急性缺血性卒中血管內治療研究進展

林育意 譚靜 路星辰

·綜述·

急性缺血性卒中血管內治療研究進展

林育意 譚靜 路星辰

急性缺血性卒中發病率、病殘率和病死率均較高，是目前對人類危害最嚴重的疾病之一。血管內治療已獲得臨床充分肯定。血管內治療適應證的選擇、治療時間窗的確定、機械取栓裝置的選擇對預后至關重要。本文擬對急性缺血性卒中血管內治療研究進展進行闡述。

卒中； 腦缺血； 血栓溶解療法； 血管成形術； 綜述

腦卒中是目前對人類危害最嚴重的疾病之一。全國第三次死因回顧抽樣調查和第二次全國殘疾人抽樣調查資料顯示，腦卒中已成為我國國民首位病殘和病死原因［1］。在美國，腦卒中是導致終身殘疾的首要原因，是第4位病死原因［2］。截至2010年，腦卒中位列全球病殘和病死原因的第3和2位［3?4］。雖然近年來腦卒中病死率有所下降，但病殘和病死的絕對病例數仍在增加［5］，據世界銀行預測，如果不采取有效措施，截至2030年，我國將有31.77×106例腦卒中患者［1］。勞動力喪失和醫療負擔成為腦卒中生存者、家庭和社會的沉重負擔。有效的治療方法是臨床醫師不懈追求的目標。

一、急性缺血性卒中靜脈溶栓治療

目前，缺血性卒中是我國腦卒中住院患者的主要類型，占全部腦卒中70%以上［1］。靜脈溶栓是經典治療方法。研究證實，腦卒中靜脈溶栓治療有效，發病后3小時為治療時間窗［6?7］。1996年，重組組織型纖溶酶原激活物（rt?PA）經美國食品與藥品管理局（FDA）批準用于腦卒中靜脈溶栓治療［8］。2008年歐洲協作組急性腦卒中研究Ⅲ（ECASSⅢ）首次將腦卒中靜脈溶栓治療時間窗自3小時延長至4.50小時［9］，并獲得臨床研究證據的支持［10?11］。

隨著臨床應用的普及，靜脈溶栓治療的局限性也逐漸凸顯。（1）治療時間窗窄：盡管已將腦卒中靜脈溶栓治療時間窗延長至發病后4.50小時，但在此時間窗內仍有較多患者，特別是偏遠地區、交通欠發達地區患者，難以到達有靜脈溶栓資質的醫院，且此治療時間窗后不良結局發生率較高。（2）血管再通率低：頸內動脈（ICA）或基底動脈閉塞后靜脈溶栓治療的血管再通率僅為4%～14%，大腦中動脈（MCA）為55%，大腦中動脈M1段閉塞為32%～37%，病殘率和病死率均較高［12?13］。（3）易導致腦出血：有文獻報道，靜脈溶栓治療后癥狀性腦出血發生率高達1.7% ～ 2.4%［9，14］。

二、急性缺血性卒中血管內治療

1.血管內治療的有效性 2013年發表于N Engl J Med的3篇關于血管內治療的隨機對照臨床試驗并未顯示血管內治療較rt?PA靜脈溶栓治療更有優勢［15?17］。此后，Singh等［2］對上述3 項臨床研究進行Meta分析，也得出相同結論。但是他們發現，對于重癥腦卒中，血管內治療效果更佳［2，15?17］。究其原因，可能是血管內治療尚缺乏大樣本多中心隨機雙盲對照臨床試驗，也可能與機械取栓裝置Merci落后、患者征募緩慢、腦組織再灌注延遲、所納入病例均質性不一致有關。隨著機械取栓裝置和取栓技術的進步，血管內治療的優勢逐漸凸顯［2，18］，較單純靜脈溶栓治療效果更佳［19］。兩項采用機械取栓裝置Stentrievers治療腦卒中的隨機對照臨床試驗結局均明顯改善［20?21］。截至2015年，5項里程碑式前瞻性隨機對照臨床試驗均顯示，與靜脈溶栓相比，血管內機械取栓治療近端動脈閉塞性缺血性卒中的治療時間窗更長、血管再通率更高、臨床預后更佳［22?26］。2013 和 2015 年的 8 項臨床研究雖然納入與排除標準不盡相同［15?17，22?26］，但 Badhiwala等［27］對其進行Meta分析后發現，與內科治療聯合rt?PA靜脈溶栓治療相比，急性缺血性卒中患者采用血管內機械取栓治療能夠更好地改善神經功能預后，腦血管造影顯示血管再通率更高，且不增加90天內癥狀性腦出血發生率和各種原因導致的病死率。

