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 Multiple Sclerosis:
The History of a Disease
 Multiple Sclerosis:
The History of a Disease

T. Jock Murray
OC, MD, FRCPC, FAAN, MACP, FRCP, LLD, DSc, D. Litt
Professor of Medical Humanities
Director, Dalhousie MS Research Unit

New York
Demos Medical Publishing, 386 Park Avenue South, New York, NY 10016
www.demosmedpub.com
© 2005 by Demos Medical Publishing. All rights reserved. This book is protected by
copyright. No part of it may be reproduced, stored in a retrieval system, or trans-
mitted in any form or by any means, electronic, mechanical, photocopying, record-
ing, or otherwise, without the prior written permission of the Publisher.

Library of Congress Cataloging-in-Publication Data

Murray, T. J.
The history of multiple sclerosis / T. Jock Murray.
p. ; cm.
Includes bibliographical references and index.
ISBN 1-888799-80-3 (softcover : alk. paper)
1. Multiple sclerosis—History.
[DNLM: 1. Multiple Sclerosis—history. WL 11.1 M984h 2005] I. Title.
RC377.M88 2005
616.8'34—dc22
2004022222
To Janet
 Contents

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Foreword by Professor W.I. McDonald . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
CHAPTER 1: Terminology and Disease Description . . . . . . . . . . . . . . . . . . 1
CHAPTER 2: The Framing of Multiple Sclerosis. . . . . . . . . . . . . . . . . . . . 13
CHAPTER 3: The Palsy without a Name: Suffering
with Paraplegia 1395–1868 . . . . . . . . . . . . . . . . . . . . . . . . . . 19
CHAPTER 4: The Steps Toward a Discovery:
The Early Medical Reports . . . . . . . . . . . . . . . . . . . . . . . . . . 61
CHAPTER 5: The Building Blocks of a Discovery. . . . . . . . . . . . . . . . . . . 95
CHAPTER 6: The Contribution of J.M. Charcot—1868 . . . . . . . . . . . . . 103
CHAPTER 7: The Medical Reports After Charcot . . . . . . . . . . . . . . . . . 139
CHAPTER 8: Clarifying the Pathology: James Dawson . . . . . . . . . . . . . 189
CHAPTER 9: The Journal of a Disappointed Man . . . . . . . . . . . . . . . . . 195
CHAPTER 10: Experimentation, Meetings, Reviews,
and Symposia, 1920–1960. . . . . . . . . . . . . . . . . . . . . . . . . . 203
CHAPTER 11: Searching for a Cause of MS . . . . . . . . . . . . . . . . . . . . . . . 229
CHAPTER 12: Classifying and Measuring MS . . . . . . . . . . . . . . . . . . . . 319
CHAPTER 13: The Nature of the MS Plaque. . . . . . . . . . . . . . . . . . . . . . 337
CHAPTER 14: Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363
CHAPTER 15: Searching for Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391

vii
viii | Multiple Sclerosis: The History of a Disease

CHAPTER 16: Multiple Sclerosis and the Public: Societies,

Narratives, and the Media . . . . . . . . . . . . . . . . . . . . . . . . . 505
Afterword. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 529
A Chronology of Events in the History of MS . . . . . . . . . . . . . . . . . . . . 535
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549
 Acknowledgments

I am indebted to many people for their assistance and inspiration in this

work. My wife Janet Murray assisted with library searches and refer-
encing at the Wellcome Institute for the History of Medicine, and with
all my work is a generous, wise, and understanding critic. Dalhousie
University, the Department of Medicine, and my colleagues in the
Division of Neurology and the Medical Humanities Program were sup-
portive of my sabbatical leave.
My tireless and efficient assistant Roxy Pelham suffered through
many drafts and was able to guide me through the complexities of organ-
izing the manuscript.
I am grateful to the Burrows-Wellcome Foundation for a grant in
1998 to work at the Wellcome Institute for the History and
Understanding of Medicine, and to Berlex Canada for an unrestricted
education, grant to complete the research and writing at the Wellcome
Library in 2000. For one period of writing during a six-month sabbatical
in 2000, Janet and I had the luxury of writing and walking the beach at
the summer home of Dr. Barrie and Martha Silverman on Sullivan’s
Island, South Carolina.
I relied heavily on the excellent historical work of my colleagues
Alastair Compston, George Ebers, and W. Ian McDonald, each of whom
has advanced the understanding of MS in so many ways over the last four
decades.
Dr. Andrea Rideout assisted with library searches when working
with me as an elective student when I was beginning this project a decade

