Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Reperfusion therapy for acute ischemic stroke

Jamary Oliveira Filho, MD, MS, PhD
Owen B Samuels, MD
Section Editor
Jose Biller, MD, FACP, FAAN, FAHA
Deputy Editor
John F Dashe, MD, PhD


The management of patients who have had an ischemic stroke involves several phases. The goals in the initial phase include:

Ensuring medical stability

Quickly reversing any conditions that are contributing to the symptoms

Determining if patients with acute ischemic stroke are candidates for thrombolytic therapy (table 1)

Uncovering the pathophysiologic basis of the neurologic symptoms


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Apr 2017. | This topic last updated: Apr 25, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Lees KR, Bluhmki E, von Kummer R, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010; 375:1695.
  2. Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013; 309:2480.
  3. Wardlaw JM, Murray V, Berge E, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet 2012; 379:2364.
  4. Emberson J, Lees KR, Lyden P, et al. 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.
  5. Prabhakaran S, Ruff I, Bernstein RA. Acute stroke intervention: a systematic review. JAMA 2015; 313:1451.
  6. Whiteley WN, Emberson J, Lees KR, et al. Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis. Lancet Neurol 2016; 15:925.
  7. Lees KR, Emberson J, Blackwell L, et al. Effects of Alteplase for Acute Stroke on the Distribution of Functional Outcomes: A Pooled Analysis of 9 Trials. Stroke 2016; 47:2373.
  8. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333:1581.
  9. Kwiatkowski TG, Libman RB, Frankel M, et al. Effects of tissue plasminogen activator for acute ischemic stroke at one year. National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study Group. N Engl J Med 1999; 340:1781.
  10. Schmülling S, Grond M, Rudolf J, Heiss WD. One-year follow-Up in acute stroke patients treated with rtPA in clinical routine. Stroke 2000; 31:1552.
  11. Marler JR, Tilley BC, Lu M, et al. Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study. Neurology 2000; 55:1649.
  12. 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.
  13. Bluhmki E, Chamorro A, Dávalos A, et al. Stroke treatment with alteplase given 3.0-4.5 h after onset of acute ischaemic stroke (ECASS III): additional outcomes and subgroup analysis of a randomised controlled trial. Lancet Neurol 2009; 8:1095.
  14. Clark WM, Albers GW, Madden KP, Hamilton S. The rtPA (alteplase) 0- to 6-hour acute stroke trial, part A (A0276g) : results of a double-blind, placebo-controlled, multicenter study. Thromblytic therapy in acute ischemic stroke study investigators. Stroke 2000; 31:811.
  15. Clark WM, Wissman S, Albers GW, et al. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999; 282:2019.
  16. Hacke W, Kaste M, Fieschi C, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet 1998; 352:1245.
  17. Wahlgren N, Ahmed N, Dávalos A, et al. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet 2008; 372:1303.
  18. Ahmed N, Wahlgren N, Grond M, et al. Implementation and outcome of thrombolysis with alteplase 3-4.5 h after an acute stroke: an updated analysis from SITS-ISTR. Lancet Neurol 2010; 9:866.
  19. IST-3 collaborative group, Sandercock P, Wardlaw JM, et al. 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 2012; 379:2352.
  20. Lyden PD. In anticipation of International Stroke Trial-3 (IST-3). Stroke 2012; 43:1691.
  21. Kleindorfer D, Kissela B, Schneider A, et al. Eligibility for recombinant tissue plasminogen activator in acute ischemic stroke: a population-based study. Stroke 2004; 35:e27.
  22. Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke 2007; 38:967.
  23. Neumann-Haefelin T, du Mesnil de Rochemont R, Fiebach JB, et al. Effect of incomplete (spontaneous and postthrombolytic) recanalization after middle cerebral artery occlusion: a magnetic resonance imaging study. Stroke 2004; 35:109.
  24. Wunderlich MT, Goertler M, Postert T, et al. Recanalization after intravenous thrombolysis: does a recanalization time window exist? Neurology 2007; 68:1364.
  25. 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.
  26. Kharitonova TV, Melo TP, Andersen G, et al. Importance of cerebral artery recanalization in patients with stroke with and without neurological improvement after intravenous thrombolysis. Stroke 2013; 44:2513.
