Explore the full ebook collection and download it now at textbookfull.

com

Escourolle and Poirier's Manual of Basic

Neuropathology 6th Edition Francoise Gray Md
(Editor)

https://textbookfull.com/product/escourolle-and-poiriers-
manual-of-basic-neuropathology-6th-edition-francoise-gray-
md-editor/

OR CLICK HERE

DOWLOAD EBOOK

Browse and Get More Ebook Downloads Instantly at https://textbookfull.com

Click here to visit textbookfull.com and download textbook now
 Your digital treasures (PDF, ePub, MOBI) await
Download instantly and pick your perfect format...

Read anywhere, anytime, on any device!

Basic Graph Theory 1st Edition Md. Saidur Rahman (Auth.)

https://textbookfull.com/product/basic-graph-theory-1st-edition-md-
saidur-rahman-auth/

textbookfull.com

The MD Anderson Manual of Medical Oncology 3rd Edition

Hagop M. Kantarjian

https://textbookfull.com/product/the-md-anderson-manual-of-medical-
oncology-3rd-edition-hagop-m-kantarjian/

textbookfull.com

Neuropathology of Drug Abuse Andreas Büttner

https://textbookfull.com/product/neuropathology-of-drug-abuse-andreas-
buttner/

textbookfull.com

Practical Management of Pain 6e May 19 2022 6th Edition

Benzon Md

https://textbookfull.com/product/practical-management-of-
pain-6e-may-19-2022-6th-edition-benzon-md/

textbookfull.com
Total Knee Arthroplasty A Technique Manual 3rd Edition
Scott Md

https://textbookfull.com/product/total-knee-arthroplasty-a-technique-
manual-3rd-edition-scott-md/

textbookfull.com

The Complete Google Manual 6th Edition Coll.

https://textbookfull.com/product/the-complete-google-manual-6th-
edition-coll/

textbookfull.com

ROBBINS amp KUMAR BASIC PATHOLOGY 11th Edition Vinay Kumar

Mbbs Md Frcpath & Abul K Abbas Mbbs & Jon C Aster Md Phd &
Andrea T Deyrup Md Phd & Abhijit Das Md
https://textbookfull.com/product/robbins-amp-kumar-basic-
pathology-11th-edition-vinay-kumar-mbbs-md-frcpath-abul-k-abbas-mbbs-
jon-c-aster-md-phd-andrea-t-deyrup-md-phd-abhijit-das-md/
textbookfull.com

Neuropathology 2nd Edition B.K. Kleinschmidt-Demasters

https://textbookfull.com/product/neuropathology-2nd-edition-b-k-
kleinschmidt-demasters/

textbookfull.com

The Complete Cloud Computing Manual 6th Edition Coll.

https://textbookfull.com/product/the-complete-cloud-computing-
manual-6th-edition-coll/

textbookfull.com
i

Escourolle & Poirier’s

Manual of Basic Neuropathology
iii

Escourolle & Poirier’s

MANUAL OF BASIC
NEUROPATHOLOGY
S I X T H E D I T IO N

EDI T E D B Y
F R A NÇ O I S E G RAY, MD , P H D
PROFES SOR OF PAT HOL OGY ( RE T.) , FACULT É DE M É D E C I N E PA R I S D I D E R O T, U N I V E R S I T É PA R I S ,
D IDER OT, S OR BONNE PARI S CI T É , PARI S, F RANCE
NEUROPATHOLOGI ST, DE PART M E NT OF PAT HOL OGY, LA R I B O I S I È R E H O S P I TA L ( R E T. ) , A P H P,
PARIS , FRANCE

C H A R L E S D U YC K A ERTS , MD , P H D
PROFES SOR OF PAT HOL OGY, UNI VE RSI T Y PI E RRE E T M A R I E C U R I E , PA R I S , FR A N C E
D IR EC TOR, NEUR OPAT HOL OGY L ABORAT ORY, PI T I É / S A LP Ê T R I È R E H O S P I TA L, PA R I S , FR A N C E

U M B E R T O D E G IRO LA MI, MD
PROFES SOR OF PAT HOL OGY, HARVARD M E DI CAL SC H O O L, B O S T O N , M A , U S A
NEUROPATHOLOGI ST, BRI GHAM AND W OM E N’S HO S P I TA L, B O S T O N , M A , U S A

1
1
Oxford University Press is a department of the University of Oxford. It furthers
the University’s objective of excellence in research, scholarship, and education
by publishing worldwide. Oxford is a registered trade mark of Oxford University
Press in the UK and certain other countries.

Published in the United States of America by Oxford University Press

198 Madison Avenue, New York, NY 10016, United States of America.

© Françoise Gray, Charles Duyckaerts, Umberto De Girolami 2019

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, without the
prior permission in writing of Oxford University Press, or as expressly permitted
by law, by license, or under terms agreed with the appropriate reproduction
rights organization. Inquiries concerning reproduction outside the scope of the
above should be sent to the Rights Department, Oxford University Press, at the
address above.

You must not circulate this work in any other form

and you must impose this same condition on any acquirer.

Library of Congress Cataloging-​in-​Publication Data

Names: Gray, Françoise, editor. | Duyckaerts, Charles, editor. | De Girolami, Umberto, editor.
Title: Escourolle & Poirier’s manual of basic neuropathology / edited by Françoise Gray,
Charles Duyckaerts, Umberto De Girolami.
Other titles: Manual of basic neuropathology
Description: Sixth edition. | New York, NY : Oxford University Press, [2019] |
Preceded by Escourolle & Poirier’s manual of basic neuropathology / [edited by] Françoise Gray,
Charles Duyckaerts, Umberto De Girolami. c2014. |
Includes bibliographical references and index.
Identifiers: LCCN 2018011890 | ISBN 9780190675011 (alk. paper)
Subjects: | MESH: Central Nervous System Diseases—pathology
Classification: LCC RC347 | NLM WL 301 | DDC 616.8/047—dc23
LC record available at https://lccn.loc.gov/2018011890

This material is not intended to be, and should not be considered, a substitute for medical or other professional advice. Treatment for the
conditions described in this material is highly dependent on the individual circumstances. And, while this material is designed to offer
accurate information with respect to the subject matter covered and to be current as of the time it was written, research and knowledge about
medical and health issues is constantly evolving and dose schedules for medications are being revised continually, with new side effects
recognized and accounted for regularly. Readers must therefore always check the product information and clinical procedures with the
most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and
safety regulation. The publisher and the authors make no representations or warranties to readers, express or implied, as to the accuracy or
completeness of this material. Without limiting the foregoing, the publisher and the authors make no representations or warranties as to the
accuracy or efficacy of the drug dosages mentioned in the material. The authors and the publisher do not accept, and expressly disclaim,
any responsibility for any liability, loss or risk that may be claimed or incurred as a consequence of the use and/or application of any of the
contents of this material.

9 8 7 6 5 4 3 2 1

Printed by Sheridan Books, Inc., United States of America

v

Contents

Foreword vii 4. Vascular Pathology 82

Martin A. Samuels
Jean-​Jacques Hauw, Steven K. Feske,
Preface to the Sixth Edition ix Pierre Amarenco, and Umberto De Girolami
Contributors xi
5. Infections of the Central Nervous
1. Basic Pathology of the Central Nervous System 122
System 1 Fabrice Chrétien, Gregory Jouvion,
Pedro de Sá Cavalcante Ciarlini, Danielle Seilhean, Kum Thong Wong, and Leroy R. Sharer
Umberto De Girolami, and Françoise Gray
6. Human Prion Diseases 159
2. Tumors of the Central Nervous James W. Ironside
System 21
Keith L. Ligon, Sandro Santagata, and Franck Bielle 7. Multiple Sclerosis and Related
Inflammatory Demyelinating
3. Central Nervous System Trauma 65 Diseases 172
Colin Smith and R. Ross Reichard Hans Lassmann and Danielle Seilhean

• v
 8. Pathology of Degenerative Diseases of 12. Pathology of Skeletal Muscle 299
the Nervous System 186 Romain Gherardi, Anthony A. Amato,
Charles Duyckaerts Hart G. Lidov, and Umberto De Girolami

9. Acquired Diseases of the Nervous 13. Pathology of Peripheral Nerves 341

System: Metabolic, Toxic, and Related Jean-​Michel Vallat, Douglas C. Anthony, and
to Systemic Disease 219 Umberto De Girolami
Leila Chimelli and Françoise Gray
14. Diseases of the Pituitary Gland 373
10. Hereditary Metabolic Diseases 244 Vânia Nosé, Sandro Santagata,
Douglas C. Anthony and Hans H. Goebel and Edward R. Laws

11. Congenital Malformations and Appendix: Brief Survey of Neuropathological

Perinatal Diseases 275 Techniques 395
Homa Adle-​Biassette, Brian Harding, and David Meredith
Jeffrey A. Golden
Index 417

vi • C ontents
vi

Foreword

Most textbooks of medicine, even the most is inexorable, reflecting as it does the increasingly
venerated, undergo a new edition every 5 years complex biology, pathophysiology, and therapeutics
or even longer. This interval reflects the relatively of the various fields. This process, which occurred
slow progress in most fields. After all, change in in internal medicine in the twentieth century, is
the practice of medicine usually reflects the ar- now in full bloom in the twenty-​first century. For
duous process of preclinical basic science followed this reason, a new edition of Escourolle and Poirier’s
by the lengthy testing of drugs in animals and then Manual of Basic Neuropathology has been hatched in
humans. As most clinical trials are negative, only only 5 years.
a small number of real changes occur in less than In generations past, the basic science of neuro-
a decade. However, this viscous process does not science was neuropathology. Over time, other fields,
hold in neuroscience. Driven mainly by advances such as genetics, imaging, neuropharmacology, and
in molecular biology, cell biology, and genetics, molecular biology have become vital to the training
the clinical neurosciences (neurology, neurosur- and practice of the clinical neurosciences. But, con-
gery, and psychiatry) are experiencing dramatic trary to becoming extinct, neuropathology has in-
change. Together with cancer, the neurosciences are corporated these newer disciplines and has, in effect,
undergoing a transformation that is analogous to reclaimed its leadership role in the understanding
cardiology in the last century. Patients are now re- and ultimately treatment of disorders of the nervous
ceiving the benefits of this momentum in the form system. In the sixth edition of the now classic
of treatments for virtually every category of nervous textbook, Escourolle and Poirier’s Manual of Basic
system disorder. The modern neurology department Neuropathology, Professors Umberto De Girolami,
is now differentiated into 15–​20 divisions. This pro- Françoise Gray, and Charles Duyckaerts have
cess may be bemoaned by the older generation, but embodied this trend by creating what is, in effect,

