The Nature of Complex Networks

Sergey N. Dorogovtsev
Visit to download the full and correct content document:
https://ebookmass.com/product/the-nature-of-complex-networks-sergey-n-dorogovtse
v/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...

Boolean Networks as Predictive Models of Emergent

Biological Behaviors (Elements in the Structure and
Dynamics of Complex Networks) Rozum

https://ebookmass.com/product/boolean-networks-as-predictive-
models-of-emergent-biological-behaviors-elements-in-the-
structure-and-dynamics-of-complex-networks-rozum/

Malware Diffusion Models for Wireless Complex Networks.

Theory and Applications 1st Edition Karyotis

https://ebookmass.com/product/malware-diffusion-models-for-
wireless-complex-networks-theory-and-applications-1st-edition-
karyotis/

The Structure of Complex Words Empson

https://ebookmass.com/product/the-structure-of-complex-words-
empson/

The Nature of Witches Rachel Griffin

https://ebookmass.com/product/the-nature-of-witches-rachel-
griffin-3/
The Nature of Witches Rachel Griffin

https://ebookmass.com/product/the-nature-of-witches-rachel-
griffin-2/

The Nature of Witches Rachel Griffin

https://ebookmass.com/product/the-nature-of-witches-rachel-
griffin/

The Nature of Witches Griffin Rachel

https://ebookmass.com/product/the-nature-of-witches-griffin-
rachel/

The Problem of Evil: Eight Views in Dialogue N N

Trakakis

https://ebookmass.com/product/the-problem-of-evil-eight-views-in-
dialogue-n-n-trakakis/

The Sacred Depths of Nature Ursula Goodenough

https://ebookmass.com/product/the-sacred-depths-of-nature-ursula-
goodenough/
THE NATURE OF COMPLEX NETWORKS
The Nature of Complex Networks

Sergey N. Dorogovtsev and José F. F. Mendes

University of Aveiro, Portugal
 Great Clarendon Street, Oxford, OX2 6DP,
United Kingdom
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 in certain other countries.
© 2022 Sergey N. Dorogovtsev and José F. F. Mendes
The moral rights of the authors have been asserted
Impression: 1
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 licence, or under terms agreed with the appropriate reprographics
rights organization. Enquiries 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.
Published in the United States of America by Oxford University Press
198 Madison Avenue, New York, NY 10016, United States of America.
British Library Cataloguing in Publication Data
Data available
Library of Congress Control Number: 2022930598
ISBN 978–0–19–969511–9
DOI: 10.1093/oso/9780199695119.001.0001
Printed and bound by
CPI Group (UK) Ltd, Croydon, CR0 4YY
Links to third-party websites are provided by Oxford in good faith and
for information only. Oxford disclaims any responsibility for the materials
contained in any third-party website referenced in this work.
For those whom we love
 Gentlemen! As is custom among our kind, we do not
plunge headlong into folly on the orders of a single madman,
but act according to our own collective madness!
Assassin’s Creed IV: Black Flag
Preface

The authors of this book are scientific workers in the field of complex net-
works. This is an explosively developing multidisciplinary area, which in-
volves practically everything, natural and artificial, in the world, and we,
theoretical physicists, explore it, armed with the standard tools of statistical
physics. What we are doing is uncovering the actual simplicity and beauty
of complex systems including the random complex networks. The book is
about the key ideas and concepts of this field which is already called the
science of networks. The highly heterogeneous networked systems, which we
explore, typically have no governing authority, no command centre taking
decisions and issuing orders. Nonetheless, even without orchestration, these
remarkably widespread systems function very effectively and reliably. More-
over, the absence of centralization in favour of distributed self-organization
is vital for their existence and robustness.
Thanks to numerous tips one can appreciate the pace and scale of ef-
forts to surveil, control, protect, and manipulate society, in essence, large
social and information networks. The sweeping reset of our ‘highly intercon-
nected and interdependent world’, induced and concerted by the Covid-19
pandemic (Schwab and Malleret, 2020), is forcefully amplifying these exer-
tions. The big problem now is how to control large complex systems that
is impossible to govern. A related fundamental problem is how to struc-
ture and efficiently process the collected big data. Similarly impressive and
costly efforts are under way to engineer and manage large cellular, tech-
nological, deep-learning, and many other networks. These extensive works
demonstrate how important it is to understand in detail the principles of
organization and function of highly heterogeneous and highly structured
random networked systems, that is the nature of complex networks.
In 2003 we published the first reference book in this research area,
the ‘Evolution of Networks: From Biological Nets to the Internet and the
WWW,’ which essentially focused on evolving networks. Our new, more
dense and advanced, book touches upon a much wider range of networks
and networked systems paying particular attention to the directions that
emerged after 2002–2003. Writing a book is about asking good questions.
So, keeping the book compact, we consider only the issues and key results

ix
PREFACE

that, we believe, will not lose their value in the future. To avoid drowning
in serious mathematics we have to present a number of basic theorems from
graph theory without even sketching the ideas of their proofs. Furthermore,
for the sake of brevity we do not include in the book chapters devoted to
numerous applications and empirical material. The reader will find detailed
discussions of these matters in a number of comprehensive books and re-
views, which we cite.
The researchers studying complex networks will acquire from this con-
cise modern book a number of new issues and ideas, not yet touched upon
in other reference volumes. We propose a statistical mechanics view of ran-
dom networks based on the concept of statistical ensembles, but approaches
and methods of modern graph theory, concerning random graphs, overlap
strongly with statistical physics. Hence mathematicians have a good chance
to discover interesting things in our book, even though it does not contain
mathematical proofs and trades off rigour for comprehension, brevity, and
relevance. We expect that this book will be useful for undergraduate, mas-
ter, and PhD students and young researchers from multidisciplinary studies,
physics, computer science, and applied mathematics wishing to gain a seri-
ous insight into the principles of complex networks. The book can be used as
a text in university courses on complex networks. We propose to determined
students not only a brief trip to the land of complex networks but an option
to stay there forever. For a more elementary and concise introduction to the
science of networks, we refer most impatient readers to the text of one of
us, S. N. Dorogovtsev, ‘Lectures on Complex Networks.’
We are deeply indebted to our friends and colleagues all over the world
for their encouragement and advice, first and foremost to Gareth Baxter,
who has read and commented on the manuscript, Alexander Goltsev, Gines-
tra Bianconi, Pavel Krapivsky, Rui Americo da Costa, Gábor Timár, João
Gama Oliveira, Nahid Azimi-Tafreshi, KyoungEun Lee, António Luı́s Fer-
reira, Sooyeon Yoon, Bruno Coutinho, Marta Santos, Nuno Araujo, Ri-
cardo Jesus, Marian Boguñá, Maria Ángeles Serrano, Dmitri Krioukov,
Edgar Wright, Romualdo Pastor-Satorras, Tiago Peixoto, Jorge Pacheco,
Francisco Santos, Peter Grassberger, Mark Newman, Byungnam Kahng,
Zdzislaw Burda, Michel Bauer, Raissa D’Souza, Doochul Kim, Mikko Alava,
Hyunggyu Park, Petter Holme, Kimmo Kaski, Hawoong Jeong, Satu Elisa
Schaeffer, José Ramasco, János Kertész, Jae Dong Noh, László Barabási,
Shlomo Havlin, Matteo Marsili, Bartlomiej Waclaw, Geoff Rodgers, Malte
Henkel, Davide Cellai, James Gleeson, Alexander Povolotsky, Alexander

