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Stroke
Pathophysiology, Diagnosis, and Management

SEVENTH EDITION

JAMES C. GROTTA, MD ENG H. LO, PhD

Director of Stroke Research and Mobile Stroke Unit Professor of Neurology and Radiology
Clinical Innovation and Research Institute Harvard Medical School
Memorial Hermann Hospital-Texas Medical Center Boston, Massachusetts
Houston, Texas Director, Neuroprotection Research Laboratories
Massachusetts General Hospital
Charlestown, Massachusetts
GREGORY W. ALBERS, MD
Professor
Department of Neurology and Neurological Sciences RALPH L. SACCO, MD
Stanford University Chairman, Department of Neurology
Stanford, California Olemberg Family Chair in Neurological Disorders
Miller Professor of Neurology, Public Health Sciences,
Human Genetics, and Neurosurgery
JOSEPH P. BRODERICK, MD University of Miami Miller School of Medicine
Professor Chief of Service, Neurology
Department of Neurology and Rehabilitation Medicine Jackson Health System
University of Cincinnati Gardner Neuroscience Institute Miami, Florida
Cincinnati, Ohio

LAWRENCE K.S. WONG, MD

ARTHUR L. DAY, MD Professor
Professor and Co-Chairman Department of Medicine and Therapeutics
Director of Cerebrovascular Surgery Chinese University of Hong Kong
Residency Program Director Shatin, Hong Kong, China
Department of Neurosurgery
University of Texas Medical School at Houston
Houston, Texas

SCOTT E. KASNER, MD
Professor, Department of Neurology
University of Pennsylvania
Director, Comprehensive Stroke Center
University of Pennsylvania Health System
Philadelphia, Pennsylvania
Elsevier
1600 John F. Kennedy Blvd.
Ste 1600
Philadelphia, PA 19103-2899

STROKE: PATHOPHYSIOLOGY, DIAGNOSIS, AND MANAGEMENT:  ISBN: 978-0-323-69424-7

SEVENTH EDITION
Copyright © 2022 by Elsevier, Inc. All rights reserved.

No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
mechanical, including photocopying, recording, or any information storage and retrieval system, without
permission in writing from the publisher. Details on how to seek permission, further information about the
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Center and the Copyright Licensing Agency can be found at our website: www.elsevier.com/permissions.

This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).

Notice

Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
using any information, methods, compounds, or experiments described herein. Because of rapid advances
in the medical sciences in particular, independent verification of diagnoses and drug dosages should be
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or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in
the material herein.

Previous editions copyrighted © 2016 by Elsevier Inc; 2011 by Saunders, an imprint of Elsevier Inc; 2004, 1998,
1992, 1986 by Churchill Livingstone.

Library of Congress Control Number: 2020952390

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Printed in the United States of America

Last digit is the print number: 9 8 7 6 5 4 3 2 1

 Video Contents

Video 30.1 Important concepts regarding Video 32.9 TTE of large posterior mitral annular
angioarchitecture, classification, and risk calcification (MAC) with central echo lucency,
factors for arteriovenous malformations. suggesting caseous MAC.
Video 30.2 Endovascular embolization of a frontal Video 33.1 Large atherosclerotic plaque in the mid-portion
arteriovenous malformation. of the aortic arch with large superimposed,
Video 30.3 Endovascular and surgical techniques in the mobile thrombus (also Fig. 33.6).
treatment of dural arteriovenous fistulae. Video 33.2 Mobile aortic plaque in the superior aspect of
Video 32.1 Mobile atheroma: An intraoperative video 3D the aortic arch, just proximal to the takeoff of
TEE image of a mobile atheroma in the aortic the innominate artery (also Fig. 33.10A and B).
arch, visualized during a transcatheter aortic Video 35.1 3D reconstruction of carotid angiography
valve replacement (TAVR), consistent with in a 40-year-old woman with right-sided
grade 5 atheromatous disease. numbness. Anterior, posterior, and left lateral
Video 32.2 (A) Positive bubble study: Markedly positive rotational video of the left internal carotid
bubble study consistent with a large atrial artery demonstrates a web.
level shunt. (B) Negative bubble study: Video 60.1 Knee-ankle-foot-orthosis: A knee-ankle-foot
Agitated saline contrast (“bubble”) study orthosis enabled this hemiplegic person with
showing no evidence of an interatrial sensorimotor loss to prevent the knee from
communication. snapping back in the mid- to late stance phase
Video 32.3 TEE bubble study with intrapulmonary of gait, prevent catching the forefoot when
shunt: A bubble study on TEE with delayed initiating swing, and improved control of the
passage of bubbles into the left atrium via the stability of foot placement during the stance
right upper pulmonary vein, suggesting an phase.
intrapulmonary shunt, such as a pulmonary Video 72.1 Minimally invasive endoscopic ICH
atriovenous malformation. evacuation. The procedure begins with a
Video 32.4 Takotsubo cardiomyopathy: TTE revealing 1.5-cm incision, a 1-cm craniectomy, and
akinesis of mid- and apical left ventricular stereotactic placement of a 19F (6.3-mm)
segments with hypercontractile basal sheath into the hematoma. The introducer
segments, consistent with a stress-mediated is then removed from the sheath, and the
cardiomyopathy (Takotsubo cardiomyopathy). endoscope is placed down the sheath with
an adjunctive aspiration device inserted
Video 32.5 Mobile atrial septum with positive bubble in the working channel of the endoscope.
study: Mobile atrial septum, consistent with
Continuous irrigation with lactated Ringers is
an atrial septal aneurysm. Agitated saline
used throughout the procedure.
contrast (“bubble”) study reveals passage
of bubbles into the left heart after the atrial Video 72.2 Minimally invasive endoport-mediated ICH
septum bulges into the left atrium, suggesting evacuation. The procedure begins with a
a transient increase in right atrial pressure. 4-cm incision, a 2.5-cm craniotomy, and
This finding is consistent with the presence of stereotactic placement of a 13.5-cm endoport
a patent foramen ovale (PFO). into the hematoma. The introducer is
then removed from the endoport, and the
Video 32.6 TTE of a large left atrial myxoma, filling the
endoport is fixed in place. A microscope or
entire left atrium and resulting in obstruction
an exoscope is then positioned to provide
to left ventricular filling.
visibility down the endoport and into the
Video 32.7 Papillary fibroelastoma: TEE of the aortic cavity.
valve revealing a linear echo density on the
Video 75.1 Surgical management of a cerebral cavernous
ventricular surface of the valve, consistent
malformation.
with a papillary fibroelastoma.
Video 32.8 2D (A) and 3D (B) images of a large burden of Video 77.1 Superficial temporal artery to middle cerebral
artery bypass.
clot in the left atrium and left atrial appendage
in a patient with a cardiomyopathy and atrial Video 78.1 Decompressive craniectomy in a patient with
flutter, presenting with a stroke. malignant middle cerebral artery infarction.

ix
 Foreword to the Seventh Edition
This original editor continues to marvel at the advances in The growing participation in stroke management by
the field of stroke, justifying the seventh edition of this book. those in allied fields has done nothing to displace the role
Among other topics, the first edition had a mere 15 chap- of neurovascular clinicians, whose commitment includes
ters, and in 347 pages covered “Stroke Therapy.” The subjects studying how the brain works. Insights from modern basic
ranged from management of risk factors to rehabilitation. biology, increasingly sophisticated imaging, prospective
This edition has no less than 28 such chapters, clustered in clinically detailed databases, and even access to video Zoom
stand-alone sections for medical and interventional therapy. follow-ups are providing windows into what was formerly
The page length for all of subjects has steadily expanded by called semiology. Decades ago, the neurology literature was
editions: proof, if needed, of progress. Gone—and good rid- dotted with titles beginning with “The Neurology of…” by
dance!—are the days when those interested in stroke were which the author(s) implied how a clinical syndrome allowed
considered clinically irrelevant for lack of definitive therapies. insight into diagnosis or prognosis. Today, a surprising number
Instead, far from an arcane subspecialty, stroke prevention of outcomes for acute focal syndromes formerly considered
and management now has an impact on the clinical practice static, prevented from their full development, or deemed
of many medical and surgical fields whose training not long modified favorably by acute interventions, are yielding insights
ago scarcely touched on the subject. into the mysteries of functional reorganization. The increasing
Stroke clinicians now find their clinical judgment opportunities to understand this effect offers literature-
tested—sometimes to their vexation—by the application of oriented neurovascular clinicians the chance to be links in an
hyperacute management algorithms driven mainly by scor- unbroken chain of inquiry dating back to antiquity.
ing systems, meta-analyses, and outcomes from the wave of
clinical trials. Few can argue with the positive effect of rapid J.P. Mohr, MD
assessment and intervention, especially for acute ischemic Daniel Sciarra Professor of Neurology
strokes. Insights spanning genetics, basic biology, computer- Department of Neurology
driven population studies, web-based meta-analyses, and Director and Neurologist
increasingly common longitudinal outcome reports are wel- Doris and Stanley Tanenbaum Stroke Center
come signs of progress. Only novelists should designate their Columbia University Irving Medical Center
published work free from revision. The current contributors New York, New York
can expect further changes to justify an eighth edition in the
foreseeable future.