• vii
a concise approach to the understanding of all the familiar manner, starting with a chapter on the basic
major categories of nervous system disease. In a very principles of the pathology of the nervous system.
creative and truly unique manner, they have added This is followed by individual chapters on tumors,
distinguished clinicians to many of the chapters to trauma, vascular diseases, infections, prion diseases,
ensure relevance of the basic information to the demyelinating processes, degenerative diseases, ac-
actual practice of medicine. This reflects the fact quired and inherited metabolic diseases, congenital
that many of the major questions in diseases of the malformations, muscles, nerves, and diseases of the
nervous system, such as regarding paralysis, pain, pituitary gland. The book ends with an appendix
disorders of consciousness, and cognitive decline, on commonly used neuropathology techniques. As
do not fit neatly into any one of the old categories examples of the new approach, the distinguished
that were artificially created in the past, as they no myologist Anthony Amato cowrote the chapter on
longer reflect the relevant pathobiology. disease of skeletal muscle, as did the eminent neu-
Interdisciplinary neuroscience is the wave rosurgeon Edward Laws for the pituitary chapter
of the future if we are to unlock the mysteries and the venerated Steven Feske for the vascular
of neurodegeneration, neuroinflammation, and diseases chapter. As Gilbert and Sullivan’s Pooh-​Bah
aging. In our own center, this is reflected in the re- famously said, this adds “artistic verisimilitude to an
cent formation of a Program in Interdisciplinary otherwise bald and unconvincing narrative.”
Neuroscience, which is meant to facilitate re- Indeed, this new edition of Escourolle and Poirier’s
search, clinical care, and education in areas that Manual of Basic Neuropathology is much more than
fall between the classic disciplines, allowing for a that. It is, in fact, a concise textbook of the modern
multiperspective approach to learning the causes and neurosciences, one that will be read and referred
creating preventive and curative strategies for the fu- to by the next generation of all those students and
ture. As one salient example, the science underlying physicians interested in diseases of the nervous
neurodegeneration and repair has vital relevance to system.
a vast array of diseases, such as amyotrophic lateral
Martin A. Samuels, MD, FANA, FAAN, FRCP,
sclerosis, Alzheimer disease, and Parkinson disease.
MACP, DSc (hon)
In the past, these would have been considered en-
Director, Program for Interdisciplinary
tirely separate illnesses, each cared for in different
Neuroscience
divisions, such as neuromuscular diseases, cognitive
Chair, Department of Neurology
and behavioral neurology, and movement disorders.
Brigham and Women’s Hospital
It is now clear that the basic science of each of these
Miriam Sydney Joseph Professor of Neurology
disorders is shared. Immunology has also taken a
Harvard Medical School
major role in understanding diseases as apparently
Boston, Massachusetts
disparate as stroke, dementia, and epilepsy.
USA
Escourolle and Poirier’s Manual of Basic
Neuropathology is organized in its successful and

viii • F oreword
ix

Preface to the Sixth Edition

The first two French editions of the Manuel de This sixth edition of the manual attempts
Neuropathologie, published in 1971 and 1977, to maintain the general intention of Professors
were conceived, written, and edited by Raymond Escourolle and Poirier for the first and subsequent
Escourolle and Jacques Poirier. After the death editions of the monograph, that is, to provide, for
of Raymond Escourolle in 1984, Françoise Gray the reader resident-​trainee and staff member, a basic
joined Jacques Poirier for the third edition; in ad- description of the lesions underlying the diseases of
dition, Jean-​Jacques Hauw and Romain Gherardi the nervous system and to limit pathophysiological
contributed to selected chapters. The first three considerations to essential principles. Historical,
editions reached the English-​speaking public thanks clinical neurologic and radiologic imaging data,
to the friendship and translating ability of the now-​ once again, have been deliberately excluded, as well
deceased Lucien Rubinstein. For the fourth edition, as bibliographic reference listings. This important
Umberto De Girolami joined as co-​editor, and the body of information essential for the practice of
scope of the monograph was expanded with the col- neuropathology can be obtained in the many com-
laborative efforts of multiple experts throughout the prehensive treatises on the subject now readily avail-
world to write the English language text. Jacques able. We also have made the assumption that the
Poirier retired, and Charles Duyckaerts then agreed reader has some familiarity with general concepts of
to join the editorial team for the fifth and now the neuroanatomy, neurohistology, and the principles of
sixth edition. For this sixth edition, there have again anatomic pathology as well as clinical neurology.
been changes in authorship of several chapters in With these guidelines in mind, our aim has been
response to the changing status of senior authors to produce a text that mainly presents those labo-
and the need to recruit active investigators to ratory aspects of neuropathology that are morpho-
replace them. logical (and molecular, where appropriate) and to

• ix
demonstrate these with accurate descriptions and metabolic disorders, developmental disorders,
good illustrations, all within the scope of a concise and neuromuscular diseases. Morphologic
and inexpensive “manual.” neuropathologic data, obtained at biopsy or
For several specific reasons, we think that the at postmortem examination, have therefore
time is now right for a new edition since the last needed to be integrated with this new knowledge
one in 2014. Over the past several years, specialty for the reinterpretation and reclassification of
training in neurology, neurosurgery, and pathology many diseases. For example, neuropathologic
has very much changed throughout much of the information obtained at biopsy, combined
world, such that in these disciplines, less time is with molecular biology and genetic data, is
being devoted to neuropathology. This has been due now required for the diagnosis, prognosis, and
in large part to the tremendous expansion of know- guidance of the choice of treatment modalities in
ledge in allied subspecialty areas, requiring that brain tumors.
more time be devoted to them. Thus, the trainee in • Last, an urgent responsibility to present an
these disciplines is now very much in need of a con- updated synopsis of neuropathology is that this
cise introductory text. knowledge is important to allied disciplines, as
In addition, several other important changes in there is constant need for surveillance of newly
medicine and society have had an impact on the field emerging diseases, including infectious and
of neuropathology and demand being addressed in iatrogenic ones.
this text.
We need to thank first of all Susan Pioli, who al-
• For a variety of social and scientific reasons, though now retired from the publishing business,
autopsy studies are currently being performed was instrumental in prior editions and led us to Craig
much less frequently than in years past. This Panner and his colleagues with Oxford University
change has been brought about in part because Press, who has given fundamental support. Second,
the progress in radiologic imaging, both we thank present and past contributing authors and
structural and functional, has decreased the their staff for the text and illustrations provided in
need to draw on clinico-​anatomic correlations this new edition.
derived from postmortem data to guide clinical In the Introduction to the first edition, Professors
practice. Oddly enough, conversely, autopsy-​ Escourolle and Poirier offered an apology to the
derived knowledge of the anatomic distribution reader that is still valid some half a century later:
and the neuropathologic basis of lesions
continues to be a valuable body of information The compilation of a basic work designed to
for the interpretation of imaging data. To familiarize physicians-​in-​training with such a
support this aim, we have amply made use of highly specialized discipline as Neuropathology
macroscopic illustrations and whole-​brain entails two opposing risks: in attempting to
celloidin/​paraffin-​embedded sections from our compress the maximum amount of information
archives. within the minimum space, the text is liable to
• Progress in molecular biology and genetics has become unintelligible to beginners; if on the con-
revolutionized the laboratory diagnosis of many trary, one tries to maintain too elementary a
groups of neurological diseases. Neuropathology level, the danger is that only the obvious will be
stands at the vanguard of the development and stated. In presenting to the non-​initiated reader
implementation of these diagnostic studies. In the neuropathological information that some may
last decade, progress in immunohistochemistry find too simple, we have preferred the hazard of
methods for in situ identification of abnormal the second pitfall.
proteins and the enormous advances in molecular
biology to uncover specific gene mutations have Françoise Gray
led to greater understanding of many hereditary Charles Duyckaerts
neurologic diseases, including degenerative and Umberto De Girolami

x • preface
xi

Contributors

Homa Adle-​Biassette, MD, PhD Douglas C. Anthony, MD, PhD

Professor of Pathology, Faculté de médecine Paris Professor of Pathology and Laboratory Medicine,
Diderot, Université Paris, Diderot, Sorbonne and Professor of Neurology, Alpert Medical
Paris Cité, Paris, France School of Brown University, Providence,
Pathologist, Neuropathologist, Fetal (neuro) RI, USA
pathologist, Department of Pathology, Pathologist-​in-​Chief, Lifespan Academic Medical
Lariboisière Hospital, APHP, Paris, France Center, Providence, RI, USA
Pierre Amarenco, MD Franck Bielle, MD, PhD
Professor and Chairman, University of Paris Assistant Professor of Pathology, University Pierre
Diderot, Sorbonne Paris Cité, Paris, France et Marie Curie, Paris, France
Department of Neurology and Stroke Centre Neuropathologist, Pitié/​Salpêtrière Hospital,
Bichat Hospital, Paris, France Paris, France
Anthony A. Amato, MD Leila Chimelli, MD, PhD
Professor of Neurology, Harvard Medical School, Professor of Pathology, Federal University of Rio de
Boston, MA, USA Janeiro, Rio de Janeiro, Brazil
Vice-​Chairman, Department of Neurology and Neuropathologist, Laboratory of Neuropathology,
Chief, Neuromuscular Division, Brigham and State Institute of Brain, Rio de Janeiro,
Women’s Hospital, Boston, MA, USA Brazil

