大动脉粥样硬化性缺血性卒中再灌注治疗的研究进展

doi:10.3969/j.issn.1673-5765.2024.09.004

摘要/Abstract

摘要： 急性缺血性卒中是一种严重威胁人类健康的疾病，其中大动脉粥样硬化性卒中症状更重，预后更差，再灌注治疗可有效改善这类患者的功能预后。近年来再灌注治疗技术发展迅速，但也面临一些挑战，如治疗时间窗内患者比例低、再灌注损伤、出血转化等。要解决这些问题，需要从多个层面采取对策，如优化急救流程、革新操作技术、加强损伤防护等。本文对大动脉粥样硬化性缺血性卒中再灌注治疗面临的挑战和对策进行了初步讨论。

文章导读： 本综述深入分析了大动脉粥样硬化性缺血性卒中再灌注治疗的时间窗、技术难度、再灌注损伤和出血风险等挑战，并针对性地提出了优化流程、改进技术、研发药物、精准治疗等策略，旨在提高再灌注治疗的有效性和安全性。

关键词: 缺血性卒中; 大动脉粥样硬化性卒中; 再灌注治疗; 现状

Abstract: Acute ischemic stroke is a serious disease that poses a significant threat to human health, with large artery atherosclerotic stroke having more severe symptoms and worse prognosis. Reperfusion therapy can effectively improve the functional outcomes of these patients. In recent years, reperfusion therapy techniques have developed rapidly, yet they also face challenges, such as a low proportion of patients within the treatment time window, reperfusion injury, and hemorrhagic transformation. Addressing these issues requires strategies from multiple aspects, including optimizing emergency procedures, innovating operational techniques, and enhancing injury protection. This article provided a preliminary discussion on the challenges and strategies of reperfusion therapy for large artery atherosclerotic ischemic stroke.

Key words: Ischemic stroke; Large artery atherosclerotic stroke; Reperfusion therapy; Current status

中图分类号:

符鹏程, 曹黎明, 朱佳倩, 赵桂玉, 徐格林. 大动脉粥样硬化性缺血性卒中再灌注治疗的研究进展[J]. 中国卒中杂志, 2024, 19(9): 1004-1011.

FU Pengcheng, CAO Liming, ZHU Jiaqian, ZHAO Guiyu, XU Gelin.

Research Progress of Reperfusion Therapy for Large Artery Atherosclerotic Ischemic Stroke [J]. Chinese Journal of Stroke, 2024, 19(9): 1004-1011.

参考文献

[1] GBD 2019 Stroke Collaborators. Global，regional，and national burden of stroke and its risk factors，1990—2019：a systematic analysis for the global burden of disease study 2019[J]. Lancet Neurol，2021，20（10）：795-820.

[2] 《中国脑卒中防治报告》编写组. 《中国脑卒中防治报告2020》概要[J]. 中国脑血管病杂志，2022，19（2）：136-144.

Report on Stroke Prevention and Treatment in China Writing Group. Brief report on stroke prevention and treatment in China，2020[J]. Chin J Cerebrovasc Dis，2022，19（2）：136-144.

[3] DERDEYN C P. Mechanisms of ischemic stroke secondary to large artery atherosclerotic disease[J]. Neuroimaging Clin N Am，2007，17（3）：303-311，Ⅶ-Ⅷ.

[4] MILLáN M，REMOLLO S，QUESADA H，et al. Vessel patency at 24 hours and its relationship with clinical outcomes and infarct volume in REVASCAT trial（randomized trial of revascularization with Solitaire FR device versus best medical therapy in the treatment of acute stroke due to anterior circulation large vessel occlusion presenting within eight hours of symptom onset）[J]. Stroke，2017，48（4）：983-989.

[5] HACKE W，KASTE M，FIESCHI C，et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European cooperative acute stroke study（ECASS）[J]. JAMA，1995，274（13）：1017-1025.

[6] HACKE W，DONNAN G，FIESCHI C，et al. Association of outcome with early stroke treatment：pooled analysis of ATLANTIS，ECASS，and NINDS rt-PA stroke trials[J]. Lancet，2004，363（9411）：768-774.

[7] LI S Y，GU H Q，LI H，et al. Reteplase versus alteplase for acute ischemic stroke[J]. N Engl J Med，2024，390（24）：2264-2273.

[8] HACKE W，KASTE M，BLUHMKI E，et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke[J]. N Engl J Med，2008，359（13）：1317-1329.

