Thrombolytic Therapy in Acute Ischemic Stroke II

336 Pages·1993·20.91 MB·English

by  L. R. Caplan

Gregory 1. del Zoppo Etsuro Mori
Werner Hacke (Eds.)
Thrombolytic Therapy
in Acute Ischemic Stroke
II
With 60 Figures and 41 Tables
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Hong Kong Barcelona
Budapest
Gregory J. del Zoppo, M.D.
Department of Molecular and Experimental Medicine,
The Scripps Research Institute
and Division of Hematology/Medical Oncology,
Scripps Clinic and Research Foundation,
10666 North Torrey Pines Road, La Jolla, CA 92037, USA
Etsuro Mori, M.D.
Neurology Service, Hyogo Brain and Heart Center at Himeji
520 Saisho-ko, Himeji, 670, Japan
Prof. Dr. Werner Hacke
Neurologische Klinik, Ruprecht-Karls-Universitat Heidelberg
1m Neuenheimer Feld 400, W-6900 Heidelberg 1, FRG
Publication of this volume was substantially underwritten by
The Roon Foundation, Inc., of La Jolla, California, USA.
ISBN-13: 978-3-540-56442-3 e-ISBN-13: 978-3-642-78061-5
DOl: 10.1007/ 978-3-642-78061-5
Library of Congress Cataloging-in-Publication Data. Thrombolytic therapy in acute ischemic stroke II/Gregory
J. del Zoppo, Etsuro Mori, Werner Hacke (eds.). p. cm. Includes bibliographical references and index.
1. Cerebrovascular disease - Chemotherapy
- Congresses. 2. Thrombolytic therapy - Congresses. 3. Tissue plasminogen activator - Therapeutic use -
Congresses. 4. Fibrinolysis - Congresses. 5. Thrombolytic Therapy - congresses. I. Del Zoppo, Gregory J. II.
Mori, Etsuro, 1951- . III. Hacke, W, (Werner), 1948- . [DNLM: 1. Cerebral Ischemia - drug therapy -
congresses. 2. Fibrinolysis - congresses. 3. Fibrinolytic Agents - therapeutic use - congresses. WL 355 T5314
1993] RC388.5.T4773 1993 616.8'10651-de20
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Preface
With the demonstration that cerebral arterial recanalization is feasible, there
has been a more active pursuit of thrombolysis as a therapeutic option for pa
tients in the acute stages of ischemic stroke. Since the inaugural symposium
held in Heidelberg in May 1990, plans for prospective controlled trials of both
fibrin-selective thrombolytic agents and fibrinogenolytic agents have matured.
Several recently completed prospective trials give insights into the profile of
hemorrhagic transformation and its risk, and limited information about
clinical benefit. The possibility of early recanalization suggests an adjunctive
role for possible neuronal protectants, new antithrombotics, and other novel
agents and marries two major investigational directions. These and related
topics provided the content for the Second International Symposium on
Thrombolysis in Acute Ischemic Stroke, held in La Jolla 1-2 May 1992. This
volume contains selected papers from that meeting, and a summary of the
discussions which accompanied the papers.
The editors wish to express their gratitude for the extraordinary support of
this symposium by a number of sponsors, including the Roon Foundation, Ab
bott Laboratories, Genentech Inc., Knoll Pharmaceuticals, Sumitomo Phar
maceuticals Co., Ltd., Dr. Karl Thomae GmbH (Boehringer Ingelheim
Deutschland), and the Upjohn Company. Preparation of the manuscripts was
facilitated by Ms. J. Koehler and her team and Ms. S. Larsen at the Scripps
Research Institute. We wish to again thank Springer-Verlag, Heidelberg, for its
generous assistance in the preparation and publication of this volume. Of
course, this effort would not have been possible without the provocative con
tributions of a growing number of investigators to this exciting area.