x
 PREFACE

Zyuzin, Santo Fortunato, Vittoria Colizza, Alessandro Vespignani, Alex Are-

nas, Guido Caldarelli, Filippo Radicchi, Adilson Motter, Sid Redner, Yamir
Moreno, Maxi San Miguel, Alain Barrat, Marc Barthelemy, Agata and Piotr
Fronczak, Konstantin Klemm, Lenka Zdeborová, Zoltán Toroczkai, Alexei
Vázquez, Florent Krzakala, Valentina Guleva, Jesus Gomez-Gardeñes, Bosi-
ljka Tadic, Piet Van Mieghem, Dima Shepelyansky, Sergey Maslov, Ernesto
Estrada, Bruno Gonçalves, Serguei Nechaev, Alexander Gorsky, Ronaldo
Menezes, Hans Herrmann, Nelly Litvak, Andrei Raigorodskii, and Dafne
Bandeira. We are enormously bound to Alexander Nikolaevich Samukhin
(1953–2018), our friend and collaborator, who showed us the essence and
logic of statistical mechanics and its mathematical apparatus. Our book
would be impossible without his friendship and tuition. Finally, our warmest
thanks to the editorial and production staff at Oxford University Press for
their guidance, encouragement, and patience.

Aveiro S.N.D.
August 2021 J.F.F.M.

xi
Contents

1 First Insight 1
1.1 Statistical mechanics view of random systems 1
1.2 History of networks 4
1.3 Small and large worlds 10
1.4 First structural characteristics of networks 13
1.5 Equilibrium versus growing trees 15
1.6 Real-world networks 19
2 Graphs 23
2.1 Types of graphs 23
2.2 Graphicality 29
2.3 Representations of graphs 30
2.4 Walks, paths, and cycles 36
2.5 Triangles 38
2.6 Cliques 40
2.7 Betweenness centrality 41
2.8 Connectivity 43
2.9 Spectra of graphs 44
3 Classical Random Graphs 55
3.1 G(N, p) model 55
3.2 Erdős–Rényi model 57
3.3 Cycles and clustering 58
3.4 Giant connected component 60
3.5 Finite connected components 64
4 Equilibrium Networks 70
4.1 The configuration model 70
4.2 Local tree-likeness 72
4.3 Generating maximally random networks 77
4.4 Hidden variables 78
4.5 Annealed networks and graphons 80
4.6 Clustering, cycles, and cliques 81
4.7 Correlations 83
CONTENTS

4.8 Cut-offs and rich club phenomenon 91

4.9 Motifs in networks 94
4.10 Equilibrium network ensembles 96
4.11 The case of triangles 99
4.12 Weighted networks 100
4.13 Random geometric graphs 104
4.14 Small-world networks 105
4.15 Networks embedded in metric spaces 109
5 Evolving Networks 113
5.1 Random recursive trees 113
5.2 Preferential attachment 116
5.3 Origin of preferential attachment 123
5.4 Condensation phenomenon 126
5.5 Berezinskii–Kosterlitz–Thouless (BKT) transition 130
5.6 Accelerated growth and densification 132
5.7 Transitions in dense networks 134
5.8 Growth and decay 135
5.9 Power of choice 137
5.10 Evolving weighted networks 137
5.11 Evolution preserving degrees 139
5.12 Evolution of simplicial complexes 140
5.13 Deterministic graphs 144
6 Connected Components 146
6.1 Giant connected component 146
6.2 Site and bond percolation 152
6.3 Message passing 155
6.4 Beyond tree-likeness 164
6.5 Bow-tie structure of directed networks 168
6.6 Finite connected components 171
6.7 k-cores 175
6.8 Dynamics of pruning 187
6.9 s-cores in weighted networks 194
6.10 k-connected components 195
6.11 Giant component in correlated networks 197
6.12 k-clique percolation 198
6.13 Explosive percolation 202
6.14 Largest component in finite networks 207

xiv
 CONTENTS

6.15 Cores and controllability 210

7 Epidemics and Spreading Phenomena 216
7.1 Bootstrap percolation 216
7.2 The Watts model 219
7.3 Main epidemic models 223
7.4 The SIS model and contact process 224
7.5 The SIR, SI, and SIRS models 233
7.6 Epidemic outbreaks 237
7.7 Epidemics in a metapopulation 243
7.8 Rumour spreading 246
7.9 Opinion formation: The voter model 248
7.10 Propagation of memes 253
8 Networks of Networks 258
8.1 Networks with vertices and edges of different types 258
8.2 Mutually connected components 259
8.3 Avalanches and cascading failures 272
8.4 Other percolation problems 274
8.5 Dynamical systems on multilayer networks 281
9 Spectra and Communities 284
9.1 Adjacency matrix spectra 284
9.2 Laplacian matrix spectra 290
9.3 Localization 299
9.4 Stochastic block model 307
9.5 Modularity 308
9.6 Detection of communities 314
9.7 Overlapping communities 323
10 Walks and Search 326
10.1 Diffusion and random walks on networks 326
10.2 Greedy routing 334
10.3 Navigability 337
10.4 Google PageRank 342
11 Temporal Networks 345
11.1 The concept of a temporal network 345
11.2 Random walks on temporal networks 348
11.3 Epidemic spreading 351

xv
CONTENTS

12 Cooperative Systems on Networks 356

12.1 The Ising model 356
12.2 Critical phenomena 360
12.3 Games on networks 363
12.4 Phase synchronization 365
13 Inference and Reconstruction 374
13.1 Finding the root of a growing tree 374
13.2 Finding missing links 378
14 What’s Next? 380
Further reading 382
Appendix A Adjacency Matrix for Hypergraphs 388
Appendix B Spectra of symmetric normalized Lapla-
cians of sample graphs 390
Appendix C Generating Functions 392
Appendix D Hyperscaling Relations for Percolation 397
Appendix E Degree Distribution of a Damaged Net-
work 401
Appendix F Non-backtracking Matrix 402
Appendix G Treating General Interdependent Networks 406
References 410
Index 440

xvi
1
First Insight

1.1 Statistical mechanics view of random systems

Look at the two graphs in Figure 1.1. Could you say which graph is random,
left or right? The typical student’s response is: ‘Of course, the right one!’
This immediate answer is dramatically incorrect. It is actually impossible to
say whether a finite graph is random or non-random (deterministic) since
one can generate any finite graph by some deterministic algorithm. The
example in Figure 1.2 explains what is really a random graph. This graph
has a number of different realizations (individual graphs), and each of them
occurs with some associated probability. Thus a random graph (random net-

Fig. 1.1 Which graph is random, left or right?