2.血管內治療患者的選擇 Chia等［28］在南澳大利亞的Adelaide西郊進行一項以人群為基礎的隊列研究，結果顯示，在嚴格［改良Rankin量表（mRS）評分0～1分，發病至入院時間＜3.50小時，梗死灶核心與缺血半暗帶區不匹配］和寬松（mRS評分0～3分，發病至入院時間＜5小時）兩種標準下，符合血管內血栓切除術（ET）治療的潛在腦卒中患者約占全部腦卒中患者的7%和13%，寬松標準預測每年符合血管內血栓切除術治療的潛在患者≤22/10萬。2015年，Urra等［29］對納入前循環大血管閉塞致急性腦卒中8小時內Solitaire FR支架取栓與內科治療隨機對照試驗（REVASCAT）的西班牙前循環大血管閉塞性缺血性卒中患者和未納入該項試驗的其他類型腦卒中患者的血管內機械取栓治療效果進行分析，結果顯示療效無明顯差異，表明血管內血栓切除術不僅適用于前循環大血管閉塞性缺血性卒中，還具有更廣泛的適應證。如何準確、快速地篩選血管內治療適應證患者，是所有神經科醫師面臨的挑戰。Alberta腦卒中計劃早期CT評分（ASPECTS）是一種采用頭部非增強CT掃描快速、簡單、可靠、系統化評價腦組織早期缺血性改變的方法［30］。該評分系統中CT檢查操作簡單、檢查時間短、設備普及率高，可以廣泛應用于血管內治療患者的篩查。研究顯示，ASPECTS評分＞7分的缺血性卒中患者，動脈或靜脈溶栓治療后預后較好［31?32］。目前，ASPECTS評分廣泛應用于選擇適合血管內治療的患者。Goyal等［33］對2015年發表的5項關于血管內治療的隨機對照臨床試驗進行Meta分析，結果顯示，ASPECTS評分優良（7～10分）的患者經血管內治療后獲益明顯，而ASPECT評分差（0～6分）的患者經血管內治療后亦未發現有害證據。Yoo等［34］對荷蘭急性缺血性卒中血管內治療多中心隨機對照臨床試驗（MR CLEAN）進行亞組分析，結果顯示，中等梗死灶（ASPECTS評分5～7分）患者經血管內治療后獲益最大，小梗死灶（ASPECTS評分8～10分）患者經血管內治療聯合常規治療后缺血性卒中復發率增加，大梗死灶（ASPECTS評分0～4分）患者經血管內治療后是否獲益仍不明確，尚待進一步研究。上述研究結論的差異可能是由于CT平掃對急性梗死灶敏感性和精確性均較差［35］；ASPECTS評分應用者之間的異質性較大，約1/3研究者對15%缺血性卒中患者的ASPECTS評分意見不一致［36］，因此，ASPECTS評分用于血管內治療適應證的選擇尚存局限性。研究顯示，缺血半暗帶血栓檢測、CTA原始圖像（CTA?SI）有助于選擇適合血管內治療的急性缺血性卒中患者［37］。然而，綜合比較CT平掃的簡便快捷（可以爭取更多時間進行血管內治療以挽救缺血半暗帶）與MRI和CTA等檢查（準確性高但檢測時間較長）之間的關系，目前尚無除ASPECTS評分外的更好評價方法［38］。

3.血管內治療時間窗 腦卒中后應盡可能縮短再灌注時間［19］，普遍認為，再灌注時間延長使臨床預后惡化，增加并發癥發生率［39］。晚近研究顯示，血管內治療對發病6 小時內患者安全、有效［22，24?25］。美國心臟協會（AHA）/美國卒中協會（ASA）制定的急性缺血性卒中血管內治療指南［40］建議，應于發病6小時內行血管內治療。《急性缺血性卒中血管內治療中國指南2015》［41］推薦，血管內機械取栓治療發病6小時內的急性前循環大動脈狹窄性缺血性卒中，如果發病4.50小時內，可在足量靜脈溶栓基礎上實施血管內機械取栓治療。但是發病6小時后行血管內治療是否獲益尚存爭議。理論上講，如果側支循環良好、可挽救的缺血半暗帶體積足夠大，即使延長治療時間窗也可以獲益。Jovin等［26］進行的REVASCAT試驗納入發病8小時內的前循環大血管閉塞性缺血性卒中患者，血管內機械取栓可顯著降低腦卒中后殘疾程度，增加生活自理［mRS評分0～2分］比例，且與單純內科治療相比，癥狀性腦出血發生率和病死率差異無統計學意義。Saver等［42］的Meta分析顯示，腦卒中發病2小時內行血管內治療聯合內科治療獲益最大，發病后7.30小時已無明顯獲益。Goyal等［23］的小梗死灶和前循環近端閉塞性缺血性卒中血管內治療并強調最短化CT掃描至再通時間（ESCAPE）試驗將納入時限延長至發病12小時內，同樣發現血管內治療可以明顯改善患者功能預后并降低病死率。Lansberg等［43］的前瞻性多中心隊列研究——擴散和灌注成像評價腦卒中進展2（DEFUSE2）研究顯示，對于發病12小時內灌注成像（PWI）?擴散加權成像（DWI）不匹配的缺血性卒中患者，血管內再灌注成功與功能和影像學預后改善（發病至接受再灌注治療時間）無時間依賴性。應注意的是，加拿大腦卒中治療指南［44］建議，發病6小時內血管內治療效果最佳，最多可延長至發病12小時內。從個體水平看，發病超過6小時的缺血性卒中患者仍有可挽救的缺血半暗帶，可采用多模式影像學檢查，如CT灌注成像（CTP）、CTA、DWI和PWI篩選適合血管內治療的患者，但是此類患者能否從急性缺血?再灌注中獲益，尚待進一步隨機對照臨床試驗的驗證［40］。

