Whether ‘malignant’ brain edema following ischemic stroke is due to or aggravated by reperfusion and therefore more frequent after thrombolytic therapy of stroke is still under debate. From 3/96 to 1/97, we treated 51 patients with acute supratentorial stroke within 3 h after symptom onset with rt-PA following a protocol similar to the NINDS study. The results of thrombolytic therapy were evaluated by repeated clinical examination and computed tomography (CT) during the first week after ictus. The incidence of space-occupying brain edema following intravenous thrombolytic therapy of acute ischemic stroke was lower than the edema frequency after conventional treatment, but mortality from ‘malignant’ edema was higher in the patients with thrombolysis. Thus, space-occupying edema after acute ischemic stroke may be aggravated by thrombolytic treatment. Forced reperfusion of already irreversibly damaged tissue increases edema formation and enlarges developing infarcts with a deleterious increase of intracranial pressure.

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;333:1581–1587.
Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boysen G, Bluhmki E, Höxter G, Mahagne MH, Hennerici M for the ECASS Study Group: Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. JAMA 1995;274:1017–1025.
Heiss WD, Hayakawa T, Waltz AG: Patterns of changes of blood flow and relationships to infarction in experimental cerebral ischemia. Stroke 1976;7:454–459.
Ito V, Ohno K, Nakamura R, Suganuma F, Yanaba Y: Brain edema and restoration of blood flow. Stroke 1979;10:542–547.
Traupe H, Kruse E, Heiss WD: Reperfusion of focal ischemia of various duration: Postischemic hyper- and hypo-perfusion. Stroke 1982;13:615–622.
Iannotti F, Hoff J: Ischemic brain edema with and without reperfusion: An experimental study in gerbils. Stroke 1983;14:562–567.
Heiss WD, Graf R, Löttgen J, Ohta K, Fujita T, Wagner R, Grond M, Wienhard K: Repeat PET studies in transient MCA occlusion in cats: Residual perfusion and efficacy of postischemic reperfusion. J Cereb Blood Flow Metab 1997;17:388–400.
Koudstaal PJ, Stibbe J, Vermeulen M: Fatal ischaemic brain oedema after early thrombolysis with tissue plasminogen activator in acute stroke. Br Med J 1988;297:1571–1574.
Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R: ‘Malignant’ middle cerebral artery territory infarction. Arch Neurol 1996;53:309–315.
Hantson L, deWeert W, deKeyser J, Diener HC, Franke C, Palm R, van Orshoven M, Schoonderwaldt H, de Klippel N, Herroelen L, Feys H: The European Stroke Scale. Stroke 1994;25:2215–2219.
Lyden P, Brott T, Tilley B, Welch KMA, Mascha EJ, Levine S, Haley EC, Grotta J, Marler J, and the NINDS TPA Stroke Study Group: Improved reliability of the NIH stroke scale using video training. Stroke 1994;25:2220–2226.
Scandinavian Stroke Study Group: Multicenter trial of hemodilution in ischemic stroke. Background and study protocol. Stroke 1985;16:885–890.
Lindenstroem E, Boysen G, Christiansen LW, Rogvi Hansen B, Nielsen PW: Reliability of the Scandinavian Neurological Stroke Scale. Cerebrovasc Dis 1991;1:103–107.
Borovich B: A proposed CT grading system for brain edema and intracranial mass effect; in Samii M (ed): Skull Base Surgery. Basel, Karger, 1994, pp 38–39.
White OB, Norris JW, Hachinski VC: Death in early stroke, causes and mechanisms (letter). Stroke 1992;23:743.
Dietrich WD: Morphological manifestations of reperfusion injury in brain. Ann NY Acad Sci 1994;723:15–24.
Bell BA, Symon L, Branston NM: CBF and time thresholds for the formation of ischemic cerebral edema, and effect of reperfusion in baboons. J Neurosurg 1985;62:31–41.
Slivka A, Murphy E, Horrocks L: Cerebral edema after temporary and permanent middle cerebral artery occlusion in the rat. Stroke 1995;26:1061–1066.
Trouillas P, Nighoghossian N, Getenet JC, Riche G, Neuschwander P, Froment JC, Turjman F, Jin JX, Malicier D, Fournier G, Gabry AL, Ledoux X, Derex L, Berthezene Y, Adeleine P, Cie J, French P, Dechavanne M: Open trial of intravenous tissue plasminogen activator in acute carotid territory stroke. Stroke 1996;27:882–890.
Davalos A, Toni D, Bastianello S, Castillo J for the ECASS Group: Predictors of early neurological deterioration in acute ischemic stroke. Stroke 1997;28:251.
Heiss WD, Grond M, Thiel A, von Stockhausen HM, Rudolf J: Ischaemic brain tissue salvaged from ischemic infarction with alteplase. Lancet 1997;349:1599–1600.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.