Fig. 1.2 Example of a random graph. The first, second, and third graphs are
realised with probability p, q, and 1 − p − q, respectively.

1
FIRST INSIGHT

work) is a statistical ensemble of individual graphs, in which each member

has its probability of realization. (Note that we do not distinguish the terms
‘graph’, or its generalization—‘hypergraph’, and ‘network’.) In particular,
all these probabilities may be equal, which provides a uniform ensemble. In
short, a random graph is a statistical ensemble of graphs. In this picture,
the result of the measurement of some characteristic of a random graph, an
observable, is the average of this characteristic over the statistical ensemble
accounting for the probabilities of realization of its members.1
This construction is identical to the foundational notion of statistical
mechanics, which is just the statistical ensemble. The statistical ensemble
is the complete set of all possible states (configurations) of a system. Each
member of a statistical ensemble is accompanied by its statistical weight,
a positive number, which is equal to the probability of realization of this
member with some unimportant factor, equal for all members. In the 1870s,
Ludwig Boltzmann explained that the statistical weights Wα of the members
α of a statistical ensemble are expressed in terms of the energy Eα of these
members (which are states or configurations),

Wα ∝ e−βEα . (1.1)

Here, β is a control parameter, a positive number, β = 1/(kB T ), where kB is

the Boltzmann constant and T is temperature. The first to comprehend that
thermodynamics is about probability and probability distributions, that is,
statistics, was James Clerk Maxwell. Maxwell first applied the term ‘sta-
tistical’ to thermodynamical systems in 1871, and in 1884, Josiah Willard
Gibbs coined the term ‘statistical mechanics’; in 1902 he essentially com-
pleted the construction of equilibrium statistical physics elaborating the
idea of statistical ensembles in his book Elementary Principles in Statistical
Mechanics.
These efforts were directed to understanding equilibrium systems where
statistical weights do not change with time. The breakthrough in under-
standing non-equilibrium systems (having evolving statistical weights) came
from Albert Einstein (1905) and Marian Smoluchowski (1906) on molecu-
lar Brownian motion, and Smoluchowski in 1916, in which he derived a
1
Note that exploring empirical material or performing simulations, a researcher often
works with only a few realizations of a random network, sometimes, with a single member
of a given ensemble. Inspecting this single graph, the researcher measures how frequently
a given structural feature occurs within this particular realization, for example, measures
the fraction of vertices with q connections. These values coincide with the corresponding
averages over the full ensemble only in the infinite size limit.

2
 1.1 STATISTICAL MECHANICS VIEW OF RANDOM SYSTEMS

linear equation for coagulation processes. The Smoluchowski equation actu-

ally provides a unified description of the evolution of statistical weights in
non-equilibrium statistical ensembles. Let us write this equation in appli-
cation to evolving random networks. Let G denote a random graph (net-
work), G denote individual members of this ensemble, and W(G, t) de-
note their statistical weights, proportional to probabilities of realization,
P(G, t) = W(G, t)/ G0 ∈G W(G0 , t). The observables in this scheme are the
P

averages over the statistical ensemble,

P
X W(G)X (G)
hX i = P(G)X (G) = G∈G P . (1.2)
G∈G G∈G W(G)

We consider a stochastic process in which members of this ensemble trans-

form into other members of the same ensemble. A graph G ∈ G transforms
to graph G0 ∈ G with probability r(G0 , G)dt. The Smoluchowski equation
for this process is
∂W(G, t) X
= [r(G, G0 )W(G0 , t) − r(G0 , G)W(G, t)]. (1.3)
∂t 0 G ∈G

How does one obtain an equilibrium ensemble from this equation? It is

actually not enough to demand the stationary statistical weights, W(G, t) =
W(G), for equilibrium. We must also take into account that non-dying-off
chains of transitions—‘flows’ or ‘currents’—are absent in equilibrium. That
is, for any cycle, we must have the equality of the kind:

r(G, G0 )r(G0 , G00 )r(G00 , G) = r(G, G00 )r(G00 , G0 )r(G0 , G). (1.4)

Furthermore, for each pair of graphs G, G0 ∈ G in the ensemble, we also

need the existence at least one connecting chain of transitions

r(G0 , Gn ) . . . r(G3 , G2 )r(G1 , G) 6= 0. (1.5)

There must not be separated parts of the ensemble. This guarantees that
the weights are determined unambiguously: ascribing an arbitrary statistical
weight to some graph, one can obtain statistical weights of all other graphs
up to a constant multiple. Equation (1.4) leads to the the detailed balance
condition
r(G, G0 )W(G0 ) = r(G0 , G)W(G), (1.6)
which provides statistical weights in terms of the transition matrix r(G, G0 ).
To satisfy Eq. (1.6) or Eq. (1.4), it is sufficient to assume the factorization:

3
Another random document with
no related content on Scribd:
COURSE AND DURATION.—The onset of the disease is sudden. The
symptoms in the first two stages may last only for a few minutes and
pass off, or the disease may pass through all the stages and
terminate in gangrene. It is usual for the first stage of ischæmia to
last several days, varying in severity; for the second stage to last
several days; and for the stage of gangrene to occupy about three
weeks. The shortest duration of a single attack has been ten days,
the longest five months. If the gangrene begins simultaneously in all
the fingers, the duration will be shorter than if it proceeds to one after
another. In one-third of the cases a recurrence of the disease within
a year of the first attack has been observed, and it is probable that
the proportion would have been larger had all the patients been kept
under observation. In some cases three and four attacks have
succeeded each other with some rapidity, some of the attacks being
much less severe and shorter than others. In some cases the
condition of gangrene has developed only in one out of three
attacks. When the condition is one of local erythema the duration
may be indefinite, the state becoming chronic and lasting for several
years.

NATURE.—The nature of the disease is a matter of deduction from the

study of the symptoms, no autopsies having as yet been made. As
already stated, the symptoms are explained on the theory of a vaso-
constrictor irritation in the stages of ischæmia and cyanosis—of a
vaso-dilator irritation in the stage of erythema. Whether this irritation
is the direct result of abnormal processes going on in the vaso-motor
centres in the spinal cord, or is the reflex result of irritation arising
elsewhere, is undetermined. Raynaud held that it must be of central
origin, since in his cases galvanization of the spinal cord modified
the arterial spasm. The latter observation has not been confirmed by
other observers. Weiss believes that the condition may occur in
response to irritation arising in the skin, in the viscera, or in the brain,
and thus prefers the theory of reflex origin. This theory is adopted by
several observers, who find a source for such irritation in the female
genital organs in their cases.
ETIOLOGY.—The disease occurs in adult life, only two cases having
been observed in persons fifty years old. It is most frequent between
the ages of fifteen and thirty, although children and adults beyond
the age of thirty are about equally liable. Females are more liable to
it than males, four-fifths of the recorded cases having been in
women. It occurs more frequently in the winter months, exposure to
cold being a common exciting cause. Other exciting causes are
nervous exhaustion, especially occurring in those who are
predisposed to nervous diseases by heredity; general weakness
from anæmia, malnutrition, or the occurrence of acute fever or
exhausting disease; and mental agitation, a fright having preceded
the attack in several cases. In women menstrual disorders and
uterine disease have been considered as etiological factors.
Occupation has something to do with its occurrence, since
washerwomen, waitresses, and chambermaids are the class most
often affected. In many cases, however, no cause of local irritation
can be found.