4.血管內治療裝置的選擇 目前，血管內取栓裝置根據取栓方法可以分為兩種類型，一種以Merci（美國Concentric Medical公司）取栓系統和Penumbra（美國Penumbra公司）吸栓系統為代表，一種以Solitaire（美國EV3公司）和Trevo（美國Stryker公司）可回收支架取栓系統為代表。支架種類、型號、形狀和物理性質對臨床實踐和預后結局的影響尚不明確，因此，機械取栓裝置的選擇也尚無定論。有5項隨機對照臨床試驗證實可回收支架取栓系統的優良效果［22?26，33］。Dippel等［45］對 MR CLEAN試驗中不同取栓裝置的臨床結局進行分析，發現Solitaire和Trevo支架取栓裝置的效果最佳，Catch（美國Guidant公司）、Lazarus（美國Lazarus Effect公司）、Merci、Penumbra、Revive（美 國 Johnsonamp;Johnson公司）等裝置取栓后7天和3個月病死率和蛛網膜下隙出血發生率均明顯高于Solitaire和Trevo支架取栓裝置，而二者的臨床結局、神經修復、血管再通率、最終梗死灶面積和病死率差異則無統計學意義。Mendon?a等［46］的前瞻性臨床研究對前循環閉塞后Solitaire和Trevo支架取栓裝置的療效進行比較，結果顯示，兩種裝置取栓后血管再通率均較高（60%對77%，P=0.456），且臨床、影像學和功能結局差異均無統計學意義；然而由于樣本量較小（僅33例），該項研究結論尚待進一步證實。Grech等［47］對2010-2013年發表的20篇關于血管內機械取栓裝置的臨床研究（包括Solitaire支架17篇、Trevo支架3篇）進行Meta分析，結果顯示，Solitaire和Trevo支架取栓后血管再通率均＞80%，二者功能結局、病死率和癥狀性腦出血發生率差異均無統計學意義。因此認為，第一種類型的吸栓系統療效未能達到預期，而第二類型的可回收支架取栓系統療效達到預期，表現卓越。

綜上所述，血管內治療已獲得臨床充分肯定，中國神經外科醫師、相關學者和科研機構也緊隨時代步伐在該領域作出大量工作［48?49］。隨著相關設備和技術的迅速發展，相信在不久的將來，血管內治療必將得到進一步的完善和普及。

［1］Wang LD.Report on the Chinese stroke prevention 2015.Beijing:Peking Union Medical College Press,2015:9?64［.王隴德.中國腦卒中防治報告2015.北京:中國協和醫科大學出版社,2015:9?64.］

［2］Singh B,Parsaik AK,Prokop LJ,Mittal MK.Endovascular therapy for acute ischemic stroke:a systematic review and meta?

［3］analysis.Mayo Clin Proc,2013,88:1056?1065.Lozano R,Naghavi M,Foreman K,Lim S,Shibuya K,Aboyans V,Abraham J,Adair T,Aggarwal R,Ahn SY,Alvarado M,Anderson HR,Anderson LM,Andrews KG,Atkinson C,Baddour LM,Barker?Collo S,Bartels DH,Bell ML,Benjamin EJ,Bennett D,Bhalla K,Bikbov B,Bin Abdulhak A,Birbeck G,Blyth F,Bolliger I,Boufous S,Bucello C,Burch M,Burney P,Carapetis J,Chen H,Chou D,Chugh SS,Coffeng LE,Colan SD,Colquhoun S,Colson KE,Condon J,Connor MD,Cooper LT,Corriere M,Cortinovis M,de Vaccaro KC,Couser W,Cowie BC,Criqui MH,Cross M,Dabhadkar KC,Dahodwala N,De Leo D,Degenhardt L,Delossantos A,Denenberg J,Des Jarlais DC,Dharmaratne SD,Dorsey ER,Driscoll T,Duber H,Ebel B,Erwin PJ,Espindola P,Ezzati M,Feigin V,Flaxman AD,Forouzanfar MH,Fowkes FG,Franklin R,Fransen M,Freeman MK,Gabriel SE,Gakidou E,Gaspari F,Gillum RF,Gonzalez?Medina D,Halasa YA,Haring D,Harrison JE,Havmoeller R,Hay RJ,Hoen B,Hotez PJ,Hoy D,Jacobsen KH,James SL,Jasrasaria R,Jayaraman S,Johns N,Karthikeyan G,Kassebaum N,Keren A,Khoo JP,Knowlton LM,Kobusingye O,Koranteng A,Krishnamurthi R,Lipnick M,Lipshultz SE,Ohno SL,Mabweijano J,MacIntyre MF,MallingerL,March L,Marks GB,Marks R,Matsumori A,Matzopoulos R,Mayosi BM,McAnulty JH,McDermott MM,McGrath J,Mensah GA,Merriman TR,Michaud C,Miller M,Miller TR,Mock C,Mocumbi AO,Mokdad AA,Moran A,Mulholland K,Nair MN,Naldi L,Narayan KM,Nasseri K,Norman P,O'Donnell M,Omer SB,Ortblad K,Osborne R,Ozgediz D,Pahari B,Pandian JD,Rivero AP,Padilla RP,Perez?Ruiz F,Perico N,Phillips D,Pierce K,Pope CA 3rd,Porrini E,Pourmalek F,Raju M,Ranganathan D,Rehm JT,Rein DB,Remuzzi G,Rivara FP,Roberts T,De León FR,Rosenfeld LC,Rushton L,Sacco RL,Salomon JA,Sampson U,Sanman E,Schwebel DC,Segui?Gomez M,Shepard DS,Singh D,Singleton J,Sliwa K,Smith E,Steer A,Taylor JA,Thomas B,Tleyjeh IM,Towbin JA,Truelsen T, Undurraga EA, Venketasubramanian N,Vijayakumar L,Vos T,Wagner GR,Wang M,Wang W,Watt K,Weinstock MA,Weintraub R,Wilkinson JD,Woolf AD,Wulf S,Yeh PH,Yip P,Zabetian A,Zheng ZJ,Lopez AD,Murray CJ,AlMazroa MA,Memish ZA.Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010:a systematic analysis for the Global Burden of Disease Study 2010.Lancet,2012,380:2095?2128.