[9] BLUHMKI E，CHAMORRO A，DáVALOS A，et al. Stroke treatment with alteplase given 3.0-4.5 h after onset of acute ischaemic stroke（ECASS Ⅲ）：additional outcomes and subgroup analysis of a randomised controlled trial[J]. Lancet Neurol，2009，8（12）：1095-1102.

[10] MA H，CAMPBELL B C V，PARSONS M W，et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke[J]. N Engl J Med，2019，380（19）：1795-1803.

[11] XIONG Y Y，CAMPBELL B C V，SCHWAMM L H，et al. Tenecteplase for ischemic stroke at 4.5 to 24 hours without thrombectomy[J]. N Engl J Med，2024，391（3）：203-212.

[12] SAVER J L，GOYAL M，BONAFE A，et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke[J]. N Engl J Med，2015，372（24）：2285-2295.

[13] SAVER J L，GOYAL M，VAN DER LUGT A，et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke：a meta-analysis[J]. JAMA，2016，316（12）：1279-1288.

[14] YAGHI S，WILLEY J Z，CUCCHIARA B，et al. Treatment and outcome of hemorrhagic transformation after intravenous alteplase in acute ischemic stroke：a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association[J/OL]. Stroke，2017，48（12）：e343-e361[2024-06-01]. https://doi.org/10.1161/STR.0000000000000152.

[15] LOKESKRAWEE T，MUENGTAWEEPONGSA S，PATUMANOND J，et al. Prediction of symptomatic intracranial hemorrhage after intravenous thrombolysis in acute ischemic stroke：the symptomatic intracranial hemorrhage score[J]. J Stroke Cerebrovasc Dis，2017，26（11）：2622-2629.

[16] ZHANG X，JI X，LUO Y，et al. Intra-arterial thrombolysis for acute central retinal artery occlusion[J]. Neurol Res，2009，31（4）：385-389.

[17] UEDA T，SAKAKI S，NOCHIDE I，et al. Angioplasty after intra-arterial thrombolysis for acute occlusion of intracranial arteries[J]. Stroke，1998，29（12）：2568-2574.

[18] FURLAN A，HIGASHIDA R，WECHSLER L，et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT Ⅱ study：a randomized controlled trial. Prolyse in acute cerebral thromboembolism[J]. JAMA，1999，282（21）：2003-2011.

[19] LINDSBERG P J，MATTLE H P. Therapy of basilar artery occlusion：a systematic analysis comparing intra-arterial and intravenous thrombolysis[J]. Stroke，2006，37（3）：922-928.

[20] POWERS W J，DERDEYN C P，BILLER J，et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment：a guideline for healthcare professionals from the American Heart Association/American Stroke Association[J]. Stroke，2015，46（10）：3020-3035.

[21] GOYAL M，DEMCHUK A M，MENON B K，et al. Randomized assessment of rapid endovascular treatment of ischemic stroke[J]. N Engl J Med，2015，372（11）：1019-1030.

[22] GOYAL M，MENON B K，VAN ZWAM W H，et al. Endovascular thrombectomy after large-vessel ischaemic stroke：a meta-analysis of individual patient data from five randomised trials[J]. Lancet，2016，387（10029）：1723-1731.

[23] BERKHEMER O A，FRANSEN P S S，BEUMER D，et al. A randomized trial of intraarterial treatment for acute ischemic stroke[J]. N Engl J Med，2015，372（1）：11-20.

[24] ALBERS G W，MARKS M P，KEMP S，et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging[J]. N Engl J Med，2018，378（8）：708-718.

[25] NOGUEIRA R G，JADHAV A P，HAUSSEN D C，et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct[J]. N Engl J Med，2018，378（1）：11-21.

[26] RABINSTEIN A A. Update on treatment of acute ischemic stroke[J]. Continuum（Minneap Minn），2020，26（2）：268-286.

[27] OSPEL J M，QIU W，MENON B K，et al. Radiologic patterns of intracranial hemorrhage and clinical outcome after endovascular treatment in acute ischemic stroke：results from the ESCAPE-NA1 trial[J]. Radiology，2021，300（2）：402-409.

[28] TURK A S，3rd，SIDDIQUI A，FIFI J T，et al. Aspiration thrombectomy versus stent retriever thrombectomy as first-line approach for large vessel occlusion（COMPASS）：a multicentre，randomised，open label，blinded outcome，non-inferiority trial[J]. Lancet，2019，393（10175）：998-1008.

