Intra-Arterial Treatment of Acute Ischemic Stroke: The Continued Evolution

  • Alex Y. Lu
  • Sameer A. Ansari
  • Karin V. Nyström
  • Eyiyemisi C. Damisah
  • Hardik P. Amin
  • Charles C. Matouk
  • Rashmi D. Pashankar
  • Ketan R. BulsaraEmail author
Cerebrovascular Disease and Stroke (D Greer, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Cerebrovascular Disease and Stroke

Opinion statement

The devastation caused by acute ischemic strokes is evident in every intensive care unit across the world. Although there is no doubt that progress has been made in treatment, it has been slow to come. With the emergence of new technologies in imaging, thrombolysis and endovascular intervention, the treatment modalities of acute ischemic stroke will enter a new era. In this review, we present the concept of the seven evolutionary phases in the treatment of acute ischemic stroke to date.


Thrombolysis Ischemia Recanalization Salvageable tissue Neuroprotection 



We would like to thank Anand Mohapatra and Ezra Baraban for their assistance on this article.

Compliance with Ethics Guidelines

Conflict of Interest

Dr. Alex Y. Lu, Dr. Sameer A. Ansari, Dr. Karin V. Nyström, Dr. Eyiyemisi C. Damisah, Dr. Hardik P. Amin, Dr. Charles C. Matouk, Rashmi D. Pashankar, and Dr. Ketan R. Bulsara all declare no potential conflicts of interest relevant to this article.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of Importance

