Advances in Intravenous Thrombolysis for Acute Ischemic Stroke

doi:10.3969/j.issn.1673-5765.2020.09.003

Abstract

Abstract:

As the time window of intravenous thrombolysis extended from 3 hours to 9 hours, the research focus shifted from the time window to the tissue window. For acute ischemic stroke patients with unknown exact time of onset, wake-up stroke or beyond the 4.5-hour time window, relevant neuroimaging examination is needed to weigh the profit and risk of intravenous thrombolysis. This article summarized thrombolytic drugs and recent various approaches of identifying patients eligible for intravenous thrombolysis based on the tissue window, to provide reference for clinical practice in this field.

Key words: Intravenous thrombolysis; Time window; Tissue window; Acute ischemic stroke

摘要：

随着静脉溶栓时间窗从3 h扩展到了9 h，研究重点也从时间窗理念扩展至组织窗理念。对于发病时间不明、醒后卒中或者一定时间内的超时间窗患者，需完善相关神经影像学检查，权衡利弊后决定是否静脉溶栓治疗。本文重点梳理了近年来根据组织窗寻找静脉溶栓获益患者的各种不同筛选方法及静脉溶栓的药物选择，希望能为临床提供参考。

关键词: 静脉溶栓; 时间窗; 组织窗; 急性缺血性卒中

LIU Hui-Hui, JIANG Qian-Mei, DAI Jing,LIU Chun-Feng. Advances in Intravenous Thrombolysis for Acute Ischemic Stroke[J]. Chinese Journal of Stroke, 2020, 15(09): 934-941.

刘慧慧，姜倩梅，戴婧，刘春风. 急性缺血性卒中静脉溶栓治疗研究新进展[J]. 中国卒中杂志, 2020, 15(09): 934-941.

References

[1] GBD 2016 Stroke Collaborators. Global，regional，

and national burden of stroke，1990-2016：a

systematic analysis for the Global Burden of Disease

Study 2016[J]. Lancet Neurol，2019，18（5）：439-

458.

[2] GBD 2016 Lifetime Risk of Stroke Collaborators，

FEIGIN V L，NGUYEN G，et al. Global，regional，

and country-specific lifetime risks of stroke，1990

and 2016[J]. N Engl J Med，2018，379（25）：2429-

2437.

[3] 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[2020-06-30]. https：//doi.org/10.

1161/STR.0000000000000211.

[4] National Institute of Neurological Disorders

and Stroke rt-PA Stroke Study Group. Tissue

plasminogen activator for acute ischemic stroke[J/

OL]. N Engl J Med，1995，333：1581-1587[2020-06-

30]. https：//doi.org/10.1056/NEJM199512143332401.

[5] 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.

[6] CAMPBELL B C V，MA H，RINGLEB P A，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[J].

Lancet，2019，394（10193）：139-147.

[7] LARRUE V，VON KUMMER R，DEL ZOPPO G，

et al. Hemorrhagic transformation in acute ischemic

stroke. Potential contributing factors in the European

Cooperative Acute Stroke Study[J]. Stroke，1997，28

（5）：957-960.

[8] ASTRUP J，SIESJÖ B K，SYMON L. Thresholds in

cerebral ischemia - the ischemic penumbra[J]. Stroke，

1981，12（6）：723-725.

[9] HEISS W D，ZARO WEBER O. Validation

of MRI determination of the penumbra by PET

measurements in ischemic stroke[J]. J Nucl Med，

2017，58（2）：187-193.

[10] KIDWELL C S，ALGER J R，SAVER J L. Beyond

mismatch：evolving paradigms in imaging the

ischemic penumbra with multimodal magnetic

resonance imaging[J]. Stroke，2003，34（11）：2729-

2735.

[11] KONSTAS A A，LEV M H. CT perfusion imaging

of acute stroke：the need for arrival time，delay

insensitive，and standardized postprocessing

algorithms?[J]. Radiology，2010，254（1）：22-25.

[12] CHUNG J W，KIM J Y，PARK H K，et al. Impact of

the penumbral pattern on clinical outcome in patients

with successful endovascular revascularization[J]. J

Stroke Cerebrovasc Dis，2017，26（2）：360-367.

[13] CEREDA C W，CHRISTENSEN S，CAMPBELL B

C V，et al. A benchmarking tool to evaluate computer

tomography perfusion infarct core predictions

against a DWI standard[J]. J Cereb Blood Flow

Metab，2016，36（10）：1780-1789.

