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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
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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

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

v

Contents

Foreword vii 4. Vascular Pathology 82

Martin A. Samuels
Preface to the Sixth Edition ix
Contributors xi
1. Basic Pathology of the Central Nervous
System 1
Pedro de Sá Cavalcante Ciarlini, Danielle Seilhean,
Umberto De Girolami, and Françoise Gray
2. Tumors of the Central Nervous
System 21
Keith L. Ligon, Sandro Santagata, and Franck Bielle
3. Central Nervous System Trauma 65
Colin Smith and R. Ross Reichard
Jean-​Jacques Hauw, Steven K. Feske,
Pierre Amarenco, and Umberto De Girolami
5. Infections of the Central Nervous
System 122
Fabrice Chrétien, Gregory Jouvion,
Kum Thong Wong, and Leroy R. Sharer
6. Human Prion Diseases 159
James W. Ironside
7. Multiple Sclerosis and Related
Inflammatory Demyelinating
Diseases 172
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
venerated, undergo a new edition every 5 years
or even longer. This interval reflects the relatively
slow progress in most fields. After all, change in
the practice of medicine usually reflects the ar-
duous process of preclinical basic science followed
by the lengthy testing of drugs in animals and then
humans. As most clinical trials are negative, only
a small number of real changes occur in less than
a decade. However, this viscous process does not
hold in neuroscience. Driven mainly by advances
in molecular biology, cell biology, and genetics,
the clinical neurosciences (neurology, neurosur-
gery, and psychiatry) are experiencing dramatic
change. Together with cancer, the neurosciences are
undergoing a transformation that is analogous to
cardiology in the last century. Patients are now re-
ceiving the benefits of this momentum in the form
of treatments for virtually every category of nervous
system disorder. The modern neurology department
is now differentiated into 15–​20 divisions. This pro-
cess may be bemoaned by the older generation, but
is inexorable, reflecting as it does the increasingly
complex biology, pathophysiology, and therapeutics
of the various fields. This process, which occurred
in internal medicine in the twentieth century, is
now in full bloom in the twenty-​first century. For
this reason, a new edition of Escourolle and Poirier’s
Manual of Basic Neuropathology has been hatched in
only 5 years.
In generations past, the basic science of neuro-
science was neuropathology. Over time, other fields,
such as genetics, imaging, neuropharmacology, and
molecular biology have become vital to the training
and practice of the clinical neurosciences. But, con-
trary to becoming extinct, neuropathology has in-
corporated these newer disciplines and has, in effect,
reclaimed its leadership role in the understanding
and ultimately treatment of disorders of the nervous
system. In the sixth edition of the now classic
textbook, Escourolle and Poirier’s Manual of Basic
Neuropathology, Professors Umberto De Girolami,
Françoise Gray, and Charles Duyckaerts have
embodied this trend by creating what is, in effect,
• vii
a concise approach to the understanding of all the
major categories of nervous system disease. In a very
creative and truly unique manner, they have added
distinguished clinicians to many of the chapters to
ensure relevance of the basic information to the
actual practice of medicine. This reflects the fact
that many of the major questions in diseases of the
nervous system, such as regarding paralysis, pain,
disorders of consciousness, and cognitive decline,
do not fit neatly into any one of the old categories
that were artificially created in the past, as they no
longer reflect the relevant pathobiology.
Interdisciplinary neuroscience is the wave
of the future if we are to unlock the mysteries
of neurodegeneration, neuroinflammation, and
aging. In our own center, this is reflected in the re-
cent formation of a Program in Interdisciplinary
Neuroscience, which is meant to facilitate re-
search, clinical care, and education in areas that
fall between the classic disciplines, allowing for a
multiperspective approach to learning the causes and
creating preventive and curative strategies for the fu-
ture. As one salient example, the science underlying
neurodegeneration and repair has vital relevance to
a vast array of diseases, such as amyotrophic lateral
sclerosis, Alzheimer disease, and Parkinson disease.
In the past, these would have been considered en-
tirely separate illnesses, each cared for in different
divisions, such as neuromuscular diseases, cognitive
and behavioral neurology, and movement disorders.
It is now clear that the basic science of each of these
disorders is shared. Immunology has also taken a
major role in understanding diseases as apparently
disparate as stroke, dementia, and epilepsy.
Escourolle and Poirier’s Manual of Basic
Neuropathology is organized in its successful and
viii • F oreword
familiar manner, starting with a chapter on the basic
principles of the pathology of the nervous system.
This is followed by individual chapters on tumors,
trauma, vascular diseases, infections, prion diseases,
demyelinating processes, degenerative diseases, ac-
quired and inherited metabolic diseases, congenital
malformations, muscles, nerves, and diseases of the
pituitary gland. The book ends with an appendix
on commonly used neuropathology techniques. As
examples of the new approach, the distinguished
myologist Anthony Amato cowrote the chapter on
disease of skeletal muscle, as did the eminent neu-
rosurgeon Edward Laws for the pituitary chapter
and the venerated Steven Feske for the vascular
diseases chapter. As Gilbert and Sullivan’s Pooh-​Bah
famously said, this adds “artistic verisimilitude to an
otherwise bald and unconvincing narrative.”
Indeed, this new edition of Escourolle and Poirier’s
Manual of Basic Neuropathology is much more than
that. It is, in fact, a concise textbook of the modern
neurosciences, one that will be read and referred
to by the next generation of all those students and
physicians interested in diseases of the nervous
system.
Martin A. Samuels, MD, FANA, FAAN, FRCP,
MACP, DSc (hon)
Director, Program for Interdisciplinary
Neuroscience
Chair, Department of Neurology
Brigham and Women’s Hospital
Miriam Sydney Joseph Professor of Neurology
Harvard Medical School
Boston, Massachusetts
USA
ix
Preface to the Sixth Edition
The first two French editions of the Manuel de
Neuropathologie, published in 1971 and 1977,
were conceived, written, and edited by Raymond
Escourolle and Jacques Poirier. After the death
of Raymond Escourolle in 1984, Françoise Gray
joined Jacques Poirier for the third edition; in ad-
dition, Jean-​Jacques Hauw and Romain Gherardi
contributed to selected chapters. The first three
editions reached the English-​speaking public thanks
to the friendship and translating ability of the now-​
deceased Lucien Rubinstein. For the fourth edition,
Umberto De Girolami joined as co-​editor, and the
scope of the monograph was expanded with the col-
laborative efforts of multiple experts throughout the
world to write the English language text. Jacques
Poirier retired, and Charles Duyckaerts then agreed
to join the editorial team for the fifth and now the
sixth edition. For this sixth edition, there have again
been changes in authorship of several chapters in
response to the changing status of senior authors
and the need to recruit active investigators to
replace them.
This sixth edition of the manual attempts
to maintain the general intention of Professors
Escourolle and Poirier for the first and subsequent
editions of the monograph, that is, to provide, for
the reader resident-​trainee and staff member, a basic
description of the lesions underlying the diseases of
the nervous system and to limit pathophysiological
considerations to essential principles. Historical,
clinical neurologic and radiologic imaging data,
once again, have been deliberately excluded, as well
as bibliographic reference listings. This important
body of information essential for the practice of
neuropathology can be obtained in the many com-
prehensive treatises on the subject now readily avail-
able. We also have made the assumption that the
reader has some familiarity with general concepts of
neuroanatomy, neurohistology, and the principles of
anatomic pathology as well as clinical neurology.
With these guidelines in mind, our aim has been