• xi
Fabrice Chrétien, MD, PhD Françoise Gray, MD, PhD
Professor of Histology, Université Paris Descartes, Professor of Pathology (ret.), Faculté de médecine
Paris, France Paris Diderot, Université Paris, Diderot,
Neuropathologist, Laboratoire de Neuropathologie, Sorbonne Paris Cité, Paris, France
Centre Hospitalier Sainte Anne, Paris, France Neuropathologist, Department of Pathology,
Unité de Neuropathologie Expérimentale, Lariboisière Hospital (ret.), APHP, Paris, France
Institut Pasteur, Paris, France
Brian Harding, MA, DPhil, BMBCh, FRCPath
Pedro de Sá Cavalcante Ciarlini, MD Professor of Pathology and Laboratory Medicine,
Auxiliary Professor of Pathology, Federal University University of Pennsylvania, Philadelphia, PA, USA
of Ceará, Sobral, CE, Brazil Neuropathologist, Children’s Hospital of
Pathologist/​Neuropathologist, Laboratório Philadelphia, Philadelphia, PA, USA
Clementino Fraga, Fortaleza, CE, Brazil
Jean-​Jacques Hauw, MD
Umberto De Girolami, MD Professor of Pathology (ret.), Pierre et Marie Curie
Professor of Pathology, Harvard Medical School, University, Paris, France
Boston, MA, USA Neuropathologist (ret.), Pitié-​Salpêtrière Hospital,
Neuropathologist, Brigham and Women’s Hospital, Paris, France
Boston, MA, USA Académie Nationale de Médecine, Paris, France
Charles Duyckaerts, MD, PhD James W. Ironside, MD
Professor of Pathology, University Pierre et Marie Professor of Clinical Neuropathology (ret.), School
Curie, Paris, France of Clinical Sciences, University of Edinburgh,
Director, Neuropathology Laboratory, Edinburgh, UK
Pitié/​Salpêtrière Hospital, Paris, France
Gregory Jouvion, PhD
Steven K. Feske, MD Unité de Neuropathologie Expérimentale, Institut
Associate Professor of Neurology, Harvard Medical Pasteur, Paris, France
School, Boston, MA, USA
Hans Lassmann, MD, PhD
Chief, Cerebrovascular Division, Department of
Professor of Neuroimmunology, Medical
Neurology, Brigham and Women’s Hospital,
University of Vienna, Vienna, Austria
Boston, MA, USA
Chairman, Department of Neuroimmunology,
Romain Gherardi, MD Center for Brain Research, Vienna, Austria
Professor of Histology, Paris-​Est University,
Edward R. Laws, Jr., MD, FACS
Créteil, France
Professor of Neurosurgery, Harvard Medical
Neuropathologist, Henri Mondor University
School, Boston, MA, USA
Hospital, Créteil, France
Neurosurgeon, Brigham and Women’s Hospital,
Hans H. Goebel, MD Boston, MA, USA
Professor of Neuropathology (ret.),
Hart G. Lidov, MD, PhD
Johannes Gutenberg University,
Associate Professor of Pathology, Harvard Medical
Mainz, Germany
School, Boston, MA, USA
Consultant Neuropathologist, Institute
Neuropathologist, Boston Children’s Hospital,
of Neuropathology, Charité, Berlin,
Boston, MA, USA
Germany
Keith L. Ligon, MD, PhD
Jeffrey A. Golden, MD
Associate Professor of Pathology, Harvard Medical
Ramzi S. Cotran Professor of Pathology, Harvard
School, Boston, MA, USA
Medical School, Boston, MA, USA
Neuropathologist, Dana-​Farber Cancer Institute/​
Chair of Pathology and Neuropathologist, Brigham
Brigham and Women’s Hospital, Boston,
and Women’s Hospital, Boston, MA, USA
MA, USA

xii • C ontributors
xi

David Meredith, MD, PhD Leroy R. Sharer, MD

Instructor of Pathology, Harvard Medical School, Professor of Pathology, Rutgers New Jersey
Boston, MA, USA Medical School, Newark,
Neuropathologist, Brigham and Women’s Hospital, NJ, USA
Boston, MA, USA Neuropathologist, University Hospital,
Newark, NJ, USA
Vânia Nosé, MD, PhD
Professor of Pathology, Harvard Medical School, Colin Smith, MD, FRCPath
Boston, MA, USA Professor of Neuropathology, University of
Associate Chief of Pathology for Anatomic and Edinburgh, Edinburgh, UK
Molecular Pathology, Massachusetts General Consultant Neuropathologist, Western General
Hospital, Boston, MA, USA Hospital, Edinburgh, UK
R. Ross Reichard, MD Jean-​Michel Vallat, MD
Associate Professor of Pathology, The Mayo Clinic Professor of Neurology, Faculté de
School of Medicine, Rochester, MN, USA Médecine, Limoges University,
Neuropathologist, Mayo Clinic, Rochester, Limoges, France
MN, USA Neurologist/​Neuropathologist, University
Hospital, Limoges, France
Sandro Santagata, MD, PhD
Assistant Professor of Pathology, Harvard Medical Kum Thong Wong, MBBS, MPath,
School, Boston, MA, USA FRCPath, MD
Neuropathologist, Brigham and Women’s Hospital, Professor, University of Malaya, Kuala Lumpur,
Boston, MA, USA Malaysia
Senior Consultant, University of Malaya
Danielle Seilhean, MD, PhD
Medical Centre, Kuala Lumpur, Malaysia
Professor of Pathology, University Pierre et Marie
Curie, Paris, France
Neuropathologist, Pitié/​Salpêtrière Hospital,
Paris, France

C ontributors • xiii
1

1
Basic Pathology of the Central
Nervous System
PE D RO D E SÁ CAVA LC A N T E C IA R L IN I, D A NIEL L E SEIL HEAN , UMBERTO DE GIROL AMI,
AN D F RA N ÇO I SE G R AY

AUTOPSY DIAGNOSIS in neuropathology co-​expression of multiple reactions to injury that may

is based on the macroscopic and microscopic study not necessarily be diagnostic in themselves. These
of the brain, brainstem, cerebellum, and spinal cord. reactions affect the cellular elements of the nervous
Increasingly, the ability to reach greater diagnostic pre- system (neurons, astrocytes, oligodendrocytes, and
cision is buttressed by the new laboratory techniques of microglia) and/or the supporting structures (me-
molecular biology and genetics. Three consecutive steps ninges, connective tissue, or blood vessels). Basic
are involved in reaching a diagnosis, and these are, in fact, cellular reactions are demonstrable on microscopic
closely interrelated: (1) a morphological/​ laboratory examination, whereas tissue lesions associated with
analysis of the lesions; (2) a topographical analysis of more extensive destructive or atrophic changes are
the lesions; and (3) a critical integration of these findings recognized to the naked eye or with the help of a
and their subsequent correlation with the clinical data magnifying lens.
and the general autopsy findings, thus permitting an eti- Although, for didactic purposes, the reactions to
ological diagnosis to be made in most instances. injury seen in the neurons, glia, connective tissue,
and vascular structures are described separately in
this chapter, we would emphasize that there is a close
1 . 1 M OR P HOL OGICAL functional interdependence of the various cellular
AN ALY S IS OF CE N T RAL elements of the nervous system. This is particularly
N ER V OUS SYST E M L E SION S important in the case of nerve cell alterations where,
except for very acute injury, the possibility of artifac-
A number of disorders of the central nervous system tual change should be entertained whenever the reac-
(CNS) are characterized morphologically by the tion is not accompanied by a glial cell response.

• 1
1 .1.1 Basi c c e l l u l a r
r e acti ons to C NS i n j u ry
1.1 . 1 . 1 . N E UR ON A L L ESI O NS
Neuronal injury may be sufficiently severe to result in
irreversible damage (cell death) or may be transient,
or minimal, and cause reversible functional damage.
Destruction of neurons may be focal or extend dif-
fusely, involving many populations of neurons
throughout the nervous system. In acute neuronal
injury, when the tissue is examined stained with he-
matoxylin and eosin (H&E) at a relatively short time
after a lethal insult to the cell (12–24 hours or some- FIGURE 1.1 Two neurons undergoing apoptosis
what longer), one observes eosinophilia of the cyto- are positively stained by in situ end labeling to demon-
plasm, shrinkage and hyperchromasia of the nucleus, strate internucleosomal DNA fragmentation. In one
and disappearance of the nucleolus; subsequent to neuron, on the left, only the nucleus is stained, whereas
the disintegration of the cell, neuronophagia by scav- in the other, which is at a later stage of the programmed
enger cells is evident at a later time interval (days cell death process, the entire cell body is stained.
later). In chronic diseases, evidence of cell death is Compared to a normal neuron, on the right, both ap-
recognized morphologically as neuronal “cell loss” optotic neurons have similar morphological features
or alternately (as “atrophy”) on macroscopic exam- and show a pyknotic nucleus and shrunken cytoplasm.
ination when the irreversible injury has occurred
relatively slowly (months or years) and has progres- amyotrophic lateral sclerosis). It is also seen in anter-
sively involved increasing numbers of cells. In some ograde and retrograde trans-​synaptic degeneration,
degenerative diseases of the nervous system where as may occur in the lateral geniculate body following
there is progressive loss or damage of neurons over a lesion of the optic nerve.
variable time periods, the affected cells have distinc- Programmed cell death (apoptosis) is an active,
tive morphologic hallmarks (e.g., neurofibrillary de- genetically controlled, energy-​consuming process
generation, neuronal storage of metabolic products, frequent in neurodegeneration and initially involves
disorders associated with intracellular inclusions). the nucleus of the cell. Neurons undergoing simple
Nerve cell loss (i.e., reduction in the number of neuronal atrophy or apoptosis have similar mor-
cell bodies in a particular brain region as compared phologic features and may show positive in situ end
to normal) when it involves less than 30% of the labeling of internucleosomal DNA fragmentation
normal cell population, may be difficult to ascertain (Fig. 1.1) or be demonstrable by activated caspase
in the absence of rigorous morphometric analysis. 3 immunostaining.
Furthermore, precise assessment depends on con- Nerve cell atrophy should not be mistaken with
sideration of the thickness of the section and on the what is referred to as “dark neurons.” This phenom-
normal cytoarchitectonics of the region examined. enon is now recognized to be an artifactual change
of the neuron cell body, seen particularly in brain
1.1.1.1.1. Nerve cell atrophy. Neuronal at- biopsies fixed in formalin by immersion, and is
rophy is the descriptive term that is given to a wide characterized by shrinkage of the neuronal cyto-
range of irreversible neuronal injuries that give rise plasm and a deeply stained, irregularly-shaped nu-
to a relatively slowly evolving death of the cell. cleus, without other cellular alterations.
Neuronal atrophy is characterized morphologically
by retraction of the cell body with diffuse basophilia 1.1.1.1.2. Acute neuronal necrosis (anoxic/​
of the cytoplasm and pyknosis and hyperchromasia ischemic neuronal change). Acute neuronal ne-
of the nucleus of the neuron, in the absence of an crosis (anoxic/​ischemic neuronal change) cell death
inflammatory reaction. Neuronal atrophy is thought occurs in not only a wide range of acute injuries, in-
to occur in many degenerative disorders that in- cluding anoxia and ischemia, but also many other
volve several interconnected neuronal systems (i.e., acute pathological processes (e.g., hypoglycemia
multiple-​system atrophy, Friedreich ataxia, and or exposure to excessive amounts of excitotoxic

