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Published in: Neurocritical Care 1/2009

01-08-2009 | Original Article

IV vs. IA TPA in Acute Ischemic Stroke with CT Angiographic Evidence of Major Vessel Occlusion: A Feasibility Study

Authors: Souvik Sen, David Y. Huang, Omid Akhavan, Susan Wilson, Piero Verro, Sten Solander

Published in: Neurocritical Care | Issue 1/2009

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Abstract

Background and Aims

Studies suggest that stroke patients with thrombus in a major cerebral vessel respond less favorably to intravenous (IV) thrombolysis. The purpose of this study was to test the feasibility of a protocol comparing IV versus intra-arterial (IA) recombinant tissue plasminogen activator (TPA) in an acute ischemic stroke with major vessel occlusion.

Methods

Consecutive ischemic stroke patients presenting <3 h from symptom onset with major vessel occlusion on CT angiogram (CTA) were randomly assigned to IV TPA (per NINDS protocol) or IA TPA (22 mg over 2 h). Demographics, times to presentation and thrombolysis, presenting NIH stroke scale (NIHSS) and 90-day NIHSS, Barthel Index, and modified Rankin Scale were recorded. CT-scans at 24-h were reviewed for presence of hemorrhage. Recanalization was determined by post-procedure MR angiograms, which are obtained the day after thrombolytic therapy.

Results

Seven patients (median NIHSS = 16) were randomized to IV (N = 4) or IA (N = 3) TPA. There were no significant differences in the presentation NIHSS, time to presentation, or time to treatment between the two groups. Hemorrhage was noted in one patient in the IA group (asymptomatic) and one patient in the IV group (symptomatic). Recanalization was seen in all patients treated with IA TPA and none treated with IV TPA (P = 0.03, Fisher’s Exact test).

