Skip to main content

Advertisement

SpringerLink
Log in

Emerging issues in acute ischemic stroke

  • Medical Progress in the Journal of Neurology
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

In this update we review studies on a wide range of topics, from diagnostic aspects of acute stroke to the clinical implications of the complex interaction between the brain and the immune system. Recent randomized trials and observational studies have reinforced the effectiveness of intravenous thrombolysis with t-PA in patients that qualify for this treatment, including patients presenting with mild symptoms or on subtherapeutic oral anticoagulation. Despite all the negative studies on the endovascular treatment of acute stroke, the utility of newer mechanical thrombectomy devices in patients with stroke and large vessel occlusion is being assessed in ongoing clinical trials. In addition to the various revascularization therapies that have a limited time window, treatments aimed at protecting the neurovascular unit may be used in more patients if their efficacy is confirmed in humans, and experimental studies suggest that the modulation of specific aspects of the immune system may increase the likelihood of successful recovery after cerebral ischemia.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hom J, Dankbaar JW, Soares BP, Schneider T, Cheng SC, Bredno J, Lau BC, Smith W, Dillon WP, Wintermark M (2011) Blood-brain barrier permeability assessed by perfusion CT predicts symptomatic hemorrhagic transformation and malignant edema in acute ischemic stroke. AJNR Am J Neuroradiol 32:41–48

    Article  PubMed  CAS  Google Scholar 

  2. Desilles JP, Rouchaud A, Labreuche J, Meseguer E, Laissy JP, Serfaty JM, Lapergue B, Klein IF, Guidoux C, Cabrejo L, Sirimarco G, Lavallée PC, Schouman-Claeys E, Amarenco P, Mazighi M (2013) Blood-brain barrier disruption is associated with increased mortality after endovascular therapy. Neurology 80:844–851

    Article  PubMed  Google Scholar 

  3. Walter S, Kostopoulos P, Haass A, Keller I, Lesmeister M, Schlechtriemen T, Roth C, Papanagiotou P, Grunwald I, Schumacher H, Helwig S, Viera J, Körner H, Alexandrou M, Yilmaz U, Ziegler K, Schmidt K, Dabew R, Kubulus D, Liu Y, Volk T, Kronfeld K, Ruckes C, Bertsch T, Reith W, Fassbender K (2012) Diagnosis and treatment of patients with stroke in a mobile stroke unit versus in hospital: a randomised controlled trial. Lancet Neurol 11:397–404. doi:10.1016/S1474-4422(12)70057-1

    Article  PubMed  Google Scholar 

  4. Strbian D, Engelter S, Michel P, Meretoja A, Sekoranja L, Ahlhelm FJ, Mustanoja S, Kuzmanovic I, Sairanen T, Forss N, Cordier M, Lyrer P, Kaste M, Tatlisumak T (2012) Symptomatic intracranial hemorrhage after stroke thrombolysis: the SEDAN score. Ann Neurol 71:634–641

    Article  PubMed  Google Scholar 

  5. Xian Y, Liang L, Smith EE, Schwamm LH, Reeves MJ, Olson DM, Hernandez AF, Fonarow GC, Peterson ED (2012) Risks of intracranial hemorrhage among patients with acute ischemic stroke receiving warfarin and treated with intravenous tissue plasminogen activator. JAMA 307:2600–2608

    Article  PubMed  CAS  Google Scholar 

  6. Urra X, Ariño H, Llull L, Amaro S, Obach V, Cervera A, Chamorro A (2013) The outcome of patients with mild stroke improves after treatment with systemic thrombolysis. PLoS ONE 8:e59420. doi:10.1371/journal.pone.0059420

    Article  PubMed  CAS  Google Scholar 

  7. IST-3 Collaborative Group, Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, Murray G, Innes K, Venables G, Czlonkowska A, Kobayashi A, Ricci S, Murray V, Berge E, Slot KB, Hankey GJ, Correia M, Peeters A, Matz K, Lyrer P, Gubitz G, Phillips SJ, Arauz A (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. Lancet 379:2352–2363

    Article  PubMed  Google Scholar 

  8. Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, O’Brien B, Bladin C, McElduff P, Allen C, Bateman G, Donnan G, Davis S, Levi C (2012) A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med 366:1099–1107

