Neurologic Complications of Cancer

651 Pages·2008·13.159 MB·English

by  Lisa M DeAngelis, Jerome B Posner

Neurologic
Complications of Cancer,
Second Edition
Lisa M. Deangelis
Jerome B. Posner,
Editors
OXFORD UNIVERSITY PRESS
NEUROLOGIC
COMPLICATIONS
OF CANCER
Second Edition
SERIES EDITOR
Sid Gilman, MD, FRCP
William J. Herdman Distinguished University Professor of Neurology
University of Michigan
CONTEMPORARY NEUROLOGY SERIES
53 SLEEP MEDICINE 65 MIGRAINE: MANIFESTATIONS,
Michael S. Aldrich, MD PATHOGENESIS, AND
MANAGEMENT,
54 BRAIN TUMORS
Second Edition
Harry S. Greenberg, MD, William F.
Robert A. Davidoff, MD
Chandler, MD, and Howard
66 CLINICAL NEUROPHYSIOLOGY,
M. Sandler, MD
Second Edition
56 MYASTHENIA GRAVIS AND
Jasper R. Daube, MD, Editor
MYASTHENIC DISORDERS
67 T HE CLINICAL SCIENCE OF
Andrew G. Engel, MD, Editor
NEUROLOGIC REHABILITATION,
57 NEUROGENETICS
Second Edition
Stefan-M. Pulst, MD, Dr. Med., Editor
Bruce H. Dobkin, MD
58 DISEASES OF THE SPINE AND
68 NEUROLOGY OF COGNITIVE
SPINAL CORD
AND BEHAVIORAL DISORDERS
Thomas N. Byrne, MD, Edward C.
Orrin Devinsky, MD and Mark
Benzel, MD, and Stephen G. Waxman,
D’Esposito, MD
MD, PhD
69 PALLIATIVE CARE
59 DIAGNOSIS AND
IN NEUROLOGY
MANAGEMENT OF PERIPHERAL
Raymond Voltz, MD, James L. Bernat,
NERVE DISORDERS
MD, Gian Domenico Borasio, MD,
Jerry R. Mendell, MD, John T. Kissel,
DipPallMed, Ian Maddocks, MD,
MD, and David R. Cornblath, MD
David Oliver, FRCGP, and
60 THE NEUROLOGY OF VISION Russell K. Portenoy, MD
Jonathan D. Trobe, MD
70 THE NEUROLOGY OF EYE
61 HIV NEUROLOGY MOVEMENTS, Fourth Edition
Bruce James Brew, MBBS, MD, FRACP R. John Leigh, MD, FRCP and
62 ISCHEMIC CEREBROVASCULAR David S. Zee, MD
DISEASE
71 P LUM AND POSNER’S
Harold P. Adams, Jr., MD, Vladimir DIAGNOSIS OF STUPOR
Hachinski, MD, and John W. Norris, MD AND COMA,
63 CLINICAL NEUROPHYSIOLOGY OF Fourth Edition
THE VESTIBULAR SYSTEM, Third Jerome B. Posner, MD, Clifford B. Saper,
Edition MD, PhD, Nicholas D. Schiff, MD, and
Robert W. Baloh, MD and Vicente Fred Plum, MD
Honrubia, MD 72 PRINCIPLES OF DRUG
64 NEUROLOGICAL COMPLICATIONS THERAPY IN NEUROLOGY,
OF CRITICAL ILLNESS, Second Second Edition
Edition Michael V. Johnston, MD and Robert A.
Eelco F.M. Wijdicks, MD, PhD, FACP Gross, MD, PhD
NEUROLOGIC
COMPLICATIONS
OF CANCER
Second Edition
LISA M. DeANGELIS, MD
Chair, Department of Neurology
Co-Executive Director, Brain Tumor Center
Lillian Rojtman Berkman Chair in Honor
of Jerome B. Posner
Memorial Sloan-Kettering Cancer Center
New York, NY
JEROME B. POSNER, MD
Evelyn Frew American Cancer Society Clinical
Research Professor
George C. Cotzias Chair of Neuro-oncology
Memorial Sloan-Kettering Cancer Center
New York, NY
1
2009
3
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Library of Congress Cataloging-in-Publication Data
DeAngelis, Lisa M.
Neurologic complications of cancer/Lisa M. DeAngelis, Jerome B. Posner.—2nd ed.
p. cm.—(Contemporary neurology series; 73)
Rev. ed. of: Neurologic complications of cancer/Jerome B. Posner. c1995.
Includes bibliographical references and index.
