Skip to main content
Log in

Time window and “tissue window”: two approaches to assist decision-making in strokes

  • Review
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Intravenous alteplase given in an appropriate time window has been recommended in guidelines and effects are on the decline over time. In general, the clinical decision is primarily based on whether ischemic stroke patients are sent to hospitals within the time window. However, some patients sent to the hospital over time limitations are eligible to receive intervention for recanalization due to good collateral circulation. In this dilemma, “tissue window” can be more reliable, which means using the penumbra as a major criterion for patient recruitment. Hence, we herein aim to address how could “tissue window” be a complementary approach when it does not conform to the time window’s indication and affirming value of the later one. Some efforts obeying the time window are discussed first. In the later sections, we give the details of the definition of “tissue window”, and then compare various neuroimaging techniques to determine the penumbra and summarize favorable patterns. Finally, we will focus on how the “tissue window” extends the therapeutic time window under specific circumstances.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Burke JF, Lisabeth LD, Brown DL, Reeves MJ, Morgenstern LB (2012) Determiningstroke’s rank as a cause of death using multicause mortality data. Stroke 43:2207–2211. https://doi.org/10.1161/STROKEAHA.112.656967

    Article  PubMed  PubMed Central  Google Scholar 

  2. Hacke W (2018) A new dawn for imaging-based selection in the treatment of acute stroke. N Engl J Med 378:81. https://doi.org/10.1056/NEJMe1713367

    Article  PubMed  Google Scholar 

  3. Toni D, Chamorro A, Kaste M, Lees K, Wahlgren NG, Hacke W et al (2004) Acute treatment of ischaemic stroke. European stroke initiative. Cerebrovasc Dis 17(Suppl 2):30–46. https://doi.org/10.1159/000074818

    Article  PubMed  Google Scholar 

  4. Lees KRBE., von Kumme R, Brott TG, Toni D, Grotta JC (2010) Time to treatment with intravenous alteplase and outcome in stroke: An updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 375:1695–1703. https://doi.org/10.1016/S0140-6736(10)60491-6

    Article  CAS  PubMed  Google Scholar 

  5. Hacke W, Brozman M, Dávalos A, Guidetti D, Larrue V et al (2008) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 359:1317–1329. https://doi.org/10.1056/NEJMoa0804656

    Article  CAS  PubMed  Google Scholar 

  6. Anderson CS, Robinson T, Lindley RI, Arima H, Lavados PM, Lee TH et al (2016) Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke. N Engl J Med 374:2313–2323. https://doi.org/10.1056/NEJMoa1515510

    Article  CAS  PubMed  Google Scholar 

  7. Peter SJM, Richard IL, Martin D, Graham V, Anna C et al (2012) The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. The Lancet 379:2352–2363. https://doi.org/10.1016/S0140-6736(12)60768-5

    Article  CAS  Google Scholar 

  8. Bhatia R, Hill MD, Shobha N, Menon B, Bal S, Kochar P et al (2010) Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke 41:2254. https://doi.org/10.1161/STROKEAHA.110.592535

    Article  CAS  PubMed  Google Scholar 

  9. Alexandrov AV, Grotta JC (2002) Arterial reocclusion in stroke patients treated with intravenous tissue plasminogen activator. Neurology 59:862–867

    Article  CAS  PubMed  Google Scholar 

  10. Huang X, MacIsaac R, Thompson JL, Levin B, Buchsbaum R, Haley EC Jr et al (2016) Tenecteplase versus alteplase in stroke thrombolysis: an individual patient data meta-analysis of randomized controlled trials. Int J Stroke 11:534–543. https://doi.org/10.1177/1747493016641112

    Article  PubMed  Google Scholar 

  11. Logallo N, Kvistad CE, Thomassen L (2015) Therapeutic potential of tenecteplase in the management of acute ischemic stroke. Cns Drugs 29:811–818. https://doi.org/10.1007/s40263-015-0280-9

    Article  CAS  PubMed  Google Scholar 

  12. Haley EC Jr, Thompson JL, Grotta JC, Lyden PD, Hemmen TG, Brown DL et al (2010) Phase IIb/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke 41:707–711. https://doi.org/10.1161/STROKEAHA.109.572040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Molina CA, Ribo M, Rubiera M, Santamarina E, Delgado-Mederos R, Maisterra O et al (2008) TNK induces faster MCA recanalization and leads to better short- and long-term clinical outcome than native tPA. The TNK-tPA reperfusion stroke study. Stroke 39:563 (Abstract)