Conclusions

We found that it is feasible to conduct a trial comparing IV vs. IA TPA in ischemic stroke patients with major vessel occlusion presenting <3 h from onset. Patients treated with IA TPA showed a trend toward higher rate of recanalization. A larger trial may be designed to test safety and effectiveness of IA TPA in this specific group of stroke patients.
Literature
1.
go back to reference NINDS Stroke Study Group. 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(24):1581–7. doi:10.1056/NEJM199512143332401.CrossRef NINDS Stroke Study Group. 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(24):1581–7. doi:10.​1056/​NEJM199512143332​401.CrossRef
2.
3.
go back to reference Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, 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(21):2003–11. doi:10.1001/jama.282.21.2003.PubMedCrossRef Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, 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(21):2003–11. doi:10.​1001/​jama.​282.​21.​2003.PubMedCrossRef
6.
go back to reference Lev MH, Farkas J, Rodriguez VR, Schwamm LH, Hunter GJ, Putman CM, et al. CT angiography in the rapid triage of patients with hyperacute stroke to intraarterial thrombolysis: accuracy in the detection of large vessel thrombus. J Comput Assist Tomogr. 2001;25(4):520–8. doi:10.1097/00004728-200107000-00003.PubMedCrossRef Lev MH, Farkas J, Rodriguez VR, Schwamm LH, Hunter GJ, Putman CM, et al. CT angiography in the rapid triage of patients with hyperacute stroke to intraarterial thrombolysis: accuracy in the detection of large vessel thrombus. J Comput Assist Tomogr. 2001;25(4):520–8. doi:10.​1097/​00004728-200107000-00003.PubMedCrossRef
8.
go back to reference Ciccone A, Valvassori L, Gasparotti R, Scomazzoni F, Ballabio E, Sterzi R. Debunking 7 myths that hamper the realization of randomized controlled trials on intra-arterial thrombolysis for acute ischemic stroke. Stroke. 2007;38(7):2191–5. doi:10.1161/STROKEAHA.106.465567.PubMedCrossRef Ciccone A, Valvassori L, Gasparotti R, Scomazzoni F, Ballabio E, Sterzi R. Debunking 7 myths that hamper the realization of randomized controlled trials on intra-arterial thrombolysis for acute ischemic stroke. Stroke. 2007;38(7):2191–5. doi:10.​1161/​STROKEAHA.​106.​465567.PubMedCrossRef
10.
go back to reference TIMI Study Group The Thrombolysis in Myocardial Infarction (TIMI) Trial. Phase I findings. N Engl J Med. 1985;312:932–6. TIMI Study Group The Thrombolysis in Myocardial Infarction (TIMI) Trial. Phase I findings. N Engl J Med. 1985;312:932–6.
11.
12.
go back to reference Bastianello S, Pierallini A, Colonnese C, Brughitta G, Angeloni U, Antonelli M, et al. Fieschi, Bozzao L. Hyperdense middle cerebral artery CT sign. Neuroradiology. 1991;33:207–11. doi:10.1007/BF00588219.PubMedCrossRef Bastianello S, Pierallini A, Colonnese C, Brughitta G, Angeloni U, Antonelli M, et al. Fieschi, Bozzao L. Hyperdense middle cerebral artery CT sign. Neuroradiology. 1991;33:207–11. doi:10.​1007/​BF00588219.PubMedCrossRef
13.
go back to reference Moulin T, Cattin F, Crépin-Leblond T, Tatu L, Chavot D, Piotin M, et al. Early CT signs in acute middle cerebral artery infarction: predictive value for subsequent infarct locations and outcome. Neurology. 1996;47:366–75.PubMed Moulin T, Cattin F, Crépin-Leblond T, Tatu L, Chavot D, Piotin M, et al. Early CT signs in acute middle cerebral artery infarction: predictive value for subsequent infarct locations and outcome. Neurology. 1996;47:366–75.PubMed
14.
go back to reference Zorzon M, Mase G, Pozzi-Mucelli F, Biasutti E, Antonutti L, Iona L, et al. Increased density in the middle cerebral artery by nonenhanced computed tomography: prognostic value in acute cerebral infarction. Eur Neurol. 1993;33:256–9. doi:10.1159/000116949.PubMedCrossRef Zorzon M, Mase G, Pozzi-Mucelli F, Biasutti E, Antonutti L, Iona L, et al. Increased density in the middle cerebral artery by nonenhanced computed tomography: prognostic value in acute cerebral infarction. Eur Neurol. 1993;33:256–9. doi:10.​1159/​000116949.PubMedCrossRef
16.
go back to reference Manelfe C, Larrue V, von Kummer R, Bozzao L, Ringleb P, Bastianello S, et al. Association of hyperdense middle cerebral artery sign with clinical outcome in patients with tissue plasminogen activator. Stroke. 1999;30:769–72.PubMed Manelfe C, Larrue V, von Kummer R, Bozzao L, Ringleb P, Bastianello S, et al. Association of hyperdense middle cerebral artery sign with clinical outcome in patients with tissue plasminogen activator. Stroke. 1999;30:769–72.PubMed
17.
go back to reference Tomsick T, Brott T, Barsan W, Broderick J, Clarke Haley E, Spilker J, et al. Prognostic value of the hyperdense middle cerebral artery sign and stroke scale score before ultraearly thrombolytic therapy. AJNR Am J Neuroradiol. 1996;17:79–85.PubMed Tomsick T, Brott T, Barsan W, Broderick J, Clarke Haley E, Spilker J, et al. Prognostic value of the hyperdense middle cerebral artery sign and stroke scale score before ultraearly thrombolytic therapy. AJNR Am J Neuroradiol. 1996;17:79–85.PubMed
18.
go back to reference The NINDS rtPA Stroke Study Group. Generalized efficacy of rtPA for acute stroke: subgroup analysis of the NINDS rtPA stroke trial. Stroke. 1997;28:2119–25. The NINDS rtPA Stroke Study Group. Generalized efficacy of rtPA for acute stroke: subgroup analysis of the NINDS rtPA stroke trial. Stroke. 1997;28:2119–25.
20.
go back to reference Agarwal P, Kumar S, Hariharan S, Eshkar N, Verro P, Cohen B, et al. Hyperdense middle cerebral artery sign: can it be used to select intraarterial versus intravenous thrombolysis in acute ischemic stroke? Cerebrovasc Dis. 2004;17:182–90. doi:10.1159/000075789.PubMedCrossRef Agarwal P, Kumar S, Hariharan S, Eshkar N, Verro P, Cohen B, et al. Hyperdense middle cerebral artery sign: can it be used to select intraarterial versus intravenous thrombolysis in acute ischemic stroke? Cerebrovasc Dis. 2004;17:182–90. doi:10.​1159/​000075789.PubMedCrossRef
24.
go back to reference Macleod MR, Davis SM, Mitchell PJ, Gerraty RP, Fitt G, Hankey GJ, et al. Results of a multicentre, randomised controlled trial of intra-arterial urokinase in the treatment of acute posterior circulation ischaemic stroke. Cerebrovasc Dis. 2005;20(1):12–7. doi:10.1159/000086121.PubMedCrossRef Macleod MR, Davis SM, Mitchell PJ, Gerraty RP, Fitt G, Hankey GJ, et al. Results of a multicentre, randomised controlled trial of intra-arterial urokinase in the treatment of acute posterior circulation ischaemic stroke. Cerebrovasc Dis. 2005;20(1):12–7. doi:10.​1159/​000086121.PubMedCrossRef
25.
go back to reference Broderick JP. Practical considerations in the early treatment of ischemic stroke. Am Fam Physician. 1998;57:73–9.PubMed Broderick JP. Practical considerations in the early treatment of ischemic stroke. Am Fam Physician. 1998;57:73–9.PubMed
26.
go back to reference Mattle HP, Arnold M, Georgiadis D, Baumann C, Nedeltchev K, Benninger D, et al. Comparison of intraarterial and intravenous thrombolysis for ischemic stroke with hyperdense middle cerebral artery sign. Stroke. 2008;39(2):379–83. doi:10.1161/STROKEAHA.107.492348.PubMedCrossRef Mattle HP, Arnold M, Georgiadis D, Baumann C, Nedeltchev K, Benninger D, et al. Comparison of intraarterial and intravenous thrombolysis for ischemic stroke with hyperdense middle cerebral artery sign. Stroke. 2008;39(2):379–83. doi:10.​1161/​STROKEAHA.​107.​492348.PubMedCrossRef
Metadata
Title
IV vs. IA TPA in Acute Ischemic Stroke with CT Angiographic Evidence of Major Vessel Occlusion: A Feasibility Study
Authors
Souvik Sen
David Y. Huang
Omid Akhavan
Susan Wilson
Piero Verro
Sten Solander
Publication date
01-08-2009
Publisher
Humana Press Inc
Published in
Neurocritical Care / Issue 1/2009
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-009-9204-1

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