2 • E scou r o l l e and P oi r ie r ’ s M anua l o f B asic N eu r opat h o l ogy

3

FIGURE 1.2 Acute ischemic nerve cell change FIGURE 1.3 Ferruginization (mineralization)
(H&E). Eosinophilic, shrunken cytoplasm and of the neurons at the edge of an old hemorrhagic
hyperchromatic nucleus. infarct (H&E).

neurotransmitters). Unlike apoptosis, the predom- axon (retrograde degeneration or axonal reaction).
inant cellular changes in acute neuronal necrosis Subsequent recovery of normal cell morphology or,
involve the cytoplasmic organelles and the cell conversely, further progression to nerve cell degen-
membrane, which ruptures, leading to cell death. eration depends on the reversibility of the axonal
In experimental animal studies and in carefully lesion (Fig. 1.5). Central chromatolysis may also be
studied human tissue at postmortem, the following seen in upper motor neurons, but the phenomenon
sequence of changes is noted by light and electron is rare and difficult to interpret correctly. Axonal
microscopy over the course of 12 to 24 hours after lesions of neurons whose axons do not leave the
the insult: (a) cytoplasmic microvacuolization due confines of the CNS apparently either do not pro-
to swelling of mitochondria and endoplasmic retic- duce changes in perikaryal cell-body morphology or
ulum; (b) shrinkage of the cell body with retraction result in a “simple” type of atrophy. Oddly enough,
of the cellular outlines and disappearance of Nissl some metabolic disorders that do not a priori affect
bodies with eosinophilic condensation of the cyto- axons (e.g., Wernicke’s encephalopathy, pellagra en-
plasm (“red neuron”); (c) condensation of nuclear cephalopathy, and porphyria) may be accompanied
chromatin and nuclear pyknosis (Fig. 1.2); (d) late by central chromatolysis in cortical neurons.
disappearance of the nuclear chromatin, resulting A confident diagnosis of central chromatolysis
in increased acidophilia of the nucleus, which requires comparison with the normal morphology
appears to merge into the surrounding cytoplasm
(karyorrhexis).
Occasionally, dead neurons, especially those
adjacent to old, mostly hemorrhagic, infarcts or to
traumatic scars, become encrusted with basophilic
mineral deposits, chiefly iron and calcium salts.
This condition is referred to as mineralization or
ferruginization of neurons (Fig. 1.3).

1.1.1.1.3. Central chromatolysis. Central

chromatolysis is characterized morphologically by
swelling of the cell body, disappearance of Nissl
bodies beginning centrally and extending outward,
and flattening and eccentric displacement of the nu-
cleus to the periphery (Fig. 1.4). It is seen usually in FIGURE 1.4 Central chromatolysis (Nissl stain).
lower motor neurons (anterior horns of the spinal Note the cellular swelling, the eccentric displace-
cord, cranial nerve nuclei), where it represents a re- ment of the nucleus, and the margination of the Nissl
parative reaction of the cell body to a lesion of the bodies.

Chapter 1 Basic Pathology of the Central Nervous System • 3

 Complete
central
chromatolysis
Normal
neuron

Recovery

Cell death
FIGURE 1.7 Fenestrated neuron in a case of olivary
Stages of hypertrophy (Nissl stain).
hyperchromasia
FIGURE 1.5 Nerve cell changes resulting from cen-
tral chromatolysis. 1.1.1.1.5. Binucleated neurons. Binucleated
neurons are seen rather infrequently, sometimes
under normal circumstances, or otherwise at the
of the affected gray matter structure, because the edge of old focal destructive lesions, as a dysplastic/​
nerve cell body in some nuclei (e.g., the mesence- malformation phenomenon (e.g., tuberous sclerosis),
phalic nucleus of the fifth cranial nerve, Clarke’s or in certain neoplasms (e.g., ganglion cell tumors).
column) normally contains rounded neurons with
marginated Nissl bodies. 1.1.1.1.6. Neuronal storage. In some heredi-
tary metabolic diseases related to enzymatic defects
1.1.1.1.4. Vacuolated neurons and neu­ involving synthetic or degradative pathways for
ropil. Vacuolated neurons and/or vacuolated neu- lipids or carbohydrates, interruption of the pathway
ropil is observed typically in Creutzfeldt-Jakob leads to cytoplasmic accumulation of interme-
disease (Fig. 1.6). In rare instances, swelling with diate substrates or their by-​products, resulting in
vacuolization of the nerve cell may result from swelling and distention of the cell body of nerve
transsynaptic degeneration, such as occurs in the cells, with eccentric displacement of the nucleus
neurons of the inferior olive in olivary hypertrophy (Fig. 1.8). In several neuronal storage disorders, the
secondary to a lesion of the ipsilateral central teg- stored material has distinctive histochemical and
mental tract or of the contralateral dentate nucleus; ultrastructural features that may help characterize
this phenomenon is also designated “fenestrated
neurons” (Fig. 1.7).

FIGURE 1.8 Distended nerve cell bodies in a case

FIGURE 1.6 Vacuolated neuron in a case of of neurolipidosis (combined Luxol fast blue and
Creutzfeldt–​Jakob disease (H&E). Bodian silver impregnation).

4 • E scou r o l l e and P oi r ie r ’ s M anua l o f B asic N eu r opat h o l ogy

5

NFTs are typically seen in small cortical neurons

(Fig. 1.10D). Large globose NFTs reminiscent of a
ball of string are more common in the nucleus basalis
of Meynert and in the brainstem (Fig. 1.10E). In the
final stages of the disease, the cell outline disappears
and only the distorted fibrils remain as “ghost NFT”
(Fig. 1.10F).
The predominant biochemical component of
NFTs is the microtubule-​associated protein tau, which
accumulates in an abnormally highly phosphorylated
form. Tangles are particularly well demonstrated by
tau immunocytochemistry, which is now used rou-
tinely in diagnostic work. NFTs may on occasion also
FIGURE 1.9 Lipofuscin in neuronal cell be immunoreactive for ubiquitin and p62. By elec-
body (H&E). tron microscopy, most NFTs consist of paired helical
filaments measuring around 20 nm across with a reg-
clinically suspected cases of a given storage disease. ular constriction to 10 nm occurring every 80 nm. In
Biochemical tests on blood, leukocytes, and other Alzheimer disease, they may also be associated with
body fluids are now particularly useful to more pre- straight filaments. In progressive supranuclear palsy
cisely diagnose many of these disorders. (PSP), tangles have been found to consist mainly of
Lipofuscin accumulation within the perikaryon of straight filaments measuring 15 nm in diameter.
neurons and other cells in the nervous system is a Granulovacuolar degeneration is a neuronal alter-
characteristic aging change. Lipofuscin accumulates ation found in pyramidal cells of Ammon’s horn; it
in neurons diffusely throughout the brain in is seen in normal aging as well as in Alzheimer di-
ceroid lipofuscinosis, a neuronal storage disorder. sease and Pick disease. The abnormality consists of
Lipofuscin is identified on H&E preparations as an accumulation of small, clear vacuoles measuring
refractile yellow-​ brown pigment aggregates (Fig. 4 to 5 μm in diameter and containing an argyrophilic
1.9). It is autofluorescent and rich in acid phospha- granule that is well stained by hematoxylin (Fig.
tase. The pigment is periodic acid–​Schiff (PAS)- 1.11). Some of the granules are immunoreactive
positive and can be stained by Luxol fast blue. It has for phosphorylated neurofilament, tubulin, tau,
distinctive ultrastructural features (see Chapter 10). and ubiquitin, suggesting that the vacuoles are
autophagic lysosomal structures in which cytoskel-
1.1.1.1.7. Alzheimer neurofibrillary degenera­ etal components are being degraded.
tion and granulovacuolar degeneration. Alzheimer
neurofibrillary degeneration is characteristically seen 1.1.1.1.8. Intraneuronal inclusion bodies.
in the brains of aged individuals and in patients with Intracytoplasmic or intranuclear inclusion bodies
senile dementia of the Alzheimer type, but it has also are important indicators of neuronal injury. They
been described in a variety of other cerebral disorders. occur in degenerative, metabolic, and viral diseases
This degenerative change is manifest by the forma- and often have diagnostic immunocytochemical
tion of neurofibrillary tangles (NFTs), structures and ultrastructural features.
that are well demonstrated by silver impregnation Pick bodies are round homogeneous intracyto­
and by immunohistochemical techniques; they plasmic neuronal inclusions (Fig. 1.12) charac-
consist of thickened and tortuous skeins within the teristic of Pick disease, where they may be seen in
neuronal perinuclear cytoplasm. The configuration pyramidal neurons and dentate granule cells of the
of the tangle may vary according to the anatomic hippocampus, as well as in affected regions of the ne-
site, the type of neuron affected, and the stage of ocortex. The structure is intensely argyrophilic and
formation (Fig. 1.10). A band-​ shaped perikaryal immunoreactive for tau and the 3R-tau isoform. Pick
NFT can be seen in both large and small pyramidal bodies are also reactive for ubiquitin and tubulin. The
cells and is perhaps an early stage of NFT develop- ultrastructure of the body is characterized by poorly
ment (Fig. 1.10A). A triangular flame-​shaped per- circumscribed masses of intermediate filaments,
ikaryal NFT is seen mainly in large pyramidal cells 15-​nm straight filaments, and some paired helical
(Fig. 1.10B, C). Small compact globose perikaryal filaments, as well as entrapped vesicular structures.

Chapter 1 Basic Pathology of the Central Nervous System • 5

 A B

C D

E F

FIGURE 1.10 Different types of neurofibrillary tangles (Bodian silver impregnation combined with Luxol fast
blue): band-​shaped perikaryal NFT (A); triangular flame-​shaped perikaryal NFT (B, C); small, compact, glo-
bose perikaryal NFT (D); large globose NFT (E); “ghost NFT” (F).