[29] KRISHNAN R，MAYS W，ELIJOVICH L. Complications of mechanical thrombectomy in acute ischemic stroke[J/OL]. Neurology，2021，97（20 Suppl 2）：S115-S125[2024-06-01]. https://doi.org/10.1212/WNL.0000000000012803.

[30] GUMBINGER C，GRUSCHKA P，BÖTTINGER M，et al. Improved prediction of poor outcome after thrombolysis using conservative definitions of symptomatic hemorrhage[J]. Stroke，2012，43（1）：240-242.

[31] ABOU-CHEBL A，LIN R，HUSSAIN M S，et al. Conscious sedation versus general anesthesia during endovascular therapy for acute anterior circulation stroke：preliminary results from a retrospective，multicenter study[J]. Stroke，2010，41（6）：1175-1179.

[32] PRABHAKARAN S，RUFF I，BERNSTEIN R A. Acute stroke intervention：a systematic review[J]. JAMA，2015，313（14）：1451-1462.

[33] MAZIGHI M，MESEGUER E，LABREUCHE J，et al. Bridging therapy in acute ischemic stroke：a systematic review and meta-analysis[J]. Stroke，2012，43（5）：1302-1308.

[34] JI X Y，SONG B，ZHU H，et al. A study on endovascular treatment alone and bridging treatment for acute ischemic stroke[J/OL]. Eur J Med Res，2023，28（1）：12[2024-06-01]. https://doi.org/10.1186/s40001-022-00966-8.

[35] ZHANG J，CHEN S J，SHI S L，et al. Direct endovascular treatment versus bridging therapy in patients with acute ischemic stroke eligible for intravenous thrombolysis：systematic review and meta-analysis[J]. J Neurointerv Surg，2022，14（4）：321-325.

[36] MITCHELL P J，YAN B，CHURILOV L，et al. Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4.5 h of stroke onset：an open-label，blinded-endpoint，randomised non-inferiority trial[J]. Lancet，2022，400（10346）：116-125.

[37] CAMPBELL B C，MITCHELL P J，KLEINIG T J，et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection[J]. N Engl J Med，2015，372（11）：1009-1018.

[38] POWERS W J，RABINSTEIN A A，ACKERSON T，et al. Guidelines for the early management of patients with acute ischemic stroke：2019 update to the 2018 guidelines for the early management of acute ischemic stroke：a guideline for healthcare professionals from the American Heart Association/American Stroke Association[J/OL]. Stroke，2019，50（12）：e344-e418[2024-06-01]. https://doi.org/10.1161/STR.0000000000000211.

[39] FASSBENDER K，BALUCANI C，WALTER S，et al. Streamlining of prehospital stroke management：the golden hour[J]. Lancet Neurol，2013，12（6）：585-596.

[40] GU H Q，RAO Z Z，YANG X，et al. Use of emergency medical services and timely treatment among ischemic stroke[J]. Stroke，2019，50（4）：1013-1016.

[41] LIN C B，PETERSON E D，SMITH E E，et al. Emergency medical service hospital prenotification is associated with improved evaluation and treatment of acute ischemic stroke[J]. Circ Cardiovasc Qual Outcomes，2012，5（4）：514-522.

[42] CACERES J A，ADIL M M，JADHAV V，et al. Diagnosis of stroke by emergency medical dispatchers and its impact on the prehospital care of patients [J/OL]. J Stroke Cerebrovasc Dis，2013，22（8）：e610-e614[2024-06-01]. https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.07.039.

[43] GAO Z H，YANG L，WANG L，et al. Identification and analysis of key risk factors for prehospital delay in patients with stroke[J/OL]. Int Emerg Nurs，2022，62：101156[2024-06-01]. https://doi.org/10.1016/j.ienj.2022.101156.

[44] ZHANG H，ZHANG B，CHEN J. The application of the emergency green channel integrated management strategy in intravenous thrombolytic therapy for AIS[J]. Am J Transl Res，2021，13（6）：7132-7139.

[45] FAIZ K W，SUNDSETH A，THOMMESSEN B，et al. Prehospital delay in acute stroke and TIA[J]. Emerg Med J，2013，30（8）：669-674.

