THE CEREBROSPINAL FLUID
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1 THE CEREBROSPINAL FLUID
2 THE CEREBROSPINAL FLUID Editors: ROBERT M. HERNDON, M.D. Chief of Neurology Good Samaritan Hospital and Professor of Neurology Oregon Health Sciences University Portland, Oregon ROGER A. BRUMBACK, M.D. Associate Professor of Pathology (Neuropathology), Neurology, Pediatrics, and Psychiatry & Behavioral Sciences University of Oklahoma College of Medicine and Veterans Administration Medical Center Oklahoma City, Oklahoma... " KLUWER ACADEMIC PUBLISHERS BOSTON/DORDRECHT ILONDON
3 Distributors for North America: Kluwer Academic Publishers, 101 Philip Drive, Assinippi Park, Norwell, Massachusetts 02061, USA Distributors for all other countries: Kluwer Academic Publishers Group, Distribution Centre, Post Office Box AH Dordrecht, The Netherlands Library of Congress Cataloging-in-Publication Data The Cerebrospinal fluid/editors, Robert M. Herndon, Roger A. Brumback. p. cm. Includes bibliographies and index. ISBN-13: e-isbn-13: DOl: / Cerebrospinal f1uid-pathophysiology. 2. Cerebrospinal fluid-cytopathology. 3. Cereprospinal fluid-cytology. J. Herndon, Robert M. II. Brumback, Roger A. [DNLM: 1. Cerebrospinal Fluid. WL 203 C4138] RBSS.C 'S-dc19 DNLM/DLC for Library of Congress CIP Copyright 1989 by Kluwer Academic Publishers, Boston Softcover reprint of tbe hardcover 1 st edition 1989 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher, Kluwer Academic Publishers, 101 Philip Drive, Assinippi Park, Norwell, Massachusetts
4 To Kathryn Mary Robert, Jr. William Cynthia Darryl Audrey Owen Jor understanding and support
5 CONTENTS Contributors IX Preface Xl Acknowledgments Xlll 1. Briefhistory of the understanding of cerebrospinal fluid ROBERT M. HERNDON, M.D. 2. Anatomic and physiologic aspects of the cerebrospinal fluid space 15 ROGER A. BRUMBACK, M.D. 3. Abnormalities of cerebrospinal fluid production and flow and hydrocephalus 45 RICHARD W. LEECH, M.D. 4. Collecting cerebrospinal fluid 97 ROGER A. BRUMBACK, M.D. 5. The medical uses of injection into the cerebrospinal fluid space (intrathecal and intraventricular injection) 131 ROBERT M. HERNDON, M.D. 6. Cerebrospinal fluid infections 143 MICHAEL GRAVES, M.D. 7. Nonimmunoglobulin proteins in human cerebrospinal fluid 167 BENJAMIN RIX BROOKS, M.D. vii
6 viii Content 8. Human cerebrospinal fluid immunology 179 JOHN L. TROTTER, M. D., and ROBERT S. RUST, M. D. 9. Light microscopic cytology of cerebrospinal fluid 227 CLAIRE E. MEENA, M.D., WILLIAM H. OLSON, M.D., and LUNG T. YAM, M.D. 10. The cytology of cerebrospinal fluid: Methods and normal constituents 245 ROBERT M. HERNDON, M. D., and ROGER A. BRUMBACK, M. D. 11. Cytopathology of the cerebrospinal fluid 261 ROBERT M. HERNDON, M.D., and ROGER A. BRUMBACK, M.D. Color Plates-Following page 178 Index 301
7 CONTRIBUTORS Benjamin Rix Brooks, M.D. Professor of Neurology and Medical Microbiology University of Wisconsin Medical School and Neurology Service William S. Middleton Memorial Veterans Adminstration Hospital Madison, Wisconsin Roger A. Brumback, M.D. Associate Professor of Pathology (Neuropathology), Neurology, Pediatrics, and Psychiatry & Behavioral Sciences University of Oklahoma College of Medicine and Laboratory Service Veterans Administration Medical Center Oklahoma City, Oklahoma Michael Graves, M.D. Associate Professor of Neurology University of California, Los Angeles School of Medicine Los Angeles, California Robert M. Herndon, M.D. Professor of Neurology Oregon Health Sciences University ix
8 x Contributors and Chairman of Neurology Good Samaritan Hospital Portland, Oregon Richard W. Leech, M.D. Professor and Former Head of Pathology University of Oklahoma College of Medicine Oklahoma City, Oklahoma Claire E. Meena, M.D. Resident in Pathology University of Louisville School of Medicine Louisville, Kentucky William H. Olson, M.D. Professor and Head of Neurology University of Louisville School of Medicine Louisville, Kentucky Robert S. Rust, M.D. Instructor in Pediatrics and Neurology Washington University School of Medicine St. Louis, Missouri John L. Trotter, M.D. Associate Professor of Neurology Washington University School of Medicine St. Louis, Missouri Lung T. Yam, M.D. Professor ofinternal Medicine University of Louisville School of Medicine. Louisville, Kentucky 40292
9 PREFACE For centuries the great minds of medical science puzzled over the importance of the cerebrospinal fluid. As far back as Hippocrates, it was thought that this "phlegm" that flooded the intracranial contents had pathological significance. However, not until the late 1800s, when Quincke introduced and popularized lumbar puncture, did physicians take an interest in the study of this fluid in relation to clinical illness. Since then a variety of techniques for obtaining cerebrospinal fluid from various sites have developed, and the relationship of cerebrospinal fluid to a variety of disease processes has received considerable study. In this volume, we have attempted to assemble reviews of some of these important developments during the past century. Chapter 1 contains a historical review of key investigations that helped shape our concepts of cerebrospinal fluid from the earliest recorded description by the author of the Edwin Smith Surgical Papyrus in the seventeenth century B.C. to contemporaries such as Kabat, Glusman, and Knaub, who introduced quantitative determinations of cerebrospinal fluid gamma globulin levels. In Chapter 2 there is a description of our current understanding of the anatomical compartment for the cerebrospinal fluid and the physiology of its formation, circulation, and absorption. Dr. Richard Leech in Chapter 3 contributes a comprehensive description of the disorders associated with excessive quantities of cerebrospinal fluid-commonly referred to as hydrocephalus. A variety of techniques for properly collecting and evaluating cerebrospinal fluid are detailed in Chapter 4. In Chapter 5, some of the ways the cerebrospinal fluid xi