Lewy bodies are neuronal cytoplasmic inclusions; single neuron (Fig. 1.13A, B). They may also be
their appearance varies according to whether they oval or elongated structures, especially when they
are found in the perikaryon or in the nerve cell occur in axonal processes or in sympathetic gan-
processes, cortex, brainstem, or sympathetic gan- glia (Fig. 1.13C, D). Cortical Lewy bodies are less
glia (Fig. 1.13). Typical (brainstem) Lewy bodies clearly outlined and consist of a homogeneous zone
are roughly spherical with an eosinophilic core of hypereosinophilia that usually lacks the char-
surrounded by a paler “halo.” One or more of these acteristic surrounding halo (Fig. 1.13E, F). Lewy
structures may be present in the cytoplasm of a bodies are immunoreactive for α synuclein as well as

6 • E scou r o l l e and P oi r ie r ’ s M anua l o f B asic N eu r opat h o l ogy

7

sclerosis (Fig. 1.15A, B). They are immunoreactive

for cystatin C. Ultrastructurally, they appear as
electron-​dense, membrane-​bound bodies.
Skein –​like inclusions are abnormal ubiquitinated,
p-​62 positive, structures occurring in anterior horn
cells in motor neuron diseases. They are linear,
thread-​like structures; in some instances, they occur
as a single inclusion, and in others, form networks of
threads. Occasionally, the threads are aggregated to
form larger and dense inclusions (Fig. 1.16). They
contain TDP-​43, ordinarily a nuclear protein, and
accumulate within the cytoplasm of motor neurons
in amyotrophic lateral sclerosis. Ultrastructurally,
FIGURE 1.11 Granulovacuolar degeneration they consist of bundles of filaments 15–​25 nm in di-
(Bodian silver impregnation). ameter, with a tubular profile on cross section.
Marinesco bodies are small eosinophilic
for ubiquitin and αB crystallin. By electron micros- intranuclear inclusions located chiefly in melanin-​
copy, they consist in an amorphous electron-​dense containing brainstem neurons (Fig. 1.17A). They
core surrounded by a halo of radiating filaments. are strongly ubiquitin positive.
Their presence defines several conditions termed When ubiquitinated, intranuclear inclusions
Lewy body disorders; the most common disorder in may occur in other regions of the brain and sug-
this group is Parkinson disease. gest other disorders. Small, round eosinophilic
Hirano bodies are brightly eosinophilic rod-​shaped inclusions (about the same size of the nucleolus),
or elliptical cytoplasmic inclusions that appear to immunoreactive for IC2 antipolyglutamine expan-
overlap the cell border of a neuron cell body (Fig. sion antibody, are found in neurons of CAG re-
1.14). They are mostly found in the CA1 field of peat diseases (including spinal cerebellar ataxias,
the hippocampus and are particularly numerous in Huntington disease, or dentatorubral-​pallidoluysian
Alzheimer disease and Pick disease and in patients with atrophy) (Fig. 1.17B). Larger eosinophilic,
the Guam parkinsonism–​ dementia complex. They ubiquitinated, inclusions are found in CGG repeats
are immunoreactive for actin and actin-​ associated (X fragile) and neuronal intranuclear inclusion disease
proteins. Ultrastructurally, they are highly character- (NIID). Similar large intranuclear inclusions are
istic and consist of parallel filaments 60–​100 nm in found in intranuclear inclusion body disease (INIBD).
length that alternate with a longer sheet-​like material. Lafora bodies are rounded structures composed of
Bunina bodies are eosinophilic, nonviral polyglucosan (polymers of sulfated polysaccharides)
intracytoplasmic inclusions found in motor neurons and are similar to corpora amylacea (see discussion
in cases of familial or sporadic amyotrophic lateral further in the chapter) in composition and staining
characteristics. They are found in large numbers
in myoclonic epilepsy both in the CNS (chiefly in
the dentate nucleus) and in certain tissues outside
the CNS, such as sweat glands, liver, and skeletal
muscle. They usually have a dense, intensely PAS-​
positive core surrounded by filamentous, fainter
PAS-​positive structures (Fig. 1.18).
Viral inclusions are eosinophilic intranuclear
inclusions that occupy a greater or a lesser pro-
portion of the nucleus and may be surrounded by
a clear halo; they are associated with some viral
infections of the CNS (cf. Chapter 5). They are
seen in herpes virus infections, particularly in
necrotizing encephalitis caused by herpes sim-
FIGURE 1.12 Neuronal argyrophilic inclusion in plex virus (Fig. 5.37C), and in subacute sclerosing
Pick disease (Bodian silver impregnation). panencephalitis (Fig. 5.31A). In rabies, the viral

Chapter 1 Basic Pathology of the Central Nervous System • 7

 A B

C D

E F

FIGURE 1.13 Lewy bodies (H&E). Single (A) and multiple (B) Lewy body(ies) in the perikaryon of
pigmented neurons of the substantia nigra in a case of Parkinson disease. Lewy bodies in axonal processes (C,
D), in the dorsal nucleus of cranial nerve X in a case of Parkinson s disease. Cortical Lewy bodies (E, F) in the
perikaryon of cortical neurons in a case of Lewy body disease.

inclusions are intracytoplasmic and are referred to be used to identify virions; however, it is now used
as Negri bodies (Fig. 5.30). In rare instances (e.g., less often in diagnostic work.
cytomegalovirus infection; (Fig. 5.38)), both
intranuclear and intracytoplasmic inclusions may 1.1.1.1.9. Axonal alterations. Following ax-
be seen. Viral inclusion bodies are immunoreactive onal lesions that disrupt the integrity and con-
with appropriate antivirus antibodies, allowing for tinuity of the cell process, the distal part of the
a specific diagnosis. Electron microscopy may also axon undergoes Wallerian degeneration, which

8 • E scou r o l l e and P oi r ie r ’ s M anua l o f B asic N eu r opat h o l ogy

9

FIGURE 1.14 Hirano bodies are brightly eo-

sinophilic and can be rod shaped, as illustrated, or FIGURE 1.16 Skein-​like inclusion in an anterior
elliptical (H&E). horn cell in a case of motor neuron disease (immuno-
cytochemistry for ubiquitin).
is described further, elsewhere in this book (see
basic lesions of the peripheral nervous system;
Chapter 13). the transport system is interrupted. Spheroid forma-
In conditions associated with nerve cell “at- tion characterizes axonal damage by diverse extrinsic
rophy” as described previously, the destruction of insults and occurs in trauma and ischemia. Spheroids
the cell body of the neuron results in degeneration are well demonstrated by either silver impregna-
of all of its processes, including the dendrites and tion (Fig. 1.19A) or immunostaining with ubi-
the axon, which becomes swollen, then fragmented, quitin (Fig. 1.19B), neurofilaments, and precursor
eventually undergoing atrophy. This phenomenon, of the beta amyloid protein (β-​APP) (Fig. 1.19C).
if widespread, as occurs in system degenerations, The latter is transported by the axonal flow and
results in thinning out and rarefaction of the white accumulates when it is disrupted. The term torpedo is
matter, demonstrable with myelin and axon stains. applied to Purkinje cell axonal swellings and occurs
In these diseases, the phenomenon seems to start at in a wide range of metabolic and degenerative cere-
the most distal portions of the longest axons. bellar diseases. They are well demonstrated by silver
Axonal swellings or spheroids are localized eo- impregnations and by the immunohistochemical
sinophilic enlargements of the axon. At these methods mentioned. They are most notable in the
sites along the axon, there is condensation of the initial portion of the axon, before the origin of the
neurofilaments, organelles, and other molecules that collateral branches (Fig. 1.19C).
are normally conveyed along the axon by an antero- The axonal swellings that develop when ax-
grade transport system but accumulate focally when onal transport is disrupted by neuronal metabolic

A B

FIGURE 1.15 Bunina bodies in anterior horn cells of the spinal cord in a case of motor neuron disease (H&E)
(A); immunocytochemistry for cystatin C (B).

Chapter 1 Basic Pathology of the Central Nervous System • 9

 A B

FIGURE 1.17 Intranuclear inclusions: (A) Marinesco bodies: small intranuclear inclusion in a pigmented
neuron of the substantia nigra (H&E); (B) ubiquitin-​positive intranuclear inclusion in a case of spinocerebellar
degeneration with CAG repeat expansion. (Courtesy of Professor Francesco Scaravilli.)

dysfunction are usually termed dystrophic. This reactive process accompanies almost any type of
occurs in some acquired (e.g., vitamin E deficiency) subacute or chronic injury of the CNS. The process
or inherited metabolic diseases. Extensive forma- of gliosis is in essence the response of astrocytes to
tion of axonal swellings is an important patholog- CNS tissue injury. The associated morphological
ical manifestation of neuroaxonal dystrophy and of changes include an increase in the number of as-
some leukodystrophies. trocyte nuclei per unit area, eosinophilia of the cy-
The term dystrophic neurite is used to describe toplasm around the nucleus, and expansion and
a neuronal process within the gray matter that distortion of the astrocytic cytoplasmic arboriza-
is distended by tau protein or other abnormal tion. For reasons that are not understood, mitotic
ubiquitinated material. These occur in several neu- figures are only rarely identified in gliotic tissue, and
rodegenerative diseases. techniques that bring out dividing cells (Mib-​1/​Ki
67) also confirm the slow turnover.
1.1 . 1 . 2 . AS T R OC YTI C L ESI O NS The morphologic aspects of the process of gliosis
will vary depending on the location, stage of evo-
1.1.1.2.1. Gliosis (astrogliosis). The presence lution, and nature of the pathological process. The
of gliosis (alternate term astrogliosis) is the most cer- early stages are characterized by hypertrophy of the
tain indication that a microscopic abnormality is nucleus, which is often hyperchromatic and eccen-
of pathologic significance and not artifactual. This trically placed in the perikaryon. As mentioned, the
cytoplasm around the nucleus and cell processes
become more extensive than normal and are found
to contain glycogen (Fig. 1.20A). Characteristically,
at this stage, in H&E preparations, the cytoplasm
is homogenized and eosinophilic; these reactive
astrocytes are referred to as gemistocytic astrocytes
(Fig. 1.20B, C).
Over time, in chronic disease states and slowly
evolving degenerative processes, astrocyte nuclei re-
turn to their resting size and shape, though their cy-
toplasmic network of cell processes is more extensive
and can best be appreciated with immunostaining
for glial fibrillary acidic protein (GFAP).
An older term, isomorphorphic fibrillary gliosis,
FIGURE 1.18 Lafora body in a case of myoclonic refers to the alignment of reactive astrocyte
epilepsy (periodic acid–​Schiff). processes conforming to a degenerating fiber tract.

