The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995; 333:1581–7.Google Scholar

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). Lancet. 1998; 352:1245–51.CrossRefGoogle ScholarPubMed

Hacke, W, Kaste, M, Bluhmki, E, et al. ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008; 359(13):1317–29.Google Scholar

The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke. 1997; 28:2109–18.Google Scholar

Fiorelli, M, Bastianello, S, von Kummer, R, et al. Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort. Stroke. 1999; 30:2280–4.Google Scholar

del Zoppo, G J, Higashida, R T, Furlan, A J, 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; 29:4–11.Google Scholar

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.Google Scholar

IMS Study Investigators. Combined intravenous and intraarterial recanalization for acute ischemic stroke: The Interventional Management of Stroke Study. Stroke. 2004; 35:904–11.Google Scholar

IMS II Trial Investigators. The Interventional Management of Stroke (IMS) II Study. Stroke. 2007; 38:2127–35.Google Scholar

Smith, W S, Sung, G, Starkman, S, et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke. 2005; 36:1432–8.Google Scholar

Smith, W S, Sung, G, Saver, J, et al. Mechanical thrombectomy for acute ischemic stroke: Final results of the Multi MERCI trial. Stroke. 2008; 39:1205–12.Google Scholar

Penumbra Pivotal Stroke Trial Investigators. 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. 2009; 40:2761–8.Google Scholar

Saver, J L, Jahan, R, Levy, E I, et al. SWIFT Trialists. 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(9849):1241–9.CrossRefGoogle Scholar

Nogueira, R G, Lutsep, H L, Gupta, R, et al. TREVO 2 Trialists. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): A randomised trial. Lancet. 2012; 380(9849):1231–40.Google Scholar

Broderick, J P, Palesch, Y Y, Demchuk, A M, et al. Interventional Management of Stroke (IMS) III Investigators. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013; 368(10):893–903.Google Scholar

Berkhemer, O A, Fransen, P S, Beumer, D, et al. MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015; 372(1):11–20.Google Scholar

Goyal, M, Demchuk, A M, Menon, B K, et al. ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015; 372(11):1019–30.Google Scholar

Campbell, B C, Mitchell, P J, Kleinig, T J, et al. EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015; 372(11):1009–18.CrossRefGoogle ScholarPubMed

Alexandrov, A V, Black, S E, Ehrlich, L E, Caldwell, C B, Norris, J W. Predictors of hemorrhagic transformation occurring spontaneously and on anticoagulants in patients with acute ischemic stroke. Stroke. 1997; 28:1198–202.CrossRefGoogle ScholarPubMed

Wang, X, Lo, E H. Triggers and mediators of hemorrhagic transformation in cerebral ischemia. Mol Neurobiol. 2003; 28:229–44.Google Scholar

Gasche, Y, Copin, J C, Sugawara, T, Fujimura, M, Chan, P H. Matrix metalloproteinase inhibition prevents oxidative stress-associated blood–brain barrier disruption after transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2001; 21:1393–400.Google Scholar

Khatri, R, Khatri, P, Khoury, J, et al. Microcatheter contrast injections during intra-arterial thrombolysis increase intracranial hemorrhage risk. J Neurointerv Surg. 2010; 2:115–19.Google Scholar

Demchuk, A M, Morgenstern, L B, Krieger, D W, et al. Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. Stroke. 1999; 30:34–9.Google Scholar

Natarajan, S K, Dandona, P, Karmon, Y, et al. Prediction of adverse outcomes by blood glucose level after endovascular therapy for acute ischemic stroke. Clinical Article J Neurosurg. 2011; 114:1785–99.Google ScholarPubMed

Molina, C A, Alvarez-Sabin, J, Montaner, J, et al. Thrombolysis-related hemorrhagic infarction: A marker of early reperfusion, reduced infarct size, and improved outcome in patients with proximal middle cerebral artery occlusion. Stroke. 2002; 33:1551–6.Google Scholar

Dubey, N, Bakshi, R, Wasay, M, Dmochowski, J. Early computed tomography hypodensity predicts hemorrhage after intravenous tissue plasminogen activator in acute ischemic stroke. J Neuroimaging. 2001; 11:184–8.Google Scholar

Barber, P A, Demchuk, A M, Zhang, J, Buchan, A M. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS Study Group. Alberta Stroke Programme Early CT Score. Lancet. 2000; 355:1670–4.Google Scholar

Dzialowski, I, Hill, M D, Coutts, S B, et al. Extent of early ischemic changes on computed tomography (CT) before thrombolysis: prognostic value of the Alberta Stroke Program Early CT Score in ECASS II. Stroke. 2006; 37:973–8.Google Scholar

Hill, M D, Rowley, H A, Adler, F, et al. PROACT-II Investigators. Selection of acute ischemic stroke patients for intra-arterial thrombolysis with pro-urokinase by using ASPECTS. Stroke. 2003; 34:1925–31.Google Scholar