ix
x | Multiple Sclerosis: The History of a Disease

ago. Susan Drain of Mount Saint Vincent University introduced me to

the case of Margaret Gatty, Maria Aguayo to William Brown, David
Shephard to Will Coffin, Nick LaRocca to Alan Stevenson, and Heather
Spears to Margaret Davies.
I have benefited from the helpful staff and the resources of the
Wellcome Institute for the History and Understanding of Medicine, The
Kellogg Library for the Health Sciences at Dalhousie, the British Library,
the National Archives of Canada, the National Hospital, Queen Square,
the Harveian Library of the Royal College of Physicians of London, the
New York City Library, and the Waring Library of the Medical
University of South Carolina. I particularly acknowledge John Simonds
of the Wellcome Library, who helped me date the atlases of Carswell and
Cruveilhier; Dr. Leslie Hall, who introduced me to the papers of
Frederick Parkes Weber, and Professor W. Ian McDonald, who assisted
me in viewing all the correspondence and the diaries related to Augustus
d’Esté. Dr. David Hopkins assisted in verifying the name of the physician
Godfreid “Zonderdank” de la Haye. Dr. Hans K. Uhthoff, Emeritus
Professor of Surgery at the University of Ottawa, kindly provided photo-
graphs of his great uncle, Wilhelm Uhthoff.
I am grateful to Jack S. Burks and Kenneth P. Johnson, editors of
Multiple Sclerosis: Diagnosis, Medical Management, and Rehabilitation and
to Demos Medical Publishing Inc. for allowing me to include material
from my chapter in that book, Chapter I: The History of Multiple
Sclerosis, which was expanded into this quite different history.
A special thanks to my friends Professor W. Ian McDonald of
London, Donald Paty of Vancouver, and George Ebers of Oxford, who
were kind enough to read a very rough first draft of the manuscript and
offer comments and advice.
I am also honored to have Professor W. Ian McDonald, Harveian
Librarian at the Royal College of Physicians of London, write the
Foreword. He has contributed to all aspects of multiple sclerosis research
in his outstanding career at the Institute of Neurology and the National
Hospital, Queen Square, and has always been a kind and supportive
friend to me and so many others who work for the cause of MS patients.
 Foreword

T he social and professional histories of multiple sclerosis are rich in

their sources and their detail. Dr. Murray, in this scholarly but at the
same time engaging book, brings together a mass of material, some not
easily accessible otherwise.
His range is wide. He gives a balanced assessment of the claims for
the existence of multiple sclerosis in historical figures and of the accounts
of sufferers from MS who have written of their experiences. He charts
the evolution of our knowledge of the nature of multiple sclerosis, of the
factors involved in its causation, how it affects the nervous system, and of
the changing strategies for treatment.
This book is a mine of information. People with multiple sclerosis,
physicians, nurses, physiotherapists, and others involved in the care of
patients, as well as historians interested in the social context of disease,
will be greatly in Dr. Murray’s debt.

W. Ian McDonald
Harveian Librarian
Royal College of Physicians, London

xi
 C h a p t e r

1
Terminology and
Disease Description

“The story of knowledge of multiple sclerosis is like a history of med-

icine in miniature.”
Tracy J. Putnam, 19381

I n earlier centuries, there were people in every community who had

symptoms of a slowly increasing paralysis, with episodes of numbness,
dizziness, blurred vision, and decreasing ability to get around. They
eventually walked with canes and later were unable to walk unassisted.
This process often took many years, usually decades.
Such people were said to be ill, but with a palsy, or a paralysis. By the
18th century, they were classified by their physicians into broader groups
such as rheumatic disease, a constitutional weakness, or a paraplegia. By
the late 18th century, the term paraplegia was used for all people who had
a progressive paralysis. Physicians divided the condition into active or
passive, functional or organic. A separate group was recognized due to
“the pox,” syphilis, which could affect the central nervous system (CNS)
in many ways. By the beginning of the 19th century, pathological studies
were beginning to show differences in the appearance of some of these