［4］Murray CJ,Vos T,Lozano R,Naghavi M,Flaxman AD,Michaud C,Ezzati M,Shibuya K,Salomon JA,Abdalla S,Aboyans V,Abraham J,Ackerman I,Aggarwal R,Ahn SY,Ali MK,Alvarado M,Anderson HR,Anderson LM,Andrews KG,Atkinson C,Baddour LM,Bahalim AN,Barker?Collo S,Barrero LH,Bartels DH,Basá?ez MG,Baxter A,Bell ML,Benjamin EJ,Bennett D,BernabéE,Bhalla K,Bhandari B,Bikbov B,Bin Abdulhak A,Birbeck G,Black JA,Blencowe H,Blore JD,Blyth F,Bolliger I,Bonaventure A,Boufous S,Bourne R,Boussinesq M,Braithwaite T,Brayne C,Bridgett L,Brooker S,Brooks P,Brugha TS,Bryan?Hancock C,Bucello C,Buchbinder R,Buckle G,Budke CM,Burch M,Burney P,Burstein R,Calabria B,Campbell B,Canter CE,Carabin H,Carapetis J,Carmona L,Cella C,Charlson F,Chen H,Cheng AT,Chou D,Chugh SS,Coffeng LE,Colan SD,Colquhoun S,Colson KE,Condon J,Connor MD,Cooper LT,Corriere M,Cortinovis M,de Vaccaro KC,Couser W,Cowie BC,Criqui MH,Cross M,Dabhadkar KC,Dahiya M,Dahodwala N,Damsere?Derry J,Danaei G,Davis A,De Leo D,Degenhardt L,Dellavalle R,Delossantos A,Denenberg J,Derrett S,Des Jarlais DC,Dharmaratne SD,Dherani M,Diaz?Torne C,Dolk H,Dorsey ER,Driscoll T,Duber H,Ebel B,Edmond K,Elbaz A,Ali SE,Erskine H,Erwin PJ,Espindola P,Ewoigbokhan SE,Farzadfar F,Feigin V,Felson DT,Ferrari A,Ferri CP,Fèvre EM,Finucane MM,Flaxman S,Flood L,Foreman K,Forouzanfar MH,Fowkes FG,Fransen M,Freeman MK,Gabbe BJ,Gabriel SE,Gakidou E,Ganatra HA,Garcia B,Gaspari F,Gillum RF,Gmel G,Gonzalez?Medina D,Gosselin R,Grainger R,Grant B,Groeger J,Guillemin F,Gunnell D,Gupta R,Haagsma J,Hagan H,Halasa YA,Hall W,Haring D,Haro JM,Harrison JE,Havmoeller R,Hay RJ,Higashi H,Hill C,Hoen B,Hoffman H,Hotez PJ,Hoy D,Huang JJ,Ibeanusi SE,Jacobsen KH,James SL,Jarvis D,Jasrasaria R,Jayaraman S,Johns N,Jonas JB,Karthikeyan G,Kassebaum N,Kawakami N,Keren A,Khoo JP,King CH,Knowlton LM,Kobusingye O,Koranteng A,Krishnamurthi R,Laden F,Lalloo R,Laslett LL,Lathlean T,Leasher JL,Lee YY,Leigh J,Levinson D,Lim SS,Limb E,Lin JK,Lipnick M,Lipshultz SE,Liu W,Loane M,Ohno SL,Lyons R,Mabweijano J,MacIntyre MF,Malekzadeh R,Mallinger L,Manivannan S,Marcenes W,March L,Margolis DJ,Marks GB,Marks R,Matsumori A,Matzopoulos R,Mayosi BM,McAnulty JH,McDermott MM,McGill N,McGrath J,Medina?Mora ME,Meltzer M,Mensah GA,Merriman TR,Meyer AC,Miglioli V,Miller M,Miller TR,Mitchell PB,Mock C,Mocumbi AO,Moffitt TE,Mokdad AA,Monasta L,Montico M,Moradi?Lakeh M,Moran A,Morawska L,Mori R,Murdoch ME,Mwaniki MK,Naidoo K,Nair MN,Naldi L,Narayan KM,Nelson PK,Nelson RG,Nevitt MC,Newton CR,Nolte S,Norman P,Norman R,O'Donnell M,O'Hanlon S,Olives C,Omer SB,Ortblad K,Osborne R,Ozgediz D,Page A,Pahari B,Pandian JD,Rivero AP,Patten SB,Pearce N,Padilla RP,Perez?Ruiz F,Perico N,Pesudovs K,Phillips D,Phillips MR,Pierce K,Pion S,Polanczyk GV,Polinder S,Pope CA 3rd,Popova S,Porrini E,Pourmalek F,Prince M,Pullan RL,Ramaiah KD,Ranganathan D,Razavi H,Regan M,Rehm JT,Rein DB,Remuzzi G,Richardson K,Rivara FP,Roberts T,Robinson C,De Leòn FR,Ronfani L,Room R,Rosenfeld LC,Rushton L,Sacco RL,Saha S,Sampson U,Sanchez?Riera L,Sanman E,Schwebel DC,Scott JG,Segui?Gomez M,Shahraz S,Shepard DS,Shin H,Shivakoti R,Singh D,Singh GM,Singh JA,Singleton J,Sleet DA,Sliwa K,Smith E,Smith JL,Stapelberg NJ,Steer A,Steiner T,Stolk WA,Stovner LJ,Sudfeld C,Syed S,Tamburlini G,Tavakkoli M,Taylor HR,Taylor JA,Taylor WJ,Thomas B,Thomson WM,Thurston GD,Tleyjeh IM,Tonelli M,Towbin JA,Truelsen T,Tsilimbaris MK,Ubeda C,Undurraga EA,van der Werf MJ,van Os J,Vavilala MS,Venketasubramanian N,Wang M,Wang W,Watt K,Weatherall DJ,Weinstock MA,Weintraub R,Weisskopf MG,Weissman MM,White RA,Whiteford H,Wiebe N,Wiersma ST,Wilkinson JD,Williams HC,Williams SR,Witt E,Wolfe F,Woolf AD,Wulf S,Yeh PH,Zaidi AK,Zheng ZJ,Zonies D,Lopez AD,AlMazroa MA,Memish ZA.Disability?adjusted life years(DALYs)for 291 diseases and injuries in 21 regions,1990-2010:a systematic analysis for the Global Burden of Disease Study 2010.Lancet,2012,380:2197?2223.Feigin VL,Forouzanfar MH,Krishnamurthi R,Mensah GA,