Hill, M D, Demchuk, A M, Tomsick, T A, Palesch, Y Y, Broderick, J P. Using the baseline CT scan to select acute stroke patients for IV-IA therapy. Am J Neuroradiol. 2006; 27:1612–16.Google Scholar

Hill, M D, Demchuk, A M, Goyal, M, et al. IMS3 Investigators. Alberta Stroke Program early computed tomography score to select patients for endovascular treatment: Interventional Management of Stroke (IMS)-III Trial. Stroke. 2014; 45(2):444–9.Google Scholar

Whiteley, W N, Slot, K B, Fernandes, P, Sandercock, P, Wardlaw, J. 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(11):2904–9.Google Scholar

Henninger, N, Lin, E, Baker, S P, et al. Leukoaraiosis predicts poor 90-day outcome after acute large cerebral artery occlusion. Cerebrovasc Dis. 2012; 33(6):525–31.Google Scholar

Orrison, W W Jr, Snyder, K V, Hopkins, L N, et al. Whole-brain dynamic CT angiography and perfusion imaging. Clin Radiol. 2011; 66:566–74.Google Scholar

Gasparotti, R, Grassi, M, Mardighian, D, et al. Perfusion CT in patients with acute ischemic stroke treated with intra-arterial thrombolysis: Predictive value of infarct core size on clinical outcome. Am J Neuroradiol. 2009; 30:722–7.Google Scholar

Bhatt, A, Vora, N A, Thomas, A J, et al. Lower pre-treatment cerebral blood volume increases hemorrhagic risks after intra-arterial revascularization in acute stroke. Neurosurgery. 2008; 63:874–9.Google Scholar

Liebeskind, D S, Tomsick, T A, Foster, L D, et al. IMS III Investigators. Collaterals at angiography and outcomes in the Interventional Management of Stroke (IMS) III trial. Stroke. 2014;45(3):759–64.CrossRefGoogle ScholarPubMed

Kidwell, C S, Chalela, J A, Saver, J L, et al. Comparison of MRI and CT for detection of acute intracerebral hemorrhage. JAMA. 2004; 292:1823–30.Google Scholar

Kakuda, W, Thijs, V N, Lansberg, M G, et al. DEFUSE Investigators. Clinical importance of microbleeds in patients receiving IV thrombolysis. Neurology. 2005; 65:1175–8.Google Scholar

Fiehler, J, Albers, G W, Boulanger, J M, et al. MR Stroke Group. Bleeding risk analysis in stroke imaging before thrombolysis. Stroke. 2007; 38:2738–44.Google Scholar

Soo, Y O, Siu, D Y, Abrigo, J, et al. Risk of intracerebral hemorrhage in patients with cerebral microbleeds undergoing endovascular intervention. Stroke. 2012; 43(6):1532–6.Google Scholar

Shi, Z S, Loh, Y, Liebeskind, D S, Saver, J L, et al. Leukoaraiosis predicts parenchymal hematoma after mechanical thrombectomy in acute ischemic stroke. Stroke. 2012; 43(7):1806–11.Google Scholar

del Zoppo, G J, von Kummer, R, Hamann, G F. Ischaemic damage of brain microvessels: inherent risks for thrombolytic treatment in stroke. JNNP. 1998; 65:1–9.Google Scholar

Warach, S, Latour, L L. Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood–brain barrier disruption. Stroke. 2004; 35(suppl I):2659–61.Google Scholar

Lansberg, M G, Thijs, V N, Bammer, R, et al. DEFUSE Investigators. Risk factors of symptomatic intracerebral hemorrhage after tPA therapy for acute stroke. Stroke. 2007; 38:2275–8.Google Scholar

Singer, O C, Kurre, W, Humpich, M C, et al. MR Stroke Study Group Investigators. Risk assessment of symptomatic intracerebral hemorrhage after thrombolysis using DWI-ASPECTS. Stroke. 2009; 40(8):2743–8.Google Scholar

Deguchi, I, Dembo, T, Fukuoka, T, et al. Usefulness of MRA-DWI mismatch in neuroendovascular therapy for acute cerebral infarction. Eur J Neurol. 2012; 19(1):114–20.Google Scholar

Yoon, W, Seo, J J, Kim, J K, et al. Contrast enhancement and contrast extravasation on computed tomography after intra-arterial thrombolysis in patients with acute ischemic stroke. Stroke. 2004; 35:876–81.Google Scholar

Broderick, J, Connolly, S, Feldmann, E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke. 2007; 38:2001–23.CrossRefGoogle ScholarPubMed