to produce a text that mainly presents those labo-
ratory aspects of neuropathology that are morpho-
logical (and molecular, where appropriate) and to
• ix
demonstrate these with accurate descriptions and
good illustrations, all within the scope of a concise
and inexpensive “manual.”
For several specific reasons, we think that the
time is now right for a new edition since the last
one in 2014. Over the past several years, specialty
training in neurology, neurosurgery, and pathology
has very much changed throughout much of the
world, such that in these disciplines, less time is
being devoted to neuropathology. This has been due
in large part to the tremendous expansion of know-
ledge in allied subspecialty areas, requiring that
more time be devoted to them. Thus, the trainee in
these disciplines is now very much in need of a con-
cise introductory text.
In addition, several other important changes in
medicine and society have had an impact on the field
of neuropathology and demand being addressed in
this text.
• For a variety of social and scientific reasons,
autopsy studies are currently being performed
much less frequently than in years past. This
change has been brought about in part because
the progress in radiologic imaging, both
structural and functional, has decreased the
need to draw on clinico-​anatomic correlations
derived from postmortem data to guide clinical
practice. Oddly enough, conversely, autopsy-​
derived knowledge of the anatomic distribution
and the neuropathologic basis of lesions
continues to be a valuable body of information
for the interpretation of imaging data. To
support this aim, we have amply made use of
macroscopic illustrations and whole-​brain
celloidin/​paraffin-​embedded sections from our
archives.
• Progress in molecular biology and genetics has
revolutionized the laboratory diagnosis of many
groups of neurological diseases. Neuropathology
stands at the vanguard of the development and
implementation of these diagnostic studies. In the
last decade, progress in immunohistochemistry
methods for in situ identification of abnormal
proteins and the enormous advances in molecular
biology to uncover specific gene mutations have
led to greater understanding of many hereditary
neurologic diseases, including degenerative and
x • preface
metabolic disorders, developmental disorders,
and neuromuscular diseases. Morphologic
neuropathologic data, obtained at biopsy or
at postmortem examination, have therefore
needed to be integrated with this new knowledge
for the reinterpretation and reclassification of
many diseases. For example, neuropathologic
information obtained at biopsy, combined
with molecular biology and genetic data, is
now required for the diagnosis, prognosis, and
guidance of the choice of treatment modalities in
brain tumors.
• Last, an urgent responsibility to present an
updated synopsis of neuropathology is that this
knowledge is important to allied disciplines, as
there is constant need for surveillance of newly
emerging diseases, including infectious and
iatrogenic ones.
We need to thank first of all Susan Pioli, who al-
though now retired from the publishing business,
was instrumental in prior editions and led us to Craig
Panner and his colleagues with Oxford University
Press, who has given fundamental support. Second,
we thank present and past contributing authors and
their staff for the text and illustrations provided in
this new edition.
In the Introduction to the first edition, Professors
Escourolle and Poirier offered an apology to the
reader that is still valid some half a century later:
The compilation of a basic work designed to
familiarize physicians-​in-​training with such a
highly specialized discipline as Neuropathology
entails two opposing risks: in attempting to
compress the maximum amount of information
within the minimum space, the text is liable to
become unintelligible to beginners; if on the con-
trary, one tries to maintain too elementary a
level, the danger is that only the obvious will be
stated. In presenting to the non-​initiated reader
neuropathological information that some may
find too simple, we have preferred the hazard of
the second pitfall.
Françoise Gray
Charles Duyckaerts
Umberto De Girolami
xi
Contributors
Homa Adle-​Biassette, MD, PhD
Professor of Pathology, Faculté de médecine Paris
Diderot, Université Paris, Diderot, Sorbonne
Paris Cité, Paris, France
Pathologist, Neuropathologist, Fetal (neuro)
pathologist, Department of Pathology,
Lariboisière Hospital, APHP, Paris, France
Pierre Amarenco, MD
Professor and Chairman, University of Paris
Diderot, Sorbonne Paris Cité, Paris, France
Department of Neurology and Stroke Centre
Bichat Hospital, Paris, France
Anthony A. Amato, MD
Professor of Neurology, Harvard Medical School,
Boston, MA, USA
Vice-​Chairman, Department of Neurology and
Chief, Neuromuscular Division, Brigham and
Women’s Hospital, Boston, MA, USA
Douglas C. Anthony, MD, PhD
Professor of Pathology and Laboratory Medicine,
and Professor of Neurology, Alpert Medical
School of Brown University, Providence,
RI, USA
Pathologist-​in-​Chief, Lifespan Academic Medical
Center, Providence, RI, USA
Franck Bielle, MD, PhD
Assistant Professor of Pathology, University Pierre
et Marie Curie, Paris, France
Neuropathologist, Pitié/​Salpêtrière Hospital,
Paris, France
Leila Chimelli, MD, PhD
Professor of Pathology, Federal University of Rio de
Janeiro, Rio de Janeiro, Brazil
Neuropathologist, Laboratory of Neuropathology,
State Institute of Brain, Rio de Janeiro,
Brazil
• xi
Fabrice Chrétien, MD, PhD
Professor of Histology, Université Paris Descartes,
Paris, France
Neuropathologist, Laboratoire de Neuropathologie,
Centre Hospitalier Sainte Anne, Paris, France
Unité de Neuropathologie Expérimentale,
Institut Pasteur, Paris, France
Pedro de Sá Cavalcante Ciarlini, MD
Auxiliary Professor of Pathology, Federal University
of Ceará, Sobral, CE, Brazil
Pathologist/​Neuropathologist, Laboratório
Clementino Fraga, Fortaleza, CE, Brazil
Umberto De Girolami, MD
Professor of Pathology, Harvard Medical School,
Boston, MA, USA
Neuropathologist, Brigham and Women’s Hospital,
Boston, MA, USA
Charles Duyckaerts, MD, PhD
Professor of Pathology, University Pierre et Marie
Curie, Paris, France
Director, Neuropathology Laboratory,
Pitié/​Salpêtrière Hospital, Paris, France
Steven K. Feske, MD
Associate Professor of Neurology, Harvard Medical
School, Boston, MA, USA
Chief, Cerebrovascular Division, Department of
Neurology, Brigham and Women’s Hospital,
Boston, MA, USA
Romain Gherardi, MD
Professor of Histology, Paris-​Est University,
Créteil, France
Neuropathologist, Henri Mondor University
Hospital, Créteil, France
Hans H. Goebel, MD
Professor of Neuropathology (ret.),
Johannes Gutenberg University,
Mainz, Germany
Consultant Neuropathologist, Institute
of Neuropathology, Charité, Berlin,
Germany
Jeffrey A. Golden, MD
Ramzi S. Cotran Professor of Pathology, Harvard
Medical School, Boston, MA, USA
Chair of Pathology and Neuropathologist, Brigham
and Women’s Hospital, Boston, MA, USA
xii • C ontributors
Françoise Gray, MD, PhD
Professor of Pathology (ret.), Faculté de médecine
Paris Diderot, Université Paris, Diderot,
Sorbonne Paris Cité, Paris, France
Neuropathologist, Department of Pathology,
Lariboisière Hospital (ret.), APHP, Paris, France
Brian Harding, MA, DPhil, BMBCh, FRCPath
Professor of Pathology and Laboratory Medicine,
University of Pennsylvania, Philadelphia, PA, USA
Neuropathologist, Children’s Hospital of
Philadelphia, Philadelphia, PA, USA
Jean-​Jacques Hauw, MD
Professor of Pathology (ret.), Pierre et Marie Curie
University, Paris, France
Neuropathologist (ret.), Pitié-​Salpêtrière Hospital,
Paris, France
Académie Nationale de Médecine, Paris, France
James W. Ironside, MD
Professor of Clinical Neuropathology (ret.), School
of Clinical Sciences, University of Edinburgh,
Edinburgh, UK
Gregory Jouvion, PhD
Unité de Neuropathologie Expérimentale, Institut
Pasteur, Paris, France
Hans Lassmann, MD, PhD
Professor of Neuroimmunology, Medical
University of Vienna, Vienna, Austria
Chairman, Department of Neuroimmunology,
Center for Brain Research, Vienna, Austria
Edward R. Laws, Jr., MD, FACS
Professor of Neurosurgery, Harvard Medical
School, Boston, MA, USA
Neurosurgeon, Brigham and Women’s Hospital,
Boston, MA, USA
Hart G. Lidov, MD, PhD
Associate Professor of Pathology, Harvard Medical
School, Boston, MA, USA
Neuropathologist, Boston Children’s Hospital,
Boston, MA, USA
Keith L. Ligon, MD, PhD
Associate Professor of Pathology, Harvard Medical
School, Boston, MA, USA