x
 Preface
The seventh edition of the text has a number of important Other unsolved areas that receive substantial updating
changes. First, this edition has even more on-line features, include intracerebral hemorrhage by new author Dr. Anderson
making it easier to access its content in a digital-friendly for- and arteriovenous malformations by Drs. Samaniego, Roa,
mat. The eBook includes the entire book plus full reference Ortega-Gutierrez, and Derdeyn. In addition, the chapters
lists (as opposed to the Key References that appear in the chap- on the surgical management of different types of brain
ters) and a larger number of videos than the previous edition. hemorrhage have all been updated by new authors.
Access to the Expert Consult eBook version is included with The previous edition appeared just as the trials demonstrating
print purchase. This enhanced eBook experience allows you the benefit of endovascular thrombectomy were published, so
to search all of the text, figures, and references on a variety of the coverage of this revolution in treatment was incomplete.
devices. The content can also be downloaded to tablets and In this edition, Dr. Broderick’s section, Interventional Therapy,
smart phones for offline use. and in particular the chapter by Drs. Saver and Jahn on the
Another important change includes our new Surgical endovascular treatment of acute ischemic stroke, have been
Therapy section editor, Arthur Day, MD. Dr. Day is an substantially updated to include the results of all those pivotal
international authority on the surgical management of clinical trials, as well as the myriad studies that followed.
cerebral aneurysms, intracranial hemorrhage, and extracranial The final unresolved topic receiving increased coverage
vascular disease. He is the recipient of numerous neurosurgical in this edition is how best to deliver these effective new
leadership awards, and from first-hand experience I can attest treatments (e.g., stroke systems of care). We have added a new
to his passion for teaching and the wisdom that has grown chapter on this topic, written by Drs. Czap, Harmel, Audebert,
out of decades of skillfully managing the complexities of the and myself, that explores different models and approaches to
entire array of neurovascular surgical cases. Of particular value reorganizing our stroke centers, resources, and staffing. and
for his role as editor, Dr. Day has been an important leader In addition, first-time contributors to this title, Drs. Kircher
of the neurosurgical field as it has emerged from open to and Adeoye, have expanded the chapter on prehospital and
endovascular approaches and as it has partnered with vascular emergency care.
neurology in the conduct of clinical trials. As a result of his While I have focused my editorial spotlight on a few of the
intimate knowledge of the entire neurovascular landscape and major unresolved topics that are receiving substantial and well-
its leaders, you will see that the authors of almost all of the deserved increased attention, I want to emphasize that each and
chapters in the Surgical Therapy section have changed and the every chapter has been updated with new information. There
chapters have all been updated. I think that the readers will be is a new chapter on posterior reversible encephalopathy, which
impressed by the combined experience, fresh perspective, and replaces the old chapter on hypertensive encephalopathy with
new information in every chapter in the section. new authors (Drs. Balu and Fischer); the imaging chapters on
Other notable changes in this edition justified enlarging CT and MRI have been updated, with expanded discussion of
attention given to several underappreciated and yet unresolved the important role of imaging in patient selection for acute
problems in the field. In line with the increasing evidence of therapy; the chapters on cardiac disease, cryptogenic stroke,
vascular disease as the most important modifiable contributor and secondary prevention provide more information on
to dementia and much-needed attention to the biology atrial fibrillation detection, other possible causes of embolic-
underlying small vessel disease, a new chapter on this topic appearing stroke without known source, and their long
has been added to the Pathophysiology section, which has term management; the antiplatelet therapy chapter includes
been overseen by the senior editor, Dr. Lo. In addition, the updated data from recent trials of dual antiplatelet therapy;
chapters on the clinical aspects of vascular dementia and and the design of stroke clinical trials chapter has been
small vessel disease have been updated by new authors (Drs. rewritten by new authors (Drs. Perez, Elm, and Saver) and
Rundek, Seshadri, and Caunca) in the Epidemiology and Risk includes emerging novel approaches to figuring out if new
Factors section, and important new information is found in the treatments work.
chapters on genetics and CADASIL. Somewhat linked to this All in all, I hope that the exciting relevant new data that fill
topic and also reflecting a maturing interest in non-imaging the pages of our journals and make stroke such a dynamic and
stroke biomarkers in general is an entirely new chapter on interesting field are distilled into these pages in a readable and
“OMICs,” written by Drs. Jickling and Sharp. authoritative format that will help the reader understand their
Disparities in stroke incidence and outcomes has become patients and their underlying disease, which they see every
a hot topic, accentuated recently by the spotlight cast on this day, and also provide the foundation for new knowledge that
issue during the COVID-19 pandemic and the racial unrest in will be the substrate for the next edition.
the United States. The already outstanding chapter on stroke
disparities by Drs. Howard, Howard, and McCullough has James C. Grotta, MD
been updated, and this topic has also been woven through
other chapters where relevant.

xi
 Contributors

Harold P. Adams Jr., MD Hugo J. Aparicio, MD, MPH Hakan Ay, MD

Professor Assistant Professor Associate Professor
Department of Neurology Department of Neurology Departments of Neurology and
Carver College of Medicine Boston University School of Medicine Radiology
University of Iowa Investigator, The Framingham Heart Massachusetts General Hospital
Iowa City, Iowa Study Harvard Medical School
Boston, Massachusetts Boston, Massachusetts
Opeolu Adeoye, MD
Takeda Pharmaceutical Company
Vice Chair, Research Ken Arai, PhD
Limited
Co-Director, UC Stroke Team Associate Professor
Cambridge, Massachusetts
Professor Neuroprotection Research Laboratory
Department of Emergency Medicine Departments of Radiology and Selva Baltan, MD, PhD
University of Cincinnati Neurology Professor and Vice Chair for Basic
Cincinnati, Ohio Massachusetts General Hospital Research
Harvard Medical School Anesthesiology and Peri-Operative
Gregory W. Albers, MD
Boston, Massachusetts Medicine
Professor
Oregon Health and Science University
Department of Neurology and Jaroslaw Aronowski, PhD, MD
School of Medicine
Neurological Sciences Professor and Vice Chair
Portland, Oregon
Stanford University Roy M. and Phyllis Gough Huffington
Stanford, California Chair in Neurology Ramani Balu, MD, PhD
McGovern Medical School Assistant Professor
Andrei V. Alexandrov, MD, RVT
University of Texas Health Science Division of Neurocritical Care
Semmes-Murphey Professor and Chairman
Center at Houston Department of Neurology
Department of Neurology
Houston, Texas University of Pennsylvania
The University of Tennessee Health
Philadelphia, Pennsylvania
Science Center Kunakorn Atchaneeyasakul, MD
Memphis, Tennessee Clinical Instructor of Neurology Mandana Behbahani, MD
StrokeNet Fellow Resident
Sepideh Amin-Hanjani, MD
Department of Neurology Department of Neurosurgery
Professor and Program Director
University of Pittsburg School of University of Illinois at Chicago
Department of Neurosurgery
Medicine Chicago, Illinois
Co-Director, Neurovascular Surgery
Pittsburg, Pennsylvania
University of Illinois at Chicago Oscar R. Benavente, MD
Stroke Vascular Fellow
Chicago, Illinois Professor
UCLA Health
Department of Medicine
Hongyu An, PhD Los Angeles, California
Director
Associate Professor
Heinrich Audebert, MD Stroke and Cerebrovascular Health
Department of Radiology
Senior Physician Research
Washington University School of
Assistant Director of the Department CBF Brain Research Center
Medicine
Department of Neurology Division of Neurology
St. Louis, Missouri
Center for Stroke Research University of British Columbia
Craig S. Anderson, MD, PhD Charité University Medicine Berlin Vancouver, British Columbia, Canada
Professor of Neurology Berlin, Germany
Eric M. Bershad, MD
The George Institute for Global Health
Roland N. Auer, MD, PhD Associate Professor
University of New South Wales
Professor and Neuropathologist Neurology, Neurosurgery, and Space
Sydney, Australia
Department of Pathology Medicine
Josef Anrather, VMD Royal University Hospital Baylor College of Medicine
Professor of Neuroscience Saskatoon, Saskatchewan, Canada Houston, Texas
Feil Family Brain and Mind Research
Issam A. Awad, MD Jimmy V. Berthaud, MD, MPH
Institute
The John Harper Seeley Professor of Assistant Professor
Weill Cornell Medicine
Surgery (Neurosurgery) Department of Neurology
New York, New York
Director, Neurovascular Surgery University of Michigan Medical School
Department of Neurosurgery Ann Arbor, Michigan
University of Chicago
Chicago, Illinois