La Jolla Gregory J. del Zoppo
Etsuro Mori
Werner Hacke
Contents
Background to Thrombolytic Therapy in Acute Ischemic Stroke
Therapy for Acute Ischemic Stroke: Clinical Needs
and Statistical Burdens
L. R. Caplan and M. Gent ..................................... 3
Clinical Outcome of Acute Ischemic Stroke:
Prospective Angiographic Studies
C. Fieschi, M. L. Sacchetti, C. Argentino, M. Fiorelli, D. Toni,
C. Gori, S. Bastianello, and G. Sette ............................ 13
The Ischemic Penumbra: Usefulness of PET
W. J. Powers .................................................. 17
Thrombolytic Agents: Lessons for Their Use in Acute Stroke
from Myocardial Infarction Experience
M. Verstraete ................................................. 22
Pathogenesis of Secondary Brain Hemorrhage After Ischemia:
Lessons from Animal Models .,. and a few from man, tool
G. F. Molinari ................................................ 29
Clinical Dials of Fibrinolytic Agents
in Carotid Territory Cerebral Ischemia
Symptom-Based 'frials of Intravenous rt-PA in Acute Stroke
T. Brott...................................................... 39
A Safety and Efficacy Study of Intravenous rt-PA in Patients
with Acute Stroke
M. J. Alberts for The rt-PA Acute Stroke Study Group ............. 45
VIII Contents
Recanalization, Infarct Volume, Cerebral Hemorrhage, and
Clinical Outcome After Intravenous Recombinant Tissue Plasminogen
Activator and Heparin in Acute Carotid Thrritory Stroke
R. von Kummer, M. Forsting, W. Hacke, and K. Sartor ............ 53
Intravenous Tissue Plasminogen Activator
in Acute Thromboembolic Stroke:
A Placebo-Controlled, Double-Blind lHal
T. Yamaguchi, T. Hayakawa, and H. Kikuchi for the Japanese
Thrombolysis Study Group ..................................... 59
The European Cooperative Acute Stroke Study (ECASS)
M. Kaste, C. Fieschi, W. Hacke, E. Lesaffre, M. Verstraete,
and J. Fr6hlich ............................................... 66
On the Estimation of the Sample Size for the ECASS Study
E. Lesaffre, I. Scheys, J. Fr6hlich, and E. Bluhmki ................ 72
Australian Streptokinase lHal (ASK)
G. A. Donnan, S. M. Davis, B. R. Chambers, P. C. Gates, G. J. Hankey,
E. G. Stewart-Wynne, D. Rosen, R. R. Thck, and J. J. McNeil ........ 80
Thrombolytic and Antithrombotic Therapy in Acute Ischemic Stroke.
Multicenter Acute Stroke ltial - Italy (MAST-I)
L. Candelise for The MAST-I Collaborative Group ................ 86
Discussion Summary: Clinical ltials in Progress
Chaired by G. Boysen ......................................... 95
Other Applications of Fibrinolytic Agents
in the Central Nervous System
Acute Central Retinal Artery Occlusion and the Role of Thrombolysis
H.-J. Freitag, H. Zeumer, and V. Knospe .......... ... . . . . . . . . . . . . . 103
Current Status of Fibrinolysis for the Rapid Dissolution
of Subarachnoid and Intraventricular Clot
B. Weir ...................................................... 106
Discussion Summary: Other Applications of Fibrinolytic Agents
in the Central Nervous System
Chaired by B. Copeland ....................................... 114
Contents IX
Insights into the Pathogenesis of Cerebral Ischemia
Relevant to Fibrinolysis
Deterioration of Acute Stroke
K. Asplund .................................................. 119
Early Spontaneous Recanalization of Thromboembolic Stroke
E. Mori and Y. Yoneda ........................................ 129
Spectacular Shrinking Deficits in Acute Ischemic Stroke
K. Minematsu ................................................ 138
The Significance of Various Factors Associated
with Hemorrhagic 1tansformation in Patients 1reated
with Recombinant Tissue Plasminogen Activator for Acute Stroke
M. S. Pessin and S. M. Wolpert for The rt-PA Acute Stroke
Study Group ................................................. 145
Thrombolysis: Stroke Subtype and Embolus 'JYpe
W. Hacke .................................................... 153
The Prognostic Value of Collateral Blood Flow
in Acute Middle Cerebral Artery Occlusion
M. Forsting, D. Krieger, R. von Kummer, W. Hacke, and K. Sartor . . 160
Morphological Evidence of Progressive Microvascular Impairment
in Middle Cerebral Artery Occlusion-Reperfusion
G.J. del Zoppo and J.H. Garcia ................................ 168
Discussion SuIiunary: Insights into the Pathogenesis
of Cerebral Ischemia Relevant to Fibrinolysis
Chaired by J. Toole and T. Yamaguchi ........................... 181
Diagnosis and Assessment of Outcomes in Acute Cerebral Ischemia
The Relevance of CT Scanning and Angiography for Patients with
Acute Stroke 1reated with Recombinant Tissue Plasminogen Activator
S. M. Wolpert and M. S. Pessin for The rt-PA Acute Stroke
Study Group ................................................. 189
Recanalization of the Embolically Occluded Middle Cerebral Artery
in Acute Stroke Patients: Noninvasive Assessment and Outcome
E.B. Ringelstein, R. Biniek, B. Ammeling, and P.N. Nolte ......... 192
x Contents
Potential Role of Magnetic Resonance Imaging in Selecting Patients
for Thrombolytic Therapy
A. J. Furlan .................................................. 199
The Role of SPECT in Acute Stroke Thrombolysis
B. Sperling, K. Overgaard, G. Boysen, N.A. Lassen 206
Clinical and Brain Hemodynamic Evaluations
of Thrombolytic Therapy in Acute Ischemic Stroke: SPECT Study
Y. Okada, S. Sadoshima, M. Katsuragi, K. Irie, H. Utsunomiya,
and M. Fujishima ............................................. 212
The Relevance of Neurological and Functional Outcome Scales
for Acute Stroke Trials
A. Ferbert and K. Willmes ..................................... 217
Discussion Summary: Diagnosis and Assessment of Outcomes
in Acute Cerebral Ischemia
Chaired by S. M. Otis and L. Wechsler ........................... 224
Ancillary Therapy for Cerebrovascular Reperfusion
Neuronal Protection and Recanalization Strategies: Is More Better?