Mokin, M, Kass-Hout, T, Kass-Hout, O, Zivadinov, R, Mehta, B. Blood pressure management and evolution of thrombolysis-associated intracerebral hemorrhage in acute ischemic stroke. J Stroke Cerebrovasc Dis. 2012; 21(8):852–9.Google Scholar

Ko, Y, Park, J H, Yang, M H, et al. The significance of blood pressure variability for the development of hemorrhagic transformation in acute ischemic stroke. Stroke. 2010; 41:2512–18.Google Scholar

Goldstein, J N, Marrero, M, Masrur, S, et al. Management of thrombolysis-associated symptomatic intracerebral hemorrhage. Arch Neurol. 2010; 67:965–9.Google Scholar

Mendelow, A D, Gregson, B A, Fernandes, H M, et al. STICH investigators. Early versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): A randomised trial. Lancet. 2005; 365:387–97.CrossRefGoogle Scholar

Williams, A, Sittampalam, M, Barua, N, Mohd Nor, A. Case series of post-thrombolysis patients undergoing hemicraniectomy for malignant anterior circulation ischaemic stroke. Cardiovasc Psychiatry Neurol. 2011; 254569.Google Scholar

Alshekhlee, A, Horn, C, Jung, R, Alawi, A A, Cruz-Flores, S. In-hospital mortality in acute ischemic stroke treated with hemicraniectomy in US hospitals. J Stroke Cerebrovasc Dis. 2011; 20:196–201.Google Scholar

Fargen, K M, Hoh, B L, Fautheree, G L, et al. Aggressive intervention to treat a young woman with intracranial hemorrhage following unsuccessful intravenous thrombolysis for left middle cerebral artery occlusion. Case report. J Neurosurg. 2011; 115:359–63.Google Scholar

The National Institute of Neurological Disorders and Stroke tPA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995; 333:1581–7.Google Scholar

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; 13:1017–25.Google Scholar

Hacke, W, Kaste, M, Fieschi, C, et al. Second European-Australasian Acute Stroke Study Investigators. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet. 1998; 352:1245–51.Google Scholar

Hacke, W, Donnan, G, Fieschi, C, et al. Association of outcome with early stroke treatment: Pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004; 363:768–74.Google Scholar

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.CrossRefGoogle ScholarPubMed

Albers, G W, Clark, W M, Madden, K P, Hamilton, S A. ATLANTIS trial: results for patients treated within 3 hours of stroke onset. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. Stroke. 2002; 33:493–5.Google Scholar

Wahlgren, N, Ahmed, N, Eriksson, N, et al. Safe Implementation of Thrombolysis in Stroke-Monitoring Study Investigators. Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-Monitoring STudy (SITS-MOST). Stroke. 2008; 3316–22.Google Scholar

Fonarow, G C, Smith, E E, Saver, J L, et al. Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: Patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes. Circulation. 2011; 7:750–8.Google Scholar

Mishra, N K, Ahmed, N, Andersen, G, et al. VISTA collaborators; SITS collaborators. Thrombolysis in very elderly people: Controlled comparison of SITS International Stroke Thrombolysis Registry and Virtual International Stroke Trials Archive. BMJ. 2010; 341:c6046. doi:10.1136.Google Scholar

Intracerebral haemorrhage after intravenous t-PA therapy for ischemic stroke. The NINDS t-PA Stroke Study Group. Stroke. 1997; 11: 2109–18.Google Scholar

Saposni, G, Raptis, S, Kapral, M K, et al. Investigators of the Registry of the Canadian Stroke Network and the Stroke Outcome Research Canada Working Group. The iScore predicts poor functional outcomes early after hospitalization for an acute ischemic stroke. Stroke. 2011; 12:3421–8.Google Scholar

Saposnik, G, Fang, J, Kapral, M K, et al. Investigators of the Registry of the Canadian Stroke Network (RCSN); Stroke Outcomes Research Canada (SORCan) Working Group. The iScore predicts effectiveness of thrombolytic therapy for acute ischemic stroke. Stroke. 2012; 5:1315–22.Google Scholar

Mazya, M, Egido, J A, Ford, G A, et al. SITS Investigators. 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; 43:1524–31.Google Scholar

Mazya, M V, Bovi, P, Castillo, J, et al. External validation of the SEDAN score for prediction of intracerebral hemorrhage in stroke thrombolysis. Stroke. 2013; 44:1595–600.Google Scholar

Butcher, K, Christensen, S, Parsons, M, et al. EPITHET Investigators. Postthrombolysis blood pressure elevation is associated with hemorrhagic transformation. Stroke. 2010; 1:72–7.Google Scholar

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; 2:288–94.Google Scholar

Martinez-Ramirez, S, Delgado-Mederos, R, Marín, R, et al. Statin pretreatment may increase the risk of symptomatic intracranial haemorrhage in thrombolysis for ischemic stroke: Results from a case-control study and a meta-analysis. J Neurol. 2012; 1:111–18.Google Scholar

