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1 the History of Cerebrospinal Fluid Cerebrospinal Fluid in Clinical Neurology Florian Deisenhammer • Finn Sellebjerg Charlotte E. Teunissen • Hayrettin Tumani Editors Cerebrospinal Fluid in Clinical Neurology Editors Florian Deisenhammer Charlotte E. Teunissen Department of Neurology Neurochemistry Laboratory and Biobank Innsbruck Medical University Department of Clinical Chemistry Innsbruck VU University Medical Center Amsterdam Austria Amsterdam The Netherlands Finn Sellebjerg Danish Multiple Sclerosis Center Hayrettin Tumani Department of Neurology Department of Neurology Rigshospitalet, University of Copenhagen University of Ulm Copenhagen Ulm Denmark Germany ISBN 978-3-319-01224-7 ISBN 978-3-319-01225-4 (eBook) DOI 10.1007/978-3-319-01225-4 Springer Cham Heidelberg New York Dordrecht London Library of Congress Control Number: 2015930740 © Springer International Publishing Switzerland 2015 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher's location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) We dedicate this book to our mentors, co-workers, and those interested in cerebrospinal fl uid. F o r e w o r d It is a pleasure to see that CSF analysis continues to march ahead. Professor Florian Deisenhammer is to be congratulated for assembling a strong team, with diverse expertise, to give us a coherent picture of the current state of the art. His spectrum of people extends all the way from the bedside to the bench. They each give an in- depth analysis as well as useful tips about how to get the most information from this important liquid-biopsy of brain fl uid. From the bedside, among other experts, we have Prof. Kaj Blennow who has been a pioneer of CSF analysis in dementia whose work has withstood the test of time and continues to be fundamental for further progress on this ever increasing disease, as we all live longer. There is also useful information from several experts on less common diseases involved in molecular mimicry, or auto-immune syn- dromes, where again it is found that CSF can provide more useful information rather than only blood tests for the same antibodies, by using the ratio of specifi c antibody titers which can be normalized to the total antibody ratio. In addition to the traditional acute infl ammatory diseases, there are also detailed chapters on chronic noninfectious infl ammatory CNS diseases as well as chronic infl ammatory diseases of the PNS. On a personal note, I am pleased to see my trusted colleague of many years, Geoff Keir, is still carrying on the basic work for CSF leakage syndromes. From the bench, the very important pre-analytical role of CSF analysis is given a detailed account which should be heeded by all who are responsible for triage of CSF, since they can have a profound effect on the fi nal results, depending on how samples are to be correctly handled. In addition, the crucial role for the technique of lumbar puncture is addressed. Although much has been written about diagnostic criteria (not least in MS), nev- ertheless in terms of basic pathophysiology, CSF offers much more direct evidence than a number of other investigations for the role of immunology in the disease processes under differential consideration. One day we may even understand the exact molecular mechanisms. This book is to be read by both practicing clinicians as well as those who are entrusted with the most careful analysis of such precious fl uid with future promise. London , UK Emeritus Prof. Edward J. Thompson , DSc, MD, PhD, FRCPath, FRCP vii Pref ace The analysis of cerebrospinal fl uid (CSF) is an invaluable diagnostic aid in clinical neurology and can be obtained with relative ease by lumbar puncture. CSF analysis is amenable to various technologies applied in haematology, cytochemistry, clinical chemistry, microbiology and virology. There are not many constituents that are measured during routine diagnostic work-up, nevertheless the combination of these variables gives a wide range of patterns that are often typical for certain neurologi- cal diseases. Therefore, it takes a profound knowledge of the particularities of the CSF for analyses and also for reporting. The relative paucity of constituents in the CSF and their low concentration pose a certain methodological