  27. Alexandrov AV, Felberg RA, Demchuk AM, et al. Deterioration following spontaneous improvement : sonographic findings in patients with acutely resolving symptoms of cerebral ischemia. Stroke 2000; 31:915.
  28. Rajajee V, Kidwell C, Starkman S, et al. Early MRI and outcomes of untreated patients with mild or improving ischemic stroke. Neurology 2006; 67:980.
  29. Nedeltchev K, Schwegler B, Haefeli T, et al. Outcome of stroke with mild or rapidly improving symptoms. Stroke 2007; 38:2531.
  30. Mazighi M, Meseguer E, Labreuche J, et al. Dramatic recovery in acute ischemic stroke is associated with arterial recanalization grade and speed. Stroke 2012; 43:2998.
  31. Alexandrov AV, Hall CE, Labiche LA, et al. Ischemic stunning of the brain: early recanalization without immediate clinical improvement in acute ischemic stroke. Stroke 2004; 35:449.
  32. Allport LE, Parsons MW, Butcher KS, et al. Elevated hematocrit is associated with reduced reperfusion and tissue survival in acute stroke. Neurology 2005; 65:1382.
  33. Grotta J, Ackerman R, Correia J, et al. Whole blood viscosity parameters and cerebral blood flow. Stroke 1982; 13:296.
  34. Thomas DJ. Whole blood viscosity and cerebral blood flow. Stroke 1982; 13:285.
  35. Zivin JA, Fisher M, DeGirolami U, et al. Tissue plasminogen activator reduces neurological damage after cerebral embolism. Science 1985; 230:1289.
  36. Mori E, Yoneda Y, Tabuchi M, et al. Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke. Neurology 1992; 42:976.
  37. Wolpert SM, Bruckmann H, Greenlee R, et al. Neuroradiologic evaluation of patients with acute stroke treated with recombinant tissue plasminogen activator. The rt-PA Acute Stroke Study Group. AJNR Am J Neuroradiol 1993; 14:3.
  38. von Kummer R, Holle R, Rosin L, et al. Does arterial recanalization improve outcome in carotid territory stroke? Stroke 1995; 26:581.
  39. Suarez JI, Sunshine JL, Tarr R, et al. Predictors of clinical improvement, angiographic recanalization, and intracranial hemorrhage after intra-arterial thrombolysis for acute ischemic stroke. Stroke 1999; 30:2094.
  40. Linfante I, Llinas RH, Selim M, et al. Clinical and vascular outcome in internal carotid artery versus middle cerebral artery occlusions after intravenous tissue plasminogen activator. Stroke 2002; 33:2066.
  41. Molina CA, Montaner J, Arenillas JF, et al. Differential pattern of tissue plasminogen activator-induced proximal middle cerebral artery recanalization among stroke subtypes. Stroke 2004; 35:486.
  42. Lee KY, Han SW, Kim SH, et al. Early recanalization after intravenous administration of recombinant tissue plasminogen activator as assessed by pre- and post-thrombolytic angiography in acute ischemic stroke patients. Stroke 2007; 38:192.
  43. Saqqur M, Uchino K, Demchuk AM, et al. Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke. Stroke 2007; 38:948.
  44. Seners P, Turc G, Maïer B, et al. Incidence and Predictors of Early Recanalization After Intravenous Thrombolysis: A Systematic Review and Meta-Analysis. Stroke 2016; 47:2409.
  45. Fulgham JR, Ingall TJ, Stead LG, et al. Management of acute ischemic stroke. Mayo Clin Proc 2004; 79:1459.
  46. Kim EY, Heo JH, Lee SK, et al. Prediction of thrombolytic efficacy in acute ischemic stroke using thin-section noncontrast CT. Neurology 2006; 67:1846.
  47. Overgaard K. Thrombolytic therapy in experimental embolic stroke. Cerebrovasc Brain Metab Rev 1994; 6:257.
  48. Brommer EJ, van Bockel JH. Composition and susceptibility to thrombolysis of human arterial thrombi and the influence of their age. Blood Coagul Fibrinolysis 1992; 3:717.
  49. Zangerle A, Kiechl S, Spiegel M, et al. Recanalization after thrombolysis in stroke patients: predictors and prognostic implications. Neurology 2007; 68:39.