DIAGNOSIS.—The diagnosis rests upon the development of vaso-

motor symptoms in the extremities, situated symmetrically, going on
to gangrene, in a person not afflicted with cardiac disease or with
endarteritis of any kind, and not having been exposed to frost-bite or
ergot-poisoning. The age of the patient, the symmetrical position of
the symptoms, the persistence of the pulse in the main arteries, and
the limitation of the gangrene to the tips of the extremities distinguish
it readily from senile gangrene. The history of the case, the absence
of itching, and the presence of pain during the arterial spasm which
passes off when the spasm ceases, serve to separate it clearly from
chilblains. Congenital cyanosis is produced by cardiac anomalies,
and the entire body is affected. Ergot-poisoning can be ascertained
by the history.

PROGNOSIS.—Life is not endangered by this disease, no fatal cases

having been recorded. Recovery from an attack is certain, but the
duration cannot be stated, as it will depend in any case on the
character, the extent, and the severity of the symptoms. The
possibility of a recurrence of the attack should be stated to the
patient.

TREATMENT.—The methods of treatment have varied, and none are

wholly satisfactory. If the causes can be met—e.g. anæmia, nervous
exhaustion—they should be treated. If not, the disease itself may be
attacked by means of electricity. Or the symptoms may be treated as
they demand it. Electricity has been used by almost all observers.
The faradic current produces an aggravation of all the symptoms
except in the stage of erythema, and has been discarded. The
galvanic current may be employed in several ways. Two methods
are in use. In the first the positive pole is applied over the cervical
region, and the negative pole over the lumbar region, a descending
current being thus sent through the spinal cord. The current should
be of moderate strength, not above twenty-five milliamperes, few
patients being able to endure the strength implied in Raynaud's
statement that he used sixty-four cells of a Daniel battery. The
duration of the application should be ten minutes, and the electricity
may be applied once daily. In the second method the anode is
applied over the brachial or lumbar plexus, as the case may be, and
the cathode passed over the affected extremity, the current being
constant and care being taken not to break it suddenly. The strength,
duration, and frequency should be the same as in the first method.
From these two methods, separately or combined, Raynaud claimed
to have seen favorable results. His assertions have not been
confirmed by other observers who have followed his directions
closely, and hence considerable doubt at present prevails as to the
efficacy of the electric current. The so-called electrical application to
the cervical sympathetic is certainly useless. In the stage of
erythema a very weak faradic current applied to the hands in a bath
may be of service.

Many observers have found that the progress of the case to recovery
was quite rapid if the limb were put at rest in an elevated position,
were kept warm by cotton batting or similar bandaging, and were
kept clean with antiseptic lotions when the stage of gangrene set in.
Massage is to be used in all cases, the limbs or affected parts being
gently rubbed with the dry hand or with aromatic liniments or oils. All
local injury, however, and especially counter-irritation, are to be
carefully avoided. General tonic treatment, especially iron and cod-
liver oil, is to be used in all cases.

The pain occurring in the early stages is often so severe as to

require the use of opium or other narcotics. And when the nervous
symptoms are especially aggravated, and irritability and insomnia
give the patient discomfort, bromide and chloral may be employed.

Diseases of the Cervical Sympathetic.

ETIOLOGY.—Diseases of the cervical sympathetic ganglia or cord may

be of two kinds—either irritative or destructive.61 They are produced
by pressure upon the cervical ganglia or upon the sympathetic cord
between these ganglia, by tumors, especially aneurisms, and
enlarged glands; by abscesses; and by cicatrices of old wounds in
the neck. They are also due to extension of inflammation from a
thickened pleura in phthisis and chronic pleuritis of the apex. They
may be caused by injuries, such as stab-wounds, gunshot wounds,
etc. Any disease which produces marked irritation of peripheral
branches of the sympathetic in the neck, or of the cerebro-spinal
cervical nerves, may cause reflex phenomena resembling the
symptoms of actual disease. From such phenomena it is not
justifiable to conclude that the sympathetic cord and ganglia are the
seat of lesions, and the only cases which will be considered here are
those in which actual disease was proven to be present by an
autopsy.
61 Ogle, Medico-Chirurgical Transactions, xli. 397-440, 1858, 27 cases; Poiteau, “Le
Nerf sympathetique,” Thèse de Paris, 1869, 19 cases; Eulenburg and Guttmann, Die
Pathologie der Sympathicus, 1873; Nicati, Le Paralysie du Nerf sympathique-
cervicale, 1873, 25 cases; Seeligmüller, Inaug. Dissertation, 1876; Mitchell, Injuries of
Nerves; Mobius, “Pathologie der Sympathicus,” Berlin. klin. Woch., 1884, Nos. 15-19.
Inasmuch as the cervical sympathetic is in close anatomical
connection with the spinal cord, especially with the eighth cervical to
the second dorsal segments (the so-called cilio-spinal centre of
Budge), and as the functions of the sympathetic are dependent upon
the integrity of the spinal cord, it is evident that any lesion of the
nerves uniting it with the cord, or any lesion in the cord itself at the
levels mentioned, may produce symptoms which resemble closely
those of disease of the sympathetic. Thus, cervical pachymeningitis,
myelitis (especially from injury of the cord, or hæmato-myelia), and
diseases of the cervical vertebræ which produce either or both
conditions, may cause a train of symptoms somewhat similar to
those to be described.62 A careful distinction must be made between
primary and secondary disease of the sympathetic, between reflex
and direct symptoms, between lesions in its substance and lesions in
its governing centres in the spinal cord. The symptoms produced by
affections of a reflex or central nature are rarely as numerous as
those of disease of the sympathetic itself. An example of such a
secondary affection is the combination of sympathetic symptoms
occurring in progressive muscular atrophy. And, finally, since mental
action of an emotional nature may cause flushing or pallor of the
face, with profuse sweating and variations in the size of the pupil and
prominence of the eyeballs, as well as palpitation or arrest of the
heart, there is reason to believe that symptoms of sympathetic
disease may be produced by cerebral lesions.
62 Ross, Diseases of the Nervous System, 2d ed., i. 686-688.