［5］Connor M,Bennett DA,Moran AE,Sacco RL,Anderson L,Truelsen T,O'Donnell M,Venketasubramanian N,Barker?Collo S,Lawes CM,Wang W,Shinohara Y,Witt E,Ezzati M,Naghavi M,Murray C;Global Burden of Diseases,Injuries and Risk Factors Study 2010(GBD 2010)and the GBD Stroke Experts Group.Global and regional burden of stroke during 1990-2010:findings from the Global Burden of Disease Study 2010.Lancet,2014,383:245?254.National Institute of Neurological Disorders and Stroke rt?PA

［6］Stroke Study Group.Tissue plasminogen activator for acute ischemic stroke.N Engl JMed,1995,333:1581?1587.Hacke W,Kaste M,Fieschi C,Toni D,Lesaffre E,von Kummer

［7］R,Boysen G,Bluhmki E,Hoxter G,Mahagne MH,Hennerici M. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke: the European Cooperative Acute Stroke Study(ECASS).JAMA,1995,274:1017?1025.Adams HP Jr,Brott TG,Furlan AJ,Gomez CR,Grotta J,

［8］Helgason CM,Kwiatkowski T,Lyden PD,Marler JR,Torner J,Feinberg W,Mayberg M,Thies W.Guidelines for thrombolytic therapy for acute stroke:a supplement to the guidelines for the management of patients with acute ischemic stroke.A statement for healthcare professionals from a Special Writing Group of the Stroke Council,American Heart Association.Circulation,1996,94:1167?1174.Hacke W,Kaste M,Bluhmki E,Brozman M,Dávalos A,

［9］Guidetti D,Larrue V,Lees KR,Medeghri Z,Machnig T,Schneider D,von Kummer R,Wahlgren N,Toni D;ECASS Investigators.Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.N Engl JMed,2008,359:1317?1329.Shobha N,Buchan AM,Hill MD;Canadian Alteplase for Stroke

［10］Effectiveness Study(CASES).Thrombolysis at 3-4.5 hours after acute ischemic stroke onset:evidence from the Canadian Alteplase for Stroke Effectiveness Study(CASES)registry.Cerebrovasc Dis,2011,31:223?228.Emberson J,Lees KR,Lyden P,Blackwell L,Albers G,

［11］Bluhmki E,Brott T,Cohen G,Davis S,Donnan G,Grotta J,Howard G,Kaste M,Koga M,von Kummer R,Lansberg M,Lindley RI,Murray G,Olivot JM,Parsons M,Tilley B,Toni D,Toyoda K,Wahlgren N,Wardlaw J,Whiteley W,del Zoppo GJ,Baigent C,Sandercock P,Hacke W;Stroke Thrombolysis Trialists'Collaborative Group.Effect of treatment delay,age,and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke:a meta?analysis of individual patient data from randomised trials.Lancet,2014,384:1929?1935.Rha JH,Saver JL.The impact of recanalization on ischemic

［12］stroke outcome:a meta?analysis.Stroke,2007,38:967?973.

［13］Bhatia R,Hill MD,Shobha N,Menon B,Bal S,Kochar P,Watson T,Goyal M,Demchuk AM.Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke:real?world experience and a call for action.Stroke,2010,41:2254?2258.

［14］Wahlgren N,Ahmed N,Davalos A,Ford GA,Grond M,Hacke W,Hennerici MG,Kaste M,Kuelkens S,Larrue V,Lees KR,Roine RO,Soinne L,Toni D,Vanhooren G;SITS?MOST investigators.Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke?Monitoring Study(SITS?MOST):an observational study.Lancet,2007,369:275?282.

［15］Broderick JP,Palesch YY,Demchuk AM,Yeatts SD,Khatri P,Hill MD,Jauch EC,Jovin TG,Yan B,Silver FL,von Kummer R,Molina CA,Demaerschalk BM,Budzik R,Clark WM,Zaidat OO,Malisch TW,Goyal M,Schonewille WJ,Mazighi M,Engelter ST,Anderson C,Spilker J,Carrozzella J,Ryckborst KJ, Janis LS, Martin RH, Foster LD, Tomsick TA;Interventional Management of Stroke(IMS)Ⅲ Investigators.Endovascular therapy after intravenous t?PA versus t?PA alone for stroke.N Engl JMed,2013,368:893?903.