  50. Georgiadis D, Oehler J, Schwarz S, et al. Does acute occlusion of the carotid T invariably have a poor outcome? Neurology 2004; 63:22.
  51. Wunderlich MT, Stolz E, Seidel G, et al. Conservative medical treatment and intravenous thrombolysis in acute stroke from carotid T occlusion. Cerebrovasc Dis 2005; 20:355.
  52. Kim YS, Garami Z, Mikulik R, et al. Early recanalization rates and clinical outcomes in patients with tandem internal carotid artery/middle cerebral artery occlusion and isolated middle cerebral artery occlusion. Stroke 2005; 36:869.
  53. Alexandrov AV, Molina CA, Grotta JC, et al. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 2004; 351:2170.
  54. Albers GW, Thijs VN, Wechsler L, et al. Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Ann Neurol 2006; 60:508.
  55. Qureshi AI, Ezzeddine MA, Nasar A, et al. Is IV tissue plasminogen activator beneficial in patients with hyperdense artery sign? Neurology 2006; 66:1171.
  56. Kimura K, Iguchi Y, Shibazaki K, et al. M1 susceptibility vessel sign on T2* as a strong predictor for no early recanalization after IV-t-PA in acute ischemic stroke. Stroke 2009; 40:3130.
  57. Kimura K, Sakamoto Y, Aoki J, et al. Clinical and MRI predictors of no early recanalization within 1 hour after tissue-type plasminogen activator administration. Stroke 2011; 42:3150.
  58. Mattle HP, Arnold M, Lindsberg PJ, et al. Basilar artery occlusion. Lancet Neurol 2011; 10:1002.
  59. Strbian D, Sairanen T, Silvennoinen H, et al. Thrombolysis of basilar artery occlusion: impact of baseline ischemia and time. Ann Neurol 2013; 73:688.
  60. Gory B, Eldesouky I, Sivan-Hoffmann R, et al. Outcomes of stent retriever thrombectomy in basilar artery occlusion: an observational study and systematic review. J Neurol Neurosurg Psychiatry 2016; 87:520.
  61. Molina CA. Editorial comment--degree of arterial recanalization: an end point for efficacy in future intravenous thrombolytic trials. Stroke 2004; 35:114.
  62. Heuschmann PU, Kolominsky-Rabas PL, Roether J, et al. Predictors of in-hospital mortality in patients with acute ischemic stroke treated with thrombolytic therapy. JAMA 2004; 292:1831.
  63. Albers GW, Bates VE, Clark WM, et al. Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) study. JAMA 2000; 283:1145.
  64. Saposnik G, Young B, Silver B, et al. Lack of improvement in patients with acute stroke after treatment with thrombolytic therapy: predictors and association with outcome. JAMA 2004; 292:1839.
  65. Saposnik G, Di Legge S, Webster F, Hachinski V. Predictors of major neurologic improvement after thrombolysis in acute stroke. Neurology 2005; 65:1169.
  66. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. The NINDS t-PA Stroke Study Group. Stroke 1997; 28:2109.
  67. Generalized efficacy of t-PA for acute stroke. Subgroup analysis of the NINDS t-PA Stroke Trial. Stroke 1997; 28:2119.
  68. Hemphill JC 3rd, Lyden P. Stroke thrombolysis in the elderly: risk or benefit? Neurology 2005; 65:1690.
  69. Mishra NK, Ahmed N, Andersen G, et al. Thrombolysis in very elderly people: controlled comparison of SITS International Stroke Thrombolysis Registry and Virtual International Stroke Trials Archive. BMJ 2010; 341:c6046.
  70. Sylaja PN, Cote R, Buchan AM, et al. Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian Alteplase for Stroke Effectiveness Study. J Neurol Neurosurg Psychiatry 2006; 77:826.
  71. Kent DM, Price LL, Ringleb P, et al. Sex-based differences in response to recombinant tissue plasminogen activator in acute ischemic stroke: a pooled analysis of randomized clinical trials. Stroke 2005; 36:62.
  72. Meseguer E, Mazighi M, Labreuche J, et al. Outcomes of intravenous recombinant tissue plasminogen activator therapy according to gender: a clinical registry study and systematic review. Stroke 2009; 40:2104.
  73. Hametner C, MacIsaac RL, Kellert L, et al. Sex and Stroke in Thrombolyzed Patients and Controls. Stroke 2017; 48:367.