PATHOLOGY.—The pathological anatomy of the cervical sympathetic

is obscure. This is probably owing to the fact that the ganglia are
rarely examined, and pathologists have not been familiar with their
histology. Lesions of the cervical sympathetic have been described
in almost every imaginable form of disease, and at one time, when
many obscure conditions were blindly termed sympathetic, the
records were filled with descriptions of fatty degeneration or
interstitial inflammation or pigment deposit in the ganglia. As no
actual symptoms of disease of the cervical sympathetic, as now
understood, were present in such cases, it is impossible to believe
that the lesion was other than hypothetical.

The conditions which have been observed in a few carefully-studied

cases of primary disease have been—(1) A parenchymatous
inflammation of the cells of the ganglia, attended by swelling, loss of
nuclei, granular and fatty degeneration, and by atrophy, together with
a degeneration of the fibres issuing from the cells. (2) A sclerotic
process in the connective tissue in and about the ganglia and in the
nerves, resulting in such an increase in the interstitial tissue as to
compress and injure the cells and axis-cylinders. These may be
observed together in the later stages of the disease. (3) In a number
of cases the capillaries within and about the ganglia have been
found dilated, tortuous, and varicose, and hemorrhages from them
are not rare.

SYMPTOMS.—The symptoms of irritation of the cervical sympathetic

are dilatation of the pupil, widening of the palpebral fissure,
protrusion of the eyeball, pallor of the entire side of the face and
head, with slight fall of local temperature and possibly an increased
secretion of perspiration, and an increased frequency of the heart. It
is rarely that these are all observed in any case, dilatation of the
pupil with slight pallor and rapid pulse being the only signs of
irritation as a rule. Such irritation is a less common occurrence than
might be supposed, many lesions which produce pressure even of a
slight degree on the sympathetic having caused symptoms of a
suspension of its function rather than of an increased activity. This is
doubtless due to the non-medullated structure of the fibres, which
thus lack protection from injury.

The symptoms of destructive disease of the cervical sympathetic are

the converse of those just mentioned, and they are all present when
the part is seriously involved. The patient will then have a marked
contraction of the pupil, which no longer responds to light or to
irritation of the skin of the neck, but may change slightly in the act of
accommodation. It resists the action of mydriatics. The vessels of the
choroid and retina may be dilated, as well as those of the iris, in
which case the patient will feel a sense of weariness on any long-
continued attempt to use the eyes. There is no actual disturbance of
vision, and the cornea is not usually flattened, as was formerly
supposed. There is a noticeable narrowing of the palpebral fissure,
the upper lid falling slightly as in a mild state of ptosis, and the lower
lid being slightly elevated. This is due to the paralysis of the muscles
of Müller in the eyelids, which are controlled by the sympathetic. It is
present in 90 per cent. of the recorded cases, and in many the
apparent size of the eye is reduced a half. Retraction of the eyeball
is a less constant symptom, and one which develops only after the
disease has existed some time. It is due partly to the paralysis of the
orbital muscle of Müller, and partly to the decrease in the amount of
fat in the orbit behind the eye. A marked symptom, and one which is
constant, is a dilatation of the vessels of the face, conjunctiva, nasal
mucous membrane, ear, and scalp. This is attended by redness, a
subjective sense of heat, and an actual rise of local temperature,
which may exceed that of the other side by 1.5° F., measured in the
auditory meatus or nose. This vascular congestion has persisted in
some cases for three years. In others it has been followed much
earlier (in nine months) by a partial or complete return to the normal
condition, and even when the local temperature remains higher on
the affected side, the visible congestion and the sensation of heat
may have disappeared. The dilatation, succeeded by the contraction
(normal tone), of the vessels has led to a division of the disease into
two stages, and in a few cases the affected side has become paler
than the other in the second stage. In both stages the part affected is
less sensitive to changes in the external temperature.

An increased secretion of tears and of perspiration has been

supposed to accompany dilatation of the vessels of the skin of the
head inevitably. This is not a constant symptom, as the recent cases
have demonstrated. And no definite statement of the effect of
disease of the cervical sympathetic on the occurrence of dryness or
dampness of the face can be made, both conditions having been
observed. A difference between the degree of moisture on the two
sides of the face on exposure to heat is usually present. Palpitation
of the heart has been an annoying symptom to the patient in many
cases, and is usually associated with a marked slowing of the pulse.
This was reduced from 74 to 66 in Möbius' case,63 and remained
slow for some weeks. The frequency of the heart may, however, be
increased after the first period of slowing, but never reaches a very
high rate (88 in the case cited). A slight atrophy of the affected side
of the face has been observed in several cases, appearing after the
disease has existed for some time. The muscles of the cheek feel
flabby and are slightly sunken; but the condition does not approach
in severity true facial hemiatrophy, nor is it sufficiently rapid to be
considered due to a trophic disturbance. Changes in the secretion of
saliva, dryness of the nasal mucous membrane, and symptoms
referable to paralysis of the intracranial vessels, such as might be
expected from the result of physiological division of the sympathetic,
have only been occasionally observed. Glycosuria has been noted in
a few cases.64
63 Berlin. klin. Woch., 1884, No. 16.

64 Gerhardt, Volkmann's Sammlung klin. Vorträge, No. 209, “Ueber Angioneurosen,”

p. 11.

COURSE.—The course of the disease has been divided into two

stages, as already mentioned, the majority of the symptoms
remaining permanently from the onset. The second stage is
characterized by the cessation of the dilatation of the vessels, by the
appearance of retraction of the eyeball, and by the development of
slight facial atrophy. In the cases where the sympathetic is
extensively destroyed by the lesion no recovery is possible. When it
is simply divided by a wound there has been a considerable degree
of recovery, probably due to a spontaneous union of the divided
ends and re-establishment of the function. From these facts the
prognosis can be deduced.

DIAGNOSIS.—The symptoms are so characteristic that there is no

difficulty in reaching a diagnosis. The most important point in any
case is to determine the cause, care being taken to consider all the
possibilities already mentioned in discussing the causation. The
symptoms of lesion are always unilateral.
TREATMENT.—If the cause can be removed, an indication for
treatment is afforded. Sources of reflex irritation are to be eliminated.
If the sympathetic has been divided by a wound, it may be well to
unite the cut ends, as in suture of other nerves, although this has not
yet been attempted; otherwise there is little hope from any method of
treatment. Electricity has been applied in vain, and galvanization of
the sympathetic in the neck is now regarded by all good authorities
as useless.

Diseases of the thoracic and abdominal sympathetic ganglia and

cords have been suspected, but nothing definite is known of their
symptoms or pathology; the statements which have recently been
made regarding visceral neurosis not being based upon any cases in
which post-mortem lesions were found.

Trophic Neuroses.