［16］Kidwell CS,Jahan R,Gornbein J,Alger JR,Nenov V,Ajani Z,Feng L,Meyer BC,Olson S,Schwamm LH,Yoo AJ,Marshall RS,Meyers PM,Yavagal DR,Wintermark M,Guzy J,Starkman S,Saver JL;MR RESCUE Investigators.A trial of imaging selection and endovascular treatment for ischemic stroke.N Engl JMed,2013,368:914?923.

［17］Ciccone A,Valvassori L,Nichelatti M,Sgoifo A,Ponzio M,Sterzi R,Boccardi E;SYNTHESIS Expansion Investigators.Endovascular treatment for acute ischemic stroke.N Engl J Med,2013,368:904?913.

［18］Goyal M,Almekhlafi M,Menon B,Hill M,Fargen K,Parsons M,Bang OY,Siddiqui A,Andersson T,Mendes V,Davalos A,Turk A,Mocco J,Campbell B,Nogueira R,Gupta R,Murphy S,Jovin T,Khatri P,Miao Z,Demchuk A,Broderick JP,Saver J.Challenges of acute endovascular stroke trials.Stroke,2014,45:3116?3122.

［19］Prabhakaran S,Ruff I,Bernstein RA.Acute stroke intervention:

［20］a systematic review.JAMA,2015,313:1451?1462.Saver JL,Jahan R,Levy EI,Jovin TG,Baxter B,Nogueira RG,Clark W,Budzik R,Zaidat OO;SWIFT Trialists.Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke(SWIFT):a randomised,parallel?group,

［21］non?inferiority trial.Lancet,2012,380:1241?1249.Nogueira RG,Lutsep HL,Gupta R,Jovin TG,Albers GW,Walker GA,Liebeskind DS,Smith WS;TREVO 2 Trialists.Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke(TREVO 2):a randomised trial.Lancet,2012,380:1231?1240.

［22］Berkhemer OA,Fransen PS,Beumer D,van den Berg LA,Lingsma HF,Yoo AJ,Schonewille WJ,Vos JA,Nederkoorn PJ,Wermer MJ,van Walderveen MA,Staals J,Hofmeijer J,van Oostayen JA,LycklamaàNijeholt GJ,Boiten J,Brouwer PA,Emmer BJ,de Bruijn SF,van Dijk LC,Kappelle LJ,Lo RH,van Dijk EJ,de Vries J,de Kort PL,van Rooij WJ,van den Berg JS,van Hasselt BA,Aerden LA,Dallinga RJ,Visser MC,Bot JC,Vroomen PC,Eshghi O,Schreuder TH,Heijboer RJ,Keizer K,Tielbeek AV,den Hertog HM,Gerrits DG,van den Berg?Vos RM,Karas GB,Steyerberg EW,Flach HZ,Marquering HA,Sprengers ME,Jenniskens SF,Beenen LF,van den Berg R,Koudstaal PJ,van Zwam WH,Roos YB,van der Lugt A,van Oostenbrugge RJ,Majoie CB,Dippel DW;MR CLEAN Investigators.A randomized trial of intraarterial treatment for acute ischemic stroke.N Engl JMed,2015,372:11?20.Goyal M,Demchuk AM,Menon BK,Eesa M,Rempel JL,

［23］Thornton J,Roy D,Jovin TG,Willinsky RA,Sapkota BL,Dowlatshahi D,Frei DF,Kamal NR,Montanera WJ,Poppe AY,Ryckborst KJ,Silver FL,Shuaib A,Tampieri D,Williams D,Bang OY,Baxter BW,Burns PA,Choe H,Heo JH,Holmstedt CA,Jankowitz B,Kelly M,Linares G,Mandzia JL,Shankar J,Sohn SI,Swartz RH,Barber PA,Coutts SB,Smith EE,Morrish WF,Weill A,Subramaniam S,Mitha AP,Wong JH,Lowerison MW,Sajobi TT,Hill MD;ESCAPE Trial Investigators.Randomized assessment of rapid endovascular treatment of ischemic stroke.N Engl JMed,2015,372:1019?1030.Campbell BC,Mitchell PJ,Kleinig TJ,Dewey HM,Churilov L,

［24］Yassi N,Yan B,Dowling RJ,Parsons MW,Oxley TJ,Wu TY,Brooks M,Simpson MA,Miteff F,Levi CR,Krause M,Harrington TJ,Faulder KC,Steinfort BS,Priglinger M,Ang T,Scroop R,Barber PA,McGuinness B,Wijeratne T,Phan TG,Chong W,Chandra RV,Bladin CF,Badve M,Rice H,de Villiers L,Ma H,Desmond PM,Donnan GA,Davis SM;EXTEND?IA Investigators.Endovascular therapy for ischemic stroke with perfusion?imaging selection.N Engl J Med,2015,372:1009?1018.Saver JL,Goyal M,Bonafe A,Diener HC,Levy EI,Pereira VM,

［25］Albers GW,Cognard C,Cohen DJ,Hacke W,Jansen O,Jovin TG,Mattle HP,Nogueira RG,Siddiqui AH,Yavagal DR,Baxter BW,Devlin TG,Lopes DK,Reddy VK,du Mesnil de Rochemont R,Singer OC,Jahan R;SWIFT PRIME Investigators.Stent?retriever thrombectomy after intravenous t?PA vs.t?PA alone in stroke.N Engl J Med,2015,372:2285?2295.Jovin TG,Chamorro A,Cobo E,de Miquel MA,Molina CA,