xii
 Contributors xiii

Spiros L. Blackburn, MD Louis R. Caplan, MD Greg Christorforids, MD

Associate Professor Professor Professor
Department of Neurosurgery Department of Neurology Department of Radiology
University of Texas Houston Health Harvard University University of Chicago
Science Center Beth Israel Deaconess Medical Center Chicago, Illinois
Houston, Texas Boston, Massachusetts
E. Sander Connolly, Jr., MD
Leo H. Bonati, MD Julián Carrión-Penagos, MD Bennett M. Stein Professor
Professor of Neurology Neurology Resident Chairman
Head Stroke Center Department of Neurology Department of Neurological Surgery
Department of Neurology University of Chicago Columbia University Medical Center
University Hospital Basel Chicago, Illinois New York, New York
Department of Clinical Research
Mar Castellanos, MD Steven C. Cramer, MD
University of Basel
Department of Neurology Professor
Basel, Switzerland
Complexo Hospitalario Universitario A Department of Neurology
Julian Bösel, MD Coruña David Geffen School of Medicine
Professor Biomedical Research Institute of A University of California, Los Angeles
Department of Neurology Coruña Los Angeles, California
Klinikum Kassel A Coruña, Spain
Brett L. Cucchiara, MD
Kassel, Germany
Michelle R. Caunca, PhD Professor
Marie Germaine Bousser, MD Medical Scientist Training Program Department of Neurology
Department of Neurology and CERVCO University of Miami Miller School of University of Pennsylvania
Reference Center for Rare Vascular Medicine Philadelphia, Pennsylvania
Diseases of the Eye and Brain Miami, Florida
Alexandra L. Czap, MD
Hôpital Lariboisiére
Hugues Chabriat, MD, PhD Neuro-oncologist
Assistance Publique Hôpital de Paris;
Department of Neurology and CERVCO Assistant Professor
Université of Paris
Reference Center for Rare Vascular Department of Neurology
Paris, France
Diseases of the Eye and Brain McGovern Medical School
Joseph P. Broderick, MD Hôpital Lariboisiére University of Texas Health Science
Professor Assistance Publique Hôpital de Paris Center at Houston
Department of Neurology and Ambroise Paré Houston, Texas
Rehabilitation Medicine INSERM U 1161
Mark J. Dannenbaum, MD
University of Cincinnati Gardner Genetics and Physiopathology of
Assistant Professor
Neuroscience Institute ­Cerebrovascular Diseases
Department of Neurosurgery
Cincinnati, Ohio Université of Paris
University of Texas Houston Health
Service de Neurologie
Martin M. Brown, MA, MD Science Center
Hôpital Lariboisière
Emeritus Professor of Stroke Medicine Houston, Texas
Paris, France
UCL Queen Square Institute of
Patricia H. Davis, MD
Neurology Angel Chamorro, MD, PhD
Professor Emeritus
University College London Professor of Neurology
Department of Neurology
London, United Kingdom Department of Neurosciences
Carver College of Medicine
Hospital Clinic of Barcelona
Wendy Brown, MD University of Iowa
Barcelona, Spain
Stroke Director Iowa City, Iowa
Sutter Roseville Medical Center Jieli Chen, MD
Ted M. Dawson, MD, PhD
Roseville California Senior Scientist
Director, Institute for Cell Engineering
Department of Neurology
John C.M. Brust, MD Professor of Neurology
Henry Ford Hospital
Professor John Hopkins University School of
Detroit, Michigan
Department of Neurology Medicine
Columbia University College of Jun Chen, MD, PhD Baltimore, Maryland
Physicians and Surgeons Professor
Valina L. Dawson, PhD
New York, New York Department of Neurology
Director, Neuroregeneration and Stem
University of Pittsburgh
Cheryl Bushnell, MD, MHS Cell Programs
Pittsburgh, Pennsylvania
Department of Neurology Institute for Cell Engineering
Wake Forest School of Medicine Michael Chopp, PhD Professor of Neurology, Neuroscience,
Winston-Salem, North Carolina Senior Scientist and Physiology
Department of Neurology Johns Hopkins School of Medicine
Patrícia Canhão, MD, PhD
Henry Ford Hospital Baltimore, Maryland
Department of Neurosciences
Detroit, Michigan
(Neurology) Arthur L. Day, MD
Distinguished Professor
Hospital de Santa Maria-CHULN Professor and Co-Chairman
Department of Physics
Instituto de Medicina Molecular João Director of Cerebrovascular Surgery
Oakland University
Lobo Antunes Residency Program Director
Rochester, Michigan
Faculdade de Medicina Department of Neurosurgery
Universidade de Lisboa University of Texas Medical School at
Lisbon, Portugal Houston
Houston, Texas
xiv Contributors

T. Michael De Silva, PhD Bruce H. Dobkin, MD Myriam Fornage, PhD

Lecturer in Physiology Professor Professor, Center for Human Genetics
Department of Physiology, Anatomy, Department of Neurology Laurence and Johanna Favrot
and Microbiology David Geffen School of Medicine Distinguished Professor in Cardiology
School of Life Sciences University of California, Los Angeles Brown Foundation Institute of
La Trobe University Los Angeles, California Molecular Medicine
Melbourne, Victoria, Australia McGovern Medical School
Imanuel Dzialowski, MD
University of Texas Health Science
Diana Aguiar de Sousa, MD, PhD Head of ELBLAND Center for
Center at Houston
Department of Neurosciences Neuro-Rehabilitation
Houston, Texas
(Neurology) Teaching Faculty
Hospital de Santa Maria-CHULN Technical University Dresden Karen L. Furie, MD, MPH
Instituto de Medicina Molecular João Dresden, Germany Neurologist-in-Chief
Lobo Antunes Rhode Island Hospital
Mitchell S.V. Elkind, MD
Faculdade de Medicina The Miriam Hospital and Bradley
Professor
Universidade de Lisboa Hospital
Department of Neurology
Lisbon, Portugal Samuel I. Kennison, MD, and Bertha
Columbia University College of
S. Kennison Professor of Clinical
Victor J. Del Brutto, MD Physicians and Surgeons
Neuroscience
Assistant Professor Professor
Chair of Neurology
Department of Neurology Department of Epidemiology
The Warren Alpert Medical School of
Stroke Division Columbia University Mailman School
Brown University
University of Miami Miller School of of Public Health
Providence, Rhode Island
Medicine New York, New York
Miami, Florida Lidia Garcia-Bonilla, PhD
Jordan Elm, PhD
Assistant Professor of Research in
Gregory J. del Zoppo, MD Associate Professor
Neuroscience
Professor Department of Public Health Sciences
Feil Family Brain and Mind Research
Division of Hematology Medical University of South Carolina
Institute
Department of Neurology Charleston, South Carolina
Weill Cornell Medicine
University of Washington
Valery L. Feigin, MD, PhD New York, New York
Seattle, Washington
Professor of Epidemiology and
Steven L. Giannotta, MD
Colin P. Derdeyn, MD Neurology
Professor
Professor and Chair National Institute for Stroke and
Chair, Neurological Surgery
Radiology and Neurology Applied Neurosciences
Department of Neurosurgery
Department of Neurology Faculty of Health and Environmental
Keck School of Medicine
Carver College of Medicine Studies
University of Southern California
University of Iowa Auckland University of Technology
Los Angeles, California
Iowa City, Iowa Auckland, New Zealand
Y. Pierre Gobin, MD
Marco R. Di Tullio, MD José Manuel Ferro, MD, PhD
Professor of Radiology in Neurology
Professor of Medicine Department of Neurosciences
and Neurosurgery
Division of Cardiology (Neurology)
Director, Interventional Neurology
Columbia University College of Hospital de Santa Maria-CHULN
Weill Cornell Medical Center
Physicians and Surgeons Principle Investigator
New York Presbyterian Hospital
Associate Director Instituto de Medicina Molecular João
New York, New York
Adult Cardiovascular Ultrasound Lobo Antunes
Laboratories Faculdade de Medicina Mark P. Goldberg, MD
Cardiologist Professor Professor of Neurology
Cardiology Division Universidade de Lisboa Associate Vice Chair of Institutional
Columbia University Irving Medical Lisbon, Portugal Advancement
Center University of Texas Southwestern
Thalia S. Field, MD
New York, New York Medical Center
Associate Professor
Dallas, Texas
Hans Christoph Diener, MD, PhD Department of Medicine
Professor of Neurology Emeritus University of British Columbia Larry B. Goldstein, MD
Medical Faculty of the University Vancouver, British Columbia, Canada Ruth L Works Professor and Chairman
Duisburg-Essen Department of Neurology
Marlene Fischer, MD, PhD
Institute for Medical Informatics, University of Kentucky
University Medical Center Hamburg-
Biometry and Epidemiology Co-Director, Kentucky Neuroscience
Eppendorf
Essen, Germany Institute
Center for Anesthesiology and Intensive
Lexington, Kentucky
Michael N. Diringer, MD Care Medicine
Professor Department of Intensive Care Medicine Nicole R. Gonzales, MD
Department of Neurology Hamburg, Germany Professor
Washington University School of Department of Neurology
Medicine McGovern Medical School
St. Louis, Missouri University of Texas Health Science
Center at Houston
Houston, Texas
 Contributors xv

