Evaluation of Local Intra-Arterial Fibrinolytic Therapy for Acute Middle Cerebral Artery Occlusion

Abstract

Fibrinolytic therapy for acute ischaemic stroke has been investigated in several clinical trials, with various protocols. This retrospective study was undertaken to evaluate the efficacy and limitation of local intra-arterial fibrinolytic therapy using urokinase (UK) in patients with acute middle cerebral artery occlusion.

Fifty patients were treated with local intra-arterial fibrinolytic therapy within six hours after onset of symptoms. The median National Institutes of Health Stroke Scale (NIHSS) score was 17 (range, 6 to 28). Two hundred and forty thousand IU of UK was administered through a mi-crocatheter for 20 minutes. When arterial recanalization was not achieved, a second or third infusion was performed. Maximum dosage of UK was 0.96 × 106 IU. Recanalization efficacy was evaluated at the end of fibrinolytic therapy and intracranial haemorrhage was assessed within 24 hours. Clinical outcome was evaluated three months after ictus with modified Rankin scale (RS).

Thirty-nine patients (78%) obtained recanalization. Twenty-nine of 39 (74%) showed clinical improvement just after treatment. On the other hand, only 18% patients (2/11) who did not recanalize demonstrated improvement. Twenty-five of 50 (50%) patients recovered to RS score 0 or 1, however, only 28% of patients (5/18) with proximal M1 occlusion obtained good outcome and 39% of them (7/18) died. The mean time interval from onset to treatment did not affect outcome. The overall incidence of haemorrhagic event (HE) within 24 hours was 36%, however, 78% of patients with proximal M1 occlusion showed HE. Only one patient with HE clinically deteriorated.

In conclusion, local intra-arterial fibrinolytic therapy could be a safe and effective method for acute middle cerebral artery occlusion, however, indication of this therapy for patients with proximal M1 occlusion should be carefully decided.

Keywords

stroke fibrinolysis intraarterial middle cerebral artery

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References

del Zoppo

Pessin

: Thrombolytic intervention in acute thrombotic and embolic stroke. Semin Neurol 11: 368–384, 1991.

Hacke

: Thrombolytic therapy in acute ischemic stroke: An update. Fibrinolysis 8: 216–220, 1994.

Brandt

von Kummer

: Thrombolytic therapy of acute basilar artery occlusion. Variables affecting recanalization and outcome. Stroke 27: 875–881, 1996.

del Zoppo

Ferbert

: Local intra-arterial fibrinolytic therapy in acute carotid territory stroke. A pilot study. Stroke 19: 307–313, 1988.

del Zoppo

Higashida

: PROACT: A phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. Stroke 29: 4–11, 1998.

Ezura

Kagawa

: Selective and superselective infusion of urokinase for embolic stroke. Surg Neurol 38: 353–358, 1992.

Hacke

Zeumer

: Intraarterial thrombolytic therapy improves outcome on patients with acute vertebrobasilar occlusive disease. Stroke 19: 1216–1222, 1988.

Mori

Tabuchi

: Intracarotid urokinase with thromboembolic occlusion of the middle cerebral artery. Stroke 19: 802–812, 1988.

Sasaki

Takeuchi

: Fibrinolytic therapy for acute embolic stroke: Intravenous, intracarotid, and intra-arterial local approaches. Neurosurgery 36: 246–253, 1995.

10.

Zeumer

: Survey of progress: Vascular recanalizing techniques in interventional neuroradiology. J Neurol 231: 287–294, 1985.

11.

Zeumer

Freitag

: Local intraarterial fibrinolysis in acute vertebrobasilar occlusion. Technical development and recent results. Neuroradiology 31: 336–340, 1989.

12.

Zeumer

Freitag

: Local intra-arterial fibrinolytic therapy in patients with stroke: Urokinase vs. recombinant tissue plasminogen activator (rt-PA). Neuroradiology 35: 159–162, 1993.

13.

Gönner

Remonda

: Local intra-arterial thrombolysis in acute ischemic stroke. Stroke 29: 1894–1900, 1998.

14.

Brott

Haley

Jr : Urgent therapy for stroke, Part I: Pilot study of tissue plasminogen activator administered within 90 minutes. Stroke 23: 632–640, 1992.

15.

del Zoppo

Poeck

: Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol 32: 78–86, 1992.

16.

Hacke

Kaste

, for the European Cooperative Acute Stroke Study (ECASS): Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. JAMA 274: 1017–1025, 1995.

17.

Haley

Brott

, for the TPA Bridging Study Group: Pilot randomized trial of tissue plasminogen activator in acute ischemic stroke. Stroke 24: 1000–1004, 1993.