Neuropathologist, Dana-​Farber Cancer Institute/​
Brigham and Women’s Hospital, Boston,
MA, USA
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
is based on the macroscopic and microscopic study
of the brain, brainstem, cerebellum, and spinal cord.
Increasingly, the ability to reach greater diagnostic pre-
cision is buttressed by the new laboratory techniques of
molecular biology and genetics. Three consecutive steps
are involved in reaching a diagnosis, and these are, in fact,
closely interrelated: (1) a morphological/​ laboratory
analysis of the lesions; (2) a topographical analysis of
the lesions; and (3) a critical integration of these findings
and their subsequent correlation with the clinical data
and the general autopsy findings, thus permitting an eti-
ological diagnosis to be made in most instances.
1 . 1 M OR P HOL OGICAL
AN ALY S IS OF CE N T RAL
N ER V OUS SYST E M L E SION S
A number of disorders of the central nervous system
(CNS) are characterized morphologically by the
co-​expression of multiple reactions to injury that may
not necessarily be diagnostic in themselves. These
reactions affect the cellular elements of the nervous
system (neurons, astrocytes, oligodendrocytes, and
microglia) and/or the supporting structures (me-
ninges, connective tissue, or blood vessels). Basic
cellular reactions are demonstrable on microscopic
examination, whereas tissue lesions associated with
more extensive destructive or atrophic changes are
recognized to the naked eye or with the help of a
magnifying lens.
Although, for didactic purposes, the reactions to
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
functional interdependence of the various cellular
elements of the nervous system. This is particularly
important in the case of nerve cell alterations where,
except for very acute injury, the possibility of artifac-
tual change should be entertained whenever the reac-
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-
what longer), one observes eosinophilia of the cyto-
plasm, shrinkage and hyperchromasia of the nucleus,
and disappearance of the nucleolus; subsequent to
the disintegration of the cell, neuronophagia by scav-
enger cells is evident at a later time interval (days
later). In chronic diseases, evidence of cell death is
recognized morphologically as neuronal “cell loss”
or alternately (as “atrophy”) on macroscopic exam-
ination when the irreversible injury has occurred
relatively slowly (months or years) and has progres-
sively involved increasing numbers of cells. In some
degenerative diseases of the nervous system where
there is progressive loss or damage of neurons over
variable time periods, the affected cells have distinc-
tive morphologic hallmarks (e.g., neurofibrillary de-
generation, neuronal storage of metabolic products,
disorders associated with intracellular inclusions).
Nerve cell loss (i.e., reduction in the number of
cell bodies in a particular brain region as compared
to normal) when it involves less than 30% of the
normal cell population, may be difficult to ascertain
in the absence of rigorous morphometric analysis.
Furthermore, precise assessment depends on con-
sideration of the thickness of the section and on the
normal cytoarchitectonics of the region examined.
1.1.1.1.1. Nerve cell atrophy. Neuronal at-
rophy is the descriptive term that is given to a wide
range of irreversible neuronal injuries that give rise
to a relatively slowly evolving death of the cell.
Neuronal atrophy is characterized morphologically
by retraction of the cell body with diffuse basophilia
of the cytoplasm and pyknosis and hyperchromasia
of the nucleus of the neuron, in the absence of an
inflammatory reaction. Neuronal atrophy is thought
to occur in many degenerative disorders that in-
volve several interconnected neuronal systems (i.e.,
multiple-​system atrophy, Friedreich ataxia, and
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
FIGURE 1.1 Two neurons undergoing apoptosis
are positively stained by in situ end labeling to demon-
strate internucleosomal DNA fragmentation. In one
neuron, on the left, only the nucleus is stained, whereas
in the other, which is at a later stage of the programmed
cell death process, the entire cell body is stained.
Compared to a normal neuron, on the right, both ap-
optotic neurons have similar morphological features
and show a pyknotic nucleus and shrunken cytoplasm.
amyotrophic lateral sclerosis). It is also seen in anter-
ograde and retrograde trans-​synaptic degeneration,
as may occur in the lateral geniculate body following
a lesion of the optic nerve.
Programmed cell death (apoptosis) is an active,
genetically controlled, energy-​consuming process
frequent in neurodegeneration and initially involves
the nucleus of the cell. Neurons undergoing simple
neuronal atrophy or apoptosis have similar mor-
phologic features and may show positive in situ end
labeling of internucleosomal DNA fragmentation
(Fig. 1.1) or be demonstrable by activated caspase
3 immunostaining.
Nerve cell atrophy should not be mistaken with
what is referred to as “dark neurons.” This phenom-
enon is now recognized to be an artifactual change
of the neuron cell body, seen particularly in brain
biopsies fixed in formalin by immersion, and is
characterized by shrinkage of the neuronal cyto-
plasm and a deeply stained, irregularly-shaped nu-
cleus, without other cellular alterations.
1.1.1.1.2. Acute neuronal necrosis (anoxic/​
ischemic neuronal change). Acute neuronal ne-
crosis (anoxic/​ischemic neuronal change) cell death
occurs in not only a wide range of acute injuries, in-
cluding anoxia and ischemia, but also many other
acute pathological processes (e.g., hypoglycemia
or exposure to excessive amounts of excitotoxic
3
FIGURE 1.2 Acute ischemic nerve cell change
(H&E). Eosinophilic, shrunken cytoplasm and
hyperchromatic nucleus.
neurotransmitters). Unlike apoptosis, the predom-
inant cellular changes in acute neuronal necrosis
involve the cytoplasmic organelles and the cell
membrane, which ruptures, leading to cell death.
In experimental animal studies and in carefully
studied human tissue at postmortem, the following
sequence of changes is noted by light and electron
microscopy over the course of 12 to 24 hours after
the insult: (a) cytoplasmic microvacuolization due
to swelling of mitochondria and endoplasmic retic-
ulum; (b) shrinkage of the cell body with retraction
of the cellular outlines and disappearance of Nissl
bodies with eosinophilic condensation of the cyto-
plasm (“red neuron”); (c) condensation of nuclear
chromatin and nuclear pyknosis (Fig. 1.2); (d) late
disappearance of the nuclear chromatin, resulting
in increased acidophilia of the nucleus, which
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
lower motor neurons (anterior horns of the spinal
cord, cranial nerve nuclei), where it represents a re-
parative reaction of the cell body to a lesion of the
Chapter 1
FIGURE 1.3 Ferruginization (mineralization)
of the neurons at the edge of an old hemorrhagic
infarct (H&E).
axon (retrograde degeneration or axonal reaction).
Subsequent recovery of normal cell morphology or,
conversely, further progression to nerve cell degen-
eration depends on the reversibility of the axonal
lesion (Fig. 1.5). Central chromatolysis may also be
seen in upper motor neurons, but the phenomenon
is rare and difficult to interpret correctly. Axonal
lesions of neurons whose axons do not leave the
confines of the CNS apparently either do not pro-
duce changes in perikaryal cell-body morphology or
result in a “simple” type of atrophy. Oddly enough,
some metabolic disorders that do not a priori affect
axons (e.g., Wernicke’s encephalopathy, pellagra en-
cephalopathy, and porphyria) may be accompanied
by central chromatolysis in cortical neurons.
A confident diagnosis of central chromatolysis
requires comparison with the normal morphology
FIGURE 1.4 Central chromatolysis (Nissl stain).
Note the cellular swelling, the eccentric displace-
ment of the nucleus, and the margination of the Nissl
bodies.
Basic Pathology of the Central Nervous System • 3
 Complete
central
chromatolysis
Normal
neuron
Recovery
Cell death
Stages of
hyperchromasia
FIGURE 1.5 Nerve cell changes resulting from cen-
tral chromatolysis.
of the affected gray matter structure, because the
nerve cell body in some nuclei (e.g., the mesence-
phalic nucleus of the fifth cranial nerve, Clarke’s
column) normally contains rounded neurons with
marginated Nissl bodies.
1.1.1.1.4. Vacuolated neurons and neu­