    Google Scholar 

  14. Disorders NIoN, Group Sr-PSS (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333:1581–1587. https://doi.org/10.1056/NEJM199512143332401

    Article  Google Scholar 

  15. Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG et al (2012) Solitaire flow restoration device versus the MERCI retriever in patients with acute ischaemic stroke (SWIFT): A randomised, parallel-group, non-inferiority trial. The Lancet 380:1241–1249. https://doi.org/10.1016/S0140-6736(12)61384-1

    Article  Google Scholar 

  16. Nogueira RG, Lutsep HL, Gupta R, Jovin TG, Albers GW, Walker GA et al (2012))TREVO versus MERCI retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. The Lancet 2012 380(12):1231–1240. https://doi.org/10.1016/S0140-6736(12)61299-9

    Article  Google Scholar 

  17. Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J et al (2015) Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 49:1019–1030. https://doi.org/10.1056/NEJMoa1414905

    Article  CAS  Google Scholar 

  18. Prabhakaran S, Ruff I, Bernstein RA (2015) Acute stroke intervention: a systematic review. JAMA 313:1451–1462. https://doi.org/10.1001/jama.2015.3058

    Article  CAS  PubMed  Google Scholar 

  19. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM et al (2015) Solitaire™ with the intention for thrombectomy as primary endovascular treatment for acute ischemic stroke (SWIFT PRIME) trial: Protocol for a randomized, controlled, multicenter study comparing the solitaire revascularization device with iv tPA alone in acute ischemic stroke. Int J Stroke Off J Int Stroke Soci 10:439–448. https://doi.org/10.1111/ijs.12459

    Article  Google Scholar 

  20. Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD et al (2013) Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 368:893–903. https://doi.org/10.1056/NEJMoa1214300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kunz A, Ebinger M, Geisler F, Rozanski M, Waldschmidt C, Weber JE et al (2016) Functional outcomes of pre-hospital thrombolysis in a mobile stroke treatment unit compared with conventional care: an observational registry study. Lancet Neurol 15:1035–1043. https://doi.org/10.1016/S1474-4422(16)30129-6

    Article  PubMed  Google Scholar 

  22. Mazighi M, Serfaty JM, Labreuche J, Laissy JP, Meseguer E, Lavallée PC et al (2009) Comparison of intravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and confirmed arterial occlusion (RECANALISE study): a prospective cohort study. Lancet Neurol 8:802. https://doi.org/10.1016/S1474-4422(09)70182-6

    Article  CAS  PubMed  Google Scholar 

  23. Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P et al (2017) Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. https://doi.org/10.1056/NEJMoa1706442

    Article  PubMed  Google Scholar 

  24. Demeestere J, Garciaesperon C, Garciabermejo P, Ombelet F, Mcelduff P, Bivard A et al (2017) Evaluation of hyperacute infarct volume using aspects and brain ct perfusion core volume. Neurology. https://doi.org/10.1212/WNL.0000000000004028

    Article  PubMed  PubMed Central  Google Scholar 

  25. Warach SJ, Luby M, Albers GW, Bammer R, Bivard A, Campbell BC et al (2016) Acute stroke imaging research roadmap III imaging selection and outcomes in acute stroke reperfusion clinical trials: Consensus recommendations and further research priorities. Stroke 47:1389. https://doi.org/10.1161/STROKEAHA.115.012364

    Article  PubMed  PubMed Central  Google Scholar 

  26. Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N et al (2015) Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 372:1009–1018. https://doi.org/10.1056/NEJMoa1414792

    Article  CAS  PubMed  Google Scholar 

  27. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM et al (2015) Stent-retriever thrombectomy after intravenous t-PA vs. T-PA alone in stroke. N Engl J Med 372:2285. https://doi.org/10.1056/NEJMoa1415061

    Article  CAS  PubMed  Google Scholar 

  28. Kidwell CS, Jahan R, Gornbein J, Alger JR, Nenov V, Ajani Z et al (2013) A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med 368:914–923. https://doi.org/10.1056/NEJMoa1212793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bivard A, Levi C, Krishnamurthy V, Mcelduff P, Miteff F, Spratt NJ et al (2015) Perfusion computed tomography to assist decision making for stroke thrombolysis. Brain A J Neurol 138:1919–1931. https://doi.org/10.1093/brain/awv071