[46] LUO Z Y，ZHOU Y，HE Y D，et al. Treatment with intravenous alteplase in ischaemic stroke patients with onset time between 4.5 and 24 hours（HOPE）：protocol for a randomised，controlled，multicentre study[J]. Stroke Vasc Neurol，2024，9（3）：318-323.

[47] CAMPBELL B C V，MITCHELL P J，CHURILOV L，et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke[J]. N Engl J Med，2018，378（17）：1573-1582.

[48] LI Y，LI Y J，CHEN H S. The effect of ultrasound-assisted thrombolysis studied in blood-on-a-chip[J]. Artif Organs，2024，48（7）：734-742.

[49] MIJAJLOVIC M D，PAVLOVIC A M，COVICKOVIC-STERNIC N. Is sonothrombolysis an effective stroke treatment？[J]. J Ultrasound Med，2013，32（7）：1117-1123.

[50] SMITH W S，SUNG G，STARKMAN S，et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke：results of the MERCI trial[J]. Stroke，2005，36（7）：1432-1438.

[51] XIONG X Y，LIU L，YANG Q W. Refocusing neuroprotection in cerebral reperfusion era：new challenges and strategies[J/OL]. Front Neurol，2018，9：249[2024-06-01]. https://doi.org/10.3389/fneur.2018.00249.

[52] LIU L P，YENARI M A. Therapeutic hypothermia：neuroprotective mechanisms[J/OL]. Front Biosci，2007，12：816-825[2024-06-01]. https://doi.org/10.2741/2104.

[53] CHEN H S，CUI Y，LI X Q，et al. Effect of remote ischemic conditioning vs. usual care on neurologic function in patients with acute moderate ischemic stroke：the RICAMIS randomized clinical trial[J]. JAMA，2022，328（7）：627-636.

[54] NG F C，CAMPBELL B C V. Imaging after thrombolysis and thrombectomy：rationale，modalities and management implications[J/OL]. Curr Neurol Neurosci Rep，2019，19（8）：57[2024-06-01]. https://doi.org/10.1007/s11910-019-0970-7.

[55] MORRIS D C. Thrombolysis 3 to 4.5 hours after acute ischemic stroke[J]. N Engl J Med，2008，359（26）：2841.

[56] OLIVEIRA R，CORREIA M A，MARTO J P，et al. Reocclusion after successful endovascular treatment in acute ischemic stroke：systematic review and meta-analysis[J]. J Neurointerv Surg，2023，15（10）：964-970.

[57] MOSIMANN P J，KAESMACHER J，GAUTSCHI D，et al. Predictors of unexpected early reocclusion after successful mechanical thrombectomy in acute ischemic stroke patients[J]. Stroke，2018，49（11）：2643-2651.

[58] KOGE J，TANAKA K，YOSHIMOTO T，et al. Early recurrent ischemic events after mechanical thrombectomy：effect of post-treatment intracranial hemorrhage[J]. J Neurol，2021，268（8）：2810-2820.

[59] 孙原，石秋艳，李艳玲，等. 替罗非班治疗阿替普酶静脉溶栓后再闭塞的疗效观察[J]. 中国实用神经疾病杂志，2018，21（1）：40-43.

SUN Y，SHI Q Y，LI Y L，et al. Observation of the clinical effect of tirofiban treatment in patients with early reocclusion after alteplase intravenous throm bolysis of acute ischemic stroke[J]. Chinese Journal of Practical Nervous Disease，2018，21（1）：40-43.

[60] SADEH-GONIK U，TAU N，FRIEHMANN T，et al. Thrombectomy outcomes for acute stroke patients with anterior circulation tandem lesions：a clinical registry and an update of a systematic review with meta-analysis[J]. Eur J Neurol，2018，25（4）：693-700.

[61] MACKEY J，KHATRI P，BRODERICK JP，et al. Increasing use of CT angiography in interventional study sites：the IMS Ⅲ experience[J/OL]. AJNR Am J Neuroradiol，2010，31（3）：E34[2024-06-01]. https://doi.org/10.3174/ajnr.A1996.

[62] ABE O，AOKI S，SHIROUZU I，et al. MR imaging of ischemic penumbra[J]. Eur J Radiol，2003，46（1）：67-78.

[63] LIU Y F，LI Y F，ZANG J K，et al. CircOGDH is a penumbra biomarker and therapeutic target in acute ischemic stroke[J]. Circ Res，2022，130（6）：907-924.