  74. Alvarez-Sabín J, Molina CA, Montaner J, et al. Effects of admission hyperglycemia on stroke outcome in reperfused tissue plasminogen activator--treated patients. Stroke 2003; 34:1235.
  75. Ahmed N, Dávalos A, Eriksson N, et al. Association of admission blood glucose and outcome in patients treated with intravenous thrombolysis: results from the Safe Implementation of Treatments in Stroke International Stroke Thrombolysis Register (SITS-ISTR). Arch Neurol 2010; 67:1123.
  76. Ribo M, Molina C, Montaner J, et al. Acute hyperglycemia state is associated with lower tPA-induced recanalization rates in stroke patients. Stroke 2005; 36:1705.
  77. Alvarez-Sabín J, Molina CA, Ribó M, et al. Impact of admission hyperglycemia on stroke outcome after thrombolysis: risk stratification in relation to time to reperfusion. Stroke 2004; 35:2493.
  78. Grotta JC, Welch KM, Fagan SC, et al. Clinical deterioration following improvement in the NINDS rt-PA Stroke Trial. Stroke 2001; 32:661.
  79. Alexandrov AV, Grotta JC. Arterial reocclusion in stroke patients treated with intravenous tissue plasminogen activator. Neurology 2002; 59:862.
  80. Rubiera M, Alvarez-Sabín J, Ribo M, et al. Predictors of early arterial reocclusion after tissue plasminogen activator-induced recanalization in acute ischemic stroke. Stroke 2005; 36:1452.
  81. Heo JH, Lee KY, Kim SH, Kim DI. Immediate reocclusion following a successful thrombolysis in acute stroke: a pilot study. Neurology 2003; 60:1684.
  82. Georgiadis D, Engelter S, Tettenborn B, et al. Early recurrent ischemic stroke in stroke patients undergoing intravenous thrombolysis. Circulation 2006; 114:237.
  83. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015; 372:11.
  84. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015; 372:1019.
  85. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015; 372:2285.
  86. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015; 372:1009.
  87. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015; 372:2296.
  88. Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016; 387:1723.
  89. van den Berg LA, Dijkgraaf MG, Berkhemer OA, et al. Two-Year Outcome after Endovascular Treatment for Acute Ischemic Stroke. N Engl J Med 2017; 376:1341.
  90. Dávalos A, Cobo E, Molina CA, et al. Safety and efficacy of thrombectomy in acute ischaemic stroke (REVASCAT): 1-year follow-up of a randomised open-label trial. Lancet Neurol 2017; 16:369.
  91. Marmagkiolis K, Hakeem A, Cilingiroglu M, et al. Safety and Efficacy of Stent Retrievers for the Management of Acute Ischemic Stroke: Comprehensive Review and Meta-Analysis. JACC Cardiovasc Interv 2015; 8:1758.
  92. Campbell BC, Donnan GA, Lees KR, et al. Endovascular stent thrombectomy: the new standard of care for large vessel ischaemic stroke. Lancet Neurol 2015; 14:846.
  93. Consensus statement on mechanical thrombectomy in acute ischemic stroke – ESO-Karolinska Stroke Update 2014 in collaboration with ESMINT and ESNR. http://2014.strokeupdate.org/consensus-statement-mechanical-thrombectomy-acute-ischemic-stroke (Accessed on July 13, 2015).
  94. Powers WJ, Derdeyn CP, Biller J, et al. 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.
  95. Fransen PS, Berkhemer OA, Lingsma HF, et al. Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke: A Randomized Clinical Trial. JAMA Neurol 2016; 73:190.
  96. Touma L, Filion KB, Sterling LH, et al. Stent Retrievers for the Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Neurol 2016; 73:275.
  97. Tsivgoulis G, Katsanos AH, Mavridis D, et al. Mechanical Thrombectomy Improves Functional Outcomes Independent of Pretreatment With Intravenous Thrombolysis. Stroke 2016; 47:1661.
  98. Saver JL, Goyal M, van der Lugt A, et al. Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis. JAMA 2016; 316:1279.
  99. Ciccone A, Valvassori L, Nichelatti M, et al. Endovascular treatment for acute ischemic stroke. N Engl J Med 2013; 368:904.