ISBN 978-0-19-536674-7
1. Neurologic manifestations of general diseases. 2. Cancer–Complications.
3. Neurophysiology. 4. Nervous system–Pathophysiology.
[DNLM: 1. Neoplasms–complications. 2. Neoplasms–therapy. 3. Central Nervous System
Neoplasms–secondary. 4. Nervous System Diseases–physiopathology. QZ 202 D281n 2008]
I. Posner, Jerome B., 1932- II. Posner, Jerome B., 1932- Neurologic complications
of cancer. III. Title. IV. Series.
RC347.P67 2008
616.8–dc22
2008000669
9 8 7 6 5 4 3 2 1
Printed in China
on acid-free paper
Preface
Much has changed in the fi eld of neuro-oncology since the publication of the fi rst
edition of this book in 1995. As the fi rst edition was being written in the early 1990s,
few a cademic centers had physicians who considered themselves neuro-oncologists.
Those who were neuro- oncologists generally dealt with primary brain tumors rather
than n eurologic c omplications of cancers that arise outside of the nervous system.
Now, most academic centers have at least one neuro-oncologist and many have neuro-
o ncology units. However, most of these units still deal primarily or exclusively with
primary CNS tumors. Thus, there remains a need for a book aimed at clinicians who do
not necessarily specialize in neuro-oncology, but who care for patients with cancer. This
book is intended for them. We hope that it will be useful to neurologists who are asked
to assist in the diagnosis and treatment of patients with cancer affecting the nervous
s ystem either directly or indirectly. We also hope that the book will be equally u seful
for oncologists and oncology nurses who encounter neurologic complications while
treating patients for cancer.
Since the fi rst edition, there have been many new developments in neuro-oncology.
The treatment of brain metastases and to a lesser degree epidural spinal cord com-
pression has been revolutionized by advances in stereotactic radiation. New therapeu-
tic agents, including new chemotherapy, monoclonal antibodies, and small molecules,
have produced new neurologic complications, involving both the peripheral and central
nervous system. Other neurologic complications of chemotherapy and radiation therapy,
although clinically described for many years, are often suffi ciently uncommon that they
are not recognized.
These advances, and many others, have required extensive rewriting of the sec-
ond edition. Every chapter has been revised and thoroughly updated. Of particular
note, new developments in the biology of metastases required a complete rewrite of
Chapter 2. Although the clinical signs and symptoms of metastases have not changed,
new treatments have required extensive revision of Chapters 5 through 8. New ther-
apeutic agents and new techniques in radiation therapy have required revisions of
Chapters 12 and 13. The references have been updated, emphasizing the most recent
papers and reviews.
Because the book is intended to help both oncologists and neurologists, oncologists
may fi nd some of the neurology more arcane than necessary (after all we are neuro-
logists), and neurologists may fi nd some of the oncology too detailed. But don’t give up;
the information contained within is of equal use to both specialists. The reader will fi nd
redundancies in the text. This is deliberate, because we hope the book will be both read
and used as a reference. The redundancies have decreased the need to keep referring to
other sections of the book when reading a specifi c topic.
The addition of Dr. Lisa DeAngelis, Chair of the Department of Neurology at
Memorial Sloan-Kettering Cancer Center, as an author brings new insights into some
of the problems discussed in this book. She was extremely helpful in preparing the fi rst
edition; many of the ideas expressed in that edition were hers. Also added to this edition
are new illustrations, beautifully drawn by Ms. Terry Helms.
We are extremely grateful to colleagues who have read portions of the book and made
extremely valuable suggestions. These include Dr. Anne Chiang, who read Chapter 2
on the biology of metastasis and made many helpful suggestions; Dr. Fabio Iwamoto,
who read Chapter 4; Dr. Edward Avila, who reviewed the section on seizures and
v
vi Preface
made helpful suggestions; Dr. Andrew Lassman, who read Chapter 5; Dr. Vivian Tabar,
who assisted in the preparation of the surgical section of Chapter 5; Dr. Mark Bilsky,
who read Chapter 6; Dr. Yoshiya (Josh) Yamada, who read the radiation oncology sec-
tion of Chapter 6; Dr. Kent Sepkowitz, who read Chapter 10; and Dr. Robert Darnell,
whose paper with Dr. Posner in the Seminars in Oncology formed the basis of
Chapter 15. All of these readers made suggestions and corrections, but they are not
responsible for any errors that may be contained in those chapters. Ms. Judy Lampron
and Ms. Carol D’Anella read the manuscript for spelling and syntax and certainly
improved its readability. Finally, we are extremely grateful to Craig Panner of Oxford
University Press for his patience, good advice, and easy availability during the prepara-
tion of the edition.
We dedicate this book not only to our spouses but also to our patients, whose illnesses
and suffering have taught us much about clinical diagnosis, treatment, and the humane
care of patients. We hope that by imparting the knowledge we have gained from these
patients, the readers of this book will be able to improve their patients’ quality of life.