David M. Greer, MD Glen C. Jickling, MD Charles E. Kircher, MD

Richard B. Slifka Chief of Neurology Associate Professor Assistant Professor
Boston Medical Center Department of Medicine Department of Emergency Medicine
Professor and Chair Division of Neurology University of Cincinnati
Department of Neurology University of Alberta Neurointensivist
Boston University School of Medicine Edmonton, Alberta, Canada Gardner Neuroscience Institute
Boston, Massachusetts University of Cincinnati Medical Center
Anne Joutel, MD, PhD
Cincinnati, Ohio
James C. Grotta, MD INSERM U 1266
Director of Stroke Research and Mobile Pathogenesis of Small Vessel Diseases of Timo Krings, MD, PhD
Stroke Unit the Brain; The David Braley and Nancy
Clinical Innovation and Research Université of Paris Gordon Chair in Interventional
Institute Paris, France Neuroradiology
Memorial Hermann Hospital-Texas Chief, Diagnostic and Interventional
Scott E. Kasner, MD
Medical Center Neuroradiology
Professor
Houston, Texas Toronto Western Hospital and
Department of Neurology
University Health Network
Ruiming Guo University of Pennsylvania
Program Director, Interventional
Department of Neurology Director, Comprehensive Stroke Center
Neuroradiology
Pittsburgh Institute of Brain Disorders University of Pennsylvania Health
Toronto Western Hospital
and Recovery System
Professor
University of Pittsburgh Philadelphia, Pennsylvania
Departments of Radiology and Surgery
Pittsburgh, Pennsylvania
Mira Katan, MD, MS University of Toronto
Jose Gutierrez, MD, MPH Assistant Professor Toronto, Ontario, Canada
Assistant Professor of Neurology Department of Neurology
Rita V. Krishnamurthi, BSc, MApplSc,
Department of Neurology University Hospital of Zurich
PhD
Columbia University College of Zurich, Switzerland
Associate Professor
Physicians and Surgeons
Christopher P. Kellner, MD National Institute for Stroke and
New York, New York
Assistant Professor Applied Neurosciences
Peter Harmel, MD Department of Neurosurgery Faculty of Health and Environmental
Department of Neurology Icahn School of Medicine at Mount Studies
Charité University Medicine Berlin Sinai Auckland University of Technology
Berlin, Germany New York, New York Auckland, New Zealand
George Howard, DrPH Muhib Khan, MD Tobias Kurth, MD, ScD
Professor Clinical Assistant Professor Professor of Public Health and
Department of Biostatistics Department of Clinical Neuroscience Epidemiology
School of Public Health Michigan State University College of Institute of Public Health
University of Alabama at Birmingham Human Medicine Charité-Universitätsmedizin Berlin
Birmingham, Alabama Division Chief, Inpatient Neurology Berlin, Germany
Director, Comprehensive Stroke Center
Virginia J. Howard, PhD Maarten G. Lansberg, MD, PhD
Spectrum Health
Professor Professor
Grand Rapids, Michigan
Department of Epidemiology Neurology and Neurological Sciences
School of Public Health Chelsea S. Kidwell, MD Stanford University
University of Alabama at Birmingham Professor Stanford, California
Birmingham, Alabama Vice Chair of Research
Elad I. Levy, MD, MBA
Department of Neurology
Jee-Yeon Hwang, PhD Professor and L. Nelson Hopkins, MD,
University of Arizona College of
Assistant Professor Chairman
Medicine
Department of Pharmacology and Department of Neurological Surgery
Tuscon, Arizona
Neuroscience Jacobs School of Medicine and
Creighton University Helen Kim, MPH, PhD Biomedical Sciences
Omaha, Nebraska Professor University at Buffalo
Department of Anesthesia and Director, Interventional Stroke Services
Costantino Iadecola, MD
Perioperative Care Endovascular Neurosurgery Fellowship
Director and Chair
Director, Center for Cerebrovascular Kaleida Health
Feil Family Brain and Mind Research
Research Buffalo, New York
Institute
University of California, San Francisco
Weill Cornell Medicine David S. Liebeskind, MD
San Francisco, California
New York, New York Professor of Neurology
Jong S. Kim, MD, PhD Director, Neurovascular Imaging
Reza Jahan, MD
Professor Research Core
Professor
Department of Neurology Director, Outpatient Stroke and
Division of Interventional
University of Ulsan Neurovascular Programs
Neuroradiology
Asan Medical Center Director, UCLA Cerebral Blood Flow
Department of Radiology
Seoul, South Korea Laboratory
David Geffen School of Medicine
Director, UCLA Vascular Neurology
University of California, Los Angeles
Residency Program
Los Angeles, California
UCLA Department of Neurology
Los Angeles, California
xvi Contributors

Sook-Lei Liew, PhD, OTR/L Jason M. Meckler, MD Maiken Nedergaard, MD, PhD
Assistant Professor Neurologist Professor and Director
Chan Division of Occupational Science Norton Neurology Services Center for Translational Neuromedicine
and Occupational Health Louisville, Kentucky University of Rochester Medical Center
Division of Biokinesiology and Physical Rochester, New York
James Frederick Meschia, MD
Therapy Professor and Director
Professor
Department of Neurology Center for Basic and Translational
Department of Neurology
Keck School of Medicine Neuroscience
Mayo Clinic
University of Southern California University of Copenhagen
Jacksonville, Florida
Los Angeles, California Copenhagen, Denmark
Steven R. Messé, MD
David J. Lin, MD Justin A. Neira, MD
Professor
Clinical Fellow Resident
Department of Neurology
Center for Neurotechnology and Department of Neurological Surgery
Perelman School of Medicine at the
Neurorecovery Columbia University Medical Center
University Hospital of Pennsylvania
Department of Neurology NY-Presbyterian Hospital
Philadelphia, Pennsylvania
Massachusetts General Hospital New York, New York
Boston, Massachusetts J Mocco, MD
Sarah Newman, NP
Professor
Benjamin Lisle, PM, PhD Beth Israel Lahey Health
Department of Neurosurgery
Department of Neurology Lahey Hospital and Medical Center
Icahn School of Medicine at Mount
University of Missouri Medical School Burlington, Massachusetts
Sinai
and Cox Health
New York, New York Patrick J. Nicholson, MB, BCh, BAO
Springfield, Missouri
Diagnostic and Interventional
Maxim Mokin, MD, PhD
Eng H. Lo, PhD Neuroradiologist
Associate Professor
Professor of Neurology and Radiology Toronto Western Hospital and
Department of Neurosurgery
Harvard Medical School University Health Network
University of South Florida College of
Boston, Massachusetts University of Toronto
Medicine
Director, Neuroprotection Research Toronto, Ontario, Canada
Vascular Neurologist
Laboratories
Neurosciences Center Bo Norrving, MD, PhD
Massachusetts General Hospital
Tampa General Hospital Professor
Charlestown, Massachusetts
Tampa, Florida Department of Clinical Sciences
Patrick D. Lyden, MD Neurology Division
Michael A. Mooney, MD
Professor Lund University
Instructor
Department of Neurology Lund, Sweden
Department of Neurosurgery
Cedars-Sinai Medical Center
Brigham and Women’s Hospital Martin O’Donnell, MB, PhD
Los Angeles, California
Harvard Medical School Department of Medicine
Takakuni Maki, MD Boston, Massachusetts NUI Galway and Saolta University
Neuroprotection Research Laboratory Healthcare Group
Lewis B. Morgenstern, MD
Departments of Radiology and Galway, Ireland
Professor
Neurology
Department of Neurology Dimitry Ofengeim, PhD
Massachusetts General Hospital
Director, Stroke Program Department of Cell Biology
Harvard Medical School
University of Michigan Medical School Harvard Medical School
Boston, Massachusetts
Ann Arbor, Michigan Boston, Massachusetts
Department of Neurology
Kyoto University Graduate School of Michael A. Moskowitz, MD Jun Ogata, MD, PhD
Medicine Professor of Neurology Internal Medicine
Kyoto, Japan Harvard Medical School Hirakata General Hospital for
Senior Neuroscientist Developmental Disorders
Georgios A. Maragkos, MD
Departments of Radiology and Hirakata-shi, Osaka, Japan
Post-Doctoral Research Fellow
Neurology
Department of Neurosurgery Christopher S. Ogilvy, MD
Massachusetts General Hospital
Beth Israel Deaconess Medical Center Professor
Boston, Massachusetts
Harvard Medical School Department of Neurosurgery
Boston, Massachusetts Michael T. Mullen, MD Harvard Medical School
Assistant Professor Director, Brain Aneurysm Institute
Miklos Marosfoi, MD
Department of Neurology Director, Endovascular and Operative
Assistant Professor of Radiology
Perelman School of Medicine at the Neurovascular Surgery
Tufts University School of Medicine
University Hospital of Pennsylvania Beth Israel Deaconess Medical Center
Beth Israel Lahey Health
Philadelphia, Pennsylvania Boston, Massachusetts
Lahey Hospital and Medical Center
Burlington, Massachusetts Steffen Nägel, MD Emanuele Orrù, MD
Departement of Neurology Assistant Professor of Radiology
Louise D. McCullough, MD, PhD
Martin-Luther-University Tufts University School of Medicine
Professor and Chair
Halle-Wittenberg Beth Israel Lahey Health
Department of Neurology
University Hospital Halle Lahey Hospital and Medical Center
McGovern Medical School
Halle, Germany Burlington, Massachusetts
University of Texas Health Science
Center at Houston
Houston, Texas
 Contributors xvii

