Background: Standard selection criteria for thrombolysis typically exclude patients with acute ischemic stroke with unclear onset. Multimodal MRI screening may be able to identify those with a favorable benefit-risk ratio for thrombolysis. We aimed to evaluate the safety and efficacy of MRI-based thrombolysis in unclear-onset stroke (UnCLOS). Methods: We reviewed the thrombolysis database registries from 3 medical centers in Korea. Subjects received thrombolysis with intravenous tissue plasminogen activator (tPA) or combined intravenous tPA and intra-arterial urokinase within 3 h, or intra-arterial urokinase within 6 h from symptom detection. For patients with UnCLOS, MRI-specific eligibility criteria (i.e. positive perfusion-diffusion mismatch and absence of well-developed fluid-attenuated inversion recovery changes of acute diffusion lesions) were applied. Rates of immediate and 5-day recanalization, early neurological improvement and symptomatic intracranial hemorrhage (ICH) within 48 h after treatment and 3-month modified Rankin Scale (mRS) scores were compared between patients with UnCLOS and those with clear-onset stroke (CLOS). Results: 32 patients with UnCLOS and 223 patients with CLOS were included. Baseline characteristics were comparable between the two groups, except that the proportion of MRI screening was higher, and detection-to-door time and door-to-needle time were longer in the UnCLOS group (p < 0.01). Rates of recanalization (immediate, 81.3 vs. 63.1%; delayed, 80.6 vs. 69.1%), early neurological improvement (on day 1, 46.9 vs. 35.9%; on day 7, 50.0 vs. 49.3%), symptomatic ICH (6.3 vs. 5.8%) and 3-month outcome (mRS 0–1, 37.5 vs. 35.0%; mRS 0–2, 50.0 vs. 49.3%) did not differ between the UnCLOS and CLOS groups. Conclusion: These preliminary results suggest that thrombolysis based on MRI criteria may safely be applied to acute stroke patients with unclear onset.

Keywords:
Acute stroke, unclear onset, Thrombolysis, time window, Magnetic resonance imaging
1.
Lago A, Geffner D, Tembl J, Landete L, Valero C, Baquero M: Circadian variation in acute ischemic stroke: a hospital-based study. Stroke 1998;29:1873–1875.
2.
Chaturvedi S, Adams HP Jr, Woolson RF: Circadian variation in ischemic stroke subtypes. Stroke 1999;30:1792–1795.
3.
Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995;333:1581–1587.
4.
Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F: Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA 1999;282:2003–2011.
5.
Todo K, Moriwaki H, Saito K, Tanaka M, Oe H, Naritomi H: Early CT findings in unknown-onset and wake-up strokes. Cerebrovasc Dis 2006;21:367–371.
6.
Serena J, Davalos A, Segura T, Mostacero E, Castillo J: Stroke on awakening: looking for a more rational management. Cerebrovasc Dis 2003;16:128–133.
7.
Fink JN, Kumar S, Horkan C, Linfante I, Selim MH, Caplan LR, Schlaug G: The stroke patient who woke up: clinical and radiological features, including diffusion and perfusion MRI. Stroke 2002;33:988–993.
8.
Schellinger PD, Warach S: Therapeutic time window of thrombolytic therapy following stroke. Curr Atheroscler Rep 2004;6:288–294.
9.
Welch KM, Windham J, Knight RA, Nagesh V, Hugg JW, Jacobs M, Peck D, Booker P, Dereski MO, Levine SR: A model to predict the histopathology of human stroke using diffusion and T2-weighted magnetic resonance imaging. Stroke 1995;26:1983–1989.
10.
Kang DW, Chalela JA, Dunn W, Warach S: MRI screening before standard tissue plasminogen activator therapy is feasible and safe. Stroke 2005;36:1939–1943.
11.
Schellinger PD, Thomalla G, Fiehler J, Kohrmann M, Molina CA, Neumann-Haefelin T, Ribo M, Singer OC, Zaro-Weber O, Sobesky J: MRI-based and CT-based thrombolytic therapy in acute stroke within and beyond established time windows: an analysis of 1,210 patients. Stroke 2007;38:2640–2645.
