ADVANCES IN THE TREATMENT OF ISCHEMIC STROKE Edited by Maurizio Balestrino Advances in the Treatment of Ischemic Stroke Edited by Maurizio Balestrino Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Maja Bozicevic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published February, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Advances in the Treatment of Ischemic Stroke, Edited by Maurizio Balestrino p. cm. ISBN 978-953-51-0136-9 Contents Preface IX Part 1 Hypothermia in the Acute Phase 1 Chapter 1 Cerebral Ischemia and Post-Ischemic Treatment with Hypothermia 3 Kym Campbell, Neville W. Knuckey and Bruno P. Meloni Chapter 2 Hypothermia as an Alternative for the Management of Cerebral Ischemia 15 Felipe Eduardo Nares-López, Gabriela Leticia González-Rivera and María Elena Chánez-Cárdenas Chapter 3 Timing of Hypothermia (During or After Global Cerebral Ischemia) Differentially Affects Acute Brain Edema and Delayed Neuronal Death 37 Masaru Doshi and Yutaka Hirashima Chapter 4 Molecular Mechanisms Underlying the Neuroprotective Effect of Hypothermia in Cerebral Ischemia 43 Yasushi Shintani and Yasuko Terao Part 2 Brain Regeneration After Stroke: Spontaneous Events and Stem Cells Therapy 67 Chapter 5 Cortical Neurogensis in Adult Brains After Focal Cerebral Ischemia 69 Weigang Gu and Per Wester Chapter 6 Brain Plasticity Following Ischemia: Effect of Estrogen and Other Cerebroprotective Drugs 89 Edina A. Wappler, Klára Felszeghy, Mukesh Varshney, Raj D. Mehra, Csaba Nyakas and Zoltán Nagy VI Contents Chapter 7 The Promise of Hematopoietic Stem Cell Therapy for Stroke: Are We There Yet? 115 Aqeela Afzal and J. Mocco Chapter 8 Toward a More Effective Intravascular Cell Therapy in Stroke 141 Bhimashankar Mitkari, Erja Kerkelä, Johanna Nystedt, Matti Korhonen, Tuulia Huhtala and Jukka Jolkkonen Part 3 Intravenous Thrombolysis and Intra-Arterial Procedures 161 Chapter 9 Thrombolysis for Ischemic Stroke in Patients Aged 90 Years or Older 163 M. Balestrino, L. Dinia, M. Del Sette, B. Albano and C. Gandolfo Chapter 10 Mechanical Embolectomy 169 Jiří Lacman and František Charvát Chapter 11 Decreased Cerebral Perfusion in Carotid Artery Stenosis, Carotid Angioplasty and Its Effects on Cerebral Circulation 183 Antenor Tavares and José Guilherme Caldas Part 4 Treatment of Intracranial Hypertension 213 Chapter 12 Medical and Surgical Management of Intracranial Hypertension 215 James Scozzafava, Muhammad Shazam Hussain and Seby John Chapter 13 An Innovative Technique of Decompressive Craniectomy for Acute Ischemic Stroke 227 Marcelo M. Valença, Carolina Martins, Joacil Carlos da Silva, Caio Max Félix Mendonça, Patrícia B Ambrosi and Luciana P. A. Andrade-Valença Preface The last decade or so has witnessed unprecedented advances in the therapy of ischemic stroke. Intensive preclinical and clinical research in what used to be an almost incurable disease is finally putting at the clinicians’ disposal powerful therapeutic tools. While intravenous thrombolysis with recombinant tissue plasminogen activator has been the first and is still the most used tool, other ways of interventions have entered the clinical arena, dramatically improving the therapy of ischemic stroke. As it always happens at times of rapid changes, clinical practice lags behind research findings. While at times it must be so, since clinical practice must wait for evidence confirmation, very often the clinician finds it difficult to receive and process the relevant information in what may appear an overflow of data. While an all-inclusive review of all available innovations in stroke therapy would probably be impossible in a single book, this one does provide reviews and updated information in several hot issues. Hypothermia is the first such issue. This powerful therapy is finally coming of age, so far the sole survivor of a host of “neuroprotective” therapies that animal research had developed. While all other neuroprotective therapies have failed in the clinics, hypothermia has grown to become now, basically, recommended practice in the rescue therapy after cardiac arrest, a condition very similar albeit not identical to ischemic stroke. Its application in stroke is currently not routine practice, because of technical difficulties, of still significant side effects (let’s not forget that cardiac arrest often occurs in young people, ischemic stroke in elder persons) and because of limited clinical trials. However, there is probably sufficient evidence for considering it on a case-by-case basis in hospitals that have experience in its application. In this book, the contribution by