ropil. Vacuolated neurons and/or vacuolated neu-
ropil is observed typically in Creutzfeldt-Jakob
disease (Fig. 1.6). In rare instances, swelling with
vacuolization of the nerve cell may result from
transsynaptic degeneration, such as occurs in the
neurons of the inferior olive in olivary hypertrophy
secondary to a lesion of the ipsilateral central teg-
mental tract or of the contralateral dentate nucleus;
this phenomenon is also designated “fenestrated
neurons” (Fig. 1.7).
FIGURE 1.6 Vacuolated neuron in a case of
Creutzfeldt–​Jakob disease (H&E).
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
FIGURE 1.7 Fenestrated neuron in a case of olivary
hypertrophy (Nissl stain).
1.1.1.1.5. Binucleated neurons. Binucleated
neurons are seen rather infrequently, sometimes
under normal circumstances, or otherwise at the
edge of old focal destructive lesions, as a dysplastic/​
malformation phenomenon (e.g., tuberous sclerosis),
or in certain neoplasms (e.g., ganglion cell tumors).
1.1.1.1.6. Neuronal storage. In some heredi-
tary metabolic diseases related to enzymatic defects
involving synthetic or degradative pathways for
lipids or carbohydrates, interruption of the pathway
leads to cytoplasmic accumulation of interme-
diate substrates or their by-​products, resulting in
swelling and distention of the cell body of nerve
cells, with eccentric displacement of the nucleus
(Fig. 1.8). In several neuronal storage disorders, the
stored material has distinctive histochemical and
ultrastructural features that may help characterize
FIGURE 1.8 Distended nerve cell bodies in a case
of neurolipidosis (combined Luxol fast blue and
Bodian silver impregnation).
5
FIGURE 1.9 Lipofuscin in neuronal cell
body (H&E).
clinically suspected cases of a given storage disease.
Biochemical tests on blood, leukocytes, and other
body fluids are now particularly useful to more pre-
cisely diagnose many of these disorders.
Lipofuscin accumulation within the perikaryon of
neurons and other cells in the nervous system is a
characteristic aging change. Lipofuscin accumulates
in neurons diffusely throughout the brain in
ceroid lipofuscinosis, a neuronal storage disorder.
Lipofuscin is identified on H&E preparations as
refractile yellow-​ brown pigment aggregates (Fig.
1.9). It is autofluorescent and rich in acid phospha-
tase. The pigment is periodic acid–​Schiff (PAS)-
positive and can be stained by Luxol fast blue. It has
distinctive ultrastructural features (see Chapter 10).
1.1.1.1.7. Alzheimer neurofibrillary degenera­
tion and granulovacuolar degeneration. Alzheimer
neurofibrillary degeneration is characteristically seen
in the brains of aged individuals and in patients with
senile dementia of the Alzheimer type, but it has also
been described in a variety of other cerebral disorders.
This degenerative change is manifest by the forma-
tion of neurofibrillary tangles (NFTs), structures
that are well demonstrated by silver impregnation
and by immunohistochemical techniques; they
consist of thickened and tortuous skeins within the
neuronal perinuclear cytoplasm. The configuration
of the tangle may vary according to the anatomic
site, the type of neuron affected, and the stage of
formation (Fig. 1.10). A band-​ shaped perikaryal
NFT can be seen in both large and small pyramidal
cells and is perhaps an early stage of NFT develop-
ment (Fig. 1.10A). A triangular flame-​shaped per-
ikaryal NFT is seen mainly in large pyramidal cells
(Fig. 1.10B, C). Small compact globose perikaryal
Chapter 1
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
be immunoreactive for ubiquitin and p62. By elec-
tron microscopy, most NFTs consist of paired helical
filaments measuring around 20 nm across with a reg-
ular constriction to 10 nm occurring every 80 nm. In
Alzheimer disease, they may also be associated with
straight filaments. In progressive supranuclear palsy
(PSP), tangles have been found to consist mainly of
straight filaments measuring 15 nm in diameter.
Granulovacuolar degeneration is a neuronal alter-
ation found in pyramidal cells of Ammon’s horn; it
is seen in normal aging as well as in Alzheimer di-
sease and Pick disease. The abnormality consists of
an accumulation of small, clear vacuoles measuring
4 to 5 μm in diameter and containing an argyrophilic
granule that is well stained by hematoxylin (Fig.
1.11). Some of the granules are immunoreactive
for phosphorylated neurofilament, tubulin, tau,
and ubiquitin, suggesting that the vacuoles are
autophagic lysosomal structures in which cytoskel-
etal components are being degraded.
1.1.1.1.8. Intraneuronal inclusion bodies.
Intracytoplasmic or intranuclear inclusion bodies
are important indicators of neuronal injury. They
occur in degenerative, metabolic, and viral diseases
and often have diagnostic immunocytochemical
and ultrastructural features.
Pick bodies are round homogeneous intracyto­
plasmic neuronal inclusions (Fig. 1.12) charac-
teristic of Pick disease, where they may be seen in
pyramidal neurons and dentate granule cells of the
hippocampus, as well as in affected regions of the ne-
ocortex. The structure is intensely argyrophilic and
immunoreactive for tau and the 3R-tau isoform. Pick
bodies are also reactive for ubiquitin and tubulin. The
ultrastructure of the body is characterized by poorly
circumscribed masses of intermediate filaments,
15-​nm straight filaments, and some paired helical
filaments, as well as entrapped vesicular structures.
Basic Pathology of the Central Nervous System • 5
Another random document with
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with their convexities to the east, indicating that they were built by
strong easterly winds. A moment’s consideration will show the truth
of the latter statement. Suppose there is an isolated round hillock of
sand exposed to strong easterly winds. The sand grains will travel up
the easterly windward slope of the hillock and roll down the westerly
leeward side. In this way the whole hillock will advance very slowly
westwards. But in the centre, where the hillock reaches its greatest
height, the grains will take longer to reach the highest point than
near the edges, where they have not to rise so high. At the edges a
strong gust will carry some of the heavier grains right over the dune,
while nearer the centre they will be left half-way, and when the gust
ceases will perhaps roll back to their original position. In this way the
margins of the dune will advance westward more rapidly than the
centre, producing the crescent shape with the convex side to the
east. At the time of their formation these dunes must have had their
steepest side to the westward, but the westerly winds which have
prevailed during the last few thousand years have succeeded in
modifying that detail, without destroying the general shape of the
dunes, and the steepest slopes are now on the eastern side. The
preservation of the original shape, in spite of the subsequent
development of westerly winds, is due in part to the coating of
vegetation, which protected the dunes as soon as more favourable
conditions occurred, and probably in part to the lesser velocity of the
westerlies. If the period of east winds and dune formation had been
long enough, we might have had another deposit of loess, but it was
short, and vegetation, which is necessary to the genesis of true
loess, had no time to establish itself before the climate changed
again with the final retreat of the ice. The climate of this period in
Rumania has been ably described by G. Murgoci: “In general the
prevailing climate of the time of the formation of loessoid soils and
blown sands must have been that which is named by E. de Martonne
the aralian climate, a dry climate with some rain in spring to call forth
a poor and transient vegetation and to maintain the flowing water in
rivers and lakes. The temperature with great extremes, in summer
up to 120° F. and in winter below 20° F., was the characteristic of this
climate; the atmosphere was very dry in the hot season, but in the
rest of the year there was some humidity in the air and moisture in
the soil, the water of the subsoil being not very deep. The
atmospheric precipitation in this region was caused by the south-
west wind just as at present; but the dominant wind giving the
character of a dry continental climate was the north-east wind
(Crivat) which has left its traces in the fossil dunes of the Baragan.”
A history of the changes of climate in Europe which followed the
maximum of the last readvance of the ice-sheet must be left to later
chapters.