1
2 | Multiple Sclerosis: The History of a Disease

cases when examined by the naked eye and the feel of the brain and
spinal cord under the fingertips.
Robley Dunglison, a Scottish physician and anatomist recruited to
the new medical school at the University of Virginia at age 26 by Thomas
Jefferson, divided all such cases into paraplegia if there was weakness, and
paraplexia if the paralysis was complete.2 Later, as forms of neurological
disease were being separated, the patient with intermittent and progres-
sive neurological symptoms might be grouped with patients diagnosed as
having paraplegia, or inflammation of the nervous system, but might also
be included among patients with general paralysis or tabes dorsalis due to
syphilis.
In 1824, a young man in France named Charles Prosper Ollivier
d’Angers published, at age 28, a remarkable 400-page book on disorders
of the spinal cord that helped make some sense out of the various condi-
tions that caused paraplegia. Before him, the spinal cord was given little
attention by clinicians, who regarded it simply as a very large nerve. In
the next few decades, the pattern of combining the clinical picture in the
patient with the pathological findings led to the separation and naming
of a number of disorders that had been previously lumped together as
paraplegia. In the great clinics of Paris, Vienna, and Berlin, clinicians
were differentiating forms of neurological disease such as locomotor
ataxia, neurosyphilis, Friedreich’s ataxia, and multiple sclerosis by corre-
lating the specific clinical findings with examination of the brain and
spinal cord at autopsy.
There are many examples of illnesses, even ones that are common,
which were probably always there, but were only recognized when some-
one conceptualized their features and framed the disease. Others then
began to see the disease among their patients, and it seemed as if the dis-
ease had suddenly appeared, in an epidemic. Examples are sleep apnea,
attention deficit disorder, dyslexia, Alzheimer’s disease, and fibromyal-
gia. Tourette syndrome was thought to be a neurological curiosity until
the Shapiros noted that haloperidol was very helpful to these patients,
and the presence of a therapy sparked a wave of recognition. Repeatedly,
clinicians wonder what patients were regarded as having before such dis-
orders were named and framed.
 Chapter 1 Terminology and Disease Description | 3

One of the physicians who classified and separated the great variety
of sick, elderly, and frail inmates of the great Salpêtrière hospital in Paris
was Jean-Martin Charcot. He and his colleague Edmé Vulpian contem-
plated the tremors of patients and attempted to differentiate a condition
of younger people from the paralysis agitans described by James
Parkinson in 1817. Charcot did not like the term paralysis agitans, as he
did not feel that paralysis was characteristic of the disease. He and
Vulpian noted a pattern that earlier clinicians had also seen and
described—a condition occurring in younger adults with tremor and
paralysis, who at autopsy were noted to have grey patches (plaques) scat-
tered throughout the spinal cord, brain stem, and brain. To separate this
type of tremor from that of Parkinson’s disease, they presented three cases
to a hospital rounds in 1866, and later Charcot gave a series of lectures on
the features of this disease, which he called sclérose en plaque disseminée.
As had occurred with Parkinson’s description of paralysis agitans,
once Charcot defined and framed this disease and gave it a name, others
could then recognize it. Over the next 150 years, medical knowledge of
the disease would build on these early descriptions, adding to its under-
standing and, recently, to the development of new therapies. As this is
being written, there are efforts to further subdivide and classify different
types of multiple sclerosis (MS) by their clinical characteristics and course,
their magnetic resonance imaging (MRI) features, and the differing
pathological findings.
I will discuss some of the people who suffered with a progressive neu-
rological disorder that resembled what we would now call multiple scle-
rosis, but who lived in the centuries before the disease was named, and
examine how they were regarded and treated. I will survey the many
early reports of this disease in the medical literature before Charcot gave
his famous lectures. The progress in knowledge of MS over the following
century will occupy the largest part of the book, followed by a more cur-
sory sweep of the developments of the last 25 years.
“The early history of MS is somewhat easier to put into context and
perspective than that of the last 50 years.”
George Ebers, 19983
4 | Multiple Sclerosis: The History of a Disease

Paradoxically, most of the research on MS has been in the last quar-

ter century, but this research is the most difficult to put into a historical
context. Recent work is still in evolution and the players are still busy
with this exciting work in their clinics and laboratories. They may be dis-
appointed to see their recent work with T-cells, cytokines, macrophages,
gene probes, and diffusion-weighted MRI given only cursory attention. It
will be left for some medical historian in the future to put much of the
current work into historical perspective.
MS is a recurrent demyelinating disease of the white matter in the
CNS, which usually becomes progressive. Thought to be a neurological
curiosity in the mid-19th century worthy of single case reports in the jour-
nals of the day, by the turn of the 20th century, it was recognized as one of
the most common causes of admission to neurology wards—“an epidem-
ic of recognition rather than the effect of altered biological factors,” said
Alistair Compston.4 Even Charcot, in his early descriptions of the disease,
said that it seemed rare, but the disease would be more frequently diag-
nosed when the variations (forme frustes) were better understood. At the
turn of the 21st century, MS is recognized as the most common serious
neurological disease in young adults living in temperate climates.
MS has also become well known to the general public because it is
common (most people know someone with the disease), because it has
been a major focus in neuroscience research, and because the MS societies
have increased public awareness. Public attention has also been captured
by the personal stories of well-known personalities who have MS and
who have discussed their struggle with the disease. The development of
new therapies in the past decade has increased public interest and creat-
ed an air of hopeful expectation.
Although the “discovery” of MS is often credited to Charcot, when he
stepped onto the lecture stage at the Salpêtrière in 1868 to give his regular
Friday Leçon on the clinical and pathological features of the disorder we
now know as MS, he was taking one further step in a process of defining
the disease that had begun in the previous century. Even as he spoke, he
acknowledged many individuals who had discussed this condition before
him, and who contributed to the knowledge that he was summarizing.
His gift and his contribution was a unique and brilliant manner of assim-
 Chapter 1 Terminology and Disease Description | 5