  100. Broderick JP, Palesch YY, Demchuk AM, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 2013; 368:893.
  101. Kidwell CS, Jahan R, Gornbein J, et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med 2013; 368:914.
  102. Hacke W. Interventional thrombectomy for major stroke--a step in the right direction. N Engl J Med 2015; 372:76.
  103. Smith WS, Sung G, Starkman S, et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke 2005; 36:1432.
  104. Brinjikji W, Rabinstein AA, Kallmes DF, Cloft HJ. Patient outcomes with endovascular embolectomy therapy for acute ischemic stroke: a study of the national inpatient sample: 2006 to 2008. Stroke 2011; 42:1648.
  105. Broderick JP, Schroth G. What the SWIFT and TREVO II trials tell us about the role of endovascular therapy for acute stroke. Stroke 2013; 44:1761.
  106. Saver JL, Jahan R, Levy EI, 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.
  107. Nogueira RG, Lutsep HL, 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.
  108. Berkhemer OA, van den Berg LA, Fransen PS, et al. The effect of anesthetic management during intra-arterial therapy for acute stroke in MR CLEAN. Neurology 2016; 87:656.
  109. Schönenberger S, Uhlmann L, Hacke W, et al. Effect of Conscious Sedation vs General Anesthesia on Early Neurological Improvement Among Patients With Ischemic Stroke Undergoing Endovascular Thrombectomy: A Randomized Clinical Trial. JAMA 2016; 316:1986.
  110. McDonald JS, Brinjikji W, Rabinstein AA, et al. Conscious sedation versus general anaesthesia during mechanical thrombectomy for stroke: a propensity score analysis. J Neurointerv Surg 2015; 7:789.
  111. Brinjikji W, Murad MH, Rabinstein AA, et al. Conscious sedation versus general anesthesia during endovascular acute ischemic stroke treatment: a systematic review and meta-analysis. AJNR Am J Neuroradiol 2015; 36:525.
  112. Furlan AJ. Endovascular therapy for stroke--it's about time. N Engl J Med 2015; 372:2347.
  113. Cohen DL, Kearney R, Griffiths M, et al. Around 9% of patients with ischaemic stroke are suitable for thrombectomy. BMJ 2015; 351:h4607.
  114. Chia NH, Leyden JM, Newbury J, et al. Determining the Number of Ischemic Strokes Potentially Eligible for Endovascular Thrombectomy: A Population-Based Study. Stroke 2016; 47:1377.
  115. Sheth KN, Smith EE, Grau-Sepulveda MV, et al. Drip and ship thrombolytic therapy for acute ischemic stroke: use, temporal trends, and outcomes. Stroke 2015; 46:732.
  116. Parsons M, Spratt N, Bivard A, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med 2012; 366:1099.
  117. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013; 44:870.
  118. Meyers PM, Schumacher HC, Higashida RT, et al. Indications for the performance of intracranial endovascular neurointerventional procedures: a scientific statement from the American Heart Association Council on Cardiovascular Radiology and Intervention, Stroke Council, Council on Cardiovascular Surgery and Anesthesia, Interdisciplinary Council on Peripheral Vascular Disease, and Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation 2009; 119:2235.
  119. Khalessi AA, Natarajan SK, Orion D, et al. Acute stroke intervention. JACC Cardiovasc Interv 2011; 4:261.
  120. Meyers PM, Schumacher HC, Connolly ES Jr, et al. Current status of endovascular stroke treatment. Circulation 2011; 123:2591.
  121. Chimowitz MI. Endovascular treatment for acute ischemic stroke--still unproven. N Engl J Med 2013; 368:952.
  122. Lee M, Hong KS, Saver JL. Efficacy of intra-arterial fibrinolysis for acute ischemic stroke: meta-analysis of randomized controlled trials. Stroke 2010; 41:932.
  123. 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.
  124. Kase CS, Furlan AJ, Wechsler LR, et al. Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial. Neurology 2001; 57:1603.
  125. del Zoppo GJ, Higashida RT, Furlan AJ, et al. PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in Acute Cerebral Thromboembolism. Stroke 1998; 29:4.
  126. Lansberg MG, O'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e601S.
  127. Lindsberg PJ, Pekkola J, Strbian D, et al. Time window for recanalization in basilar artery occlusion: Speculative synthesis. Neurology 2015; 85:1806.