BIBLIOGRAPHY

Brooks, C. E. P. “The correlation of the Quaternary deposits of the British Isles with
those of the continent of Europe.” Ann. Rep. Smithsonian Inst., 1917, pp.
277-375. [Full list of references.]
Penck, A., and Brückner, E. “Die Alpen in Eiszeitalter.” 3 Vols. Leipzig, 1901-9.
Gagel, C. “Die Beweise für eine mehrfache Vereisung Norddeutschlands in
diluvialer Zeit.” Geol. Rundschau, 4, 1913, p. 39.
Wahnschaffe, F. “Die Oberflächengestaltung des norddeutschen Flachlandes.”
Stuttgart, 1910.
Svastos, R. “Le postglaciare dans l’Europe centrale du nord et orientale.” Ann. Sci.
Univ. Jassy, 4, 1908, p. 48.
 CHAPTER VI

THE MEDITERRANEAN REGIONS DURING THE GLACIAL

PERIOD

Our knowledge of the history of the Mediterranean basin during the

Glacial period is not nearly so complete as is that of the more
northern regions, chiefly for the reason that during most of the period
the land lay above its present level, and except for local glaciers in
the mountain regions there was no ice to leave us a record of the
changing climates. Most of what we do know relates to the relatively
brief periods of submergence.
At the beginning of the Glacial period the sea lay some 500 feet
above its present level, and we can trace the first appearance of a
northern marine fauna. This stage is known as the Calabrian; it is
divided into two horizons—a lower, in which northern forms are still
rare, and an upper, in which they are becoming abundant. The most
typical species are two mollusca whose present habitat is the coast
of Iceland—Chlamys (Pecten) islandicus and Cyprina islandica.
The Calabrian beach is not found on the coast of Spain or at
Gibraltar, and in Algeria it probably occurs at a lower level. This
suggests that the subsidence at this period was local, and the
western lands stood up as a barrier against the Atlantic. There must
have been a channel of some sort, however, on the site of the
present Straits of Gibraltar, to provide an inlet for the immigrating
northern mollusca. In the Maritime Alps, and again in the eastern
Mediterranean, the Calabrian beaches are at a much greater height
owing to local elevation.
After the formation of the Calabrian beach the whole
Mediterranean region was elevated above its present level. This
elevation must be contemporaneous with the period of maximum
elevation in north-west Europe associated with the great Mindelian
glaciation. It is suggested that the “sill” of the outlet channel at
Gibraltar was raised above the level of the Atlantic, and the
Mediterranean became, first a closed salt lake, and then a pair of
lakes, the eastern fresh draining into the western, which was salt, the
two being separated by a ridge of land between Italy and Tunis. This
period of elevation was long enough for a great deal of denudation to
take place. Even in the Mediterranean this was a time of severe
climate. On the eastern side of Gibraltar there are breccias, known
as the “Older Limestone Agglomerate,” which reach a thickness of
100 feet in places, and are now much weathered. Similar
agglomerates are found in Malta. These resemble the “head” of the
south of England, and appear to be due to frost action in a severe
climate. In Corsica there are traces of four periods of mountain
glaciation, and the two oldest of these are provisionally correlated
with the Gunzian and Mindelian of the Alps. In the Balkan highlands
there are traces of two distinct glaciations: the older, which was the
more general and reached the greater intensity, probably
corresponding to the Mindelian. In the Atlas Mountains there are
great boulder moraines which seem to belong to three distinct
glaciations, the oldest extending to about 2000 feet above sea-level,
and the second terminating at about 4000 feet, while the third
glaciation consisted of small valley glaciers only.
Towards the close of the Mindelian glacial period the land sank or
the ocean rose again, and the waters of the Atlantic poured in,
bringing with them a great number of high northern and Arctic
mollusca. The theory has been put forward that this influx was in the
nature of a debacle and carved out a deep gorge through the
present Straits of Gibraltar. The beaches deposited by this sea lie at
a height of 250 to 330 feet above the present sea-level. The fauna
resembles that inhabiting the northernmost parts of Europe at the
present day, and the waters must have been several degrees colder
than at present. This stage is termed the Sicilian.
As the climate improved the land gradually rose again, and the
next general raised beach lies at a height of only about 100 feet in
southern Italy (except where it has been elevated by local earth-
movements). Further west it lies still nearer the present sea-level—
twenty feet in the Balearic Islands and only seven feet on the coast
of Spain. On the coast of Algeria and Tunis this beach is found at a
height of about forty-five feet.
The beach contains no trace of the northern fauna found in the
Sicilian stage; instead it is marked by an assemblage of mollusca of
a sub-tropical aspect, including Strombus bubonius, Mytilus
senegalensis and Cardita senegalensis. The bones of large
mammals are also found, including the hippopotamus and southern
forms of elephant (E. antiquus) and rhinoceros (Rh. merckii). This
warm stage corresponds to the Chellean interglacial fauna of
northern Europe, though so far as I am aware no Chellean
implements have been found associated with it.
About this time the Older Limestone Agglomerate of Gibraltar had
been worn into caves, in which are found the bones of ibex, wild
boar, leopard, spotted hyena, Rhinocerus leptorhinus, Elephas
meridionalis, lion, southern lynx, bear, wolf, stag, horse, etc., so that
the rock must have been covered by a rich vegetation, and must
have had a greater extent than now, and a connexion with the
continent of Africa. This is said to have been followed by a
submergence of about 700 feet with numerous oscillations. This
submergence, if it is really attributable to the interglacial, must have
been extremely local, and possibly it is much older.
After the warm Chellean period the Mediterranean region rose
again, probably contemporaneously with the rise which caused the
Rissian glaciation of northern Europe. But the climate was nothing
like so severe as in the Sicilian. We have no old beaches containing
a molluscan fauna of this period, but at the Grotte au Prince near
Mentone, investigated by M. Boule, the Strombus beach is overlain
by a bed of cemented pebbles and “hearths” containing Mousterian
implements and bones of a temperate fauna. The Newer Limestone
Agglomerate on the east of Gibraltar may have been formed during
this period. The Mediterranean lands remained above their present
level until the close of the Glacial period.
 Each glaciation of northern Europe must have been a time of
greater rainfall as well as of lower temperature in the Mediterranean.
The glacial anticyclone in the north displaced the storms from the
Atlantic, which now mostly either skirt the north-west coast of
Norway or pass across Denmark into the Baltic. These storms had to
take a more southerly course, and entered the Mediterranean basin
either across the south of France or in the neighbourhood of
Gibraltar: tracks which are still occasionally followed in winter. These
storms brought a rainfall much heavier than the present, and of a
different character. The Mediterranean is now a “winter rain region,”
and the north of Africa is entirely rainless for several months in the
summer. But during the “Pluvial periods” it is probable that rain fell
throughout the year, though the winter still had more than the
summer. The winter rains were in the form of steady falls of long
duration, such as we experience now in England, while the summer
rains fell in short, heavy showers, perhaps accompanied by thunder.
The Older Pluvial period, which corresponds to the Mindelian
glaciation, had these conditions in their greatest development.
Depressions cannot live long without a supply of moisture, either
from the sea or from transpiring vegetation, and at present such
winter storms as enter the Mediterranean are almost confined to its
surface, and on the African side rarely penetrate more than one
hundred miles inland. But at the period of greatest elevation the
shrunken Mediterranean offered no such great attraction, and with a
comparatively well-watered Sahara the storms were able to pass
much further south. Consequently, northern Africa possessed a
number of large and permanent rivers which reached the sea. It was
along these rivers and their banks that the fauna still inhabiting the
Saharan oases made its way, to be isolated there by the decrease of
the rainfall, so that crocodiles and many species of fish now live in
isolated pools and in rivers which lose themselves in the sand.
In Egypt and Syria the first Pluvial period is double, corresponding
to the Gunz and Mindel glaciations, with an intervening phase of
feeble desert conditions, during which, however, the rainfall
remained greater than the present. The second stage, corresponding
to the Mindelian, indicates very great activity; at this time the Jordan
Sea (Dead Sea) reached its greatest area, extending to the northern
end of the Sea of Tiberias.
Conditions in Egypt at this time are very interesting. South of Cairo
the alluvial Nile muds are at most thirty to thirty-five feet thick, and
ten feet of this thickness has been deposited since the time of
Ramesis II. If the rate of deposition has been uniform, this gives a
period of only 14,000 years for the deposition of the whole thickness
of the muds. The theory put forward by Hume and Craig (British
Association Report, 1911, p. 382) is briefly as follows: The mud
deposits of the Nile valley are carried down with the flood waters of
the Blue Nile, Atbara, etc. These rivers rise in the highlands of
Abyssinia, where they are fed by the rains of the south-west
monsoon. The incidence of the monsoon is determined by a number
of factors, prominent among which is the temperature of southern
Asia. During the winter, at present, the low temperature of the
Himalayan and Tibetan region results in a great outflow of cold air,
which strikes the coast of Africa as the cool dry north-east monsoon.
During this time there is very little rain in Abyssinia. It is only when
the Asiatic land-mass warms up in summer that the south-west
monsoon is established.
But during the Glacial period, as we shall see, there was a great
development of snow and ice on the Himalayas. The result was that
winter conditions, i.e. the north-east monsoon, prevailed more or
less throughout the year, and the rivers which feed the Nile
contained only a small volume of water. Hence they lost themselves
in the desert before reaching Cairo, and the Nile in its present form
did not exist. On the other hand, the westerly winds which at present
bring a moderate winter rainfall to the coast of Syria were greatly
increased in intensity and extended further south, replacing the dry
north and south winds now occupying the Nile valley. The northerly
winds prevailing in the Nile valley in summer are associated with the
low pressure area over the neighbourhood of the Persian Gulf, which
in turn is due to the extremely high temperature experienced there.
Even at the present day the highest hills of Sinai penetrate above the
north winds into a westerly current, and a moderate fall of
temperature over the Persian Gulf would inhibit the north winds in
the Nile valley altogether and allow the westerly winds to reach the
surface. These strong westerly winds brought a heavy rainfall to the
hills, now almost rainless, between the Nile and the Red Sea.
Powerful streams descended the western slopes of these hills,
bringing great quantities of debris, which formed delta-terraces forty
of fifty feet thick where the streams debouched on to the Egyptian
plain. These are especially well developed at Oina, the meeting
place of several dry valleys from the hills, and it is remarkable that
they actually cross the present site of the Nile valley and reach the
desert on its western side, additional evidence that the Nile was not
then in existence.
These gravel terraces contain numerous stone implements of
early (pre-Chellean) types, showing that at this time Egypt had
sufficient rainfall of its own to support human life.
The moist westerly winds carried the climate of the Mediterranean
coast far into the desert. For instance, in the oasis of Khargeh, in
latitude 25°, grew the evergreen oak and other plants not now found
south of Corsica and southern France.
The Mindelian Pluvial period was followed by a long dry period
corresponding to the Chellean, when desert conditions supervened.
The Nile as we know it first appeared during this period. Terraces
were formed on the sides of the valley, probably during the
submergence which produced the Strombus beaches of the western
Mediterranean; these contain Chellean implements. During the
succeeding elevation the Nile cut its bed below the present level.
The Rissian glaciation of northern Europe is represented in Egypt
by a second rainy period, the Lesser Pluvial period. Rain again fell
on the Red Sea hills, forming a newer set of gravel terraces, but
these are much smaller than the great Mindelian terraces. No
terraces are known representing the Wurmian period, and the
country does not seem to have been inhabited at this time. Probably
the climate was semi-desert, with not enough rainfall of its own to
support human life, and yet without the fertilizing Nile floods to
enable human life to exist without rainfall. As has been said, the
present regime did not begin until the last glaciation was nearly over,
about 12,000 b.c.