18.

Haley

Jr Levy

: Urgent therapy for stroke, part II: Pilot study of tissue plasminogen activator administered 91–180 minutes from onset. Stroke 23: 641–645, 1992.

19.

Mori

Yoneda

: Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke. Neurology 42: 976–982, 1992.

20.

The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333: 1581–1587, 1995.

21.

Trouillas

Nighoghossian

: Open trial of intravenous tissue plasminogen activator in acute carotid territory stroke. Correlation of outcome with clinical and radiological data. Stroke 27: 882–890, 1996.

22.

von Kummer

Hacke

: Safety and efficacy of intravenous tissue plasminogen activator and heparine in acute middle cerebral artery stroke. Stroke 23: 646–652, 1992.

23.

Yamaguchi

Hayakawa

Kikuchi

for the Japanese Thrombolysis Study Group: Intravenous tissue plasminogen activator ameliorates the outcome of hyperacute embolic stroke. Cerebrovasc Dis 3: 269–272, 1993.

24.

Lyden

Brott

, and the NINDS TPA stroke study group: Improved reliability of the NIH stroke scale using video training. Stroke 25: 2220–2226, 1994.

25.

TIMI Study Group. Special report: The Thrombolysis in Myocardial Infarction (TIMI) trial. N Engl J Med 312: 932–936, 1985.

26.

Pessin

del Zoppo

Estol

: Thrombolytic agents in the treatment of stroke. Clin Neuropharmacol 13: 271–289, 1990.

27.

van Swieten

Koudstaal

: Interobserver agreement for the assessment of handicap in stroke patients. Stroke 19: 604–607, 1988.

28.

Astrup

Siesjö

Symon

: Thresholds in cerebral ischemia — The ischemic penumbra. Stroke 12: 723–725, 1981.

29.

Heiss

Rosner

: Functional recovery of cortical neurons as related to degree and duration of ischemia. Ann Neurol 14: 294–301, 1983.

30.

Jones

Morawetz

: Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg 54: 773–782, 1981.

31.

Lassen

Astrup

: Ischemic penumbra. In: Wood

(ed): Cerebral blood flow, physiological and clinical aspects. McGraw-Hill, New York 1987: 458–466.

32.

Fisher

: Diffusion and perfusion imaging for acute stroke. Surg Neurol 43: 606–609, 1995.

33.

Barber

Darby

: Prediction of stroke outcome with echoplanner perfusion- and diffusion-weighted MRI. Neurology 51: 418–426, 1998.

34.

Marks

Tong

: Evaluation of early reperfusion and IV tPA therapy using diffusion- and perfuison-weighted MRI. Neurology 52: 1792–1798, 1999.

35.

Ueda

Sakaki

: Outcome in acute stroke with successful intra-arterial thrombolysis and predictive value of initial single-photon emission-computed tomography. J Cereb Blood Flow Metab 19: 99–108, 1999.

36.

Fisher

Adams

: Observation on brain embolism with special reference to the mechanism of hemorrhagic infarction. J Neuropathol Exp Neurol 10: 92–94, 1951.

37.

Jorgensen

Torvik

: Ischemic cerebrovascular diseases in an autopsy series, part II: Prevalence, location, pathogenesis, and clinical course of cerebral infarct. J Neurol Sci 9: 285–320, 1969.

38.

Lodder

Krijne-Kubat

Broekman

: Cerebral hemorrhagic infarction at autopsy: Cardiac embolic cause and the relationship to the cause of death. Stroke 17: 626–629, 1984.

39.

Hornig

Dorndorf

Agnoli

: Hemorrhagic infarction: A prospective study. Stroke 17: 179–185, 1986.

40.

Lodder

: CT-detected hemorrhagic infarction, relation with the size of the infarct, and the presence of midline shift. Acta Neurol Scand 2: 329–335, 1984.

41.

Ott

Zamani

: The clinical spectrum of hemorrhagic infarction. Stroke 17: 630–637, 1986.

42.

Wardlaw

Warlow

: Thrombolysis in acute ischemic stroke: Does it work? Stroke 23: 1826–1839, 1992.

43.

Mori

: Safety and efficacy of fibrinolytic agents in acute ischemic stroke. Cerebrovasc Dis 3: 264–268, 1993.

44.

Ogata

Yutani

: Hemorrhagic infarct of the brain without a reopening of the occluded arteries in cardioembolic stroke. Stroke 20: 876–883, 1989.

45.

del Zoppo

Higashida

: PROACT: A phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. Stroke 29: 4–11, 1998.

46.

Furlan

Higashida

: Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: A randomized controlled trial. JAMA 282: 2003–2011, 1999.