  128. Polak JF. Ultrasound energy and the dissolution of thrombus. N Engl J Med 2004; 351:2154.
  129. Meairs S, Alonso A, Hennerici MG. Progress in sonothrombolysis for the treatment of stroke. Stroke 2012; 43:1706.
  130. Ricci S, Dinia L, Del Sette M, et al. Sonothrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2012; :CD008348.
  131. Nacu A, Kvistad CE, Naess H, et al. NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study): Randomized Controlled Contrast-Enhanced Sonothrombolysis in an Unselected Acute Ischemic Stroke Population. Stroke 2017; 48:335.
  132. Reinhard M, Hetzel A, Krüger S, et al. Blood-brain barrier disruption by low-frequency ultrasound. Stroke 2006; 37:1546.
  133. Dinia L, Rubiera M, Ribo M, et al. Reperfusion after stroke sonothrombolysis with microbubbles may predict intracranial bleeding. Neurology 2009; 73:775.
  134. Tsivgoulis G, Alexandrov A. Ultrasound-enhanced thrombolysis: from bedside to bench. Stroke 2008; 39:1404.
  135. IMS Study Investigators. Combined intravenous and intra-arterial recanalization for acute ischemic stroke: the Interventional Management of Stroke Study. Stroke 2004; 35:904.
  136. Mazighi M, Chaudhry SA, Ribo M, et al. Impact of onset-to-reperfusion time on stroke mortality: a collaborative pooled analysis. Circulation 2013; 127:1980.
  137. Leng X, Fang H, Leung TW, et al. Impact of collaterals on the efficacy and safety of endovascular treatment in acute ischaemic stroke: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2016; 87:537.
  138. Leigh R, Zaidat OO, Suri MF, et al. Predictors of hyperacute clinical worsening in ischemic stroke patients receiving thrombolytic therapy. Stroke 2004; 35:1903.
  139. Hacke W, Albers G, Al-Rawi Y, et al. The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke 2005; 36:66.
  140. Hacke W, Furlan AJ, Al-Rawi Y, et al. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol 2009; 8:141.
  141. Furlan AJ, Eyding D, Albers GW, et al. Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset. Stroke 2006; 37:1227.
  142. Siebler M, Hennerici MG, Schneider D, et al. Safety of Tirofiban in acute Ischemic Stroke: the SaTIS trial. Stroke 2011; 42:2388.
  143. Ciccone A, Motto C, Abraha I, et al. Glycoprotein IIb-IIIa inhibitors for acute ischaemic stroke. Cochrane Database Syst Rev 2014; :CD005208.
  144. Li W, Lin L, Zhang M, et al. Safety and Preliminary Efficacy of Early Tirofiban Treatment After Alteplase in Acute Ischemic Stroke Patients. Stroke 2016; 47:2649.
  145. Pancioli AM, Broderick J, Brott T, et al. The combined approach to lysis utilizing eptifibatide and rt-PA in acute ischemic stroke: the CLEAR stroke trial. Stroke 2008; 39:3268.
  146. Gupta R, Vora NA, Horowitz MB, et al. Multimodal reperfusion therapy for acute ischemic stroke: factors predicting vessel recanalization. Stroke 2006; 37:986.
  147. Karaszewski B, Houlden H, Smith EE, et al. What causes intracerebral bleeding after thrombolysis for acute ischaemic stroke? Recent insights into mechanisms and potential biomarkers. J Neurol Neurosurg Psychiatry 2015; 86:1127.
  148. Whiteley WN, Slot KB, Fernandes P, et al. Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies. Stroke 2012; 43:2904.
  149. Mazya MV, Lees KR, Collas D, et al. IV thrombolysis in very severe and severe ischemic stroke: Results from the SITS-ISTR Registry. Neurology 2015; 85:2098.
  150. Tanne D, Kasner SE, Demchuk AM, et al. Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey. Circulation 2002; 105:1679.
  151. Jaillard A, Cornu C, Durieux A, et al. Hemorrhagic transformation in acute ischemic stroke. The MAST-E study. MAST-E Group. Stroke 1999; 30:1326.
  152. Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995; 274:1017.
  153. Grotta JC, Chiu D, Lu M, et al. Agreement and variability in the interpretation of early CT changes in stroke patients qualifying for intravenous rtPA therapy. Stroke 1999; 30:1528.