Diedler, J, Ahmed, N, Glahn, J, et al. Is the maximum dose of 90 mg alteplase sufficient for patients with ischemic stroke weighing >100 kg? Stroke. 2011; 6:1615–20.Google Scholar

Putaala, J, Sairanen, T, Meretoja, A, et al. Post-thrombolytic hyperglycemia and 3-month outcome in acute ischemic stroke. Cerebrovasc Dis. 2011; 1:83–92.Google Scholar

Mustanoja, S, Meretoja, A, Putaala, J, et al. Helsinki Stroke Thrombolysis Registry Group. Outcome by stroke etiology in patients receiving thrombolytic treatment: descriptive subtype analysis. Stroke. 2011; 1:102–6.Google Scholar

Qureshi, A I, Chaudhry, S A, Hassan, A E, et al. Thrombolytic treatment of patients with acute ischemic stroke related to underlying arterial dissection in the United States. Arch Neurol. 2011; 12:1536–42.Google Scholar

Mazya, M V, Ahmed, N, Ford, G A, et al. Remote or extraischemic intracerebral hemorrhage – an uncommon complication of stroke: Results from the Safe Implementation of Treatments in Stroke – International Stroke Thrombolysis Register. Stroke. 2014; 45:1657–63.Google Scholar

Castellanos, M, Sobrino, T, Millán, M, et al. Serum cellular fibronectin and matrix metalloproteinase-9 as screening biomarkers for the prediction of parenchymal hematoma after thrombolytic therapy in acute ischemic stroke: A multicenter confirmatory study. Stroke. 2007; 6:1855–914.Google Scholar

Albers, G W, Thijs, V N, Wechsler, L, et al. DEFUSE Investigators. 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; 5:508–17.Google Scholar

Campbell, B C, Christensen, S, Butcher, K S, et al. EPITHET Investigators. Regional very low cerebral blood volume predicts hemorrhagic transformation better than diffusion-weighted imaging volume and thresholded apparent diffusion coefficient in acute ischemic stroke. Stroke. 2010; 1:82–8.Google Scholar

Fiehler, J, Albers, G W, Boulanger, J M, et al. MR STROKE Group. Bleeding Risk Analysis in Stroke Imaging before thromboLysis (BRASIL): Pooled analysis of T2*-weighted magnetic resonance imaging data from 570 patients. Stroke. 2007; 2738–44.Google Scholar

Dannenberg, S, Scheitz, J F, Rozanski, M, et al. Number of cerebral microbleeds and risk of intracerebral hemorrhage after intravenous thrombolysis. Stroke. 2014; 10:2900–5.Google Scholar

Gratz, P P, El-Koussy, M, Hsieh, K, et al. Preexisting cerebral microbleeds on susceptibility-weighted magnetic resonance imaging and post-thrombolysis bleeding risk in 392 patients. Stroke. 2014; 6:1684–8.Google Scholar

Jung, S, Mono, M L, Findling, O, et al. White matter lesions and intra-arterial thrombolysis. J Neurol. 2012; 7:1331–6.Google Scholar

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: 2463–6.Google Scholar

Broderick, J P, Palesch, Y Y, Demchuk, A M, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013; 368:893–903.Google Scholar

Kidwell, C S, Jahan, R, Saver, J L. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013; 368:2434–5.Google Scholar

Ciccone, A, Valvassori, L, Nichelatti, M, et al. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013; 368:904–13.Google Scholar

Berkhemer, O A, Fransen, P S, Beumer, D, et al. MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015; 1:11–20.Google Scholar

Goyal, M, Demchuk, A M, Menon, B K, et al. ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015; 11:1019–30.Google Scholar

Saver, J L, Goyal, M, Bonafe, A, et al. SWIFT PRIME Investigators. 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 with IV tPA alone in acute ischemic stroke. Int J Stroke. 2015; 3:439–48.Google Scholar

Campbell, B C, Mitchell, P J, Kleinig, T J, et al. EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015; 11:1009–18.Google Scholar

Bang, O Y, Saver, J L, Kim, S J, et al. Collateral flow averts hemorrhagic transformation after endovascular therapy for acute ischemic stroke. Stroke. 2011; 42:2235–9.Google ScholarPubMed

Warach, S, Latour, L L. Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood–brain barrier disruption. Stroke. 2004; 35:2659–61.Google Scholar

Khatri, R, McKinney, A M, Swenson, B, et al. Blood–brain barrier, reperfusion injury, and hemorrhagic transformation in acute ischemic stroke. Neurology. 2012; 79:S52–7.Google Scholar

Giraud, M, Cho, T H, Nighoghossian, N, et al. Early blood brain barrier changes in acute ischemic stroke: A sequential MRI study. J Neuroimaging. 2015; 25:959–63.Google Scholar