ilating information from diverse observations and visualizing a unitary

concept. He was, as many observed, a visuel, one who sees.
It would be easy to trivialize Charcot’s contribution by noting that
many knew of this disease and its features before him. But his clear
description, derived from only a few well-observed patients, gave other
clinicians a picture they could then recognize in their patients. Over the
next century and a half, reports of the disease increased, each observer
adding observations and speculations upon which the next could build.
The knowledge grew and the questions expanded, but the answers in
most cases remained tantalizingly out of view.
In the 1940s and 1950s, interest in the disease increased as therapeu-
tic advances increased, not only for MS, but in other fields. As therapies
for other diseases developed, they were applied to MS. Although most
would prove to be of little help, there was a move from an atmosphere of
therapeutic nihilism to one of hopeful polypharmacy. Although clinicians
in the 19th and 20th centuries stated flatly in print that therapy was hope-
less, all employed a long list of agents and procedures in the hopes that
something might help their individual patients. In the 1930s, Brickner
listed 29 pages of therapies that had been applied to MS, and Putnam
believed that half of them improved the patients.
By the 1950s, a dramatic change occurred with the development of the
MS societies, founded by Sylvia Lawry, a young woman in New York dis-
tressed by the lack of information and helpful treatments for her brother
Bernard, whose MS was worsening. There was now a lay interest in fos-
tering research, in seeking public support for the funding needed, and a
serious effort at patient and public education about MS. The “rare curios-
ity” of the mid-19th century was now becoming one of the foremost areas
of neuroscience interest, and research on the disease became a major focus
of the new National Institute of Neurological Disease and Blindness
(NINDB), which had a close link with the new but very active National
MS Society (NMSS). Advances in other areas of medicine, new technolo-
gies, and discoveries in other fields led to a “spillover effect” that increased
the capacity to address the questions in MS.
The theories about what causes MS changed as the major advances in
medical science changed. In the era of Pasteur and Koch, it seemed to be
6 | Multiple Sclerosis: The History of a Disease

an infectious disease; in the era of environmental illnesses, it seemed a dis-

ease due to some toxin; when epidemiological techniques improved,
interest centered on mysterious demographic and environmental factors;
as immunology flourished, it became an immunological disease, and in
this age of genetics, gene probes, and the human genome, there is great
interest in a genetic factor. With advances in virology, slow virus infec-
tions, and now prions, it is again being considered an infectious disease,
with the virus perhaps acting as a trigger in a genetically predisposed
individual. One might well ask if the theories of MS just follow the cur-
rent interests in science, but it is evident that each stage provided impor-
tant building blocks for the next. As a new theory in MS developed, it did
not become an either/or conflict with previous theories. When a new
therapy arose, it was included in a new overarching concept. This
umbrella concept included a new theory to explain some clues and fea-
tures, while retaining older theories for which there was still some evi-
dence, and placed it within a framework.
There does seem to be a genetic predisposition to the disease, but it is
not the result of a simple genetic defect. Some trigger is likely to deter-
mine if someone with the predisposition actually gets the disease and the
most likely agent is a virus. Many viruses have been accused but not yet
found guilty, including the usual suspects: measles virus, herpes simplex
6, Epstein-Barr virus, or the C. pneumonia agent. Whatever the trigger,
it likely causes episodic breakdown in the blood–brain barrier, allowing
immunologically active cells to enter the CNS and damage myelin, initi-
ating an immunological reaction that involves nitrous oxide and
cytokines and that continues the process. Scavenger cells have a number of
roles in the demyelination, and later a thinner myelin re-forms.
Eventually, repeated and widespread patches of myelin damage occur
with increasing damage as well to the central axon, which cannot regen-
erate, and progression of the disease becomes evident. There is evidence
that the axonal damage may be more widespread than the scattered
lesions seen on MRI scans, and that this damage occurs earlier in the dis-
ease than the first symptoms would suggest. Even in this simplistic con-
struct, we can incorporate most of the prominent theories of etiology,
many of them first enunciated in the 19th century.
 Chapter 1 Terminology and Disease Description | 7