    Article  Google Scholar 

  30. Lansberg MG, Christensen S, Kemp S, Mlynash M, Mishra N, Federau C et al (2017) Computed tomographic perfusion to predict response to recanalization in ischemic stroke. Ann Neurol 81:849–856. https://doi.org/10.1002/ana.24953

    Article  PubMed  PubMed Central  Google Scholar 

  31. Lansberg MG, Straka M, Kemp S, Mlynash M, Wechsler LR, Jovin TG et al (2012) Magnetic resonance imaging profile and response to endovascular reperfusion: results of the DEFUSE 2 prospective cohort study. Lancet Neurol 11:860. https://doi.org/10.1016/S1474-4422(12)70203-X

    Article  PubMed  PubMed Central  Google Scholar 

  32. Simonsen CZ, Andersen G, González RG, Yoo AJ (2013) Selection of patients for intra-arterial therapy. Lancet Neurol 12:225–225 https://doi.org/10.1016/S1474-4422(13)70018-8

    Article  PubMed  Google Scholar 

  33. Lansberg MG, Straka M, Kemp S, Mlynash M, Wechsler LR, Jovin TG et al (2012) MRI profile and response to endovascular reperfusion after stroke(DEFUSE 2): a prospective cohort study. Lancet Neurol 11:860 https://doi.org/10.1016/S1474-4422(12)70203-X

    Article  PubMed  PubMed Central  Google Scholar 

  34. Parsons MW, Albers GW (2013) Mr rescue: is the glass half-full or half-empty? Stroke 44:2055. https://doi.org/10.1161/STROKEAHA.113.001443

    Article  PubMed  Google Scholar 

  35. Fisher M, Albers GW (2013) Advanced imaging to extend the therapeutic time window of acute ischemic stroke. Ann Neurol 73:4–9. https://doi.org/10.1002/ana.23744

    Article  PubMed  Google Scholar 

  36. Kate M, Riaz P, Gioia L, Buck B, Jeerakathil T et al (2018) Penumbral imaging-based thrombolysis with tenecteplase is feasible up to 24 hours after symptom onset. Int J of Stroke. https://doi.org/10.5853/jos.2017.00178

    Article  Google Scholar 

  37. Harston GWJ, Tee YK, Blockley N, Okell TW, Thandeswaran S, Shaya G et al (2015) Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging. Brain A J Neurol 138:36–42. https://doi.org/10.1093/brain/awu374

    Article  Google Scholar 

  38. Evans NR, Tarkin JM, Buscombe JR, Markus HS, Jhf R, Warburton EA (2017) PET imaging of the neurovascular interface in cerebrovascular disease. Nat Rev Neurol 13(11):676–688. https://doi.org/10.1038/nrneurol.2017.129

    Article  PubMed  Google Scholar 

  39. Sheinberg DL, McCarthy DJ, Peterson EC (2016) DEFUSE-3 Trial: REINFORCING EVIDENCE FOR EXTENDED ENDOVASCULAR INTERVENTION TIME WINDOW FOR ISCHEMIC STROKE. World Neurosurg 112:275–276. https://doi.org/10.1016/j.wneu.2018.02.064

    Article  Google Scholar 

  40. Albers GW, Goyal M, Jahan R et al (2016) Ischemic core and hypoperfusion volumes predict infarct size in SWIFT PRIME. Ann Neurol 79:76–89. https://doi.org/10.1002/ana.24543

    Article  PubMed  Google Scholar 

  41. Carrera E (2017) Imaging-based selection of patients for acute stroke treatment : is it ready for prime time? Neurology 88:2242–2243. https://doi.org/10.1212/WNL.0000000000004051

    Article  PubMed  Google Scholar 

  42. Wheeler HM, Mlynash M, Inoue M et al (2016) The growth rate of early DWI lesions is highly variable and associated with penumbral salvage and clinical outcomes following endovascular reperfusion. Int J Stroke 10:723–729. https://doi.org/10.1111/ijs.12436

    Article  Google Scholar 

Download references

Acknowledgements

This review was supported by Grants from Guangdong Techpool Bio-Pharmaceutical Company Limited.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fei Cao.

Ethics declarations

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiang, X., Cao, F. Time window and “tissue window”: two approaches to assist decision-making in strokes. J Neurol 266, 283–288 (2019). https://doi.org/10.1007/s00415-018-8933-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-018-8933-5

Keywords

Navigation