TROPHIC NERVES AND NERVOUS CENTRES.—The nutrition of the body

depends upon the nutrition of the individual cells of which it is made
up. Each cell has the power of appropriating from the blood such
substances as will preserve its existence, enable it to perform its
functions, and produce a successor. Whether this power is inherent
in the cell or is controlled by the nervous system is a question upon
which authorities are divided. Those who hold the first position deny
the existence of trophic nervous centres and of trophic nerves from
those centres to the organs and elements of the body, claiming that
this hypothetical trophic system has not been demonstrated
anatomically, and that the facts urged in its support are capable of
another interpretation. Those who believe in the existence of a
trophic system have been able to demonstrate the existence of fine
peripheral nerve-fibres passing to and ending in individual cells of
the skin, glands, and other organs,65 and have brought forward a
large collection of facts which merit a careful examination.66 They are
as follows:
 65 Bericht der Section für Dermatologie, Versammlung Deutscher aerzte, Strasburg,
1885; Vierteljahrschrift für Dermatologie und Syphilis, 1885, 4 Heft, S. 683.

66 “Tropho-neurosen,” Real Cyclopædie f. d. gesammt. Medicin, vol. xiv., 1883; Erb,

Ziemssen's Cyclopædia, xi. pp. 408-423.

ATROPHY.—When a nerve is cut certain changes occur in it which are

known as Wallerian degeneration.67 This affects the peripheral end
of a severed nerve, the peripheral end of a severed anterior nerve-
root, and the central end of a posterior nerve-root. To maintain its
integrity a motor nerve must be in direct continuity with a normal cell
of the anterior cornu of the spinal cord; a sensory nerve must be in
connection with the intervertebral spinal ganglion on the posterior
nerve-root. Nerves which pass between two such ganglia do not
degenerate when cut. The degeneration consists68 in a coagulation
of the myelin in the medullary sheath, a fatty degeneration of the
coagulum, and a gradual absorption of the débris. The axis-cylinder
is compressed, and finally disintegrated, by a mass of protoplasm
which develops about the nuclei of the interannular segments, and
after undergoing fatty degeneration its débris becomes mingled with
that of the myelin, and is also absorbed. The sheath of Schwann,
whose nuclei have in the mean time increased by a process of
subdivision, is partly filled by the protoplasm (from which the new
axis-cylinder develops if regeneration occurs), remaining as a fine
thread of connective tissue when all other traces of the nerve-fibre
have disappeared. There may be a proliferation of cells of the endo-
and perineurium at the same time which aids in the transformation of
the nerve into a connective-tissue strand. This process of
degeneration involves the terminal plates by which the nerves join
the muscles, but the terminations of the sensory nerves—i.e. tactile
corpuscles—do not appear to be affected. The central end of the cut
nerve may display a similar change for a distance not greater than
one centimeter; it usually develops a bulbous swelling of connective
tissue, and retains its conducting power indefinitely.
67 Waller, Philosoph. Transactions, 1850, ii. p. 423; Comptes rendus de l'Acad. de
Sci., 1852-55.
 68 Ranvier, Leçons sur l'Histologie de Système nerveux, Paris, 1878; Von
Recklinghausen, Pathologie der Ernahrung, 1883.

Degeneration in the tracts of the spinal cord occurs after various

forms of lesion,69 and is similar in its processes to degeneration in
the peripheral nerves. The increase in the connective-tissue
elements is more noticeable in contrast with the parts unaffected,
and from the density of the tract involved the result has been called
sclerosis. The recent researches of Homen70 have shown that the
process of degeneration begins in the entire length of the affected
tract, and does not proceed from the point of lesion onward, as was
formerly supposed.
69 See Vol. V., “Myelitis—The Secondary Scleroses,” p. 892; Schültze, Arch. für
Psych., xiv. 2.

70 Fortschritte der Medicin, 1885, No. 9.

When a muscle is separated from its connection with the central

nervous system, either by a division of the nerve passing to it or by a
destruction of the cells in the anterior cornu of the spinal cord from
which that nerve arises, it undergoes an atrophy which is peculiar in
being immediate and rapidly progressive, thus contrasting strongly
with the gradual and slighter atrophy from disuse in cases of cerebral
paralysis where the cells mentioned and the nerve-fibres are intact.
There is at first a simple diminution in the number of the fibrillæ of
which the muscular fibre is made up, together with an increase in the
interstitial connective tissue nuclei. Then an albuminoid and fatty
degeneration of the muscular elements occurs, with a proliferation of
muscle-corpuscles or nuclei, and a gradual absorption of the débris.
The interstitial connective tissue then increases rapidly, forming
fibrous bands through the degenerated muscle which compress the
few muscular fibres remaining, until as a result the muscle is
transformed into a mere ribbon of connective tissue without any
power of contractility.71 As these changes go on the electrical
reactions change, the three degrees of reaction of degeneration
corresponding to the three stages of atrophy described.72 These
phenomena of nerve- and muscle-degeneration are observed in
traumatic or idiopathic neuritis, in acute and chronic poliomyelitis
anterior, in general myelitis involving the anterior cornua, and in
bulbar paralysis.
71 Hayem, G., Recherches sur l'Anatomie pathologique des Atrophies musculaires,
Paris, 1873; Ross, Diseases of the Nervous System, vol. i. p. 238.

72 See Vol. V., “Electric Reactions.”

The influence of the nervous system on the nutrition of the bones

has also been ascertained. When a bone is developing, a lesion of
the nerve to it, or of the deeper portion of the anterior cornua of the
spinal cord from which these nerves arise, will modify and partly
arrest its growth. This is often seen in anterior poliomyelitis and in
hemiatrophy of the face occurring in children. In the adult a no less
marked effect is produced, although the results are less noticeable.
A condition known as osteoporosis is caused, consisting of an
enlargement of the Haversian canals and an infiltration of fatty
matter into them and an actual decrease in all the inorganic
constituents of the bone, which loses in weight, becomes thinner and
more fragile, so that spontaneous fractures may occur.73 This
condition has been noticed more frequently in diseases of the spinal
cord than in neuritis; it is said to occur in locomotor ataxia. It has
been found in a few cases of long-standing hemiplegia and also in
dementia paralytica, no explanation of its pathogeny in these
instances, however, being offered. In a case of ataxia with a lesion in
the medulla which involved the nuclei of the fifth, ninth, tenth, and
eleventh nerves on one side, all the teeth of the upper jaw on that
side fell out within a few weeks, those in the lower jaw remaining.74
Changes in the nutrition of the bones have also been recorded in
cases of progressive muscular atrophy in the paralyzed limbs.75
73 Weir Mitchell, Amer. Journ. of the Med. Sci., 1873, p. 113; Charcot, Arch. de Phys.,
1874, p. 166.