BIBLIOGRAPHY

Gignoux, M. “Les formations marines pliocènes et quaternaires de l’Italie du Sud et

de la Sicilie.” Ann. l’Univ. Lyon, n.a., Vol. 1, fasc. 36, Paris, 1911, pp. 693.
Depéret, C. “Les anciennes lignes de rivage de la côte française de la
Mediterranée.” Bull. Soc. Geol. de France, ser. 4, Vol. 6, pp. 207-30.
Douvillé, R. “Espagne,” Handbuch regional Geol., H. 7, 1911. (Includes Gibraltar
and Balearic Is.)
Hume, W. F., and Craig, J. I. “The Glacial period and climatic change in North-east
Africa.” Rep. Brit. Assoc., 1911, p. 382.
 CHAPTER VII

ASIA DURING THE GLACIAL PERIOD

The great area of Asia is at present but little explored for glacial
traces, but a certain amount of evidence has been collected, and the
data from the various mountain districts are consistent enough to
map out the general trend of the history of the continent during the
Ice Age.
The earth-movements which brought about the present
configuration of Asia were completed as regards their major details
by the close of the Tertiary period. These movements left a number
of great basins closed in on all sides by enormous mountain walls; at
first all these basins contained lakes, and the subsequent
geographical history has consisted largely in the gradual silting up of
the lakes and the development of more and more arid conditions.
The fluctuations of the Ice Age were superposed on this secular
desiccation, but except in northern Siberia the part played by
glaciation in the history of the country has been relatively small.
Consider for a moment the relief of Asia. The orographic centre
may be taken as the great Pamir plateau, the “Roof of the World,”
with an average elevation exceeding the height of Mont Blanc,
diversified by ranges of mountains exceeding 25,000 feet in places.
East of this is the great plateau of Tibet, 10,000 to 17,000 feet,
bounded on the south by the mighty Himalayas, and on the north by
the mountains of Kuen Lun. On the north the Pamir plateau is
bounded by the Alai range, passing north-east into the Tian-Shan
mountains, rising to 24,000 feet in Khan-tengri. Still further north-
east comes the Altai range, with an elevation of 9000 feet. East of
Lake Baikal lie a series of ranges averaging 8000 feet in height, and
passing into the Stanovoi range of eastern Siberia and the
mountains of Kamchatka.
The Himalayas, owing to their heavy snowfall derived from the
south-west monsoon, bear numerous great glaciers, but with the
series of ranges extending from the Pamirs to north-east Siberia the
case is different. These ranges all rise above the snow-line in places,
but owing to the scanty snowfall they bear at most a few small
glaciers on their northern sides, and none at all on the slopes which
face towards the deserts of western China, and in all cases the
glaciation is very slight in comparison with their elevation.
This distribution was characteristic also of the Ice Age. In the
Pamirs there is evidence of two periods when the glaciers had a
greater extent; in the first they extended to a level of 5000 feet, in the
second to 7000 feet. The present limit of the glaciers lies at about
10,000 feet. The first glaciation was remote, for the moraines are
worn and weathered, but the second was much more recent, for the
moraines are fresh, and in some cases there are still masses of
“dead” ice buried beneath great accumulations of debris and
occasionally exposed by slips.
In the Tian-Shan mountains there are remains of two glaciations.
The earlier was the greater, and the glaciers descended well below
10,000 feet. This glaciation was followed by a long interval, when the
erosion of the rivers converted the U-shaped glacial valleys into V-
shaped gorges. A second glaciation descended to a level of 10,000
feet, and again developed U-valleys to this level; the end-moraines
of these glaciers are young and fresh-looking. In the Altai range
there were also two glacial periods. In the older and greater the
snow-line was depressed by 3000 feet. The glaciers attained a
length of twelve miles and descended to a level of only 3000 feet
above the sea. The second glaciation was less extensive.
So far we have been dealing with small mountain glaciers only.
But in north-eastern Siberia we find a different state of affairs. The
Stanovoi and Verkhoiansk mountains were heavily glaciated, and
during the first glaciation were probably the centre of an actual ice-
sheet similar to that of Scandinavia. The ice descended the valleys
of the rivers Yana, Indijirka and Kolyma and covered the New
Siberian Islands, which were at that time connected with the
mainland. The upper valley of the Lena was also heavily glaciated by
an ice-sheet moving southward, probably from the Patom highlands.
When this glaciation drew to a close the source of supply among the
mountains ceased, and the ice on the lowlands and in the lower
parts of the river valleys was left stranded as “dead” ice. When the
mountains became free of ice, the re-born rivers carried great
quantities of moraine-clay and other debris with them, and flooding
the ice-surface over wide areas deposited their load above the ice. In
course of time the remains of the ice-sheet were deeply covered by
a layer of earth and stones, which prevented the ice from melting
and preserved it to the present day. This is the probable origin of the
well-known “fossil ice” of Siberia. Other theories have been put
forward, such as the freezing of ground water during the winter, but
none are satisfactory, and that given here was generally adopted by
Russian geologists.
During the long warm interglacial which followed, the surface of
the thick earth-layer covering the ice bore low-growing herbage in
the same way as any other earth-surface. (A parallel to this is found
in Alaska, where the glaciers terminate among the forests, which
actually grow over the moraines covering their snouts.) The rivers
cut their way down through the earth and ice, exposing ice-cliffs,
which were quickly buried by talus from above. The mammoth and
woolly rhinoceros roamed the land, and their tusks remain in great
numbers as the “fossil ivory” of Siberia and the Arctic Ocean. Still
more remarkable is the fact that mammoths have been found buried
entire, and preserved by the frozen ground to the present day. It is
difficult to say how the animals reached such a position, but most
probably they sank into swamps formed during the summer and
were quickly frozen.
In western Europe the mammoth and woolly rhinoceros are
regarded as indications of severe climate, but their presence in
north-eastern Siberia in large numbers is evidence of a climate
probably somewhat warmer than that of the present day, especially
as regards the length of the vegetation period. Probably the winter
snowfall also was less than now. It is difficult to see how the fauna
could have moved from, say, the New Siberian islands into a warmer
climate each winter, for the winter climate becomes markedly more
severe as one penetrates south from the Arctic coast into the interior.
It is possible that the mammoth and woolly rhinoceros hibernated
during the winter.
After this interglacial there came a recrudescence of glacial
conditions. In this case, however, the Stanovoi and Verkhoiansk
mountains and the Patom highlands were not buried in an ice-sheet,
but became the centre of great valley glaciers, which reproduced the
well-known glacial phenomena—corries, glacial terraces, U-valleys,
etc. The ice extended down the great river valleys, leaving a typical
moraine landscape on either side, and again reached the New
Siberian islands. In course of time the climate ameliorated, again
commencing in the south, and again the ice of the glaciers was
buried. In the New Siberian islands the happenings are summarized
very expressively by a rock-section described by Vollossovitsch. The
bottom of the section is formed by the older layer of “fossil ice.”
Above this is a sandy clay with remains of meadow vegetation and
shrubs, followed by a fine clay with remains of alder and white birch,
and the bones of mammoth and rhinoceros. Above this comes
another layer of “fossil ice,” followed by clay with the dwarf birch,
Arctic willow, and bones of musk ox, horse and later mammoth. After
this the coastal regions sank beneath the sea for a time and marine
clays were formed in a climate somewhat warmer than the present.