Santiago Ortega-Gutiérrez, MD Miguel A. Perez-Pinzon, PhD Christina P. Rossitto, BS

Associate Clinical Professor Professor and Vice-Chair for Basic Medical Student
Neurology, Neurosurgery, Radiology, Science of Neurology Icahn School of Medicine at Mount
and Anesthesia Peritz Scheinberg Endowed Professor in Sinai
Department of Neurology Neurology New York, New York
Carver College of Medicine Director, Peritz Scheinberg Cerebral
Tatjana Rundek, MD, PhD
University of Iowa Vascular Disease Research
Professor of Neurology
Iowa City, Iowa Laboratories
Department of Neurology
Department of Neurology
Matthew Maximillian Padrick, MD Evelyn F. McKnight Endowed Chair for
University of Miami Miller School of
Resident Physician Learning and Memory in Aging
Medicine
Department of Neurology Scientific Director, Evelyn F. McKnight
Miami, Florida
Cedars-Sinai Medical Center Brain Institute
Los Angeles, California John M. Picard, MD University of Miami Miller School of
Fellow Medicine
Kaushik Parsha, MD
Division of Neurocritical Care and Miami, Florida
Institute for Stroke and Cerebrovascular
Emergency Neurology
Diseases Jonathan J. Russin, MD
Yale New Haven Hospital
Department of Neurology Assistant Professor
New Haven, Connecticut
McGovern Medical School Director, Cerebrovascular Surgery
University of Texas Health Science Sean P. Polster, MD Department of Neurosurgery
Center at Houston Neurosurgery Resident Keck School of Medicine
Houston, Texas Department of Neurosurgery University of Southern California
University of Chicago Los Angeles, California
Mark Parsons
Chicago, Illinois
Professor of Medicine and Neurology Ralph L. Sacco, MD
Department of Neurology William J. Powers, MD Chairman, Department of Neurology
South Western Sydney Clinical School Professor of Neurology Olemberg Family Chair in Neurological
University of New South Wales Department of Neurology Disorders
Sydney, Australia University of North Carolina School of Miller Professor of Neurology, Public
Liverpool Hospital Medicine Health Sciences, Human Genetics,
Ingham Institute for Applied Medical Chapel Hill, North Carolina and Neurosurgery
Research University of Miami Miller School of
Volker Puetz, MD
Liverpool, Australia Medicine
Department of Neurology
Chief, Department of Neurology
Neil V. Patel, MD University Clinics Carl Gustav Carus
Jackson Memorial Hospital
Assistant Professor of Radiology Technische Universität Dresden
Miami, Florida
Tufts University School of Medicine Dresden, Germany
Beth Israel Lahey Health Apostolos Safouris, MD, PhD
Jukka Putaala, MD, PhD
Lahey Hospital and Medical Center Acute Stroke Unit
Associate Professor
Burlington, Massachusetts Metropolitan Hospital
Department of Neurology
Piraeus, Greece
Virendra I. Patel, MD, MPH Helsinki University Hospital and
Chief of Vascular Surgery University of Helsinki Edgar A. Samaniego, MD
Co-Director, Aortic Center Helsinki, Finland Associate Professor
Columbia University Irving Medical Neurology, Neurosurgery, and Radiology
Margarita Rabinovich, NP
Center Department of Neurology
Beth Israel Lahey Health
New York, New York Carver College of Medicine
Lahey Hospital and Medical Center
University of Iowa
Ludmila Pawlikowska, PhD Burlington, Massachusetts
Iowa City, Iowa
Associate Professor
Bruce R. Ransom, MD, PhD
Department of Anesthesia and Lauren H. Sansing, MD, MSTR
Professor and Chair
Perioperative Care Associate Professor
Department of Neuroscience
Center for Cerebrovascular Research Academic Chief
City University of Hong Kong
University of California, San Francisco Division of Stroke and Vascular
Hong Kong, China
San Francisco, California Neurology
Jorge A. Roa, MD Department of Neurology
Adriana Pérez, PhD
Post-doctoral Research Fellow Yale School of Medicine
Professor
Neurology and Neurosurgery New Haven, Connecticut
Department of Biostatistics and Data
University of Iowa Hospitals and Clinics
Science Nikunj Satani, MD, MPH
Iowa City, Iowa
The University of Texas Health Science Institute for Stroke and Cerebrovascular
Center at Houston Gary A. Rosenberg, MD Diseases
Austin, Texas Professor Department of Neurology
Department of Neurology McGovern Medical School
University of New Mexico Health University of Texas Health Science
Sciences Center Center at Houston
Director, Center for Memory and Aging Houston, Texas
University of New Mexico
Albuquerque, New Mexico
xviii Contributors