TERMS USED FOR MULTIPLE SCLEROSIS

“A peculiar disease state.”
Robert Carswell, 18385
Multiple sclerosis has been known by many names over the last century
and a half. Carswell, in one of the earliest illustrations of the disease,
referred to it simply as a “peculiar disease state”5 and in the same period
Cruveilhier commented on “gray degeneration of the cord” without giving
it a name.6 Charcot was impressed by the sclerosis in the scattered lesions
and called it sclérose en plaque disseminée.7 Shortly after, Moxon in England
was impressed by the characteristic islets of change (the plaques) and pre-
ferred the name insular sclerosis, which was then favored by the English and
their Commonwealth partners.8 Sachs, in his 1895 textbook, uses the three
terms multiple sclerosis, insular sclerosis, and disseminated sclerosis inter-
changeably.9 In their 1899 textbook, Church and Peterson would use the
term multiple cerebrospinal sclerosis, but indicate that multiple sclerosis, insu-
lar sclerosis, sclérose en plaque, cerebro-spinal disseminated sclerosis, multilocu-
lar sclerosis, and spinal sclerosis were all terms in use.10 Some of these terms
suggested they were different conditions, but most felt it was all one.
Some of the old terms persisted, and the World Health Organization
used the term cerebral sclerosis up to the 1950s. Disseminated sclerosis (DS)
was a common term in England during the first half of the 20th century,
while multiple sclerosis was widely used in the United States. Physicians in
Canada, characteristically finding themselves somewhere in the middle,
used both terms. William Osler in Montreal used the term insular sclero-
sis in his 1880 paper. Fisher in Ontario in 1926 used both terms inter-
changeably in the same article. Although Risien Russel in his excellent
1899 review used a slightly shortened “disseminate sclerosis,” in a foot-
note his lenient editor, Sir Thomas Clifford Allbutt, commented that “it
would be better to use the term insular sclerosis; for, even docked of a syl-
lable, disseminate sclerosis is too long.”11
At a major meeting on MS of the Association for Research in
Nervous and Mental Diseases (1921), both Multiple Sclerosis and
Disseminated Sclerosis were used in the title of their publication (1922).12
8 | Multiple Sclerosis: The History of a Disease

The French still use the term sclérose en plaque (SP). The term multiple
sclerosis is derived from the German term “multiplen sklerose,” and
became generally accepted by the 1950s when it was adopted by the newly
formed MS societies, and by its use in the now classic book on MS by
McAlpine, Compston, and Lumsden in 1955.13 By 1965, the term used in
virtually all English publications was multiple sclerosis.
In this brief review of the history of the disease, I use the term multi-
ple sclerosis for clarity and consistency, even when discussing the work of
contributors who may themselves have used one of the other terms in
their publications. Thus, I refer to the contributions to the understanding
of MS by Jean-Martin Charcot, William Gowers, William Osler, Kinnier
Wilson, and others, although they did not use that term.

Earlier Terms for Multiple Sclerosis

Sclérose en tache ou en îsles Multiple cerebral sclerosis
Sclérose en îles Cerebral sclerosis
Îsles de substance blanche Spinal sclerosis
Grise masses disseminée Disseminate sclerosis
Multiplen Sklerose Lobular and diffuse sclerosis
Hirnsklerose Multiple cerebral spinal sclerosis
Multiple Sklerose Disseminated cerebral spinal
Inselförmige sklerose sclerosis
Multiple Sklerose des Cerebro-spinal sclerosis
Nervensystems Polysclerosis
La Sclérose en plaques disseminée Polynesic sclerosis
La sclérose multiloculaire Sclerosis multiplex
La sclérose generalisée Dissemineret sklerose
Sclérose en plaque Multiple inselförmige Sklerose
Sclerosi in plache Disseminated sclerosis
Insular sclerosis Lobular sclerosis
Multilocular sclerosis Cerebrospinal disseminated
sclerosis
 Chapter 1 Terminology and Disease Description | 9