J. Grotta ..................................................... 229
Strategies Which Decrease Post-Reperfusion Lipid Peroxidation
E. D. Hall .................................................... 239
Anti-PMN Leukocyte Strategies and Their Application
to Focal Cerebral Ischemia
G. W. Schmid-SchOnbein and G. J. del Zoppo ..................... 245
Von Willebrand Factor as a Thrget for Antithrombotic Intervention
Z. M. Ruggeri ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 256
Neuronal Protection: Is There a Role for Gangliosides
or Ca2+ -Channel Blockers?
G.-L. Lenzi, H. Baasch, and R. Bruno..... . . . .... .... . ... . ...... 265
Discussion Summary: Ancillary Therapy
for Cerebrovascular Reperfusion
Chaired by M. Hennerici and P. Lyden .......................... 271
Contents XI
Open Communications
A Meta-Analysis of All Published Data on the Use
of Thrombolytic Therapy to Treat Acute Ischemic Stroke
J. M. Wardlaw and C. P. Warlow ................................ 275
Causes of Delayed 1J:eatment of Stroke Patients Enrolled
in t-PA Protocols
M. J. Alberts and A. Perry ..................................... 278
A Demming Approach to Recruiting: The National Institute
of Neurological Disease
and Stroke (NINDS) t-PA Stroke 1J:ial Experience
B. C. Tilley for The NINDS t-PA Stroke 1J:ial Investigators ......... 282
Local Intra-arterial FibrinolytiC Therapy Within the Cerebral Arteries:
Effectiveness of rt-PA Concerning Recanalization Rate and Time
H. Zeumer, H.-J. Freitag, F. Zanella, A. Thie, and C. Arning ....... 285
Relation of Thrombolytic Reperfusion and of Collateral Circulation
to Outcome in Patients Suffering Cerebral Main Artery Occlusion
A. B. Brucker, H. Potuschak, E. Laich, J. 1J:enkler,
H. Be>hm-Jurkovic, and E. Deisenhammer ........................ 288
Factors Related to Intracranial Hematoma Formation in Patients
Receiving t-PA for Acute Ischemic Stroke
D. E. Levy, T. Brott, E. C. Haley, Jr., and J. R. Marler ............. 294
1J:anscranial Doppler Sonographic (TCD) Monitoring
of Basilar Artery Thrombolysis
M. A. Williams, A. Y. Razumovsky, M. N. Diringer, L. H. Monsein,
G. M. Debrun, R. Nick Bryan, and D. F. Hanley .................. 298
HMPAO SPECT Measures Reperfusion After Thrombolytic Therapy
in Acute Stroke
A. E. Baird, G. A. Donnan, M. C. Austin, G. J. Fitt, and W. J. McKay 301
A Cell Culture Model of Reperfusion Injury:
Neutrophil-Mediated Brain Endothelial Cytotoxicity
D. C. Hess, X. Chen, A. Griezkiewicz, and J. Catravas 304
Modification of Brain Ischemia Due to Embolic Stroke by Tissue-1yPe
Plasminogen Activator With and Without Heparin in a Rabbit Model
o.
L.P. Carter, A.N. Guthkelch, J. Orozco, and Temeltas .......... 308
XII Contents
Reduction of Infarct Volume and Mortality by Thrombolysis
with rt-PA in an Embolic Stroke Model
T. Sereghy, K. Overgaard, G. Boysen, H. Pedersen, and N. H. Diemer 311
Discussion Summary: Open Communications
Chaired by E. Feldmann and A. J. Furlan ........................ 316
Clinical Dial Development
Clinical 1tials Sponsored by Companies versus the NIH
J. P. Mohr and D. E. Levy ...................................... 323
Blindness and Thrombolysis
D. Stump and J. Breed ........................................ 327
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331