  1. 1.
    Thompson JE. The evolution of surgery for the treatment and prevention of stroke. The Willis Lecture. Stroke. 1996;27:1427–34.PubMedCrossRefGoogle Scholar
  2. 2.
    Nilsen M. A historical account of stroke and the evolution of nursing care for stroke patients. J Neurosci Nurs: J Am Assoc Neurosci Nurs. 2010;42:19–27.CrossRefGoogle Scholar
  3. 3.
    Barnhart RK, Steinmetz S. The barnhart dictionary of etymology. Bronx: H.W. Wilson Co.; 1988.Google Scholar
  4. 4.
    Caplan LR. Cerebrovascular disease: historical background, with an eye to the future. Cleve Clin J Med. 2004;71 Suppl 1:S22–24.PubMedCrossRefGoogle Scholar
  5. 5.
    Paciaroni M, Bogousslavsky J. The history of stroke and cerebrovascular disease. Handbook Clin Neurol. 2009;92:3–28.CrossRefGoogle Scholar
  6. 6.
    Wolf PA, Grotta JC. Cerebrovascular disease. Circulation. 2000;102:IV75–80.PubMedCrossRefGoogle Scholar
  7. 7.
    Go A, Mozaffarian D, Roger V, et al. Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation 2013, 127.Google Scholar
  8. 8.
    del Zoppo GJ, Poeck K, Pessin MS, et al. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol. 1992;32:78–86.PubMedCrossRefGoogle Scholar
  9. 9.
    The national institute of neurological disorders and stroke rt-PA stroke study Group. Tissue plasminogen activator for acute ischemic stroke. N Eng J Med. 1995;333:1581–7.CrossRefGoogle Scholar
  10. 10.
    Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359:1317–29.PubMedCrossRefGoogle Scholar
  11. 11.
    Kasner S. Editorial comment–More than one way to lyse a clot. Stroke; J Cereb Circul. 2004;35:911–2.Google Scholar
  12. 12.
    de Los Ríos la Rosa F, Khoury J, Kissela B, et al. Eligibility for Intravenous recombinant tissue-type plasminogen activator within a population: the effect of the european cooperative acute stroke study (ECASS) III trial. Stroke; J Cereb Circul. 2012;43:1591–5.CrossRefGoogle Scholar
  13. 13.
    Alexandrov AV, Grotta JC. Arterial reocclusion in stroke patients treated with intravenous tissue plasminogen activator. Neurology. 2002;59:862–7.PubMedCrossRefGoogle Scholar
  14. 14.
    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. JAMA. 1999;282:2003–11.PubMedCrossRefGoogle Scholar
  15. 15.
    Rha J-H, Saver J. The impact of recanalization on ischemic stroke outcome: A meta-analysis. Stroke; J Cereb Circul. 2007;38:967–73.CrossRefGoogle Scholar
  16. 16.
    Bhatia R, Hill MD, Shobha N, et al. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke. 2010;41:2254–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Phan TG, Wright PM, Markus R, Howells DW, Davis SM, Donnan GA. Salvaging the ischaemic penumbra: more than just reperfusion? Clin Exp Pharm & Physiol. 2002;29:1–10.CrossRefGoogle Scholar
  18. 18.
    Nogueira RG, Schwamm LH, Hirsch JA. Endovascular approaches to acute stroke, part 1: Drugs, devices, and data. AJNR. 2009;30:649–61.PubMedCrossRefGoogle Scholar
  19. 19.
    Gobin Y, Starkman S, Duckwiler G, et al. MERCI 1: A phase 1 study of mechanical embolus removal in cerebral ischemia. Stroke; J Cereb Circul. 2004;35:2848–54.CrossRefGoogle Scholar
  20. 20.
    Smith W, Sung G, Saver J, et al. Mechanical thrombectomy for acute ischemic stroke: final results of the multi MERCI trial. Stroke; J Cereb Circul. 2008;39:1205–12.CrossRefGoogle Scholar
  21. 21.
    Smith W, Sung G, Starkman S, et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke; J Cereb Circul. 2005;36:1432–8.CrossRefGoogle Scholar
  22. 22.
    Penumbra Pivotal Stroke Trial I. The penumbra pivotal stroke trial: safety and effectiveness of a new generation of mechanical devices for clot removal in intracranial large vessel occlusive disease. Stroke; J Cereb Circul. 2009;40:2761–8.CrossRefGoogle Scholar
  23. 23.
    Tarr R, Hsu D, Kulcsar Z, et al. The POST trial: initial post-market experience of the Penumbra system: Revascularization of large vessel occlusion in acute ischemic stroke in the United States and Europe. J Neurointerventional Surg. 2010;2:341–4.CrossRefGoogle Scholar
  24. 24.
    Nogueira R, Lutsep H, Gupta R, et al. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet. 2012;380:1231–40.PubMedCrossRefGoogle Scholar
  25. 25.
    Saver J, Jahan R, Levy E, et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet. 2012;380:1241–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Riedel CH, Zimmermann P, Jensen-Kondering U, Stingele R, Deuschl G, Jansen O. The importance of size: successful recanalization by intravenous thrombolysis in acute anterior stroke depends on thrombus length. Stroke. 2011;42:1775–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Hussein H, Georgiadis A, Vazquez G, et al. Occurrence and predictors of futile recanalization following endovascular treatment among patients with acute ischemic stroke: a multicenter study. AJNR. 2010;31:454–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Baker W, Colby J, Tongbram V, et al. Neurothrombectomy devices for the treatment of acute ischemic stroke: state of the evidence. Ann Intern Med. 2011;154:243–52.PubMedCrossRefGoogle Scholar