A BRIEF SUMMARY OF THE DISEASE

Multiple sclerosis is a common neurological disease, which usually affects
young adults, most often beginning with episodic attacks of neurological
symptoms, but entering a progressive phase some years later. It usually
begins between the ages of 15 and 50 (average age 30), and occurs in about
1 in 500 individuals of European ancestry living in temperate climates.
There appears to be a complex interaction between a genetic predisposi-
tion and an environmental “trigger” that initiates the disease.
The disease may have a number of different courses after the onset of
symptoms, such as a relapsing-remitting course (85 percent), with attacks
and remissions of symptoms. Many patients will later make the transition
to a secondary-progressive course. Or, they may begin with a primary-
progressive course (15 percent), with slow progression without attacks.
Recently, there has been an attempt to separate the small number of
patients whose cases begin as progressive, but who later have one or more
acute relapses, and to call this progressive-relapsing type of disease. After
many years, it may be evident that some of the cases have had a very long
mild course, and can be called benign. The benign type, which represents
10 percent of cases, is more difficult to define and can only be recognized
after many years have passed.
Symptoms may occur in any area served by the myelinated nerves of
the central white matter of the brain, brain stem, and spinal cord. Thus,
the person may have weakness or sensory changes in the limbs, particu-
larly the legs; unsteadiness; difficulty with bladder control; visual changes
because of involvement of the optic nerve; vertigo; facial numbness or
weakness; or double vision.
MS affects the myelinated nerves of the CNS, but not the peripheral
nerves. The optic nerve is affected, as it is an extension of the brain and
contains central CNS myelinated nerves, not peripheral nerves. The cli-
nician can often find signs on the neurological examination that verify
the presence and location of the abnormality experienced by the patient.
Sometimes the symptoms are subjective, experienced by the patient, but
little can be found by the examining physician. Also, remission may have
begun by the time the patient sees the physician and the signs may have
10 | Multiple Sclerosis: The History of a Disease

cleared or disappeared. It is common to hear that the patient has had

vague symptoms off and on for many years before it is evident that MS is
the cause.
Overall, there is little effect on life expectancy, but there is a signifi-
cant effect on the person’s quality of life, even early in the disease, and
there is often serious disability in the later years. People with MS usually
learn to cope with the difficulties the disease brings, but it has a major
effect on their life plans, employment, and hopes for the future, as they
are mostly young adults who are just beginning to develop their families
and careers. Another stressful aspect of the disease is the uncertainty
about the future, and even how they will feel next week. Just when they
may have adapted to the disability left by previous attacks, another attack
brings still more limitations and requires yet another period of adaptation
and life change.
Although the cause is uncertain, MS appears to involve an immune-
mediated inflammatory process in the CNS characterized by breakdown
in the myelin that surrounds the nerve axon. Myelin is necessary for the
rapid (saltatory) conduction in myelinated nerves. There appears to be a
breakdown in the blood–brain barrier, allowing immunologically active
cells in the blood to enter the brain and cause patchy damage to myelin.
These scattered circumscribed lesions, or plaques, cause the symptoms of
MS by slowing or disrupting conduction in the nerve axons. The plaques
are characterized by inflammation, demyelination, and scarring (gliosis).
The axons may remyelinate again, which explains to some extent how
remissions may occur after a relapse (attack). The remyelinated axons
may appear to be functioning normally, as the symptoms may have
cleared, but electrophysiological measurements (evoked potential studies)
may show that conduction is slower than normal. Perhaps more impor-
tant in the long-term is the amount of damage that occurs to the axons.
The immune reaction in the nervous system is accompanied by
inflammation and gliosis, which are evident on MRI scans and which
may also cause increased antibodies in the spinal fluid. The MRI appear-
ance of many lesions in characteristic areas, and the spinal fluid tests (ele-
vated gamma globulin and oligoclonal banding), are helpful in
confirming that MS is present, but do not correlate well with specific
 Chapter 1 Terminology and Disease Description | 11

symptoms. For this reason, they are not usually used to follow the course
of the disease once it has been confirmed. Although these tests can help
confirm the suspicion of MS, they do not by themselves make the diag-
nosis, because similar changes can occur in other conditions.
Confirmation of the clinical diagnosis requires correlation with the clin-
ical picture, the presence of characteristic changes on the MRI, evoked
potential studies, and spinal fluid analyses.
MS occurs two to three times more often in women and is more com-
mon in temperate climates. The reasons are unclear. Perhaps the genetic
predisposition is one that is primarily in those of European stock, and
those people tended to migrate to more temperate climates during the last
centuries.
The earliest investigators recognized that this disease was difficult to
treat, especially when the cause was unclear. This is still the case, but
drugs are now available that can modify the acute attacks and reduce
many of the symptoms. More importantly, for the first time, there are
new agents that can reduce the number and severity of the attacks and
perhaps slow the progression of the disease.
Tracy Putnam said in 1938 that the history of MS was like the histo-
ry of medicine in miniature, but added that neither is yet complete. This
book will chronicle the early part of the MS story.
For those interested in a fuller review of current knowledge of MS, I
recommend the overview by John Noseworthy and colleagues14 or the
comprehensive text by Donald Paty and George Ebers15 and the classic
McAlpines’s Multiple Sclerosis.16