10 xii Preface space is used for therapeutic delivery of pharmaceuticals are discussed. This route is increasingly important for delivery of a variety of therapeutic agents, and there will probably be a great deal of research in this area over the next several years. The ever important problem of infections of the cerebrospinal fluid space is discussed by Dr. Michael Graves in Chapter 6. Dr. Benjamin Brooks (Chapter 7) and Drs. John Trotter and Robert Rust (Chapter 8) detail some of the more exciting recent research on the chemical composition of cerebrospinal fluid. These studies have been particularly important in leading to new concepts regarding the pathophysiology of diseases such as multiple sclerosis. Chapter 9 (by Drs. Claire Meena, William Olson, and Lung Yam) and Chapters 10 and 11 detail the cytologic and cytopathologic findings in cerebrospinal fluid in normals and in a variety of disease states. As one reads this volume, it will be amply apparent that even though we know quite a lot about the cerebrospinal fluid as compared to the knowledge of physicians a century ago, there is still an enormous amount to be learned. For instance, while most physicians are familiar with the counting and characterization of blood cells (erythrocytes and leukocytes) that can be found in cerebrospinal fluid and often use this for diagnosing illnesses, careful cytologic preparations as described in the last three chapters of this book are rarely performed except in larger medical centers. Advances in the use of cerebrospinal fluid for evaluation of disease states have been disturbingly slow, despite what appears to be considerable diagnostic potential. In fact, we are almost in the dark ages when it comes to the use of cerebrospinal fluid for diagnosis and treatment. In most instances, the extent of sophistication in the use of cerebrospinal fluid trails our use of other equally valuable body fluids (such as blood and urine) by several decades. There is clearly a great deal of as yet untapped clinical and research potential for cerebrospinal fluid study. It is hoped that this small volume will not only bring the reader up to date with regard to many aspects of cerebrospinal fluid evaluation, but will also suggest directions for future investigation. Robert M. Herndon Roger A. Brumback
11 ACKNOWLEDGMENTS This volume had its inception in discussions between the coeditors about the perceived need for an updated and more comprehensive treatment of the cerebrospinal fluid. However, in a larger sense, the book is the culmination of inputs and contributions from many individuals. The interest of one coeditor (RMH) in this subject began with his clinical training under Dr. John Stirling Meyer and received a major impetus from a discussion with Dr. Erland Nelson, who first suggested the possibility of using the electron microscope to study the cerebrospinal fluid. Dr. Lucien Rubinstein provided important encouragement and support early in these studies, as did Drs. Richard T. Johnson and Guy M. McKhann. Dr. Larry Davis was instrumental in a number of the studies, and his contribution was critical to the electron microscopic studies in mumps meningitis. A number of individuals made important technical contributions, including Marjorie Johnson, who assisted in the early development of the electron microscopic techniques, and Liliana Rena-Descalzi, who is responsible for several of the electron micrographs published in this volume. The other coeditor (RAB) developed his interest in the problem of cerebrospinal fluid analysis first while a pediatric house officer at the Johns Hopkins Hospital Harriet Lane Home, having been influenced by a number of the dynamic young investigators in the then relatively new Department of Neurology under Dr. Guy M. McKhann. Later, while a neurology resident at the Washington University (St. Louis) School of Medicine, sage words from Drs. xiii
12 xiv Acknowledgments William Landau and Philip Dodge regarding the importance of understanding cerebrospinal fluid piqued this interest. However, both coeditors were pursuing other areas of study until a chance conversation between them in the bookstore of the University of Rochester Medical Center led to the project that culminated in this volume. Along the way we have been fortunate to have the support of several prominent medical scientists who have carefully prepared chapters for this book. The publisher, Kluwer, has also been considerate of our many missed deadlines. Finally, both of us want to thank our wives and children for allowing us the time to complete this project. Robert M. Herndon Roger A. Brumback
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