［26］Rovira A,San Román L,Serena J,Abilleira S,RibóM,Millán M,Urra X,Cardona P,López?Cancio E,Tomasello A,Casta?o C,Blasco J,Aja L,Dorado L,Quesada H,Rubiera M,Hernandez?Pérez M,Goyal M,Demchuk AM,von Kummer R,Gallofré M,Dávalos A;REVASCAT Trial Investigators.Thrombectomy within 8 hours after symptom onset in ischemic stroke.N Engl JMed,2015,372:2296?2306.Badhiwala JH,Nassiri F,Alhazzani W,Selim MH,Farrokhyar

［27］F,Spears J,Kulkarni AV,Singh S,Alqahtani A,Rochwerg B,Alshahrani M,Murty NK,Alhazzani A,Yarascavitch B,Reddy K,Zaidat OO,Almenawer SA.Endovascular thrombectomy for acute ischemic stroke:a Meta?analysis.JAMA,2015,314:1832?1843.Chia NH,Leyden JM,Newbury J,Jannes J,Kleinig TJ.

［28］Determining the number of ischemic strokes potentially eligible for endovascular thrombectomy:a population?based study.Stroke,2016,47:1377?1380.Urra X,Abilleira S,Dorado L,RibóM,Cardona P,Millán M,

［29］Chamorro A,Molina C,Cobo E,Dávalos A,Jovin TG,Gallofré M; Catalan Stroke Code and Reperfusion Consortium.Mechanical thrombectomy in and outside the REVASCAT trial:insights from a concurrent population?based stroke registry.Stroke,2015,46:3437?3442.

［30］Barber PA,Demchuk AM,Zhang J,Buchan AM;ASPECTS Study Group.Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy.Alberta Stroke Programme Early CT Score.Lancet,2000,355:1670?1674.

［31］Demchuk AM,Hill MD,Barber PA,Silver B,Patel SC,Levine SR;NINDS rtPa Stroke Study Group,NIH.Importance of early ischemic computed tomography changes using ASPECTS in NINDSrtPA Stroke Study.Stroke,2005,36:2110?2115.

［32］Hill MD,Rowley HA,Adler F,Eliasziw M,Furlan A,Higashida RT,Wechsler LR,Roberts HC,Dillon WP,Fischbein NJ,Firszt CM,Schulz GA,Buchan AM;PROACT?ⅡInvestigators.Selection of acute ischemic stroke patients for intra?arterial thrombolysis with pro?urokinase by using ASPECTS.Stroke,2003,34:1925?1931.

［33］Goyal M,Menon BK,van Zwam WH,Dippel DW,Mitchell PJ,Demchuk AM,Dávalos A,Majoie CB,van der Lugt A,de Miquel MA,Donnan GA,Roos YB,Bonafe A,Jahan R,Diener HC,van den Berg LA,Levy EI,Berkhemer OA,Pereira VM,Rempel J,Millán M,Davis SM,Roy D,Thornton J,Román LS,RibóM,Beumer D,Stouch B,Brown S,Campbell BC,van Oostenbrugge RJ,Saver JL,Hill MD,Jovin TG;HERMES collaborators.Endovascular thrombectomy after large?vessel ischaemic stroke:a meta?analysis of individual patient data from five randomised trials.Lancet,2016,387:1723?1731.

［34］Yoo AJ,Berkhemer OA,Fransen PSS,van den Berg LA,Beumer D,Lingsma HF,Schonewille WJ,Sprengers ME,van den Berg R,van Walderveen MAA,Beenen LFM,Wermer MJH,Nijeholt GJLA,Boiten J,Jenniskens SFM,Bot JCJ,Boers AMM,Marquering HA,Roos YBWEM,van Oostenbrugge RJ,Dippel DWJ,van der Lugt A,van Zwam WH,Majoie CBLM;MR CLEAN investigators.Effect of baseline Alberta Stroke Program Early CT Score on safety and efficacy of intra?arterial treatment:a subgroup analysis of a randomised phase 3 trial(MR CLEAN).Lancet Neurol,2016,15:685?694.

［35］Lansberg MG,Albers GW,Beaulieu C,Marks MP.Comparison of diffusion?weighted MRI and CT in acute stroke.Neurology,2000,54:1557?1561.

［36］Farzin B,Fahed R,Guilbert F,Poppe AY,Daneault N,Durocher AP,Lanthier S,Boudjani H,Khoury NN,Roy D,Weill A,Gentric JC,Batista AL,Létourneau ?Guillon L,Bergeron F,Henry MA,Darsaut TE,Raymond J.Early CT changes in patients admitted for thrombectomy:intrarater and interrater agreement.Neurology,2016,87:249?256.

［37］Abstracts of the SNIS(Society of NeuroInterventional Surgery)9th Annual Meeting,July 23-26,2012.San Diego,California,

［38］USA.JNeurointerv Surg,2012,Suppl 1:A1?81.Jadhav AP, Wechsler LR. Patient selection for stroke thrombectomy:is CT head good enough?Neurology,2016,87:

［39］242?243.Khatri P,Yeatts SD,Mazighi M,Broderick JP,Liebeskind DS,Demchuk AM,Amarenco P,Carrozzella J,Spilker J,Foster LD,Goyal M,Hill MD,Palesch YY,Jauch EC,Haley EC,Vagal A,Tomsick TA;IMSⅢTrialists.Time to angiographic reperfusion and clinical outcome after acute ischaemic stroke:an analysis of data from the Interventional Management of Stroke(IMSⅢ)phase 3 trial.Lancet Neurol,2014,13:567?574.