10 • E scou r o l l e and P oi r ie r ’ s M anua l o f B asic N eu r opat h o l ogy

1

A B

FIGURE 1.19 Axonal swellings in the white matter identified on silver impregnation (A) (Bodian stain)
and on ubiquitin immunostain (B). Torpedo (axonal swelling) on a Purkinje cell axon identified by β-​APP
immunostaining (C).

1.1.1.2.2. Alzheimer type II glia. Alzheimer ultrastructural study, they are shown to contain nu-
type II glia is seen particularly in hyperammonemic merous mitochondria.
states such as occur in Wilson disease and in liver
failure from acquired or hereditary metabolic disease, 1.1.1.2.3. Rosenthal fibers. By light micros-
but can also be found in a variety of other systemic copy, Rosenthal fibers are rounded, oval, or elon-
metabolic disorders (e.g., renal failure). This reac- gated beaded structures measuring 10 to 40 μm
tion of astrocytes is characterized by enlargement of that appear homogeneous and brightly eosinophilic
the nucleus, reaching 15 to 20 μm in diameter, which (Fig. 2.4B). On electron microscopy, they con-
appears irregular in shape and pale and empty looking sist of swollen astrocytic processes that are filled
because of the disappearance of chromatin granules with electron-​dense amorphous granular material
(Fig. 1.21). One or two dense, rounded PAS-​positive and glial filaments. With immunohistochemical
bodies resembling nucleoli are often seen next to the method peripheral labeling for GFAP, ubiquitin
nuclear membrane, which is always sharply defined. and αB-​crystallin can be demonstrated. Rosenthal
The cell body is not usually visible on conventional fibers are seen in various pathological conditions
preparations and stains poorly with GFAP. Alzheimer that have in common intense fibrillary gliosis of
II glia are unrelated to Alzheimer disease; they tend to long standing, as seen throughout the brain in
occur in the gray matter, involving particularly deep multiple sclerosis plaques, in the spinal cord in
gray nuclei, especially the pallidum and the dentate syringomyelia, and in the hypothalamus around
nuclei, and also the cerebral cortex. Alzheimer type craniopharyngiomas. They are also characteristic of
II glia are metabolically active cells engaged in the certain neoplasms (pilocytic astrocytoma, partic-
catabolism of toxic substances such as ammonia; on ularly of the cerebellum, but also elsewhere in the

Chapter 1 Basic Pathology of the Central Nervous System • 11

 A B

FIGURE 1.20 Gliosis. Fibrillary gliosis (A) hypertrophy of nucleus and of cytoplasm and processes that
are very visible on GFAP stain. Gemistocytic astrocytes with large homogenized and eosinophilic cytoplasm
(H&E) (B), (GFAP) (C).

brain) (cf. Chapter 2), and in Alexander disease (cf. 1.1.1.2.4. Inclusions and storage mate­
Chapter 10). rial. Accumulation of lipofuscin occurs in astrocytes
Eosinophilic granular bodies are rounded hya- as part of aging as it does in neurons. Similarly, in
line droplet aggregates that occupy the cytoplasm lipid storage diseases, glial lipid storage may accom-
of astrocytes and are particularly seen in tumors, pany neuronal storage.
including pilocytic astrocytoma, pleomorphic Tau protein, which is the main component of
xanthoastrocytoma, and ganglion cell tumors. NFTs, can also accumulate in astrocytes, particularly
in PSP and corticobasal degeneration (cf. Chapter 8).
Tufted astrocytes are considered to be highly char-
acteristic of PSP (Fig. 8.20A). The whole length
of their processes contains tau protein, and they
are often binucleated. They may be demonstrated
by Gallyas stain or tau immunocytochemistry. In
corticobasal degeneration, accumulation of tau pro-
tein in astroglia forms distinctive structures in gray
matter areas termed astrocytic plaques: Tau protein
accumulates at the end of the astrocytic processes,
while the center of the plaque is devoid of tau
immunoreactivity (Fig. 8.23).
Thorn-​shaped astrocytes and have an argyrophilic
FIGURE 1.21 Alzheimer type II glial cells (H&E). cytoplasm with a few short processes (Fig. 8.20B)

12 • E scou r o l l e and P oi r ie r ’ s M anua l o f B asic N eu r opat h o l ogy

13

immunoreactive for ubiquitin, αB crystallin, and α

synuclein.
Accumulation of tau protein in oligodendrocytes,
known as “coiled body,” may be found in PSP,
corticobasal degeneration and argyrophilic grain
disease (cf. Chapter 8). These consist of fibrillary
structures “coiling” around the nucleus.
Similar coiled bodies, but tau negative and p62
and TDP-​43 positive, are seen in the brain and
spinal cord in TDP-​43–​related frontotemporal de-
generation and amyotrophic lateral sclerosis.
FIGURE 1.22 Numerous corpora amylacea in the
subependymal region (H&E).
1. 1. 1. 4. MIC R OGLIAL LES IONS
Microglial cells are of monocyte lineage and
and often a small excentric nucleus. They are com-
have important phagocytic functions. They can
monly associated with granular-​fuzzy astrocytes and
be demonstrated by silver impregnation, lectin-​
seen in aging-​related tau astrogliopathy (ARTAG).
binding techniques, and immunohistochemical
Viral inclusion bodies may also be found
techniques using antibodies that react with mono-
in astrocytes, such as in subacute sclerosing
cyte/​macrophages (e.g., CD68, CD163, IBA-​1, and
panencephalitis and CMV infection (cf. Chapter 5).
Tmem119) (Fig. 1.23B).
Corpora amylacea are spherical, basophilic, PAS-​
In normal brain, microglia have been subdivided
positive inclusions, 10 to 50 μm in diameter, that
into (a) resident microglia, with little turnover and
are predominantly found in astrocyte processes,
present throughout the CNS parenchyma, and
although they occasionally occur within axons.
(b) perivascular microglia, found within the perivas-
Ultrastructurally, they consist of densely packed 6-​
cular basal lamina and with characteristic turnover
to 7-​nm filaments that may be admixed with amor-
as with hematogenous monocytes. Microglial ac-
phous granular material and are not membrane
tivation occurs in inflammatory conditions of the
bound. Corpora amylacea increase in number with
CNS and involves (a) increased entry of hematoge-
aging, particularly in the subpial and subependymal
nous monocytes into the CNS; (b) proliferation of
regions (Fig. 1.22), around small blood vessels,
resident microglia; (c) expression or secretion of a
and in the posterior columns of the spinal cord.
wide range of proteins, most of which are concerned
Adult polyglucosan body disease (cf. Chapter 10)
with antigen presentation and inflammation.
is characterized by diffuse accumulation of corpora
Microglia reactive processes are typically
amylacea, involving the cortex and white matter and
associated with diffuse or focal myelin damage.
• Macrophage proliferation and phagocytosis (the
cells are also known as compound granular
1. 1 . 1 . 3 . L E S IONS O F
corpuscles, foam cells, lipid phagocytes, or
OL IGODE N DR OC YTES
gitter cells). This is a frequent finding in many
Like neurons and astrocytes, oligodendrocytes may brain lesions, particularly those associated with
be infected by virus and manifest intranuclear or demyelinating processes or with traumatic or
intracytoplasmic inclusions (e.g., progressive mul- ischemic tissue destruction. After a destructive
tifocal leukoencephalopathy) (cf. Chapter 5) or be or demyelinating insult, macrophages invade
affected by excess storage of lipid or glycogen in the damaged region within 48 hours of injury.
genetically determined enzymopathies (e.g., meta- These are rounded cells with distinct cytoplasmic
chromatic leukodystrophy). borders and measure 20 to 30 μm in diameter.
Cytoplasmic inclusions involving mainly They have small, darkly staining, and sometimes
oligodendrocytes have been shown to be a char- eccentric nuclei and a clear, granular cytoplasm
acteristic feature of certain degenerative diseases that can contain lipids, hemosiderin pigment, or
including multiple system atrophy (cf. Chapter 8). any other phagocytized material (Fig. 1.23A, B).
These inclusions are usually flame or sickle shaped, The number of these scavenger cells increases
can be demonstrated by silver impregnation, and are over a period of days and weeks and may be still

Chapter 1 Basic Pathology of the Central Nervous System • 13

 A B

FIGURE 1.23 Perivascular lipid-​laden macrophages (compound granular corpuscles, foam cells, or gitter
cells) in a demyelinating lesion (Luxol fast blue combined with Bodian silver impregnation) (A) and with CD68
immunostaining) (B).

be present in injured tissue months after the 1. 1. 1. 5. EP ENDY MAL C ELLS

injury. Most derive from blood monocytes.
Ependyma have a limited range of reactions to in-
•​ Rod cell proliferation (Figs. 1.24 and 5.27)
jury. Along with neurons and other glial cells, epen-
is a form of microglial response to subacute
dymal cells may be infected in viral diseases. In the
parenchymal injury in which necrosis is
adult CNS, ependymal cells do not proliferate in
minimal or absent. Rod cells are elongated,
response to injury and cell loss. Their destruction
spindle-​shaped cells that can be recognized
leaves bare stretches of the ventricular lining; this
on hematoxylin and eosin preparations by the
is accompanied by proliferation of subependymal
presence of a cigar-​shaped nucleus. The best
astrocytes, which form small hillocks along the ven-
descriptions of this glial change are found in
tricular surface: ependymal granulations. Occasionally,
reports of cases of general paresis in the older
surviving ependymal cells may be overgrown by the
literature (cf. Chapter 5). Rod cells are also seen
astrocytic reaction and appear as clusters of tubules
in cases of subacute encephalitis and evolving
buried within the ependymal granulations.
ischemic lesions.
•​ Microglial nodules consist of discrete clusters
of microglial cells that are typically found in 1 .1 .2 . G e n e r a l t is s u e
subacute encephalitis in and around sites of
neuronal destruction: neuronophage nodules (cf. r e a c t io n s o f t h e C N S
Chapter 5). t o in ju r y a n d h e r n ia t io n s
A set of general tissue reactions is known to occur in
the CNS that stand apart from the reactions to spe-
cific pathological processes (i.e., vascular, infectious,
inflammatory, demyelinating, metabolic, degener-
ative). As described in other chapters of this book,
these may accompany one or more of the specific
pathologic processes described previously that are
visible under the microscope or may result in more
extensive changes that can be visible to the naked eye.