Lisa M. DeAngelis
Jerome B. Posner
Contents
Part 1. General Principles
1. OVERVIEW 3
INTRODUCTION 3
RATIONALE FOR NEURO-ONCOLOGY 4
Nervous System Complications of Cancer Are Common 4
Neurologic Complications of Cancer Are Increasing 8
Neurologic Complications of Systemic Cancer Are Serious 10
Diagnosis Is Often Diffi cult 10
Treatment Helps 11
Problems in Neuro-Oncology Are Unique 13
Research Is Essential 15
Relationships between the Brain and Systemic Cancer
Are Biologically Important 15
CLASSIFICATION OF NEURO-ONCOLOGIC DISORDERS 16
Spread of Cancer to the Nervous System (Metastatic or Direct
Effects of Cancer) 17
Indirect Neurologic (Nonmetastatic or Paraneoplastic)
Complications of Cancer 18
APPROACH TO THE PATIENT 19
Known Cancer 20
No Known Cancer 22
EVALUATING THE PATIENT 23
REFERENCES 28
2. P ATHOPHYSIOLOGY OF NERVOUS
SYSTEM METASTASES 31
INTRODUCTION 31
PATHOPHYSIOLOGY OF THE METASTATIC PROCESS 32
Transformation and Growth 32
Vascularization (Angiogenesis) 35
Invasion 36
Intravasation 36
Circulation 37
Arrest: First Capillary Bed 39
vii
viii Contents
Passage to Arterial Circulation 39
Arrest: Final Capillary Bed 40
Tumor Emboli 41
Extravasation 41
Dormancy 41
Growth in the CNS 43
CLINICAL CONSIDERATIONS RELEVANT
TO NERVOUS SYSTEM METASTASIS 44
Tumor Size and Lymph Node Involvement 44
Properties of Metastases 45
Differences between a Primary Tumor and Its Metastases 45
Site of Metastases 45
PATHOPHYSIOLOGIC FACTORS RELEVANT TO SPREAD AND
GROWTH OF CANCER TO SPECIFIC NEURAL STRUCTURES 49
Brain 49
Spinal Cord 50
Leptomeninges 52
Cranial and Peripheral Nerves 55
REFERENCES 57
3. BLOOD–NERVOUS SYSTEM BARRIER DYSFUNCTION:
PATHOPHYSIOLOGY AND TREATMENT 64
INTRODUCTION 64
ANATOMY AND PHYSIOLOGY 67
Blood–Brain Barrier 68
Blood–Peripheral Nerve Barrier 71
Blood–Cerebrospinal Fluid Barrier 71
DISRUPTION OF BLOOD–CENTRAL NERVOUS
SYSTEM BARRIERS 72
Brain Edema 73
Other Sources of Disruption 75
Other Substances Causing Blood–Brain Barrier Disruption 76
CONSEQUENCES OF BLOOD–BRAIN BARRIER DISRUPTION:
INCREASED INTRACRANIAL PRESSURE, PLATEAU WAVES,
AND CEREBRAL HERNIATION 78
Treatment of Cerebral Herniation 81
T RANSPORT OF CHEMOTHERAPEUTIC DRUGS ACROSS
THE BLOOD–BRAIN BARRIER 82
RESTORATION OF BLOOD–CENTRAL NERVOUS
SYSTEM BARRIERS 84
Lowering Intracranial Pressure 84
Corticosteroids 84
REFERENCES 89
Contents ix
4. SUPPORTIVE CARE AND ITS COMPLICATIONS 95
INTRODUCTION 95
EDEMA/CORTICOSTEROIDS 98
Salutary Effects of Corticosteroids 99
Unwanted Effects of Corticosteroids 100
SEIZURES/ANTICONVULSANTS 107
Incidence/Epidemiology 107
Therapy 109
Untoward Effects of Anticonvulsants 114
VENOUS THROMBOSIS/ANTICOAGULANTS 117
PAIN/ANALGESIA 120
PSYCHOLOGICAL DISTRESS/PSYCHOTROPIC
AGENTS 123
FATIGUE 124
NAUSEA, VOMITING/ANTIEMETIC AGENTS 125
INFECTION/ANTIBIOTICS 125
INTENSIVE CARE/COMMON AGENTS 130
REFERENCES 130
Part 2. Metastases
5. INTRACRANIAL METASTASES 141
GENERAL PRINCIPLES 141
Introduction 141
Classifi cation 142
Incidence 144
BRAIN METASTASES (PARENCHYMAL) 146
Source 146
Pathophysiology of Neurologic Symptoms and Signs 148
Pathology 150
Clinical Findings 150
Laboratory Findings 155
Differential Diagnosis 158
Approach to the Patient without Known Cancer 160
Treatment 160
Prognosis 172
SPECIFIC TUMORS 173
Small Cell Lung Cancer 173
Non–Small Cell Lung Cancer 173
Breast 174
Melanoma 175