Ronald J. Sattenberg, MD Omar K. Siddiqi, MD Hiroo Takayama, MD, PhD

Radiologist Assistant Professor Director of Cardiovascular Institute
Louisville, Kentucky Section of Cardiovascular Medicine Co-Director, HCM Program, Division of
Department of Medicine Cardiac, Vascular & Thoracic Surgery
Jeffrey L. Saver, MD
Boston University School of Medicine Co-Director, Aortic Program
Professor of Neurology
Boston, Massachusetts Co-Director, Marfan Clinic
David Geffen School of Medicine
Columbia University Irving Medical Center
Director, UCLA Stroke Center Aneesh B. Singhal, MD
New York, New York
University of California, Los Angeles Vice Chair of Neurology
Los Angeles, California Massachusetts General Hospital Joseph Tarsia, MD
Associate Professor of Neurology Neurologist
Sean I. Savitz, MD
Harvard Medical School Ochsner Health
Professor of Neurology
Boston, Massachusetts New Orleans, Louisiana
Stroke Program Director
Institute for Stroke and Cerebrovascular Christopher G. Sobey, PhD Turgut Tatlisumak, MD, PhD
Diseases NHMRC Senior Research Fellow and Professor of Neurology and Stroke
Department of Neurology Professor in Physiology Medicine
McGovern Medical School Department of Physiology, Anatomy, Department of Clinical Neuroscience
University of Texas Health Science and Microbiology Institute of Neuroscience and
Center at Houston School of Life Sciences Physiology
Houston, Texas La Trobe University Sahlgrenska Academy at University of
Melbourne, Victoria, Australia Gothenburg
Christian Schmidt, MD
Chief Physician
Neurologist Clemens J. Sommer, MD
Department of Neurology
Department of Neurology Director, Institute of Neuropathology
Sahlgrenska University Hospital
Klinikum Kassel University Medical Center of the
Gothenburg, Sweden
Kassel, Germany Johannes Gutenberg-University Mainz
Department of Neurology Mainz, Germany Ajith J. Thomas, MD
Faculty of Human Medicine Assistant Professor
Robert F. Spetzler, MD
Georg August University Department of Neurosurgery
Emeritus President and Chief Executive
Göttingen, Germany Harvard Medical School
Officer
Co-Director
Sudha Seshadri, MD Emeritus Chair, Department of
Brain Aneurysm Institute
Director, Glenn Biggs Institute for Neurosurgery
Beth Israel Deaconess Medical Center
Alzheimer’s and Neurodegenerative Barrow Neurological Institute
Boston, Massachusetts
Diseases Phoenix, Arizona
University of Texas Health Sciences Center John W. Thompson, PhD
Christopher J. Stapleton, MD
San Antonio, Texas Director of Basic Science Research
Instructor
Senior Investigator Department of Neurosurgery
Department of Neurosurgery
Framingham Heart Study University of Miami Miller School of
Massachusetts General Hospital
Framingham, Massachusetts Medicine.
Boston, Massachusetts
Adjunct Professor Miami, Florida
Department of Neurology Ben A. Strickland, MD
Georgios Tsivgoulis, MD, PhD, RVT
Boston University School of Medicine Department of Neurosurgery
Professor of Neurology
Boston, Massachusetts Keck School of Medicine
Second Department of Neurology
University of Southern California
Vijay K. Sharma, MD National and Kapodistrian University of
Los Angeles, California
Associate Professor Athens
Yong Loo Lin School of Medicine Hua Su, MD School of Medicine
National University of Singapore Professor Attikon University Hospital
Senior Consultant Department of Anesthesia and Athens, Greece
Department of Neurology Perioperative Care
Elizabeth Tournier-Lasserve, MD, PhD
National University Hospital Center for Cerebrovascular Research
Molecular Genetics Department and
Singapore University of California, San Francisco
CERVCO Reference Center for Rare
San Francisco, California
Frank R. Sharp, MD Vascular Diseases of the Eye and Brain
Professor José I. Suarez, MD Hopital Lariboisiére
Department of Neurology Director, Division of Neurosciences Assistance Publique Hôpital de Paris;
School of Medicine Critical Care Université of Paris
University of California, Davis Professor Paris, France
Sacramento, California Departments of Anesthesia and Critical
Gabriel Vidal, MD
Care Medicine, Neurology, and
Kevin N. Sheth, MD Neurologist
Neurosurgery
Professor of Neurology and System Stroke Medical Director
The Johns Hopkins University School of
Neurosurgery Ochsner Health
Medicine
Chief, Division of Neurocritical Care New Orleans, Louisiana
Baltimore, Maryland
and Emergency Neurology
Ajay K. Wakhloo, MD PhD FAHA
Associate Chair, Clinical Research
Professor of Radiology
Department of Neurology
Tufts University School of Medicine
Yale School of Medicine and Yale New
Beth Israel Lahey Health
Haven Hospital
Lahey Hospital and Medical Center
New Haven, Connecticut
Burlington, Massachusetts
 Contributors xix

Babette B. Weksler, MD Shadi Yaghi, MD John H. Zhang, MD, PhD

Professor Emerita Associate Professor Professor of Neurosurgery,
Department of Medicine Department of Neurology Anesthesiology, Neurology, and
Weill Cornell Medicine NYU Grossman School of Medicine Physiology and Pharmacology
New York, New York Director, Vascular Neurology Director of Neuroscience Research
NYU Langone Hospital-Brooklyn Associate Chair and Physiology
Joshua Z. Willey, MD
Director, Clinical Vascular Neurology Graduate Program Coordinator
Associate Professor
Research Loma Linda University School of
Department of Neurology
NYU Langone Health Medicine
Columbia University Irving Medical
New York, New York Loma Linda, California
Center
New York, New York Takenori Yamaguchi, MD, PhD Zhitong Zheng, MD
President Emeritus Visiting Fellow
Max Wintermark, MD
National Cerebral and Cardiovascular Department of Neurology
Professor
Center Henry Ford Hospital
Department of Radiology/Neuroimaging
Suita, Osaka, Japan Detroit, Michigan
and Neurointervention
Stanford University Tuo Yang, MD R. Suzanne Zukin, PhD
Stanford, California Research Instructor Professor
Department of Neurology Department of Neuroscience
Lawrence K.S. Wong, MD
Pittsburgh Institute of Brain Disorders F.M. Kirby Chair in Neural Repair and
Professor
and Recovery Protection
Department of Medicine and
University of Pittsburgh Director, Neuropsychopharmacology
Therapeutics
Pittsburgh, Pennsylvania Center
Chinese University of Hong Kong
Albert Einstein College of Medicine
Shatin, Hong Kong, China Masahiro Yasaka, MD, PhD
Bronx, New York
Director, Cerebrovaascular Center
Guohua Xi, MD
National Hospital Organization Kyushu Richard M. Zweifler, MD
Professor of Neurosurgery
Medical Center Associate Medical Director
Associate Director, Crosby Neurosurgical
Fukuoka, Japan Medical Services
Laboratories
Co-Medical Director of Neurosciences
Richard C. Schneider Research Professor Darin B. Zahuranec, MD
System Chair of Neurology
University of Michigan Associate Professor
Ochsner Health
Ann Arbor, Michigan Department of Neurology
New Orleans, Louisiana
University of Michigan Medical School
Jinchong Xu, PhD
Ann Arbor, Michigan
Assistant Professor
Neuroregeneration and Stem Cell Feng Zhang, MD, PhD
Programs Assistant Professor
Institute for Cell Engineering Department of Neurology
Johns Hopkins University School of Pittsburgh Institute of Brain Disorders
Medicine and Recovery
Baltimore, Maryland University of Pittsburgh
Pittsburgh, Pennsylvania
 AHA Evidence-Based Classifications
TABLE 1 Applying Classification of Recommendations and Level of Evidence

SIZE OF TREATMENT EFFECT

CLASS III No Benefit
CLASS I CLASS IIa CLASS IIb or CLASS III Harm
Benefit > > > Risk Benefit > > Risk Benefit ≥ Risk Procedure/ Treatment
Additional studies with Additional studies with Test
Procedure/
focused objectives broad objectives
Treatment COR Not No Proves
needed needed; additional
SHOULD be III: No Helpful Benefit
registry data would be
performed/ IT IS REASONABLE to benefit
helpful
administered perform procedure/
administer treatment Procedure/Treatment COR Excess Harmful to
MAY BE CONSIDERED III: Cost w/o Patients
Harm Benefit or
Harmful
LEVEL A • Recommendation • Recommendation in • Recommendation’s • Recommendation that procedure or
ESTIMATE OF CERTAINTY (PRECISION) OF TREATMENT EFFECT

Multiple that procedure or favor of treatment usefulness/efficacy treatment is not useful/effective

populations treatment is or procedure being less well established and may be harmful
evaluated* useful/effective useful/effective • Greater conflicting • Sufficient evidence from multiple
Data derived from • Sufficient • Some conflicting evidence from randomized trials or meta-analyses
multiple evidence from evidence from multiple randomized
randomized multiple multiple randomized trials or meta-
clinical trials or randomized trails trials or meta- analyses
meta-analyses or meta-analyses analyses
LEVEL B • Recommendation • Recommendation in • Recommendation’s • Recommendation that procedure or
Limited that procedure or favor of treatment usefulness/efficacy treatment is not useful/effective
populations treatment is or procedure being less well established and may be harmful
evaluated* useful/effective useful/effective • Greater conflicting • Evidence from single randomized
Data derived from • Evidence from • Some conflicting evidence from single trial or nonrandomized studies
a single single evidence from randomized trial or
randomized trial randomized trial single randomized nonrandomized
or nonrandomized or nonrandomized trial or studies
studies studies nonrandomized
studies
LEVEL C • Recommendation • Recommendation in • Recommendation’s • Recommendation that procedure or
Very limited that procedure or favor of treatment usefulness/efficacy treatment is not useful/effective
populations treatment is or procedure being less well established and may be harmful
evaluated* useful/effective useful/effective • Only diverging expert • Only expert opinion, case studies,
Only consensus • Only expert • Only diverging opinion, case or standard of care
opinion of experts, opinion, case expert opinion, case studies, or standard
case studies, or studies, or studies, or standard of care
standard of care standard of care of care
Suggested phrases should is reasonable may/might be considered COR III COR III
for writing is recommended can be useful/effective/ may/might be reasonable No Benefit Harm
recommendations† is indicated beneficial usefulness/effectiveness is
is not potentially
is useful/effective/ is probably unknown/unclear/
recommended harmful
beneficial recommended or uncertain or not well
is not indicated causes harm
indicated established
should not be associated with
Comparative treatment/strategy A treatment/strategy A is done excess morbidity/
effectiveness is recommended/ probably recommended/ is not useful/ mortality
phrases† indicated in indicated in preference beneficial/effective should not be done
preference to to treatment B
treatment B treatment it is reasonable to
A should be chosen choose treatment A over
over treatment B treatment B

Reprinted with permission Circulation. 2010;121:1544–1579 ©2010, American Heart Association, Inc.

xx
 AHA Evidence-Based Classifications xxi

BOX 1   Evidence Classifications 

1. Size of treatment effect 2. Certainty of treatment effect
• Class I: Benefit >>> Risk. Procedure/treatment SHOULD be • Level A: Data derived from multiple randomized clinical trials or
performed/administered. meta-analyses.
• Class IIa: Benefit >> Risk. IT IS REASONABLE to perform • Level B: Data derived from a single randomized trial or
procedure/administer treatment. nonrandomized studies.
• Class IIb: Benefit ≥ Risk. Procedure/treatment MAY BE • Level C: Only consensus opinion of experts, case studies, or
CONSIDERED. standard of care.
• Class III: No Benefit/Harm. Procedure/treatment is not useful/
effective and may be harmful.