1. 1. 2. 1. C ER EBR AL ATR OP HY
Cerebral atrophy is the end stage of a number of
neurological diseases. The brain is lighter than a
FIGURE 1.24 Rod-​shaped microglia in a case of normal age-​matched control. Macroscopically, there
general paresis of the insane (Nissl stain). is narrowing of the gyri and widening of sulci. On

14 • E scou r o l l e and P oi r ie r ’ s M anua l o f B asic N eu r opat h o l ogy

 Another Random Document on
Scribd Without Any Related Topics
 language, 338.

Games, of Lenapé, 186.

Generation, gods of, 120.
Georgia, antiquities in, 80.
Ghosts, superstitions about, 127.
Giant bison, the American, 41, note.
Giant Grab, 176;
Stone of the, 274 sq.
Glacial age in North America, date of, 41, 44, 54;
in South America, 42, 55.
Gluskap the Liar, a Micmac hero, 130.
Grammatic forms, origin of, 331.
Grammatical categories, the, 405.
Graphic systems, phonetic elements of, 195 sq.
Graphic system of Mayas, 245.
Greek language, the, 344, 348.
Green, as a color symbol, 118.
Greenland, poetry from, 287–290.
Grijalva, Juan de, his expedition, 232.
Guadalajara, University of, 326.
Guarani, language, 35, 380 sq., 398, 399, 400;
love words in, 428.
Guarayos, bearded Indians, 39, note.
Guatemala, dialects in, 104;
tribes of, 105, 420.
Gucumatz, derivation of, 116;
 transformations of, 171.
Gucumatz Cotuha, a king, 114.
Guiana, shell-heaps in, 31;
ethnology of, 39, 40.
Gulf States, antiquities of, 72–80.

Hades, derivation of, 141;

descent to, 125–6.
Hair, of American Indians, 62;
of the Sun-god, 99, 140, 146;
long, as symbol, 146, 280.
Hare, the Great, 132.
Harmachis, Egyptian divinity, 138.
Hatchet, burying the, 71.
Haiti, mythology of, 116, 121.
“Heart of the Lake,” a sacred name, 116.
Heart, as a symbol, 117.
Hell, words for, 126, 127;
descent to, 123–130.
Hemenway Exploring Expedition, 25.
Heraldry, methods of, 218, 219.
Hermapolis, eight gods of, 140.
Hesperides, garden of the, 142.
Hidatsa language, 407.
Hieroglyphs, Maya, 201, 265–7.
Hog, the, as a god, 113.
Holophrasis, explained, 322, 354 sq.
Homo alalus, the, 390–392.
Homophones in languages, 198, 215, 216.
Hooks, used in fishing, 184.
Horus, the Egyptian, 138.
Horse, Delaware word for, 321;
fossil, in America, 31, 32, 42.
Houses, of beams, 97;
communal, 185.
Huasteca language, the, 221, 331, 343;
love words in, 422.
Hueman, an Aztec hero-god, 96.
Huguenots, settlement of, 74.
Huitzilopochtli, an Aztec god, 85, 88;
derivation of, 95;
birth of, 96;
temple of, 25.
Huitznahua, Aztec divinities, 94, 95.
Human species, divisions of, 38.
Humor, among native Americans, 288.
Hun-ahpu, birth of, 125.
Hun-ahpu-utiu, derivation, 112.
Hun-ahpu-vuch, derivation of, 109.
Hun-came, a Quiche god, 124.
Hunhun-ahpu, a Quiche god, 124.
Hunting, ancient methods of, 184.
Hunyecil, meaning of, 237.
Hurakan, god of the storm, 120–123.
Hurons, burial customs, 69.
Hurricane, derivation of, 121, 122;
lord of, 167.

Ichcanziho, ancient name of Merida, 233.

Ideograms in phonetic writing, 197;
of Mayas, 248.
Idols of Lenâpé, 187;
of Itzas, 240;
priest of, 248.
Idols, superstitions concerning, 177.
Ikonographic writing, 213.
Ikonomatic method of phonetic writing, 86, 89, 207, 211, 213–229,
281.
Illinois, archæology of, 40, 81.
Implements, simple and compound, 30, 51, 52.
Inca bone, the, 62.
Incas of Peru, false lists of, 23.
Incorporative character of American languages, 36.
Incorporation, explained, 321, 340, 341, 352–357, 403.
Indo-Aryans, myths of, 146.
Industrial art in ancient America, 29.
Ioskeha, Iroquois hero-god, 130.
Iron, Age of, 49, 50.
Iroquois, 24, 68, 69;
Lenâpé name for, 184.
Itza, town in Yucatan, 302.
Ytzamal, temples of, 236.
Itzamna, hero-god of Mayas, 238.
Itzas, the tribe of, 239.
Itzmiquilpan, hieroglyph of, 223.

Jaguar, as sacred animal, 128.

Japanese writing, 231.
Jesuits, settlement near Savannah, 76.
Jew, Book of the, 273.
Jonaz language, the, 368.

Katun, lord of the, 249;

of Mayas, 260.
Katuns, of Mayas, 159.
Káua, Book of Chilan Balam of, 268.
Kentucky, archæology of, 82.
Khetsua language, see Qquichua.
Kiches, see Quiches.
Kichigouai, Algonkin divinities, 111.
Kin Ich, a Maya deity, 170.
Kinich-ahau, hero-god of Mayas, 238.
Kioways, songs of, 293.
Klamath language, the, 321, 398.
Koonak, Mt., poem about, 290.
Kitchen-middens, in America, 27.
Labrador, natives of, 311.
Lacandon, province of, 239.
Lagoa Santa, skulls from, 40.
La Naulette, jaw from, 390.
Language, ethnologic value of, 193;
origin of, 390.
Languages discussed: See tribal names.
Laws of Thought, 402.
Lead, known to Mexicans, 450.
Leif Erikson, his voyage, 22.
Left hand, as stronger, 95.
Legends, value in savage tribes, 24.
Lenâpé, Folk-lore of the, 181;
derivation of, 183.
Lenâpé dialect, pronunciation of, 189;
grammar of, 190, 191, 313.
Letters, single, significant, 394.
Life, the Tree of, 161.
Light, the mother of, 119;
divinity of, 112, 129.
Lightning, as a deity, 121, 133, 174.
Lingoa Geral, of Brazil, 380.
Limonite skeletons from Florida, 41.
Lineal measures, American, 433 sq.
Linguistic stocks, number of in America, 34;
origin of, 392.
Lithuanian dialect, the, 316.
Lorelei, an American, 178.
Love, songs of, 293–7;
conceptions of in American languages, 410 sq.;
definition of, 432.
Lule language, the, 331, 342.

Mbaya language, the, 331, 342, 343.

Mackenzie River, tribes of, 35.
Madrid, Maya MSS. at, 253.
Maguey, the, a sacred plant, 88;
paper, 253.
Maize, origin and extension of, 33.
Malayan race, the, 349.
Malinalxochitl, an Aztec goddess, 88.
Mammoth, remains of, 32.
Manabozho, a Chipeway hero, 131, 133.
Man, not developed in America, 43;
oldest remains of, in America, 53;
a singing animal, 284;
subdivisions of, 348.
Manco Capac, his date, 22.
Mandioca, a native food-plant, 33.
Manhattan, derivation of, 183.
Mani, the Book of Chilan of, 264.
Manuscripts in Maya characters, 250.
Mapachtepec, hieroglyph of, 222.
Maps of Mayas, 438.
Markets, Mexican, 449.
Marriage song, 460.
Masks, used in rites, 114, 187.
Mass, the field, 165.
Maya language, the, 181, 345;
love words in, 420;
civilization, 84;
witch story, 171;
year-counts, 159;
phonetic characters, 199,
hieroglyphic system, 227, 228;
Mayas, ancient, writings and records of, 230–254;
earliest ancestors of, 24;
the, traditions of, 22;
conversion of, 164;
folk-lore of, 162;
burial customs of, 119;
lineal measures of, 434;
maps of, 438.
Mayacimil, meaning of, 237.
Mayapan, ancient city of, 239.
Maya-Quiche linguistic stock, 104.
Mazahua language, the, 368, 372 sq.
Meco language, the, 368.
Meconetzin, a name of Quetzalcoatl, 88.
Meday magic, figures in, 157.
Meda sticks of Chipeways, 228.
Medical practice among Delawares, 187.
Medicines of the Mayas, 272.
Medicine-songs, native, 292.
Mengwe, name of Iroquois, meaning of, 184.
Merida, ancient ruins at, 26, 233.
Messier Mound, the, 80.
Messianic hope, among natives, 183.
Messou, see Michabo.
Meta river, tribes of, 329.
Metrical standards, native, 446–8.
Mexcalla, an island, 88.
Mexi or Mexica, 85, 87.
Mexican phonetic writing, 205.
Mexitl, an Aztec chief, 88.
Mexico, ancient, 23, 84, 88, 282;
human remains in, 42.
Mexican grammar, 324, 341, 344, 346.
See Aztec, Nahuatl.
Mexico-Tenochtitlan, 85.
Micmacs, mythology of, 130.
Michabo, a Chipeway deity, 131, 132–4.
Michoacan, 88.
Mictlan, the Aztec Hades, 143.
Mictlantecutli, the Aztec Pluto, 145.
Migration, lines of in America, 44, 45.
Minsi tribe, 181;
derivation of, 189.
Mississippi, the, 74, 77.
Mitla, ruins of, 448.
Mixteca language, the, 331, 345.
Mongolian affinities, alleged, of the American race, 56.
Mongolian eye, the, in America, 63.
Mongoloid traits in Americans, 38, 39, 56.
Monosyllabism in languages, 215.
Montejo, Francisco de, 233.
Montezuma, his hieroglyphs, 208, 209, 282;
his forebodings, 302.
Montezuma, Rio de, 86.
Months, hieroglyphs of, of Mayas, 265–7.
Moon, origin of, 125.
Moraines, the line of, in North America, 54.
Moteuczomatzin, 283.
Mound-Builders, their nationality, 67;
their metrical standard, 447.
Mounds in Ohio and Mississippi valleys, age of, 27.
Mural paintings, of Mayas, 254.
Muskokees, 71, 75.
Mutsun language, 386 sq.
Mythology, interpretations of, 101.

Nabula, the book of, 259.