Campbell et al. provide a fine review of both preclinical and clinical issues of hypothermia. Both Nares-López et al. and Shintani and Terao convincingly review the very extensive mechanisms of protection by hypothermia, while Doshi and Hirashima report results from animal research concerning duration and timing of hypothermia, results that are relevant to clinical applications of this technique. Second, brain regeneration is considered. The last decade of the 20th century has finally rejected the old myth that neurons remain unchanged in number from birth to death and, if damaged, cannot be replaced. On the contrary, we now know that a X Preface lively neuronal regeneration is routinely under way in the brain (for example, new neurons are continuously generated in the hippocampal dentate gyrus, a fact that is probably important for memory). Endogenous regeneration is certainly a repair mechanism that occurs after stroke, although still a poorly understood one. In this book, two chapters (by Gu and Wester and by Wappler et al.) provide novel interesting knowledge on the relevance and on the mechanisms of endogenous regeneration after experimental animal ischemic stroke. Moreover, stem cells administration has been extensively investigated, in the hope to replace the neurons that had died after stroke. Unfortunately, human clinical trials in this field have been surprisingly scarce, a fact that still leaves largely unanswered basic questions like: is stem cells administration really useful for stroke, does it really work by replacing dead neurons, or does it rather favor endogenous regeneration and healing, what types of stem cells are better, what stroke types benefit the most from this therapy. Answer to these questions is of paramount importance also because several private hospitals are now offering expensive stem cells transplantation, a legitimate business that however underlines an urgent need to answer the above questions. In this book the two chapters by Afzal and Mocco and by Mitkari et al. help the interested professional navigate this difficult field. Clot-removal therapies for ischemic stroke (both intravenous thrombolysis and endovascular techniques) entered the neurological armamentarium at the very end of the last century, changing forever the way stroke is treated. As we all recall, they were met with a mix of enthusiasm for their effectiveness and fear for their side effects, chiefly haemorrage. Fear of haemorrhage caused a long list of exclusion criteria that, at least in Europe, prevented intravenous thrombolysis from being administered to many, probably most, patients. In the following years several such criteria were challenged or revised, for example the maximum acceptable time from onset is currently no longer considered 3 hours (as it is still stated in the official approval documents of the therapy) but rather 4.5 hours, following the successful ECASS-III study, and most centers are now administering intravenous thrombolysis off-label between 3 and 4.5 hours from symptoms onset. At the time of this writing (January 2012) we are waiting for the results of the IST-3 trial, that will hopefully clarify other issues in the administration of intravenous thrombolysis (for example, time up to 6 hours from onset, simptoms very mild or too severe, onset with epileptic seizures, and so on). A major issue is patients’ age, in fact in Europe r-TPA for intravenous thrombolysis is still officially approved for treatment only in patients younger than 80 y.o. However, this boundary is being strongly challenged, and in this book we (Balestrino et al.) are reporting our so far successful experience with intravenous thrombolysis in patients even older than 90 years. Endovascular therapy has recently raised great interest both in the therapy of acute stroke and in the therapy of symptomatic or asymptomatic carotid artery stenosis. As for acute stroke, the only randomized, controlled, multicenter, open-label clinical trial with blinded follow-up that has been so far completed is the PROACT-II, that . is, in theory, the ideal therapy, with multiple mechanisms of action in opposition to the consequences of ischemia. Advances in the Treatment of Ischemic Stroke 4 2. Background of therapeutic. unprecedented advances in the therapy of ischemic stroke. Intensive preclinical and clinical research in what used to be an almost incurable disease is finally putting at the clinicians’ disposal. ADVANCES IN THE TREATMENT OF ISCHEMIC STROKE Edited by Maurizio Balestrino Advances in the Treatment of Ischemic Stroke Edited by Maurizio Balestrino Published