REFERENCES
1. Putnam TJ. The Centenary of Multiple Sclerosis. Arch Neurol Psych. 1938;40(4):806-813.
2. Dunglison R. A Dictionary of Medical Sciences. Philadelphia: Henry C. Lea; 1868.
3. Ebers G. A Historical Overview. In: Paty D, and Ebers G, eds. Multiple Sclerosis.
Philadelphia: FA Davis; 1998:1-4.
4. Compston A, ed. McAlpine’s Multiple Sclerosis. London: Churchill Livingstone; 1998:3.
5. Carswell R. Pathological Anatomy: Illustrations of the Elementary Forms of the Disease.
London: Longman, Orme, Brown, Green and Longman; 1838.
6. Cruveilhier J. Anatomie pathologique du corps humain. Paris: JB Baillière; 1829-1842.
(Individual livraisons in this work appeared separately but Livraisons 32 and 38, both
of which deal with MS, also can be found in Volume 2, published in 1842. In the
12 | Multiple Sclerosis: The History of a Disease

Wellcome Library a number of copies can be found, bound differently. In Copy 2, the
two illustrations of MS are found in Planches V, Anatomie de l’appareil des sensations
et l’innervation.)
7. Charcot JM. Histologie de la sclérose en plaques. Gaz Hôp Civils Milit (Paris). 1868;
41:554-558.
8. Moxon W. Eight cases of insular sclerosis of the brain and spinal cord. Guy Hosp Rep.
1875;20:437-478.
9. Sachs B. A Treatise on the Nervous Diseases of Children. New York: William Wood;
1895:345-356.
10. Church A, Peterson F. Nervous and Mental Diseases. London: Rebman Publishing
Company Ltd.; 1899:434-442.
11. Russell JSR. Disseminated Sclerosis. In: Albutt TC, ed. A System of Medicine. London:
Macmillan & Co.; 1899:50-94.
12. Association for Research in Nervous and Mental Disease. Multiple Sclerosis
(Disseminated Sclerosis). New York: Paul B Hoeber; 1922.
13. McAlpine D, Compston ND, Lumsden CE. Multiple Sclerosis. Edinburgh: E&S
Livingston; 1955.
14. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple Sclerosis.
NEJM. 2000;343:938-952.
15. Paty DW, Ebers GC, eds. Multiple Sclerosis. Philadelphia: FA Davis; 1998.
16. Compston A, ed. McAlpine’s Multiple Sclerosis. London: Churchill Livingstone; 1998.
 C h a p t e r

2
The Framing of
Multiple Sclerosis

“Medicine, an often-quoted Hippocratic teaching explains, consists in

many things—the disease, the patient, and the physician. … But dis-
ease is an elusive entity. It is not simply a less than optimum physio-
logical state. The reality is obviously a good deal more complex;
disease is at once a biological event, a generation-specific repertoire of
verbal constructs reflecting medicine’s intellectual and institutional
history, an occasion of and potential legitimization for public policy,
an aspect of social and individual—intrapsychic—identity, a sanction
for cultural values, and a structuring element in doctor and patient
interactions. In some ways disease does not exist until we have agreed
that it does, by perceiving, naming and responding to it.”
Charles E. Rosenberg
Framing Disease, 19921

T he medical historian Charles Rosenberg indicated that in one aspect,

disease is a biological event unrelated to its social context. Just as dis-
ease occurs in an animal, which suffers unassociated with a social con-
struct for the pain and dysfunction, in our culture, a disease exists only

13
14 | Multiple Sclerosis: The History of a Disease

when it is named. And the complex social, psychological, medical, politi-

cal, and personal aspects that surround the biological change go to make
up the experience, or the disease.
We can construct “disease” out of a behavior or complaints that were
not previously regarded as disease, such as alcoholism, hyperactivity, per-
sonality disorder, premenstrual syndrome, seasonal affective disorder,
gambling addiction, and chronic fatigue. Once named, it is experienced
differently and the reaction of family, friends, and health professionals is
different.
Access to the health care system and therapy may depend on having
a disease that is named and thus accepted as existing. Conversely, many
patients suffer not only their symptoms, but the rejection and perhaps
derision of the health care system and society if there is no name and thus
no diagnosis for their problems. This reminds me of the cartoon of the
physician saying to a patient, “Our tests show that whatever you have
doesn’t exist.”
The naming and acceptance of existence of a disease is heavily influ-
enced by many cultural and social factors.2 It is also characterized by
specificity and having a logical mechanism and concept for the disorder.
The reductionist approach that can outline the specific nature of a disease
will give it legitimacy and acceptance. But it should be emphasized that
the defining and naming of a disease have many consequences in the lives
of those suffering those symptoms. It also can alter public policy, how the
health care system responds to them, and how they are regarded by oth-
ers, including their friends and family. For instance, chronic pain with-
out an evident physical abnormality to explain the pain has lacked the
specificity and logical explanation that would allow its acceptance as a
disease. For this reason, physicians, workers’ compensation agencies, and
insurance companies, as well as fellow workers and friends, are often
reluctant to recognize that the person has a legitimate condition.3 People
with multiple sclerosis (MS) who complained of their symptoms for
many years before being diagnosed often show relief when they find they
have MS because they now have an understanding of their problem, and
now know it is not imaginary or “all in my head.” Having a name for
their disease has made their suffering legitimate. They can now be given
 Chapter 2 The Framing of Multiple Sclerosis | 15