Nagualism, in Central America, 170.
Nahua ollin, the, 161.
Nahuatl hieroglyphs, dictionary of, 210;
 geographic names, 210;
lineal measures, 444.
Nahuatl language, 23, 59, 205, 363, 366, 399;
love words in, 417.
Nahuas, tribes of, 22, 85, 418.
See Aztecs, Mexicans.
Names, bestowal of, 114.
Nanabojoo, a Chipeway hero, 131.
Nanahuatl, an Aztec divinity, 116.
Nanih Waiya, the Sloping Hill, 80.
Nanticokes, native name of, 189.
Napiw, a Blackfoot hero, 131.
Nasal index in American Indians, 39, 64.
Natchez, 71, 77, 78, 463.
Navaho language, 394.
Nebraska, ancient lake-beds of, 31.
Nenaboj, a Chipeway hero, 131.
Neolithic period, the, 30, 51.
New England Indians, 131.
Newfoundland, natives of, 311.
New Granada, tribes of, 330;
languages, 400.
New Jersey, archæology of, 32, 53.
New Mexico, ruins in, 25.
New York State, earthworks in, 69.
Nezahualcoyotl, a chief, 445.
Nicaragua, ancient human footprints in, 42.
Night, master of the, 113.
Nim-ak, meaning of, 113.
Nine Waters, river of, 143.
Nith songs of Eskimo, 287.
Norsemen, myths of, 142.
North Pacific coast, tribes of, 65.
Northmen, voyages of, 22, note.
Nova Scotia, discovered by Northmen, 22.
Nun, the celestial river, 137, 139.
Numbers, sacred or mystic, 99.
See Four, Seven, Twelve, etc.
Numerals, deficiency of, 326.
Numeration, Maya signs of, 268;
words for, 406.

Oblique eye as racial trait, 39, 63, 64.

Obsidian found in Ohio, 32.
Occipital bone in American skulls, 62.
Ocelotl, or jaguar, in myths, 128.
Ocnakuchil, meaning of 237.
Ogier the Dane, 142.
Ohio, mounds in, 27, 67–81;
obsidian in, 32.
Ojibway picture writing, 153, 154.
Offogoula, tribe, 77.
Ollanta, drama of, 300.
Omagua language, 405.
Oriental symbols in America, 148 sqq.
Origin of language, 317.
Orinoco, tribes of, 405.
Orizaba, inscribed stone at, 274.
Orosi, natives at, 375.
Os Incæ, the, in Americans, 62.
Osiris, the Egyptian god, 137–140.
Otchipwe language, the, 364.
Otherness, how expressed, 396.
Otomis, or Othomis, the tribe, 117;
war songs, 298.
Otomi language, the, 59, 366 sq.
Ouspie, tribe, 77.
Owl, superstitions concerning, 114, 169.

Pacaha, a province, 74.

Paducas, tribe of, 291.
Pah ah tun, Maya deities, 166, 173.
Palæoliths, American and other, 48.
Palæolithic period, the, 30, 51, 390.
Palæolithic man, his habitat, 54;
language, 390 sq.
Palenque, the ruins of, 26, 84, 126, 254, 448.
Palpan, a place name, 87.
Pame language, the, 368, 373.
Pampas, lacrustine deposits of, 31;
skulls from, 40.
Papa, name of Quetzalcoatl, 99.
Paper of Maya MSS., 253.
Paradise, the Aztec, 144.
Patagonians, height of, 39.
Patine, as a sign of age, 51.
Pavant Indians, the, 321.
Pawnees, poetry of, 291–2.
Pech, a Maya priest, 302.
Pennsylvania, ancient works in, 70;
Indian names in, 309;
relics found in, 53.
Penobscots, mythology of, 130.
Personality, idea of in language, 320.
Peru, ruined cities of, 26.
Peruvians, language of, 397;
songs of, 300.
Peten, Lake, conquest of, 239.
Petroglyph, near Orizaba, 274.
Philosophy of language, 328.
Phonetic elements, origin of, 393.
Phonetics of Mexican and Maya writing, 195.
Phoneticism in writing, origin of, 216.
Picture writing, 213, 231;
Ojibways, 153, 154, 228;
 of Mexicans, 221 sq.
Pirinda language, the, 368, 372.
Pisote, the white, 113.
Pleasure, physiological principle of, 285.
Pleistocene epoch, human remains in, 29.
Plumed serpents, house of, 97.
Plummet, unknown in America, 442, 450.
Pluto, the Greek god, 141.
Poetry, native American, 284 sq.
Pokonchi dialect, the, 104, 112.
Polished stone, period of, 50.
Polychromatic hieroglyphs, 223.
Polynesians, alleged migrations of, 18, 43.
Polysynthesis, explained, 36, 321, 351 sq.
Pontemelo, ancient skull from, 40.
Pop, name of a Maya month, 249.
Popol Vuh, the, 105 sq.
Potato, the, its extension, 33.
Pottery, designs on, 157, 159;
of Lenâpé, 185.
Pound-the-stones, Miss, 179.
Prehistoric archæology, 392.
Prepositions, in American languages, 345.
Pronominal languages, 320.
Pronouns, in American languages, 396–8.
Proper names, in early times, 218.
Prophecies of Mexicans and Mayas, 302.
Pueblo Indians, 25, 87.
Pulque, liquor made from, 254.

Quetzalcoatl, 24, 84 sq.;

baths of, 86;
absent, 145.
Quiches, myths of, 104 sq., 124, 171;
dialect of the, 104, 423;
king of, 114;
lineal measures of, 433;
writing of, 228;
sacred book of, 105 sq., 171.
Qquichua language, the, 346, 365, 425;
traditions, 22;
love-words in, 425 sq.
Qux cah, a sacred name, 116.
Qux cho, a sacred name, 116, 120.
Qux palo, a sacred name, 116.

Ra, the sun-god, 137, 140.

Rabbit myths, 112, 132, 179, 276.
Races of men, 348.
Rain, the gods of, 175.
“Rakan,” meaning of, 122.
Rattlesnake bites, cure for, 188.
“Rax,” in Quiche, meaning of, 118.
Raxa-cakulha, a Quiche god, 120.
Rebus, method of writing by, 211, 215, 219.
Red, as sacred color, 144, 166, 176.
Refref, serpent in Egyptian myth, 137.
Relative pronouns, in American languages, 346.
Religious sentiment, the, 432.
Remedies, native, 272.
Repetition, in poetry, 285.
Reproductive principle, worship of, 119.
Rhyme, unknown in native poetry, 285.
Ring-cross, the, 158.
Rio de Montezuma, 86.
Rio de Tula, 86.
Ritual of the dead, in Egypt, 139.
Rituals of Mayas, 247.
River, the celestial and infernal, 137–145.
Rock Bluff, skulls from, 40.
Rosetta stone, the, 218.

St. Augustine, Florida, 74, 75, 77.

St. John River, 74.
St. Louis, “big mound” at, 81.
San Isidro, stone relics from, 391.
Sacred book of the Quiches, 105, 107.
Saliva, in myths, 124.
Salonge, an ogre, 176.
Salt, magic power of, 171.
Sanscrit language, the, 340, 344, 415;
alleged affinity with Nahuatl, 57.
Sambaquis, shell heaps in Brazil, 28, 29.
Sarbacane, the, 109.
Sauteux, language of, 400.
Savacon, a Carib deity, 123.
Schipka cave, bones from, 390.
Sciences of the Mayas, 245.
Seminoles, 71, 77.
Semitic traditions, supposed in America, 21.
Serpent, as sacred animal, 116, 132, 133.
Serpent mount, the, 86.
Serpent, fabulous, of Mayas, 179.
Seven, as sacred number, 124, 129, 171, 439.
Seven Caves, land of the, 23.
Sex distinctions in grammar, 406.
Shell-heaps, the age of, 27;
in Florida, Tennessee, Costa Rica, Brazil, 28;
in Gulf States, 72.
Shooting stars, in myths, 174.
Shoshonian family, languages of, 23.
Signatures of natives, 234.
Skin, color of, in American Indians, 39.
Skull, shape of, in Americans, 63.
Skulls, types of, in Brazil, 29.
Sky, soul of the, 120.
Snake-Hill, the, 86.
Sodomy, not found in Yucatan, 235.
Sonora, languages of, 23.
Soto, Hernando de, his expedition, 72, 74.
Soul, seat of, 117;
food of the, 168;
Journey of the, 135–145.
Sound-writing, 213, 230.
Span, as measure, 441.
Speech, earliest form of, 390 sq.
Speechless man, 390–392.
Spiral, development of the, 159, note.
Spittle, as genetic fluid, 124.
Squaw, word for, 181.
Stars, origin of, 125.
Stature of American Indians, 39.
Stone, age of, its subdivisions, 50;
survivals of, 183.
Stone and brick edifices, 25.
Stone of the Giants, 274 sq.
Stone implements, oldest specimens, 391.
Stone, the clear, divination by, 165.
Stones, adoration of, 40;
column of, 70.
Storm, Quiche gods of, 120.
Straw bird, the, 179.
Sun-god, Aztec myth of, 116;
in Yucatan, 167.
Sun, origin of, 125;
worship in Egypt, 137–140;
in America, 146;
in picture writing, 156–8.
Sun worship in Apalacha, 76;
“brother of,” 77, 78;
the mother of, 119;
four motions of, 157, 161;
worship, 170;
place of the, 93;
creation of, 95;
rays of in symbolism, 146, 280.
Svastika, the, as a symbol, 148 sqq.
Sweat lodge, of Lenâpé, 187.
Syllabic writing, 231.
Symbols, phonetic, 197;
the sacred, in America, 149 sqq.
Symbolic writing, 213.
Syncope in American languages, 371.
Syphilis, sacred associations of, 115, 116, 144.

Taensa language, the hoax of, 452 sq.

Ta Ki, a Chinese symbol, 148 sqq.
Tales, Indian, 182.
Tamanaca language, the, 331.
Tamaulipas, Sierra of, 295.
Welcome to our website – the ideal destination for book lovers and
knowledge seekers. With a mission to inspire endlessly, we offer a
vast collection of books, ranging from classic literary works to
specialized publications, self-development books, and children's
literature. Each book is a new journey of discovery, expanding
knowledge and enriching the soul of the reade

Our website is not just a platform for buying books, but a bridge
connecting readers to the timeless values of culture and wisdom. With
an elegant, user-friendly interface and an intelligent search system,
we are committed to providing a quick and convenient shopping
experience. Additionally, our special promotions and home delivery
services ensure that you save time and fully enjoy the joy of reading.

Let us accompany you on the journey of exploring knowledge and

personal growth!

textbookfull.com