When the land rose again the conditions resembled those now
prevailing.
Though not part of Asia, reference may be made here to the
glaciation of Spitzbergen, which runs strictly parallel with that of
northern Siberia. The first glaciation was of the “ice-sheet” type,
originating in the region north of Storfjiord, filling the whole of that
fiord and extending south of South Cape. Barentz Land and Stans
Foreland were at least partially ice-covered. The ice-floor of
Spitzbergen, which resembles that of Siberia, may have originated
during this glaciation. This was followed by subsidence to 230 feet
below present level, and the ice retreated, giving place to an
“interglacial,” during which frost was very active and largely
obliterated the traces of the ice-sheet. This “interglacial” was
followed by a second extension of the ice, which affected the valleys
and fiords only, leaving the plateaux free. This again was followed by
subsidence and a warm period.
In southern Kamchatka there was a great development of ice, but
in the form of a network of glaciers rather than of an inland ice-sheet.
In the east the ice reached the sea, but on the west it left a zone
forty to sixty miles broad, and up to a thousand feet high unglaciated,
so that there was the same difference then as now between the rainy
east side and the drier west side of the peninsula. The present snow-
line in the centre of southern Kamchatka is about 5500 feet, and at
the maximum of the glaciation it must have been fully 3000 feet
lower.
This glaciation was followed after an interval by a second, which
was confined to the mountains. The moraines of this glaciation are
much fresher than are those of the earlier one.
In Japan the mountains were only just high enough for glaciers to
develop in the north. The moraines are old and weathered, and their
meaning has been disputed; but recent work by Simotomai and
Oseki seems to have established their glacial origin. The depression
of the snow-line necessary to produce them—about 3000 feet—fits
in very well with that observed in adjoining parts of the continent.
The phenomena were confined to small hanging glaciers in the Hida
mountains which cut out corries and descended to a level of about
8000 feet, leaving small morainic ridges. This glaciation was
probably contemporaneous with the earlier and greater glaciation of
Siberia. To the succeeding interglacial may be attributed the marine
deposits found near Tokio containing corals, at present living some
distance further south. No trace of any subsequent glaciation of
Japan has yet been found.
J. S. Lee has recently called attention to the existence of a
glaciated area in northern China, the evidence for which consists of
moraines and striated slabs found in southern Chi-li, and a glaciated
valley with travelled boulders in the north of Shan-si. The glacial
deposits in Chi-li are closely associated with a layer of quartzite
pebbles which continues southward beneath the loess on the
eastern side of the Tai-hang range, and is attributed to either
torrential rain or the melting of glaciers. J. Geikie had long ago stated
that there once existed ice-masses all over northern China, and
considered that the ice came from the Himalayas. This origin is
impossible, the probable source of the ice being the Yablonoi
mountains in southern Mongolia.
In the Himalayas the glaciers formerly had a much greater
extension. The glaciers at present extend downwards to 11-13,000
feet, but old moraines are found at 7000 feet, and near Dalhousie on
the southern slopes of the Dholadar range to 4740 feet.
On the northern side of the Himalayas there was a great
development of ice over Tibet, but there was not a real ice-sheet
such as occurred further north. Oldham records three separate
periods of glaciation in Kashmir, but it is not yet possible to discuss
the glacial history of the Himalayas in detail. The latter is likely to
prove complicated, since the range is still rising, and has probably
been doing so either continually or intermittently throughout the
Quaternary.
The great development of ice in Tibet, which is now semi-arid,
owing to interception of the rain-bearing winds by the Himalayan
range, suggests a considerable alteration in the present
meteorological conditions. The Tibetan snowfall was probably due to
the Mediterranean storms, which now give a small winter rainfall in
north-west India, and which during the Glacial period greatly
increased in strength and frequency and occurred throughout the
year (Chapters IV and VI), giving the Pluvial period of North Africa.
These storms would pass across Persia and continue to the north of
the Himalayas, probably breaking up over the Tibetan plateau.
It is evident that, taking northern Asia as a whole, there have been
two general glaciations, of which the first was the more severe,
separated by a long interglacial, during which, in Japan at least, the
climate became appreciably warmer than the present. The first
glaciation is related to elevation in the Arctic basin, which closed
Bering Strait and united the New Siberian islands to the mainland. It
was almost certainly contemporaneous with the first glaciation
(Gunz-Mindel) of Europe. The ice began as glaciers on the
mountains as in Scandinavia, but, owing to the scanty supply of
snow, developed more slowly and only reached the dignity of ice-
sheets in north-east Siberia. Then followed subsidence below the
present level, wider opening of the Bering Strait, warm ocean
currents and a long interglacial. After this there was again elevation
and a re-development of ice-sheets, but apparently once only, and
not twice as in Europe. This glaciation probably corresponded in
point of time more or less with the Rissian, for the post-glacial dry of
central Asia appears to have been of enormous period length.
There is one other phenomenon which must be considered in
connexion with the glacial history of Asia, and that is the loess.
Loess has already been referred to in connexion with the glaciation
of Europe, but in China its development is much greater. Richthofen,
who first studied this deposit attentively, and to whom we owe the
æolian theory of its origin, found that it was formerly deposited in
China over a much greater area than that over which it is
accumulating at present, and attributes this cessation of growth to
the heavier rainfall brought by the Glacial period, which enabled the
rivers to cut back their valleys and drain some of the mountain
basins, formerly enclosed. He considered that loess can accumulate
more rapidly in a closed basin, where occasional floods leave behind
them layers of bare sand and mud, easily dried to dust, than in a
well-drained river valley where floods are rare.
In western Asia outside the limits of glaciation we have further
evidence of at least one Pluvial period in the former far greater
extent of all the enclosed lakes, due partly to greater precipitation
and partly to decreased evaporation. The Caspian Sea and Aral Sea
were extended to several times their present size and united into a
single sheet of inland water. Lake Lop-Nor was greatly increased in
size, and many of the desert basins, at present dry, were the sites of
salt lakes. This is especially the case in central Persia, where there
were large salt or brackish lakes.
 These Pluvial conditions have not yet been correlated with the
glaciations of Asia, but, by analogy with the conditions in America
discussed in the next chapter, there is little doubt that they were
contemporaneous with one at least of the glaciations, and probably
there were two main Pluvial periods coinciding with the two Glacial
periods. At Baku, on the shores of the Caspian river, Pumpelly has
found old shore lines at heights of 600, 500, and 300 feet above the
present level of the water. Still more interesting are the conditions
found by Sven Hedin in the Kavir basin of Persia. Here there are
lacustrine clays and silts referable to a Pluvial period covered by
beds of almost pure salt, suggesting a rapid and complete drying up
of the lake. Above this again are further silts indicating a return of
Pluvial conditions. In addition to this the succession of silts and clays
show that there were several minor fluctuations superposed on the
main wet periods, giving ten moist phases altogether.