a diagnosis, an explanation for the problem, a therapeutic regime, and a

prognosis. This process is central to the role of a physician and the
patient–physician process.4
Rosenberg5 indicated that ways of seeing the disease and explanations
for the patients’ symptoms altered over the centuries. Initially, there were
references to cooking as explanations for how the body worked and dis-
ease produced symptoms, and we now do it with descriptions of hor-
monal feedback loops and alterations of physiology, immune
mechanisms, or the delayed effects of viral infections. If the understand-
ing of a disease was in terms of altered balance of humors, then purging,
bloodletting, and diuresis were a logical therapeutic approach, but if the
problem is seen as an overactive or deranged immune system, the
approach might be a drug known to suppress or alter immune function.
The framing not only allows differentiation of the disease from others,
but permits a construct that determines the understanding of how the
disease affects the body, and how it might be eradicated or modified.
Rosenberg also makes the interesting point, well understood by many
people diagnosed with a disease, that the framing of the disease can then
frame the person with the disease. In other words, they may perceive that
they have become the disease, not only have it. For instance, the person is
an epileptic, a tubercular, a schizophrenic, a sexual deviant, a migraineur,
not only to the insensitive physician who refers to “the liver case in bed
number seven,” but also to the community and the people who now
define themselves by their disease. Their diagnosis has implications for
their present, but also for their future, and may redefine how they see
their past.6 They are part of a dynamic narrative that changes if the dis-
ease is redefined and reframed. This is why Rosenberg says a disease can
be viewed as existing only when it is named—before that the experience
would have been quite different.7
The naming and classification of disease, nosology, also changes.
Charcot may have been remarkably complete in his definition of the
characteristics of the disease and its patterns, but MS has been repeatedly
redefined since then, and there are currently a number of separate com-
mittees redefining and reclassifying the types and patterns of the disease
in order to better comply with concepts of pathophysiology, clinical types
16 | Multiple Sclerosis: The History of a Disease

and courses, and responses to therapies. At the turn of the 20th century, a
person might be diagnosed simply as having MS, but at the turn of the
21st century, another patient may be diagnosed as having primary pro-
gressive MS with evidence of widespread MS lesions in the brain and
spinal cord, some cerebral atrophy, and an Expanded Disability Status
Score (EDDS) of 6.0, all of which will govern how he or she is regarded
and what therapies, services, and opportunities for clinical trials and
experimental therapies will be offered.
There have been differing views on the historical existence of MS. It
might have been present in the population for many centuries, relatively
similar in prevalence, but more evident recently because of increased
recognition of the disease. There have been increasingly refined criteria
and greater awareness of clinical variations, coupled with remarkable
tools that can diagnose MS in mildly involved patients who would not
have been diagnosed at this stage in the past. On the other hand, MS may
be a new disease (only a few centuries old and increasing), defined in the
early and mid-19th century because that is when it began to appear in
increasing numbers. Or perhaps it was always there, blending into many
diagnostic categories as they developed, changed, and became more
focused. People with MS may have been residing in the categories of con-
ditions known as paraplegia, apoplexy, flying gout, creeping paralysis,
hysteria, rheumatic disease, myelitis, paralysis agitans, general paresis,
tabes dorsalis, muscular dystrophy, Fredreich’s ataxia, locomotor ataxia,
chorea, and more general categories that included people with a slowly
progressive debility and infirmity.
As I will outline, cases of MS, by our current definitions, have exist-
ed for centuries, but were framed differently in different eras. Thomas
Willis would have included a patient with MS under the classification of
a Habitual Palsy, which he felt should be treated with bleeding and chyli-
fication, purging, and the use of salt of vitriol, sulphur of antimony, cro-
cus metallorum, mercury, and a long list of other herbal preparations and
drugs that took up many pages of his book, The London Practice of Physick
(1685).8 People could just be regarded as having a condition that caused
chronic lameness and was unresponsive to treatments, as was Margaret
Davis in the late 1600s. Or they might be regarded as having a palsy that
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