  154. Patel SC, Levine SR, Tilley BC, et al. Lack of clinical significance of early ischemic changes on computed tomography in acute stroke. JAMA 2001; 286:2830.
  155. Gilligan AK, Markus R, Read S, et al. Baseline blood pressure but not early computed tomography changes predicts major hemorrhage after streptokinase in acute ischemic stroke. Stroke 2002; 33:2236.
  156. Khatri P, Wechsler LR, Broderick JP. Intracranial hemorrhage associated with revascularization therapies. Stroke 2007; 38:431.
  157. Demchuk AM, Morgenstern LB, Krieger DW, et al. Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. Stroke 1999; 30:34.
  158. Kidwell CS, Saver JL, Carneado J, et al. Predictors of hemorrhagic transformation in patients receiving intra-arterial thrombolysis. Stroke 2002; 33:717.
  159. Neumann-Haefelin T, Hoelig S, Berkefeld J, et al. Leukoaraiosis is a risk factor for symptomatic intracerebral hemorrhage after thrombolysis for acute stroke. Stroke 2006; 37:2463.
  160. Palumbo V, Boulanger JM, Hill MD, et al. Leukoaraiosis and intracerebral hemorrhage after thrombolysis in acute stroke. Neurology 2007; 68:1020.
  161. Singer OC, Humpich MC, Fiehler J, et al. Risk for symptomatic intracerebral hemorrhage after thrombolysis assessed by diffusion-weighted magnetic resonance imaging. Ann Neurol 2008; 63:52.
  162. Saqqur M, Tsivgoulis G, Molina CA, et al. Symptomatic intracerebral hemorrhage and recanalization after IV rt-PA: a multicenter study. Neurology 2008; 71:1304.
  163. Derex L, Nighoghossian N. Intracerebral haemorrhage after thrombolysis for acute ischaemic stroke: an update. J Neurol Neurosurg Psychiatry 2008; 79:1093.
  164. Cucchiara B, Kasner SE, Tanne D, et al. Factors associated with intracerebral hemorrhage after thrombolytic therapy for ischemic stroke: pooled analysis of placebo data from the Stroke-Acute Ischemic NXY Treatment (SAINT) I and SAINT II Trials. Stroke 2009; 40:3067.
  165. Diedler J, Ahmed N, Sykora M, et al. Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset. Stroke 2010; 41:288.
  166. Ruecker M, Matosevic B, Willeit P, et al. Subtherapeutic warfarin therapy entails an increased bleeding risk after stroke thrombolysis. Neurology 2012; 79:31.
  167. Miedema I, Luijckx GJ, De Keyser J, et al. Thrombolytic therapy for ischaemic stroke in patients using warfarin: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2012; 83:537.
  168. Mazya M, Egido JA, Ford GA, et al. Predicting the risk of symptomatic intracerebral hemorrhage in ischemic stroke treated with intravenous alteplase: safe Implementation of Treatments in Stroke (SITS) symptomatic intracerebral hemorrhage risk score. Stroke 2012; 43:1524.
  169. Diener HC, Foerch C, Riess H, et al. Treatment of acute ischaemic stroke with thrombolysis or thrombectomy in patients receiving anti-thrombotic treatment. Lancet Neurol 2013; 12:677.
  170. Rocco A, Heuschmann PU, Schellinger PD, et al. Glycosylated hemoglobin A1 predicts risk for symptomatic hemorrhage after thrombolysis for acute stroke. Stroke 2013; 44:2134.
  171. Curtze S, Haapaniemi E, Melkas S, et al. White Matter Lesions Double the Risk of Post-Thrombolytic Intracerebral Hemorrhage. Stroke 2015; 46:2149.
  172. Zinkstok SM, Roos YB, ARTIS investigators. Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet 2012; 380:731.
  173. Prabhakaran S, Rivolta J, Vieira JR, et al. Symptomatic intracerebral hemorrhage among eligible warfarin-treated patients receiving intravenous tissue plasminogen activator for acute ischemic stroke. Arch Neurol 2010; 67:559.
  174. Seet RC, Zhang Y, Moore SA, et al. Subtherapeutic international normalized ratio in warfarin-treated patients increases the risk for symptomatic intracerebral hemorrhage after intravenous thrombolysis. Stroke 2011; 42:2333.