BIBLIOGRAPHY

Many of the more important references are in Russian, and for these reference
is made to summaries in other languages.
Sevastianov, D. P. “On the glaciation of the extreme north-east of Siberia.” J. 12
Congr. Russ. Nat., Moscow, 1910, No. 10, p. 491. (Russian, see Geol.
Centralblatt, 15, p. 205.)
Riesnitschanko, W. “Ancient and modern glaciers of the south-western Altai.”
Mem. Russ. Geogr. Soc., 48, 1912, p. 357. (Russian, see Geol.
Centralblatt, 19, p. 131.)
Komarov, W. “On the Quaternary glaciation of Kamchatka—Travels in Kamchatka
in 1908-9,” Vol. 1 (Russian, see N. J. Min., 1915, Pt. 2, P. 117).
Merzbacher, G. “Zur Eiszeitfrage in der nordwestlichen Mongolei.” Peterm. Mitt.,
Gotha, 57, 1911, p. 18.
Prinz, Gyula. “Die Vergletscherung des nördlichen Teiles des zentralen Tien-
schan-Gebirges.” Wien, Mitt. K. K. geogr. Gesellsch, 52, 1909, p. 10.
Obrutschev, W. A. “Geological map of Lena gold-bearing region.” St. Petersburg,
1907. [Text in Russian; see Geol. Centralblatt, 12, pp. 507-9.]
Simotomai, H. “Die diluviale Eiszeit in Japan.” Berlin, Zs. Ges. Erdkunde, 1914, p.
56.
Oseki, K. “Some notes on the glacial phenomena in the North Japanese Alps.”
Edinburgh, Scot. Geogr. Mag., 31, 1915, p. 113.
Lee, J. S. “Note on traces of recent ice-action in North China.” Geol. Mag., 59,
1922, p. 14.
Burrard, S. G., and Hayden, H. H. “A sketch of the geography and geology of the
Himalaya Mountains and Tibet.” Calcutta, 1907-8.
Hogböm, G. “Bidrag till Isfjordsomradets kvartargeologi.” Geol. Foren. Stockholm
Forb., 1911. (Spitsbergen; résumé in German.)
Richthofen, F. Freih. von. “China.” 5 Vols., 1907-12. (Loess, see Vol. 1, p. 74 ff.)
Hedin, Sven. “Some physico-geographical indications of post-Pluvial climatic
changes in Persia.” Internat. Geol. Congr., Stockholm, 1911. “Die
Veränderung des Klimas.”
 CHAPTER VIII

THE GLACIAL HISTORY OF NORTH AMERICA

The glaciation of North America was even greater and more

complicated than was that of Europe. It spread from three main
centres, the Cordilleran or Rocky Mountain centre, the Keewatin
centre west of Hudson Bay, and the Labradorean centre. Vancouver
Island in the west and New Brunswick and Newfoundland in the
east, were also independent centres of glaciation, and ice from the
latter may have reached the coast of the United States in places.
The ice covered an area of about 4,000,000 square miles, and the
main ice-sheet extended to 38° N., or twelve degrees further south
than the Scandinavian ice-sheet. Nine stages are recognized by
American geologists, though opinion is divided as to whether all the
stages of “deglaciation” represent real interglacial periods. The
sequence is as follows:
1. Nebraskan, Jerseyan or pre-Kansan glaciation.
2. Aftonian deglaciation.
3. Kansan glaciation.
4. Yarmouth deglaciation.
5. Illinoian glaciation.
6. Sangamon deglaciation.
7. Iowan glaciation.
8. Peorian deglaciation.
9. Wisconsin glaciation.
On the other hand, in the northern part of the Rocky Mountains
there is evidence of only two Glacial periods, separated by a single
long interglacial, though perhaps the second glaciation was double.
Further south, out of reach of the main ice-sheets, there are traces of
two and in places three separate developments of valley glaciers
resembling those of the Alps.
As in the case of Europe, the literature of the subject is extensive
and conflicting, but the following summary of the course of events
represents the views of most moderate American geologists.
The Quaternary period opened with extensive elevation of the
whole North American continent, which raised the Rocky Mountains
several thousand feet above their present level and extended the
continental area over much of the northern archipelago. In the east
Newfoundland is considered to have been raised at least 1000 feet,
a movement which converted the banks into dry land and interposed
a large cold area in the path of the moisture-bearing southerly winds.
As in northern Europe the high mountains of the west were the first
to develop large glaciers, which coalesced into an ice-sheet, filling
the valleys and rising up the slopes of the mountains until it reached
a thickness of 5000 feet. In Puget Sound the ice was 4000 feet thick,
but seawards the slope is very rapid and the ice was unable to
extend far from the shore. This ice-sheet extended south-eastwards
some distance into the United States, forming the first ground-
moraine of that district. Probably while this Cordilleran glaciation was
still in progress ice began to spread outwards also from the
Labradorean centre, forming the oldest drift of that region. These
oldest deposits are, however, not yet well understood.
This oldest boulder-clay is separated from the moraines of the
main glaciation near its southern limit by river gravels containing the
remains of mollusca and large herbivorous mammals—extinct
species of horse, the hairy mammoth of the old world (Elephas
primigenius), and two other extinct species of elephant, and also the
true American mammoth. This is the Aftonian fauna, which has been
claimed as evidence of an Interglacial period. That it evidences a
retreat of the ice-edge in that particular region is certain, but that the
climate became really temperate is very doubtful. More probably it
corresponds to the Gunz-Mindel “interglacial” of the Alps, and was
formed when the Cordilleran ice-sheet was retreating, but before the
Keewatin sheet had reached its maximum.