Adapted from Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement
for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke. Stroke. 2006;37:577–617.
Other documents randomly have
different content
perfect flower, per diem, till all the blossoms on the spike are exhausted;
which, in this species, are much more abundant than in any of the others. It
is increased by the root or seed.
This plant, we presume, is the same as those specified under the different
titles of Lilium Longiflorum, and L. Japonicum, in Willdenow’s new edition
of the Species Plant.; the L. candidum, and L. Japonicum, of Thunberg’s
Japan; and the L. Longiflorum of the Linn. Trans. Vol. II. P. 333. The
Hemerocallis formerly figured by us, under the specific title of Cærulea, we
take to be, the Hemerocallis Japonica, and Lilium Cordifolium of
Willdenow; the H. Cordata of Thunberg’s Japan; and the Hemerocallis
Japonica, and Lilium Cordifolium of the Linn. Trans. Vol. II. p. 332.
Willdenow, who had never seen even dried specimens of the plants in
question, has hence been led to place the same plant, under different genera;
and to consider the Hemerocallis of the Botanists Repository, as only a
variety of H. Japonica, but still admitting it as an Hemerocallis. Now, as we
have no doubt, (nor do we think any one can, that will take the trouble to
examine the dissections given with each figure,) that if the one is an
Hemerocallis, the other must be admitted of the same family; so, have we
made no scruple in rejecting the generic name of Lilium, for the present
plant; although we would gladly have adopted the specific one of Longiflora,
had not that of Alba, already obtained so generally in our gardens; a rule, for
our direction, paramount to all others as to specific denomination.
 PLATE CXCV.

HYPOXIS OBLIQUA.

Oblique-leaved Hypoxis.

CLASS VI. ORDER I.

HEXANDRIA MONOGYNIA. Six Chives. One Pointal.

ESSENTIAL GENERIC CHARACTER.

Corolla sex-partita, persistens, supera. Capsula basi angustior. Spatha

bivalvis.
Blossom six-parted, remaining, above. Capsule narrower at the base.
Sheath two-valved.
See Hypoxis stellata. Pl. CI. Vol. II.

SPECIFIC CHARACTER.

Hypoxis scapo subtrifloro, piloso, longitudine foliorum; pedunculis flore

triplo longioribus; foliis lineari-lanceolatis, oblique flexis, glabris; radice
fibrosa.
Hypoxis with mostly three flowers on the stem, which is hairy, the length
of the leaves; foot-stalks three times the length of the flower; leaves linearly
lance-shaped, obliquely bent downward, smooth; root fibrous.

REFERENCE TO THE PLATE.

1. A Petal of the Blossom, with its Chive, as attached to its base.

2. The Seed-bud, on its foot-stalk, with a part of the tube of the
blossom, to which the Chives are fixed.
3. The Seed-bud, Shaft and Summit, magnified.
This species of Hypoxis is from the Cape of Good Hope; and, we believe,
solely in the possession of G. Hibbert, Esq. Clapham; from whose collection
our drawing was made, in June, this year, 1801. It appears to be a hardy
green-house plant; but, is certainly more curious than handsome, and, from
its general character, we should judge the propagation would be from the
root.
Professor Jacquin has given the Hypoxis Obliqua in his Icones Plantarum
Rariorum, 2. t. 371; and in his Supplement to the Collectanea, 54; but, we
must suppose from a more vigorous specimen than ours; as, the appearance
of a woolly character, at the margin of the leaves, was not to be traced in our
plant, although every other part is exact. Wherefore, we have retained his
name, though we have rejected the latter part of his specific character, to
introduce one, which we consider, of more consequence, as opposed to those
with bulbous roots, this being fibrous.
 PLATE CXCVI.

IXIA MACULATA.

Spotted-flowered Ixia.

CLASS III. ORDER I.

TRIANDRIA MONOGYNIA. Three Chives. One Pointal.

ESSENTIAL GENERIC CHARACTER.

Corolla 6-petala, patens, æqualis.

Stamina tria, erectiusculo-patula.
Blossom 6 petals, spreading, equal.
Chives three, upright, spreading.
See Ixia Reflexa, Pl. XIV. Vol. I.

SPECIFIC CHARACTER.

Ixia foliis ensiformibus, glabris, scapo duplo brevioribus; floribus

alternis, sub-spicatis; petalis basi obscuris, ovatis, concavis; stigmatibus
bifidis.
Ixia with sword-shaped, smooth leaves, half the length of the flower-
stem; flowers alternate, rather spiked; petals dark at the base, egg-shaped
and concave; summits two-cleft.

REFERENCE TO THE PLATE.

1. The two valves of the Empalement.

2. A Flower cut and spread open, with the Chives in their natural
station.
3. The Pointal complete, with one of the Summits detached and
magnified.
This Ixia has been long cultivated in Britain, so says Millar, &c. but, till
within these few years, we have not seen it in our gardens; perhaps it has
been (like many others) lost to us, and recently introduced with the multitude
of other species, which now decorate our green-houses; either from the Cape
of Good Hope or Holland. It is one of the most desirable of the genus, from
the length of time it continues in flower; which is, at least a month, from the
first flowers beginning to expand. It increases by the bulb, and is to be
cultivated as other common Ixias. Flowers in May or June.
 PLATE CXCVII.

NYMPHÆA CŒRULEA.

Blue Water-Lily.

CLASS XIII. ORDER I.

POLYANDRIA MONOGYNIA. Many Chives. One Pointal.

GENERIC CHARACTER.

Calyx. Perianthium inferum, tetraphyllum, magnum, supra coloratum,

persistens.
Corolla. Petala numerosa (quindecem sæpe,) germinis lateri insidentia,
serie plus quam simplici.
Stamina. Filamenta numerosa (septuaginta sæpe,) plana, curva, obtusa,
brevia. Antheræ oblongæ, filamentorum margini adnatæ.
Pistillum. Germen ovatum, magnum. Stylus nullus. Stigma orbiculatum,
planum, peltato-sessile, radiis notatum, margine crenatum, persistens.
Pericarpium. Bacca dura, ovata, carnosa, rudis, collo angustata apice
coronata, multilocularis (decem ad quindecem loculis,) pulpa plena.
Semina plurima, subrotunda.
Empalement. Cup beneath, four leaved, large, coloured above,
permanent.
Blossom. Petals numerous (often fifteen,) placed on the side of the seed-
bud, in more than one row.
Chives. Threads numerous (often seventy,) flat, curved, blunt, short. Tips
oblong, fixed to the margin of the threads.
Pointal. Seed-bud egg-shaped, large. Shaft, none. Summit round, flat,
central, sitting, marked in rays, scolloped at the edge, remaining.
Seed-vessel. Berry hard, egg-shaped, fleshy, rough, narrowed at the
neck, crowned at the top, many-celled (from ten to fifteen cells,) full of pulp.
Seeds many, roundish.
 SPECIFIC CHARACTER.

Nymphæa foliis cordato-orbiculatis, senioribus crenatis, lobis acutis

imbricatis, acuminatis; petalis acutis, lanceolatis, cæruleis.
Nymphæa with between heart-shaped and round leaves, the old ones
scolloped, lobes sharp, tiled, and tapered; petals sharp, lance-shaped, and
blue.

REFERENCE TO THE PLATE.