  29. 29.
    Fargen K, Meyers P, Khatri P, Mocco J. Improvements in recanalization with modern stroke therapy: a review of prospective ischemic stroke trials during the last two decades. Journal of Neurointerventional Surgery 2012.Google Scholar
  30. 30.•
    Broderick J, Palesch Y, Demchuk A, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Eng J Med. 2013;368:893–903. This RCT study stopped at 656 participants after a futility analysis showed no functional benefit of endovascular therapy combined with IV thrombolysis compared to IV thrombolysis alone in patients with acute ischemic stroke..CrossRefGoogle Scholar
  31. 31.•
    Ciccone A, Valvassori L, Nichelatti M, et al. Endovascular treatment for acute ischemic stroke. N Eng J Med. 2013;368:904–13. This RCT suggests that intra-arterial therapy does not have clinical benefits compared to IV thrombolysis; however, the study was criticized for study design such as not controlling for IV tPA and delayed treatment in endovascular therapy..CrossRefGoogle Scholar
  32. 32.•
    Kidwell C, Jahan R, Gornbein J, et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N Eng J Med. 2013;368:914–23. This RCT study found no favorable clinical benefits in treating acute ischemic stroke patients with penumbral cores than those with non-penumbral cores..CrossRefGoogle Scholar
  33. 33.•
    Lansberg M, Straka M, Kemp S, et al. MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study. Lancet neurology. 2012;11:860–7. This prospective cohort study showed that patients with target mismatch demonstrated better clinical response and functional outcomes to endovascular therapy than those without target mismatch..PubMedCrossRefGoogle Scholar
  34. 34.
    Khalessi A, Fargen K, Lavine S, Mocco J. Commentary: societal statement on recent acute stroke intervention trials: results and implications. Neurosurgery 2013.Google Scholar
  35. 35.
    Liebeskind DS. Trials of endovascular therapies or collaterals? Int J Stroke. 2013;8:258–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Pierot L, Gralla J, Cognard C, White P. Mechanical thrombectomy after IMS III, synthesis, and MR-RESCUE. AJNR American journal of neuroradiology 2013Google Scholar
  37. 37.
    Leker R, Eichel R, Gomori J, Ramirez-de-Noriega F, Ben-Hur T, Cohen J. Stent-based thrombectomy versus intravenous tissue plasminogen activator in patients with acute middle cerebral artery occlusion. Stroke; J Cereb Circul. 2012;43:3389–91.CrossRefGoogle Scholar
  38. 38.
    Broderick J, Tomsick T, Palesch Y. Endovascular treatment for acute ischemic stroke. N Eng J Med. 2013;368:2432–3.CrossRefGoogle Scholar
  39. 39.
    Jadhav A, Jovin T. Intra-arterial reperfusion strategies in acute ischemic stroke. J Neurointerventional Surg. 2013;5(1):9.Google Scholar
  40. 40.
    Singh V, Edwards N. Advances in the critical care management of ischemic stroke. Stroke Res Treat. 2013;2013:510481.PubMedCentralPubMedGoogle Scholar
  41. 41.
    Teramoto S, Shimura H, Tanaka R, et al. Human-derived physiological heat shock protein 27 complex protects brain after focal cerebral ischemia in mice. PloS one 2013, 8.Google Scholar
  42. 42.
    O'Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW. 1,026 experimental treatments in acute stroke. Ann Neurol. 2006;59:467–77.PubMedCrossRefGoogle Scholar
  43. 43.
    Howells D, Donnan G. Where will the next generation of stroke treatments come from? PLoS medicine 2010, 7.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Alex Y. Lu
    • 1
    • 6
  • Sameer A. Ansari
    • 2
  • Karin V. Nyström
    • 3
    • 7
  • Eyiyemisi C. Damisah
    • 1
  • Hardik P. Amin
    • 4
  • Charles C. Matouk
    • 1
    • 8
  • Rashmi D. Pashankar
    • 5
    • 9
  • Ketan R. Bulsara
    • 1
    • 9
    Email author
  1. 1.Department of NeurosurgeryYale School of MedicineNew HavenUSA
  2. 2.Department of RadiologyNorthwestern University Feinberg School of MedicineChicagoUSA
  3. 3.Yale-New Haven Stroke CenterYale-New Haven HospitalNew HavenUSA
  4. 4.Department of NeurologyYale University School of Medicine, Yale New Haven Stroke CenterNew HavenUSA
  5. 5.University of ConnecticutStorrsUSA
  6. 6.New HavenUSA
  7. 7.Yale-New Haven Stroke CenterNew HavenUSA
  8. 8.Yale NeurosurgeryNew HavenUSA
  9. 9.New HavenUSA

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