https://doi.org/10.1056/nejmoa2310392
Xiong Y, Campbell BCV, Schwamm LH, Meng X, Jin A, Parsons MW, et al. Tenecteplase for ischemic stroke at 4.5 to 24 hours without thrombectomy. N Engl J Med. 2024;391(3):203-12. https://doi.org/10.1056/nejmoa2402980
Cheng X, Hong L, Lin L, Churilov L, Ling Y, Yang N, et al. Tenecteplase thrombolysis for stroke up to 24 hours after onset with perfusion imaging selection: the CHABLIS-T II randomized clinical trial. Stroke. 2025;56(2):344-54. https://doi.org/10.1161/strokeaha.124.048375
Wang Z, Li J, Wang X, Yuan B, Li J, Ma Q. Tenecteplase for acute ischemic stroke at 4.5 to 24 hours: a meta-analysis of randomized controlled trials. Stroke. 2025;57(1):50-62. https://doi.org/10.1161/strokeaha.125.053256
Strbian D, Tsivgoulis G, Ospel J, Räty S, Cimflova P, Georgiopoulos G, et al. European Stroke Organisation and European Society for Minimally Invasive Neurological Therapy guideline on acute management of basilar artery occlusion. J Neurointerv Surg. 2024;16(9):e7. https://doi.org/10.1136/jnis-2024-022053
Gonzalez F, Albuquerque FC, McDougall CG, editores. Neurointerventional techniques: tricks of the trade. Nueva York, Estados Unidos: Thieme Medical; 2025.
Marks MP, Lansberg MG, Mlynash M, Kemp S, McTaggart R, Zaharchuk G, et al. Correlation of AOL recanalization, TIMI reperfusion and TICI reperfusion with infarct growth and clinical outcome. J Neurointerv Surg. 2014;6(10):724-8. https://doi.org/10.1136/neurintsurg-2013-010973
Berkhemer OA, Fransen PSS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11-20. https://doi.org/10.1056/nejmoa1411587
Vela-Duarte D, Spelle L. LINNC Trials Book. Francia: LINNC; 2025.
Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015;372(24):2296-306. https://doi.org/10.1056/nejmoa1503780
Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al. Stent-retriever thrombectomy after intravenous t-PA vs. T-PA alone in stroke. N Engl J Med. 2015;372(24):2285-95. https://doi.org/10.1056/nejmoa1415061
Vela-Duarte D, Spelle L. LINNC Trials Book. Francia: LINNC; 2024.
Goyal M, Menon BK, van Zwam WH, Dippel DWJ, Mitchell PJ, Demchuk AM, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723-31. https://doi.org/10.1016/s0140-6736(16)00163-x
Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378(1):11-21. https://doi.org/10.1056/nejmoa1706442
Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378(8):708-18. https://doi.org/10.1056/nejmoa1713973
Olthuis SGH, Pirson FAV, Pinckaers FME, Hinsenveld WH, Nieboer D, Ceulemans A, et al. Endovascular treatment versus no endovascular treatment after 6-24 h in patients with ischaemic stroke and collateral flow on CT angiography (MR CLEAN-LATE) in the Netherlands: a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial. Lancet. 2023;401(10385):1371-80. https://doi.org/10.1016/s0140-6736(23)00575-5
Langezaal LCM, van der Hoeven EJRJ, Mont’Alverne FJA, de Carvalho JJF, Lima FO, Dippel DWJ, et al. Endovascular therapy for stroke due to basilar-artery occlusion. N Engl J Med. 2021;384(20):1910-20. https://doi.org/10.1056/nejmoa2030297
Liu X, Dai Q, Ye R, Zi W, Liu Y, Wang H, et al. Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial. Lancet Neurol. 2020;19(2):115-22. https://doi.org/10.1016/s1474-4422(19)30395-3
Jovin TG, Li C, Wu L, Wu C, Chen J, Jiang C, et al. Trial of thrombectomy 6 to 24 hours after stroke due to basilar-artery occlusion. N Engl J Med. 2022;387(15):1373-84. https://doi.org/10.1056/nejmoa2207576
Tao C, Nogueira RG, Zhu Y, Sun J, Han H, Yuan G, et al. Trial of endovascular treatment of acute basilar-artery occlusion. N Engl J Med 2022;387(15):1361-72. https://doi.org/10.1056/nejmoa2206317
Nogueira RG, Jovin TG, Liu X, Hu W, Langezaal LCM, Li C, et al. Endovascular therapy for acute vertebrobasilar occlusion (VERITAS): a systematic review and individual patient data meta-analysis. Lancet. 2025;405(10472):61-9. https://doi.org/10.1016/s0140-6736(24)01820-8
Gonzalez NR, Khatri P, Albers GW, Dumitrascu OM, Goyal M, Leonard A, et al. Large-core ischemic stroke endovascular treatment: a science advisory from the American Heart Association. Stroke. 2025;56(2):e87-97. https://doi.org/10.1161/str.0000000000000481
Yoshimura S, Sakai N, Yamagami H, Uchida K, Beppu M, Toyoda K, et al. Endovascular therapy for acute stroke with a large ischemic region. N Engl J Med. 2022;386(14):1303-13. https://doi.org/10.1056/nejmoa2118191
Huo X, Ma G, Tong X, Zhang X, Pan Y, Nguyen TN, et al. Trial of endovascular therapy for acute ischemic stroke with large infarct. N Engl J Med. 2023;388(14):1272-83. https://doi.org/10.1056/nejmoa2213379
Sarraj A, Hassan AE, Abraham MG, Ortega-Gutierrez S, Kasner SE, Hussain MS, et al. Trial of endovascular thrombectomy for large ischemic strokes. N Engl J Med. 2023;388(14):1259-71. https://doi.org/10.1056/nejmoa2214403
Writing Committee for the TESLA Investigators, Yoo AJ, Zaidat OO, Sheth SA, Rai AT, Ortega-Gutierrez S, et al. Thrombectomy for stroke with large infarct on noncontrast CT: the TESLA randomized clinical trial. JAMA. 2024;332(16):1355-66. https://doi.org/10.1001/jama.2024.13933
Mokin M, Jovin TG, Sheth SA, Nguyen TN, Asif KS, Hassan AE, et al. Endovascular therapy in patients with acute ischemic stroke with large infarct: a guideline from the Society of Vascular and Interventional Neurology. Stroke Vasc Interv Neurol. 2025;5(2):e001581. https://doi.org/10.1161/svin.124.001581
Goldman D, Mehta A, Majidi S, De Leacy R. Thrombectomy for MeVO and DVO: the end of the road or just a detour? Stroke Vasc Interv Neurol. 2025;5(3):e001785. https://doi.org/10.1161/svin.125.001785
Clarençon F, Durand-Zaleski I, Premat K, Baptiste A, Chabert E, Ferrier A, et al. Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: a randomized controlled trial. Int J Stroke. 2024;19(3):367-72. https://doi.org/10.1177/17474930231205213
Goyal M, Ospel JM, Ganesh A, Dowlatshahi D, Volders D, Möhlenbruch MA, et al. Endovascular treatment of stroke due to medium-vessel occlusion. N Engl J Med. 2025;392(14):1385-95. https://doi.org/10.1056/nejmoa2411668
Psychogios M, Brehm A, Ribo M, Rizzo F, Strbian D, Räty S, et al. Endovascular treatment for stroke due to occlusion of medium or distal vessels. N Engl J Med. 2025;392(14):1374-84. https://doi.org/10.1056/nejmoa2408954
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