challenge; on the other hand it has the advantage of low background activity which makes it better accessible for exploration of new biomarkers. This development has led to discov- ery of a variety of diagnostic markers expanding the use of CSF in everyday clinical decision making. In this book we try to give an up-to-date overview as to how the CSF can be applied in clinical neurology. The intention was to create a book of reference for which we invited numerous experts in the fi eld to contribute. The chapters not only focus on technical aspects of CSF analyses but discuss CSF fi ndings in a broader clinical context too. We do hope you will enjoy reading and fi nd the book helpful not only in your clinical work but also in increasing your knowledge in a wide range of CSF-related topics. Innsbruck , Austria Florian Deisenhammer Copenhagen , Denmark Finn Sellebjerg Amsterdam , The Netherlands Charlotte E. Teunissen Ulm , Germany Hayrettin Tumani ix Acknowledgment by Florian Deisenhammer I want to thank my co-editors who not only contributed by writing chapters but also helped with the overall work by reviewing the single chapters by our authors and providing extremely valuable input. Further, I want to thank my long standing chief lab technician, Ingrid Gstrein, whose invaluable work made the Innsbruck CSF laboratory what it is today. xi C o n t e n t s Part I Basic Aspects of the Cerebrospinal Fluid 1 The History of Cerebrospinal Fluid . 3 Florian Deisenhammer 2 Anatomy of CSF-Related Spaces and Barriers Between Blood, CSF, and Brain . 17 Hayrettin Tumani 3 Physiology and Constituents of CSF . 25 Hayrettin Tumani 4 Techniques, Contraindications, and Complications of CSF Collection Procedures . 35 Ellis Niemantsverdriet , Hanne Struyfs , Flora Duits , Charlotte E. Teunissen , and Sebastiaan Engelborghs 5 Importance of Pre-analytical Stability for CSF Biomarker Testing . 59 Eline A. J. Willemse and Charlotte E. Teunissen Part II Methods of CSF Analyses 6 Cell Count and Staining . 81 Herwig Strik and Ingelore Nagel 7 Glucose and Lactate . 101 Hayrettin Tumani and Harald Hegen 8 CSF Total Protein . 107 Hayrettin Tumani and Harald Hegen 9 CSF Albumin: Albumin CSF/Serum Ratio (Marker for Blood-CSF Barrier Function) . 111 Hayrettin Tumani and Harald Hegen 10 Immunoglobulins in Cerebrospinal Fluid . 115 Finn Sellebjerg xiii xiv Contents 11 Detection of Infectious Agents . 131 Annette Spreer 12 Immunohistochemistry . 143 Romana Höftberger , Simone Mader , and Markus Reindl 13 Methods for Biomarker Analysis . 159 Diego Franciotta , Massimo Alessio , Livia Garzetti , and Roberto Furlan Part III CSF in Clinical Syndromes 14 Acute Infectious Diseases . 175 Erich Schmutzhard and Bettina Pfausler 15 Chronic Infectious Inflammatory Diseases of the Central Nervous System . 211 Pille Taba and Irja Lutsar 16 Autoimmune Encephalitis . 247 Agnes van Sonderen and Maarten J. Titulaer 17 Chronic Noninfectious Inflammatory CNS Diseases . 277 Irina Elovaara , Sanna Hagman , and Aki Hietaharju 18 CSF Findings in Guillain-Barré Syndrome: Demyelinating and Axonal Acute Inflammatory Polyneuropathies . 293 Zsolt Illes and Morten Blaabjerg 19 Alterations of the Cerebrospinal Fluid in Chronic Inflammatory Diseases of the Peripheral Nervous System . 311 Zsolt Illes and Morten Blaabjerg 20 Alzheimer’s Disease and Other Neurodegenerative Disorders . 329 Christoffer Rosén , Henrik Zetterberg , and Kaj Blennow 21 Paraneoplastic Neurological Syndromes. 353 Jan Lewerenz and Frank Leypoldt 22 Laboratory Diagnosis of Subarachnoid Haemorrhage . 387 Markus Otto, Karin Nagy, and Niklas Mattson 23 CSF-orrhoea . 395 Geoffrey Keir and Ligy Thomas 24 Guidelines on Cerebrospinal Fluid Analysis . 407 Harald Hegen , Charlotte E. Teunissen , Finn Sellebjerg , Hayrettin Tumani , and Florian Deisenhammer Index . 429 P a r t I Basic Aspects of the Cerebrospinal Fluid The History of Cerebrospinal Fluid 1 Florian Deisenhammer Contents 1.1 Introduction. 4 1.2 The Edwin Smith Surgical Papyrus . 4 1.3 The Greek Physicians and Philosophers. 5 1.4 Claudius Galenus (Galen of Pergamon) . 7 1.5 Leonardo Da Vinci, Andreas Vesalius, Costanzo Varolio (Varolius) and Colleagues . 7 1.6 The Next Generation of Neuroanatomists: Monro, Sylvius, Von Luschka and Magendie .
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