1. A Chive.
2. The Seed-bud and Summit.
3. The Seed-bud, cut transversely, to shew the number of cells.
Amongst aquatic or water plants, the Nymphæas are undoubtedly the
most desirable in cultivation; although, we should agree to the exclusion of
N. Nelumbo, &c. now forming a distinct genus in the Sp. Plant. of
Willdenow; taken from Usteri’s Ed. of Jussieu’s Gen. Plant. classed from the
natural characters, under the title of Nelumbium’s. This plant may be kept in
the green-house, or hot-house, in a large tub filled with water and a small
portion of mud at the bottom. It propagates by the root, and the flowers,
which are extremely fragrant, are produced in August, in which month, this
year, our drawing was made, from a large plant in the Hibbertian collection;
but, from an omission in the figure, we were obliged to finish the plate from
a plant, in the collection of J. Vere, Esq. Kensington Gore, still in flower, the
beginning of October. The leaves of this species are most beautifully
scolloped, and near a foot in diameter; but the indentitions are scarcely to be
perceived in the younger; one of which, as we could not introduce the larger,
is shewn on the plate of the natural size.
It is a native of the Cape of Good Hope, and was introduced to the Royal
Gardens, Kew, by Mr. F. Masson, about the year 1792.
 PLATE CXCVIII.

BAUERA RUBIOIDES.

Three-leaved Bauera.

CLASS XIII. ORDER II.

POLYANDRIA DIGYNIA. Many Chives. Two Pointals.

GENERIC CHARACTER.

Calyx. Perianthium octophyllum, foliolis persistentibus, acuminatis,

reflexis, dentatis.
Corolla. Petala octo, ovata, concava, patentia, æqualia, calyce majora.
Stamina. Filamenta numerosa, capillaria, corolla breviora, receptaculo
inserta. Antheræ latiusculæ, obtusæ, erectæ.
Pistilla. Germen subovatum, villosum. Styli duo, filiformes, longi, apice
curvati. Stigmata simplicia.
Pericarpium. Capsula subrotunda, pilosa, apice dehiscens, bilocularis,
bivalvis.
Semina plurima, subrotunda.
Empalement. Cup eight-leaved, remaining, leaflets tapered, reflexed, and
toothed.
Blossom. Eight petals, egg-shaped, concave, spreading, equal, larger than
the cup.
Chives. Threads numerous, hair-like, shorter than the blossom, fixed into
the receptacle. Tips broadish, obtuse and erect.
Pointals. Seed-bud nearly egg-shaped, hairy. Shafts two, thread-shaped,
long, curved at the ends. Summits simple.
Seed-vessel. Capsule roundish, hairy, splitting at the top, two cells, two
valves.
Seeds many, roundish.
 SPECIFIC CHARACTER.

Bauera foliis ternatis, apice dentatis, sessilibus, oppositis.

Bauera with leaves composed of three leaflets, toothed at the point,
growing close to the stem, and opposite.

REFERENCE TO THE PLATE.

1. The Empalement, with the Chives and Pointal.

2. The Chives and Pointal magnified.
3. The Empalement, Seed-bud, Shafts, and Summits, magnified.
4. The Seed-bud cut transversely, with the seeds in the cells,
magnified.
This handsome shrub, a native of Port Jackson, New Holland, was first
raised at the seat of the Hon. the Marchioness of Rockingham, Hillingdon,
Middlesex, in the year 1793; and, from a plant, in the conservatory, still in
flower, this present month November, our drawing was made, at the Nursery,
Hammersmith. It is hardy, although delicate in structure, and flourishes in
the green-house. The stem of the plant from which our figure was taken,
although the oldest in the kingdom, and near six feet high, is scarce the
thickness of a quill at the base, therefore must be supported. The young
shoots and leaves are covered with a slight pile; the smaller branches stand
out at right angles, proceeding from the insertion of the leaves, and the
whole plant has, at first sight, much the appearance of a Rubus. It is
propagated by cuttings, made in the month of March, and put under a small
bell-glass on the heat of a hot-bed; the cuttings should be from the extreme
ends of the young shoots. Sir J. Banks, Bart. P. R. S. &c. from whose natural
genius and love for the science, and by whose fostering and liberal hand to
promote it, the study of Botany has become so general a taste; has named
this genus, in honour of two most eminent Botanical painters, of the name of
Bauer, natives of Germany, and brothers. The one, now under the immediate
patronage of Sir Joseph, as Botanical Painter to his Majesty at Kew; well
known for his superb and excellent coloured engravings of Heaths, &c. in
large folio. The younger considered no less able, engaged under the same
influence, with the other artists, &c. who are now upon the last expedition
for discovery to the South Sea; but not equally known to Botanists, as the
person who accompanied the late Dr. Sibthorpe, on his voyages through
Greece; and whose pencil has produced all those drawings, designed to
decorate and illustrate the famous Flora Græca, preparing for the public,
under the auspices of the intelligent Dr. Smith, P. L. S. &c. &c.
 PLATE CXCIX.

CAMELLIA JAPONICA. Var. flo. rubro pleno.

Double red Camellia.

CLASS XVI. ORDER VI. of Schreber’s 6th edit. of Gen.

Plant.
MONADELPHIA POLYANDRIA. Threads united. Many Chives.

ESSENTIAL GENERIC CHARACTER.

Calyx imbricatus, polyphyllus; foliolis interioribus majoribus.

Empalement tiled, many-leaved; the inner leaflets the largest.
SPECIFIC CHARACTER OF VARIETY.
Camellia foliis senioribus basi attenuatis, junioribus rubentibus; petalis
interioribus divaricato-erectis; floribus plenis, rubris.
Camellia with the older leaves tapered at the base, the younger ones
reddish; the inner petals stand upright spreading different ways; flowers
double and red.
Again have we to call upon the indulgence of our Botanical friends for
their sufferance, in a third intrusion on the forms of our own prescription.
But, as we had given the two other varieties of this fine plant; and taking it
for granted, by judging from our own feelings, that a figure of this very
scarce variety would be agreeable to most; that they might be (by
comparison) able to decide upon the difference which does exist, but has
been denied by many, between this, and the Striped Var.; see our figure, Vol.
II. Pl. XCI. It has been thought by most, who have not seen this plant; that it
was but the Striped Var. which had lost its variegation. This is certainly not
the case; for, it stands as distinct from the Striped, as from the White variety;
which may be readily traced, either from the plants themselves, or our
figures; by comparing the specific, or rather differing character we have
assigned to each. The Double red Camellia was introduced about the year
1794 from China, by R. Preston, Esq. Woodford, Essex.
The largest plant now in Europe, of this variety, is in the select and most
valuable collection of the Hon. T. Greville, Esq. Paddington, imported, last
year, from China in the highest perfection. It is propagated by cuttings, or
layers; and delights in a light, sandy loam; with about one-third of the pot,
from the bottom, filled with peat earth. It flowers from November, till
February, in the Hothouse; or from January, till April, if kept in the Green-
house. Our figure was taken, in November, this year, at the Hammersmith
Nursery.
 PLATE CC.

MELALEUCA HYPERICIFOLIA.

St. John’s-wort-leaved Melaleuca.

CLASS XVIII. ORDER IV.

POLYADELPHIA POLYANDRIA. Threads in many Sets. Many Chives.

ESSENTIAL GENERIC CHARACTER.

Calyx quinquefidus, semisuperus. Petals quinque. Filamenta multa,

longissima, connata in quinque corpora. Pistillum unum. Capsula
trilocularis.
Cup five-cleft, half above. Petals five. Threads numerous, very long,
united into five bodies. Pointal one. Capsule three-celled.
See Melaleuca ericæfolia, Pl. CLXXV. Vol. III.

SPECIFIC CHARACTER.

Melaleuca foliis oppositis, eliptico-oblongis, uninerviis; floribus

consertis; filamentis longissimis, linearibus, apice radiato-multifidis.
Melaleuca with opposite leaves, eliptic-oblong, one-nerved; flowers
clustered; threads very long, linear, rayed and many-cleft at the top.

REFERENCE TO THE PLATE.

1. A flower, natural size.

2. One of the five bundles of Chives, with its petal, to which it is
attached at the base, magnified.
3. The cup, seed-bud, shaft and summit, natural size, the summit
detached and magnified.
About the year 1792 this plant was first raised from seeds, by the late Mr.
William Malcolm, Nurseryman, at Stockwell, Surry; and was, from the very
great resemblance it bears to the St. John’s-worts, so denominated, until it
flowered. It has now become one of the commonest, of what are generally
termed, Botany Bay plants; yet unquestionably ranks with the handsomest
whether for its foliage, form of growth, or flowers, which are of a most
beautiful red-purple, scarcely to be imitated in painting. The singular manner
in which the flower-stem is thrown out, as it were, from the old wood, in a
horizontal direction, is common to many other species of the Genus. It grows
to the height of four or five feet, very erect in every part; is easily increased
by cuttings, and thrives best in peat earth. Although it is said to grow in
swampy grounds in New South Wales, see Linnæan Transactions, Vol. III. p.
279, nevertheless, with us, a dry, or damp situation in the green-house,
appears equally congenial to it. In the month of September 1799, our
drawing was taken at the Conservatory of R. James, Esq. Grosvenor Place.