［40］Powers WJ,Derdeyn CP,Biller J,Coffey CS,Hoh BL,Jauch EC,Johnston KC,Johnston SC,Khalessi AA,Kidwell CS,Meschia JF,Ovbiagele B,Yavagal DR;American Heart Association Stroke Council.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.Stroke,2015,46:3020?3035.

［41］Gao F,Xu AD.Chinese guide for endovascular therapy for acute ischemic stroke 2015.Zhongguo Zu Zhong Za Zhi,2015,10:590?606［.高峰,徐安定.急性缺血性卒中血管內治療中國指南2015.中國卒中雜志,2015,10:590?606.］

［42］Saver JL,Goyal M,van der Lugt A,Menon BK,Majoie CB,Dippel DW,Campbell BC,Nogueira RG,Demchuk AM,Tomasello A,Cardona P,Devlin TG,Frei DF,du Mesnil de Rochemont R,Berkhemer OA,Jovin TG,Siddiqui AH,van Zwam WH,Davis SM,Casta?o C,Sapkota BL,Fransen PS,Molina C,van Oostenbrugge RJ,Chamorroá,Lingsma H,Silver FL,Donnan GA,Shuaib A,Brown S,Stouch B,Mitchell PJ,Davalos A,Roos YB,Hill MD;HERMES Collaborators.Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke:a Meta?analysis.JAMA,2016,

［43］316:1279?1288.Lansberg MG,Cereda CW,Mlynash M,Mishra NK,Inoue M,Kemp S,Christensen S,Straka M,Zaharchuk G,Marks MP,Bammer R,Albers GW;Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2(DEFUSE 2)Study Investigators.Response to endovascular reperfusion is not time?dependent in patients with salvageable tissue.Neurology,

［44］2015,85:708?714.Casaubon LK,Boulanger JM,Blacquiere D,Boucher S,Brown K,Goddard T,Gordon J,Horton M,Lalonde J,LaRivière C,Lavoie P,Leslie P,McNeill J,Menon BK,Moses B,Penn M,Perry J,Snieder E,Tymianski D,Foley N,Smith EE,Gubitz G,Hill MD,Glasser E,Lindsay P;Heart and Stroke Foundation of Canada Canadian Stroke Best Practices Advisory Committee.Canadian stroke best practice recommendations:hyperacute stroke care

［45］guidelines,update 2015.Int JStroke,2015,10:924?940.Dippel DW,Majoie CB,Roos YB,van der Lugt A,van Oostenbrugge RJ,van Zwam WH,Lingsma HF,Koudstaal PJ,Treurniet KM,van den Berg LA,Beumer D,Fransen PS,Berkhemer OA;MR CLEAN Investigators.Influence of device choice on the effect of intra?arterial treatment for acute ischemic stroke in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic

［46］Stroke in the Netherlands).Stroke,2016,47:2574?2581.Mendon?a N,Flores A,Pagola J,Rubiera M,Rodríguez?Luna D,De Miquel MA,Cardona P,Quesada H,Mora P,Alvarez?Sabín J,Molina C,RibóM.Trevo versus solitaire a head?to?head comparison between two heavy weights of clot retrieval.J

［47］Neuroimaging,2014,24:167?170.Grech R,Pullicino R,Thornton J,Downer J.An efficacy and safety comparison between different stentriever designs in acute ischaemic stroke:a systematic review and meta?analysis.Clin

［48］Radiol,2016,71:48?57.Li YK,Liu XF.Current status and future prospect of endovascular treatment for ischemic stroke.Zhongguo Xian Dai Shen Jing Ji Bing Za Zhi,2011,11:152?159［.李永坤,劉新峰.缺血性卒中血管內治療的現狀與展望.中國現代神經疾病雜

［49］ 志,2011,11:152?159.］Miao ZR, Ma N. Endovascular therapy of ischemic cerebrovascular disease.Zhongguo Xian Dai Shen Jing Ji Bing Za Zhi,2013,13:170?173［.繆中榮,馬寧.缺血性腦血管病的血管內治療.中國現代神經疾病雜志,2013,13:170?173.］

Research progress of endovascular therapy for acute ischemic stroke

LIN Yu?yi1,TAN Jing2,LU Xing?chen3

1Department of Neurosurgery,Southeast Hospital of Chongqing,Chongqing 401336,China

2Department of Neurology,Chongqing Armed Corps Police Hospital,Chongqing 400061,China

3Medical Team,Unit 78526 of Chinese PLA,Leshan 614100,Sichuan,China
Corresponding author:LU Xing?chen(Email:410484527@qq.com)

Acute ischemic stroke which has the high mobidity,disability rate and mortality is one of the most serious diseases threatening mankind.Endovascular therapy is difinite.Slection of patient,therapeutic time window and device is closely associated with the prognosis.This paper reviews the issues mentioned above.

Stroke;Brain ischemia;Thrombolytic therapy;Angioplasty;Review

10.3969/j.issn.1672?6731.2017.09.013

401336重慶市東南醫院神經外科（林育意）；400061武警重慶總隊醫院神經內科（譚靜）；614100樂山，解放軍78526部隊衛生隊（路星辰）

路星辰（Email：410484527@qq.com）

2017?08?21）