74 Demange, Rev. de Médecine, 1882, p. 247.

75 Friedreich, Progressive Muskelatrophie, p. 347, 1873.

The condition of the skin and its appendages is influenced decidedly
by changes in the nervous system, either in the nerves, in the spinal
ganglia, or in the central gray matter. Here it is the sensory nerves
which convey the trophic influence, not the motor nerves, as in the
cases hitherto considered; and when the lesion producing trophic
changes in the skin is central, it is situated in the posterior cornua of
the spinal cord or in the gray matter near the central canal. The
glossy skin seen on the fingers after injuries to the nerves is a type
of such atrophy from disturbance of trophic impulses. Glossy fingers
present a smooth, shining appearance, are dry from the diminution in
the secretion of sweat, feel soft and satin-like to the touch from the
marked thinning of the skin, and frequently show a defective or
irregular growth of the nails, which may be ridged, curved, or
deformed.76 They are red and mottled from accompanying vaso-
motor paralysis, and are usually hot and painful. Changes in the
pigmentation of the skin and hair are recorded as a not infrequent
accompaniment of severe neuralgia and as a result of great mental
anxiety. Thus in several cases of supraorbital neuralgia the eyebrow
on the affected side has turned white; in infraorbital neuralgia the
beard has become gray; and in both the hair has been observed to
fall out.77 The sudden turning white of the hair is ascribed to a
swelling of the hair by air within it.78 In one case, frequently cited, the
hair and nails fell out after a stroke of lightning.
76 Weir Mitchell, Injuries of Nerves. See also Vol. IV. p. 683.

77 Seeligmüller, Lehrbuch der Krankheiten d. Peripheren Nerven, p. 157, 1882.

78 Arch. f. Path. Anat., xxxv. 5, 575, Landois.

When a gland is cut off from its nervous connection with the cord or
cerebral axis by section of its nerves, its function is impaired and its
nutrition suffers, so that after a time it loses weight and undergoes a
progressive total atrophy. This has been proven experimentally in
animals in the submaxillary gland. It has been observed in the
testicle in man after division of the spermatic nerve (Nélaton) and
after destruction of the spinal cord by traumatic and idiopathic
myelitis (Klebs, Föster).79 The sweat-glands are known to be under
the control of a central nervous mechanism, as cases of
hyperidrosis, anidrosis, and chromiodrosis prove;80 and an atrophy of
them and of the sebaceous glands has been observed81 after
nervous lesions.
79 Cited by Samuel, Realcyclop., loc. cit. See also Obolensky, Centralblatt für med.
Wissen., 1867, 5, 497.

80 See Vol. IV. pp. 583-586.

81 See Vol. IV. pp. 683 et seq.

Progressive hemiatrophy of the face is treated elsewhere. The

following case of progressive hemiatrophy of the entire body may be
mentioned here: A boy, aged fourteen, dislocated his ankle, which in
a few days became swollen, red, hot, and painful. The inflammation
extended up the leg, but did not involve the knee, and soon
subsided. After a short time the foot began to atrophy. The atrophy
extended up the leg, and involved the thigh; it then progressed to the
trunk and the arm, and lastly to the face on the affected side, until in
the course of two years there had developed a unilateral atrophy of
the entire body. Muscles, fat, and bones were all affected, but no
difference in the skin or hair of the two sides was noticed. Fibrillary
tremors were present in the muscles. The electric reactions were not
altered, but were gradually lost. There was a hypersensitiveness to
touch and to cold, but no other sensory disturbance. The boy was
alive and fairly well when the case was reported.82 It is unique.
82 Heuschen, Schmidt's Jahrbuch., vol. cxcviii. p. 130.

These various instances of atrophy cannot be ascribed to simple

disuse, since they differ markedly in their pathological changes and
in the rapidity of their progress from such atrophy. Nor are they to be
referred to vaso-motor disturbances, since in many cases no
vascular changes are evident. Their distribution in the body often
corresponds exactly with that of peripheral nerves, and they
accompany nerve lesions too frequently to be explained on any
theory of coincidence. There are many authorities, however, who
refuse to ascribe them to a lesion of trophic nerves.83 In regard to the
degeneration of nerves it is said that each nerve axis-cylinder is a
part of the nerve-cell from which it arises, and hence destruction of
the cell or division of the cylinder, by disturbing the unity of
existence, results in the death of the part. The fibre shares all the
changes of nutrition which the nerve-cell undergoes, and if
separated from it necessarily perishes. To this it is replied that
trophic paths and motor paths are distinct at some points in their
course, at least in the central nervous system, since each can be
affected alone. Erb, who has studied this subject carefully,84 believes
that trophic are distinct from motor centres in the spinal cord, but that
both impulses may be conveyed by the same axis-cylinder in the
peripheral nerves—a middle ground which is widely accepted. It is
now known that each axis-cylinder is made up of several fibrils, so
that this theory gains probability. This would also explain the
occurrence of atrophy in the muscles, the trophic centres being
affected when the muscle atrophies, and unaffected when it is
paralyzed without atrophy. Mayer, however, denies this explanation
of the muscular atrophy, holding that the motor system, cell, nerve,
and muscle-fibre, forms a nutritive as well as functional unit, and that
the simple suspension of function, by interfering with the special
conditions of nutrition attendant upon physiological excitement, is
competent to cause a pathological change. To this it is replied that
the parts of the motor system are not interdependent, since disease
of the muscle does not produce degeneration of the nerve and of the
cell, and the fact of a degeneration in a peripheral direction alone is
evidence of central trophic influence. The attempt to ascribe trophic
changes in the skin, nails, and hair to vaso-motor disturbance has
been equally unsuccessful in covering all the observed cases.
83 See Handfield Jones, St. George's Hospital Reports, 1868, vol. iii. pp. 89-110;
Sigmund Meyer, Hermann's Handbuch d. Physiol., ii. Th. 2, “Trophische Nerven,”
1879; Gowers, Diseases of the Brain, 1885, p. 4.

84 Arch. f. Psych., v. S. 445, 1875; also Ziemssen's Cyclo., vol. xiii. p. 117 (Amer.
trans.); also Deut. Arch. f. klin. Med., v. S. 54.
 FIG. 58.

Diagram of the Arrangement and Connection of Motor and Trophic

Centres and Fibres in the Spinal Cord and Motor Nerve (after Erb): a,
motor fibre of spinal cord from the brain to d, the motor cell, which is
 joined to the muscle m by the motor nerve; b, trophic cell in the spinal
cord for the muscle, to which it is joined by the trophic fibre bʹ; c, trophic
cell in the spinal cord for the motor nerve, to which it is joined by the
trophic fibre cʹ; s, a fibre bringing sensory (reflex) impulses to the cell.

If d is destroyed, the fibres from b and c perish with it, and the result is
paralysis and atrophy of the muscle and degeneration in the motor nerve
—e.g. poliomyelitis anterior. If b is destroyed, the muscle atrophies, and
paralysis is a secondary result—e.g. progressive muscular atrophy. If c is
destroyed, the nerve degenerates, and paralysis and atrophy of the
muscle are secondary results—e.g. neuritis with reaction of
degeneration. If a is destroyed, voluntary power is lost, but reflex power
remains, and no atrophic changes occur—e.g. lateral sclerosis. If the
motor nerve is cut between d and m, the result is the same beyond the
division as when the motor cell is destroyed.