  175. Meretoja A, Putaala J, Tatlisumak T, et al. Off-label thrombolysis is not associated with poor outcome in patients with stroke. Stroke 2010; 41:1450.
  176. Kim YD, Lee JH, Jung YH, et al. Safety and outcome after thrombolytic treatment in ischemic stroke patients with high-risk cardioembolic sources and prior subtherapeutic warfarin use. J Neurol Sci 2010; 298:101.
  177. Ibrahim MM, Sebastian J, Hussain M, et al. Does current oral antiplatelet agent or subtherapeutic anticoagulation use have an effect on tissue-plasminogen-activator-mediated recanalization rate in patients with acute ischemic stroke? Cerebrovasc Dis 2010; 30:508.
  178. Levin D, Smith DB, Cumbler E, et al. Warfarin therapy does not increase risk of symptomatic intracerebral hemorrhage in eligible patients after intravenous thrombolysis. Arch Neurol 2011; 68:135; author reply 135.
  179. Vergouwen MD, Casaubon LK, Swartz RH, et al. Subtherapeutic warfarin is not associated with increased hemorrhage rates in ischemic strokes treated with tissue plasminogen activator. Stroke 2011; 42:1041.
  180. Brunner F, Tomandl B, Schröter A, et al. Hemorrhagic complications after systemic thrombolysis in acute stroke patients with abnormal baseline coagulation. Eur J Neurol 2011; 18:1407.
  181. Xian Y, Liang L, Smith EE, et al. Risks of intracranial hemorrhage among patients with acute ischemic stroke receiving warfarin and treated with intravenous tissue plasminogen activator. JAMA 2012; 307:2600.
  182. Seiffge DJ, Hooff RJ, Nolte CH, et al. Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome. Circulation 2015; 132:1261.
  183. Tong DC, Adami A, Moseley ME, Marks MP. Prediction of hemorrhagic transformation following acute stroke: role of diffusion- and perfusion-weighted magnetic resonance imaging. Arch Neurol 2001; 58:587.
  184. Selim M, Fink JN, Kumar S, et al. Predictors of hemorrhagic transformation after intravenous recombinant tissue plasminogen activator: prognostic value of the initial apparent diffusion coefficient and diffusion-weighted lesion volume. Stroke 2002; 33:2047.
  185. Oppenheim C, Samson Y, Dormont D, et al. DWI prediction of symptomatic hemorrhagic transformation in acute MCA infarct. J Neuroradiol 2002; 29:6.
  186. Alsop DC, Makovetskaya E, Kumar S, et al. Markedly reduced apparent blood volume on bolus contrast magnetic resonance imaging as a predictor of hemorrhage after thrombolytic therapy for acute ischemic stroke. Stroke 2005; 36:746.
  187. Umemura A, Suzuka T, Yamada K. Quantitative measurement of cerebral blood flow by (99m)Tc-HMPAO SPECT in acute ischaemic stroke: usefulness in determining therapeutic options. J Neurol Neurosurg Psychiatry 2000; 69:472.
  188. Khatri P, Broderick JP, Khoury JC, et al. Microcatheter contrast injections during intra-arterial thrombolysis may increase intracranial hemorrhage risk. Stroke 2008; 39:3283.
  189. Yoon W, Seo JJ, Kim JK, et al. Contrast enhancement and contrast extravasation on computed tomography after intra-arterial thrombolysis in patients with acute ischemic stroke. Stroke 2004; 35:876.
  190. Desilles JP, Rouchaud A, Labreuche J, et al. Blood-brain barrier disruption is associated with increased mortality after endovascular therapy. Neurology 2013; 80:844.
  191. Ohta H, Nakano S, Yokogami K, et al. Appearance of early venous filling during intra-arterial reperfusion therapy for acute middle cerebral artery occlusion: a predictive sign for hemorrhagic complications. Stroke 2004; 35:893.
  192. Charidimou A, Shoamanesh A, Wilson D, et al. Cerebral microbleeds and postthrombolysis intracerebral hemorrhage risk Updated meta-analysis. Neurology 2015; 85:927.
  193. Tsivgoulis G, Zand R, Katsanos AH, et al. Risk of Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis in Patients With Acute Ischemic Stroke and High Cerebral Microbleed Burden: A Meta-analysis. JAMA Neurol 2016; 73:675.
Topic Outline