[14] CAMPBELL B C V，CHRISTENSEN S，LEVI C R，

et al. Cerebral blood flow is the optimal CT perfusion

parameter for assessing infarct core[J]. Stroke，2011，

42（12）：3435-3440.

[15] BIVARD A，MCELDUFF P，SPRATT N，et

al. Defining the extent of irreversible brain

ischemia using perfusion computed tomography[J].

Cerebrovasc Dis，2011，31（3）：238-245.[16] WU L，WU W，TALI E T，et al. Oligemia，

penumbra，infarction：understanding hypoperfusion

with neuroimaging[J]. Neuroimaging Clin N Am，

2018，28（4）：599-609.

[17] LIN L T，BIVARD A，KRISHNAMURTHY V，et

al. Whole-brain CT perfusion to quantify acute

ischemic penumbra and core[J]. Radiology，2016，

279（3）：876-887.

[18] MARTINS N，AIRES A，MENDEZ B，et al. Ghost

infarct core and admission computed tomography

perfusion：redefining the role of neuroimaging in

acute ischemic stroke[J]. Interventional neurology，

2018，7（6）：513-521.

[19] BONED S，PADRONI M，RUBIERA M，et al.

Admission CT perfusion may overestimate initial

infarct core：the ghost infarct core concept[J]. J

Neurointerv Surg，2017，9（1）：66-69.

[20] GEUSKENS R R E G，BORST J，LUCAS

M，et al. Characteristics of misclassified CT

perfusion ischemic core in patients with acute

ischemic stroke[J/OL]. PLoS One，2015，10（11）：

e0141571[2020-06-30]. https：//doi.org/10.1371/

journal.pone.0141571.

[21] VAGAL A，WINTERMARK M，NAEL K，et al.

Automated CT perfusion imaging for acute ischemic

stroke：pearls and pitfalls for real-world use[J].

Neurology，2019，93（20）：888-898.

[22] KUDO K，SASAKI M，YAMADA K，et al.

Differences in CT perfusion maps generated by

different commercial software：quantitative analysis

by using identical source data of acute stroke

patients[J]. Radiology，2010，254（1）：200-209.

[23] FAHMI F，MARQUERING H A，STREEKSTRA G

J，et al. Differences in CT perfusion summary maps

for patients with acute ischemic stroke generated by

2 software packages[J]. AJNR Am J Neuroradiol，

2012，33（11）：2074-2080.

[24] GLE?A，CHRZAN R，URBANIK A. The

effect of software post-processing applications

on identification of the penumbra and core within

the ischaemic region in perfusion computed

tomography[J/OL]. Pol J Radiol，2019，84：

e118-e125[2020-06-30]. https：//doi.org/10.5114/pjr.

2019.83182.

[25] MOKIN M，LEVY E I，SAVER J L，et al. Predictive

value of RAPID assessed perfusion thresholds on

final infarct volume in SWIFT PRIME（Solitaire

With the Intention for Thrombectomy as Primary

Endovascular Treatment）[J]. Stroke，2017，48（4）：

932-938.

[26] AUSTEIN F，RIEDEL C，KERBY T，et al.

Comparison of perfusion CT software to predict the

final infarct volume after thrombectomy[J]. Stroke，

2016，47（9）：2311-2317.

[27] KUDO K，CHRISTENSEN S，SASAKI M，et

al. Accuracy and reliability assessment of CT and

MR perfusion analysis software using a digital

phantom[J]. Radiology，2013，267（1）：201-211.

[28] CHEN C S，BIVARD A，LIN L T，et al. Thresholds

for infarction vary between gray matter and white

matter in acute ischemic stroke：a CT perfusion

study[J]. J Cereb Blood Flow Metab，2019，39（3）：

536-546.

[29] PALLESEN L P，GERBER J，DZIALOWSKI I，et al.

Diagnostic and prognostic impact of pc-ASPECTS

applied to perfusion CT in the Basilar Artery

International Cooperation Study[J]. J Neuroimaging，

2015，25（3）：384-389.

[30] SPORNS P，SCHMIDT R，MINNERUP J，et

al. Computed tomography perfusion improves

diagnostic accuracy in acute posterior circulation

stroke[J]. Cerebrovasc Dis，2016，41（5/6）：242-247.