HYPERTROPHY.—Trophic changes are not limited to the process of

atrophy. There are conditions of hypertrophy of supposed nervous
origin. Samuel considers the hypertrophy of one testicle which
attends atrophy of the other from section of its nerve as an example
of this. It has been ascertained that one kidney hypertrophies when
the other is atrophied or extirpated. When the spleen is removed the
lymphatic glands increase in size. But these facts are capable of
another explanation—viz. that increased demand upon the organ
leads to its increased growth. Hypertrophy of the skin and of the
tongue is seen in cretins in contrast with the deformity of the body
and atrophy of the limbs. A hemihypertrophy of the face has been
noticed in several cases, the counterpart of hemiatrophy; and in one
case a unilateral hypertrophy of the entire body was observed.85 The
local thickening of the skin known as ichthyosis hystrix, and other
hypertrophies of the skin, certain deposits of pigment, and vitiligo,
have been ascribed to nervous causes. Mitchell has recorded cases
of abnormal growth of the nails and hair after injuries to the nerves,
and similar phenomena have followed central lesions. He has also
described a thickening of the skin of the first three fingers and of the
back of the hand following a wound of the brachial plexus. These
conditions of the skin and its appendages indicate an abnormal
activity in the cells of the affected part, a rapid metabolism and
reproduction, resulting in an undue production of tissue, apparently
dependent on nervous impulses reaching the cells from a distance.
The insane ear may be mentioned in this connection as a trophic
disturbance due to central lesion.
85 Ziel, Virchow's Archiv, xci., S. 92.

MYXŒDEMA (cachexie pachydermique) is a disturbance of nutritive

processes characterized by a production of mucin, which is
deposited in all the tissues of the body, but especially in the
subdermal connective tissue.86 It is considered by the majority of
authors a trophic neurosis, and is therefore considered here.
86 Sir William W. Gull, “On a Cretinoid State supervening in Adult Life,” Trans. Clin.
Soc. London, 1874, vol. vii. p. 170; Ord, “On Myxœdema,” Med.-Chir. Trans., 1878,
vol. lxi. p. 57; Mahomed, Lancet, 1881, ii. No. 26; Hadden, Brain, 1882; W. A.
Hammond, Neurological Contributions, 1881, i. p. 36; Ballet, Archives de Neurologie,
1881, vol. iii. p. 30; Schmidt's Jahrbucher, vol. clxxxix. p. 30, and cxcviii. 264; “The
Brown Lectures,” Victor Horseley, Lancet, Jan., 1886.

PATHOLOGY.—In the few autopsies which have been made an

increase in the connective tissue of all the organs has been found, in
the meshes of which a thick, transparent, slimy substance (called
animal gum), consisting of mucin, is present. This may compress
and destroy the parenchyma of the organs involved. There is also
found a thickening of the coats (adventitia and media) of the vessels.
An atrophy of the thyroid gland has occurred in every case, and
experimental extirpation of the thyroid in animals produces
symptoms so nearly identical with those of myxœdema that this is
considered the chief pathological feature of the disease. Whether
this atrophy is due to a compression by the mucin deposited, or is
due to a disease of the trophic centres of the thyroid in the medulla,
or is a primary affection of the gland, remains to be determined.

ETIOLOGY.—The actual causation is unknown. Cold and mental shock

have been considered exciting causes in some cases. Women are
much more liable to the disease than men, and it develops after the
age of forty in the majority of cases. It may occur in childhood and
result in a cretinoid state. Syphilis and tuberculosis do not appear to
be etiological factors.
SYMPTOMS.—The disease begins gradually, and the nervous
symptoms or the local œdema may appear together or in
succession. The patient notices a thickening of the skin, which
becomes dry, rough, and scaly. The thickening is uniform and
involves the entire body. It is most marked where the subdermal
connective tissue is loose, as in the cheeks, lips, eyelids, and in all
parts where the skin is thrown into folds. The hands and feet do not
escape. The thickened skin is hard, and does not pit on pressure,
thus differing from ordinary œdematous swelling. It appears of a
waxy color, and is free from perspiration, the sweat-glands becoming
atrophied from pressure. The hair may fall out or become woolly and
brittle, and may change its color. In a few cases spots of pigment
have appeared on various regions.87 The nails are brittle. The teeth
are carious. The mucous membranes show similar changes, and the
mouth and tongue, rectum and vagina, may be so swollen as to
impair their respective functions. Digestive disturbances,
constipation alternating with diarrhœa, and uterine hemorrhages,
which occur, are ascribed to this cause. Albumen is occasionally
found in the urine, but is not a constant symptom. The nervous
symptoms are constant. The patients complain of paræsthesiæ and
anæsthesia of the extremities or over the entire body, and the
special senses may be impaired, as well as the tactile sense. They
are very liable to severe attacks of neuralgia. They suffer from
subjective sensations of cold, and are easily affected by changes of
temperature. Motion is interfered with; tremors occur early;
movements become slow and awkward; the gait is unsteady; the
voice is rough and nasal; but no true paralysis or muscular atrophy
has been observed. The patella-tendon reflex is occasionally lost,
but not in all cases.
87 Allan McLane Hamilton, Journ. Nerv. and Ment. Dis., 1885, April, p. 180.

These symptoms have been ascribed to the pressure of the mucin

upon the terminal filaments of the nerves, and also to changes in the
central nervous system. That the latter theory is probably correct is
shown by the occurrence of mental symptoms in the majority of
cases. The patients become apathetic and all mental action is slowly
performed. Indifference to surroundings, loss of memory, and
inability to concentrate the attention may be succeeded by transient
delirium, hallucinations, and occasionally by delusions of
persecution, and the patient finally lapses into a state of imbecility. If
the disease develops in early life, education is impossible, and the
patient remains in an infantile condition.

Whether the changes in the nervous system are due to pressure by

deposit of mucin (Hadden), or are due to an altered nutrition of the
most delicate tissues of the body consequent upon the general
metabolic derangement (Horseley), is undetermined. In experimental
myxœdema the degenerative processes have been found in the
nerve-cells.

There are no symptoms referable to the heart or lungs, and if

cirrhosis of the kidney and liver develop, their symptoms supervene
upon and are secondary to those of myxœdema. High arterial
tension has been noticed in the majority of the cases.

The COURSE of the disease is a chronic one, and is progressive.

There are, however, intermissions in the severity of the symptoms in
some cases. Recovery does not occur.

DIAGNOSIS.—The diagnosis from the accumulation of fat is made by

observing the thickening of the nose, lips, fingers, and tongue, and
the changes in the skin and its appendages. Scleroderma is not
universal like myxœdema. In scleroderma the skin is harder and
more adherent to subjacent parts, is not transparent and waxy, and
the nervous symptoms are wanting. Cretinism seems to be closely
allied to myxœdema, but is only observed before the age of seven
and is accompanied by hypertrophy of the thyroid gland.

TREATMENT.—The treatment is only palliative. Simple nutritious diet,

especially milk diet, with the use of such tonics as iron and quinine,
has been found useful. The progress of the disease is hastened by
exposure to cold, and in a very warm climate the symptoms may
remain stationary for several years. Jaborandi or pilocarpine has
been used in some cases with a moderate degree of success. Nitro-