    Article  PubMed  CAS  Google Scholar 

  9. 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 JRTR, Ryckborst KJ, Janis LS, Martin RH, Foster LD, Tomsick TA, The Interventional Management of Stroke (IMS) III Investigators (2013) Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 368:893–903

    Article  PubMed  CAS  Google Scholar 

  10. Ciccone A, Valvassori L, Nichelatti M, Sgoifo A, Ponzio M, Sterzi R, Boccardi E, The SYNTHESIS Expansion Investigators (2013) Endovascular treatment for acute ischemic stroke. N Engl J Med 368:904–913

    Article  PubMed  CAS  Google Scholar 

  11. Lansberg MG, Straka M, Kemp S, Mlynash M, Wechsler LR, Jovin TG, Wilder MJ, Lutsep HL, Czartoski TJ, Bernstein RA, Chang CW, Warach S, Fazekas F, Inoue M, Tipirneni A, Hamilton SA, Zaharchuk G, Marks MP, Bammer R, Albers GW, DEFUSE 2 Study Investigators (2012) MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study. Lancet Neurol 11:860–867

    Article  PubMed  Google Scholar 

  12. 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, The MR RESCUE Investigators (2013) A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med 368:914–923

    Article  PubMed  CAS  Google Scholar 

  13. Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG, Clark W, Budzik R, Zaidat OO, for the SWIFT Trialists (2012) Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet 380:1241–1249

    Article  PubMed  Google Scholar 

  14. Nogueira RG, Lutsep HL, Gupta R, Jovin TG, Albers GW, Walker GA, Liebeskind DS, Smith WS, for the TREVO 2 Trialists (2012) Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet 380:1231–1240

    Article  PubMed  Google Scholar 

  15. Amaro S, Chamorro Á (2011) Translational stroke research of the combination of thrombolysis and antioxidant therapy. Stroke 42:1495–1499

    Article  PubMed  CAS  Google Scholar 

  16. Zinkstok SM, Roos YB, on behalf of the ARTIS Investigators (2012) Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet 380:731–737

    Article  PubMed  CAS  Google Scholar 

  17. Amaro S, Cánovas D, Castellanos M, Gállego J, Martí-Fábregas J, Segura T, Chamorro A (2010) The URICO-ICTUS study, a phase 3 study of combined treatment with uric acid and rt-PA administered intravenously in acute ischaemic stroke patients within the first 4.5 h of onset of symptoms. Int J Stroke 5:325–328

    Article  PubMed  Google Scholar 

  18. Amaro S, Urra X, Gómez-Choco M, Obach V, Cervera A, Vargas M, Torres F, Rios J, Planas AM, Chamorro A (2011) Uric acid levels are relevant in patients with stroke treated with thrombolysis. Stroke 42:S28–S32

    Article  PubMed  CAS  Google Scholar 

  19. Amaro S, Soy D, Obach V, Cervera A, Planas AM, Chamorro A (2007) A pilot study of dual treatment with recombinant tissue plasminogen activator and uric acid in acute ischemic stroke. Stroke 38:2173–2175

    Article  PubMed  CAS  Google Scholar 

  20. Amaro S, Obach V, Cervera A, Urra X, Gómez-Choco M, Planas AM, Chamorro A (2009) Course of matrix metalloproteinase-9 isoforms after the administration of uric acid in patients with acute stroke: a proof-of-concept study. J Neurol 256:651–656

    Article  PubMed  CAS  Google Scholar 

  21. van der Worp HB, Sena ES, Donnan GA, Howells DW, Macleod MR (2007) Hypothermia in animal models of acute ischaemic stroke: a systematic review and meta-analysis. Brain 130:3063–3074

    Article  PubMed  Google Scholar 

  22. Silasi G, Klahr AC, Hackett MJ, Auriat AM, Nichol H, Colbourne F (2012) Prolonged therapeutic hypothermia does not adversely impact neuroplasticity after global ischemia in rats. J Cereb Blood Flow Metab 32:1525–1534

    Article  PubMed  CAS  Google Scholar 

  23. van der Worp HB, Macleod MR, Kollmar R, European Stroke Research Network for Hypothermia (EuroHYP) (2010) Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials? J Cereb Blood Flow Metab 30:1079–1093. doi:10.1038/jcbfm.2010.44

    Article  PubMed  Google Scholar 

  24. Dávalos A, Alvarez-Sabín J, Castillo J, Díez-Tejedor E, Ferro J, Martínez-Vila E, Serena J, Segura T, Cruz VT, Masjuan J, Cobo E, Secades JJ, International Citicoline Trial on acUte Stroke (ICTUS) Trial Investigators (2012) Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). Lancet 380:349–357