[31] VAN DER HOEVEN E J，DANKBAAR J W，

ALGRA A，et al. Additional diagnostic value of

computed tomography perfusion for detection of

acute ischemic stroke in the posterior circulation[J].

Stroke，2015，46（4）：1113-1115.

[32] SCHAEFER P W，GRANT P E，GONZALEZ R

G. Diffusion-weighted MR imaging of the brain[J].

Radiology，2000，217（2）：331-345.

[33] CAMPBELL B C V，PURUSHOTHAM A，

CHRISTENSEN S，et al. The infarct core is well

represented by the acute diffusion lesion：sustained

reversal is infrequent[J]. J Cereb Blood Flow Metab，

2012，32（1）：50-56.

[34] LABEYRIE M A，TURC G，HESS A，et al.

Diffusion lesion reversal after thrombolysis：a MR

correlate of early neurological improvement[J].

Stroke，2012，43（11）：2986-2991.

[35] THOMALLA G，SIMONSEN C Z，BOUTITIE

F，et al. MRI-guided thrombolysis for stroke with

unknown time of onset[J]. N Engl J Med，2018，379

（7）：611-622.

[36] BOUSLAMA M，BOWEN M T，HAUSSEN D C，et

al. Selection paradigms for large vessel occlusion

acute ischemic stroke endovascular therapy[J].

Cerebrovasc Dis，2017，44（5/6）：277-284.

[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] 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.

[39] 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.

[40] RINGLEB P，BENDSZUS M，BLUHMKI E，et

al. Extending the time window for intravenous

thrombolysis in acute ischemic stroke using magnetic

resonance imaging-based patient selection[J]. Int J

Stroke，2019，14（5）：483-490.

[41] 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.

[42] KOGA M，YAMAMOTO H，INOUE M，et

al. Thrombolysis with alteplase at 0.6 mg/kg for

stroke with unknown time of onset：a randomized

controlled trial[J]. Stroke，2020，51（5）：1530-1538.

[43] YU W G，JIANG W J. A simple imaging guide for

endovascular thrombectomy in acute ischemic stroke：

from time window to perfusion mismatch and

beyond[J/OL]. Front Neurol，2019，10：502[2020-06-

30]. https：//doi.org/10.3389/fneur.2019.00502.

[44] KENT D M，HILL M D，RUTHAZER R，et al.

"Clinical-CT mismatch" and the response to systemic

thrombolytic therapy in acute ischemic stroke[J].

Stroke，2005，36（8）：1695-1699.

[45] MESSÉ S R，KASNER S E，CHALELA J A，et al.

CT-NIHSS mismatch does not correlate with MRI

diffusion-perfusion mismatch[J]. Stroke，2007，38

（7）：2079-2084.

[46] BONAVENTURA A，MONTECUCCO F，

DALLEGRI F. Update on the effects of treatment

with recombinant tissue-type plasminogen activator

（rt-PA）in acute ischemic stroke[J]. Expert Opin Biol

Ther，2016，16（11）：1323-1340.

[47] LOGALLO N，KVISTAD C E，NACU A，et al.

The Norwegian tenecteplase stroke trial（NORTEST）：

randomised controlled trial of tenecteplase

vs. alteplase in acute ischaemic stroke[J/OL]. BMC

Neurol，2014，14：106[2020-06-30]. https：//doi.

org/10.1186/1471-2377-14-106.

[48] KVISTAD C E，NOVOTNY V，KURZ M W，et al.

Safety and outcomes of tenecteplase in moderate

and severe ischemic stroke[J]. Stroke，2019，50（5）：

1279-1281.

[49] CAMPBELL B C，MITCHELL P J，CHURILOV

L，et al. Tenecteplase versus alteplase before

endovascular thrombectomy（EXTEND-IA TNK）：

a multicenter，randomized，controlled study[J]. Int J

Stroke，2018，13（3）：328-334.

[50] CAMPBELL B C V，MITCHELL P J，CHURILOV

L，et al. Determining the optimal dose of

tenecteplase before endovascular therapy for

ischemic stroke（EXTEND-IA TNK Part 2）：a

multicenter，randomized，controlled study[J]. Int J

Stroke，2019，15（5）：567-572.

[51] YANG P F，ZHANG Y W，ZHANG L，et al.

Endovascular Thrombectomy with or without

intravenous alteplase in acute stroke[J]. N Engl J

Med，2020，382（21）：1981-1993.