12.
Lewandowski CA, Frankel M, Tomsick TA, Broderick J, Frey J, Clark W, Starkman S, Grotta J, Spilker J, Khoury J, Brott T: Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial. Stroke 1999;30:2598–2605.
13.
Berger C, Fiorelli M, Steiner T, Schabitz WR, Bozzao L, Bluhmki E, Hacke W, von Kummer R: Hemorrhagic transformation of ischemic brain tissue: asymptomatic or symptomatic? Stroke 2001;32:1330–1335.
14.
Sheehan FH, Braunwald E, Canner P, Dodge HT, Gore J, Van Natta P, Passamani ER, Williams DO, Zaret B: The effect of intravenous thrombolytic therapy on left ventricular function: a report on tissue-type plasminogen activator and streptokinase from the Thrombolysis in Myocardial Infarction (TIMI phase I) trial. Circulation 1987;75:817–829.
15.
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE: Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35–41.
16.
Albers GW, Bates VE, Clark WM, Bell R, Verro P, Hamilton SA: Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) study. JAMA 2000;283:1145–1150.
17.
Hill MD, Buchan AM: Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study. CMAJ 2005;172:1307–1312.
18.
Wahlgren N, Ahmed N, Davalos A, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kuelkens S, Larrue V, Lees KR, Roine RO, Soinne L, Toni D, Vanhooren G: Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007;369:275–282.
19.
Combined intravenous and intra-arterial recanalization for acute ischemic stroke: the Interventional Management of Stroke Study. Stroke 2004;35:904–911.
20.
Marler JR, Tilley BC, Lu M, Brott TG, Lyden PC, Grotta JC, Broderick JP, Levine SR, Frankel MP, Horowitz SH, Haley EC Jr, Lewandowski CA, Kwiatkowski TP: Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study. Neurology 2000;55:1649–1655.
21.
Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, Frankel M, Grotta JC, Haley EC Jr, Kwiatkowski T, Levine SR, Lewandowski C, Lu M, Lyden P, Marler JR, Patel S, Tilley BC, Albers G, Bluhmki E, Wilhelm M, Hamilton S: Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004;363:768–774.
22.
Ribo M, Molina CA, Rovira A, Quintana M, Delgado P, Montaner J, Grive E, Arenillas JF, Alvarez-Sabin J: Safety and efficacy of intravenous tissue plasminogen activator stroke treatment in the 3- to 6-hour window using multimodal transcranial Doppler/MRI selection protocol. Stroke 2005;36:602–606.
23.
Hacke W, Albers G, Al-Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, Fischer M, Furlan A, Kaste M, Lees KR, Soehngen M, Warach S: 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;36:66–73.
24.
Hacke W, Furlan A; for the DIAS-2 Investigators: Results from the phase III study of Desmoteplase in Acute Ischemic Stroke Trial 2 (DIAS 2). Cerebrovasc Dis 2007;23(suppl 2):54.
25.
Kohrmann M, Juttler E, Fiebach JB, Huttner HB, Siebert S, Schwark C, Ringleb PA, Schellinger PD, Hacke W: MRI versus CT-based thrombolysis treatment within and beyond the 3 h time window after stroke onset: a cohort study. Lancet Neurol 2006;5:661–667.
26.
Hjort N, Butcher K, Davis SM, Kidwell CS, Koroshetz WJ, Rother J, Schellinger PD, Warach S, Ostergaard L: Magnetic resonance imaging criteria for thrombolysis in acute cerebral infarct. Stroke 2005;36:388–397.
27.
Davalos A, Blanco M, Pedraza S, Leira R, Castellanos M, Pumar JM, Silva Y, Serena J, Castillo J: The clinical-DWI mismatch: a new diagnostic approach to the brain tissue at risk of infarction. Neurology 2004;62:2187–2192.
28.
Prosser J, Butcher K, Allport L, Parsons M, MacGregor L, Desmond P, Tress B, Davis S: Clinical-diffusion mismatch predicts the putative penumbra with high specificity. Stroke 2005;36:1700–1704.
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2008
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