    Article  PubMed  Google Scholar 

  25. Cook DJ, Teves L, Tymianski M (2012) Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature 483:213–217

    Article  PubMed  CAS  Google Scholar 

  26. Hill MD, Martin RH, Mikulis D, Wong JH, Silver FL, Terbrugge KG, Milot G, Clark WM, Macdonald RL, Kelly ME, Boulton M, Fleetwood I, McDougall C, Gunnarsson T, Chow M, Lum C, Dodd R, Poublanc J, Krings T, Demchuk AM, Goyal M, Anderson R, Bishop J, Garman D, Tymianski M, ENACT Trial Investigators (2012) Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double blind, placebo-controlled trial. Lancet Neurol 11:942–950

    Article  PubMed  CAS  Google Scholar 

  27. Kaste M (2012) Is the door open again for neuroprotection trials in stroke? Lancet Neurol 11:930–931

    Article  PubMed  Google Scholar 

  28. Chamorro Á, Meisel A, Planas AM, Urra X, van de Beek D, Veltkamp R (2012) The immunology of acute stroke. Nat Rev Neurol 8:401–410

    Article  PubMed  CAS  Google Scholar 

  29. Planas AM, Gómez-Choco M, Urra X, Gorina R, Caballero M, Chamorro Á (2012) Brain-derived antigens in lymphoid tissue of patients with acute stroke. J Immunol 188:2156–2163

    Article  PubMed  CAS  Google Scholar 

  30. Becker KJ, Kalil AJ, Tanzi P, Zierath DK, Savos AV, Gee JM, Hadwin J, Carter KT, Shibata D, Cain KC (2011) Autoimmune responses to the brain after stroke are associated with worse outcome. Stroke 42:2763–2769. doi:10.1161/STROKEAHA.111.619593

    Article  PubMed  CAS  Google Scholar 

  31. Shichita T, Hasegawa E, Kimura A, Morita R, Sakaguchi R, Takada I, Sekiya T, Ooboshi H, Kitazono T, Yanagawa T, Ishii T, Takahashi H, Mori S, Nishibori M, Kuroda K, Akira S, Miyake K, Yoshimura A (2012) Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain. Nat Med 18:911–917

    Article  PubMed  CAS  Google Scholar 

  32. Gliem M, Mausberg AK, Lee JI, Simiantonakis I, van Rooijen N, Hartung HP, Jander S (2012) Macrophages prevent hemorrhagic infarct transformation in murine stroke models. Ann Neurol 71:743–752. doi:10.1002/ana.23529

    Article  PubMed  CAS  Google Scholar 

  33. Misra V, Ritchie MM, Stone LL, Low WC, Janardhan V (2012) Stem cell therapy in ischemic stroke: role of IV and intra-arterial therapy. Neurology 79:S207–S212

    Article  PubMed  CAS  Google Scholar 

  34. Oki K, Tatarishvili J, Wood J, Koch P, Wattananit S, Mine Y, Monni E, Tornero D, Ahlenius H, Ladewig J, Brüstle O, Lindvall O, Kokaia Z (2012) Human-induced pluripotent stem cells form functional neurons and improve recovery after grafting in stroke-damaged brain. Stem Cells 30:1120–1133

    Article  PubMed  CAS  Google Scholar 

  35. Rosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ (2011) Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 334:98–101. doi:10.1126/science.1209985

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was partially supported by the Melchior Colet Foundation.

Conflicts of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Functional Unit of Cerebrovascular Diseases, Hospital Clínic, Barcelona, Spain

    Xabier Urra & Ángel Chamorro

  2. Institut d’Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain

    Xabier Urra & Ángel Chamorro

  3. Medicine Department, School of Medicine, UB, Barcelona, Spain

    Ángel Chamorro

  4. Institute of Neurosciences, 170 Villarroel, 08036, Barcelona, Spain

    Ángel Chamorro

Authors
  1. Xabier Urra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ángel Chamorro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ángel Chamorro.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Urra, X., Chamorro, Á. Emerging issues in acute ischemic stroke. J Neurol 260, 1687–1692 (2013). https://doi.org/10.1007/s00415-013-6919-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-013-6919-x

Keywords

Search

Navigation