MEDICAL HISTORY ABSTRACT: One of the seminal events in the history of neurology was the

identification of primary diseases of muscle and their separation from dis-

eases in which muscle weakness was secondary to injury involving the
anterior horns of the spinal cord (“progressive muscular atrophy”). Not
surprisingly, one of the first groups of primary muscle diseases to be satis-
factorily characterized belonged to what would today be classified as mus-
cular dystrophies. Pride of place in this group belongs to Duchenne muscu-
lar dystrophy (DMD). DMD’s primacy as the first well-characterized muscular
dystrophy was due both to the fact that it is relatively common, as well as to
the clinically striking feature, apparent in many cases, of apparent paradox-
ical enlargement of severely weakened muscles (“pseudo-hypertrophy”).
This review traces the historical roots of DMD in the 19th century, from the
early papers by Conte, Bell, Partridge, and Meryon through the classic
monographs by Duchenne and Gowers. In addition, the first American
contributions to DMD are reviewed, including those by Pepper, Hammond,
and S. Weir Mitchell. Many of the original papers describing this disease are
now unavailable outside of major medical libraries, and several important
contributions, excepting those of Duchenne, which are recognized epony-
mously, are now virtually forgotten.
Muscle Nerve 28: 402– 422, 2003

ORIGINS AND EARLY DESCRIPTIONS OF

“DUCHENNE MUSCULAR DYSTROPHY”
KENNETH L. TYLER, MD

Department of Neurology B-182, University of Colorado Health Sciences Center

and Neurology Service, Denver Veterans Affairs Medical Center,
4200 East 9th Avenue, Denver, Colorado 80262, USA

Accepted 28 April 2003

Isolated cases of what almost certainly represent
Duchenne muscular dystrophy (DMD) were initially
described in the first half of the 19th century.2,14,21,22
These early depictions generally present patients
with childhood onset of slowly progressive weakness
beginning typically in the legs, and occurring in the
absence of associated sensory findings or other signs
to suggest spinal cord disease. For example, in 1830,
the eminent English physician Charles Bell (1774 –
1842) briefly described a Case of Partial Paralysis of the
Lower Extremities (Case LXXXIX).4 The patient was a
man of 18 in whom:
All the muscles of the lower extremities, the hips,
and the abdomen, are debilitated and wasted. . . .
He has no defect of sensibility in the lower extrem-
ities. The upper part of the body, the shoulders,
Abbreviations: DMD, Duchenne muscular dystrophy
Key words: Becker muscular dystrophy; Duchenne muscular dystrophy;
Gowers’ sign; historical aspects; muscular dystrophy; pseudohypertrophic
muscular dystrophy
Correspondence to: K.L. Tyler; e-mail: ken.tyler@uchsc.edu
© 2003 Wiley Periodicals, Inc.
and arms, are strong. There is no defect percepti-
ble in the evacuation of the bladder or of the
bowels. . . .The paralytic debility of the muscles
came on gradually; he was first sensible of it at a
public school, about eight years ago. It began with
a weakness in the thighs, which disabled him from
rising; and it is now curious how he will twist and
jerk his body to throw himself upright from his
seat.4
At nearly the same time, a series of physicians in
Italy described two brothers with progressive weak-
ness, but emphasized for the first time the associated
finding of striking enlargement of affected muscles,
and the development of contractures as the disease
progressed. In 1836, Gaetano Conte (1798 –1858)
and L. Gioja in the Annali Clinici dell’Ospedale degli
Incurabili di Napoli (The Clinical Annals of the Hos-
pital for Incurables of Naples) reported on these
brothers in a paper entitled “Scrofola del sistema
muscolare”(Scrofula of the muscular system).10,11
This paper was almost certainly not reviewed in its
original form by later authors on the subject, who
typically referenced a synopsis of its contents pre-
pared in a widely circulated yearbook which ab-
stracted foreign medical proceedings,50 or an even

402 History of Duchenne Dystrophy MUSCLE & NERVE October 2003

later mention in another case synopsis.3 Unfortu-
nately, the errors in the yearbook citation, which
were perpetuated by later authors in reviews, and the
inaccessibility of the original Italian article, virtually
guaranteed that Conte and Gioja’s contribution
would become lost to posterity. Inspired by Dubo-
witz’s lament about the lost article,14 Giovanni Nigro,
whose father had been a Department Head at the
Ospedale degli Incurabli in Naples, was able to lo-
cate the original paper,45 and have it republished in
the Italian journal Cardiomyology (1986).11 Unfortu-
nately, this journal ceased publication in 1988, and
was never indexed by Medline/PubMed, so the pa-
per again lapsed into obscurity.
Conte and Gioja describe two brothers who de-
veloped progressive muscular hypertrophy particu-
larly localized in the calves and deltoids.10,11 They
mention that the two brothers had previously been
briefly described by another Italian physician, Gio-
vanni Semmola (1793–1865) in 1829, with their dis-
ease described as “Ipertrofia muscolare” (muscular
hypertrophy), in a report to the Accademia Pontani-
ana in Naples. Unfortunately, we have not yet been
able to locate this report, which if presented in 1829
would have antedated Bell’s description by a year,
and made these two brothers the first reported cases
of DMD. Alan and Marcia Emery located a paper by
Semmola published in 1834, but not the earlier 1829
report,21 so the chronology and priority remain un-
settled.
The two described brothers developed a syn-
drome of progressive leg weakness. Beginning at
about the age of 8 –10 years, the boys “found them-
selves victims of a strange disease manifested by the
muscles, especially those of the lower extremities
growing in size without, however causing any discom-
fort.” The older of the two boys was more severely
afflicted and died “with signs of an enlarged heart”
as a teenager. By age 17, the younger brother
(Nicola Caruso) was “unable to carry out any volun-
tary movement and in this state he presented himself
at this hospital [Hospital for Incurables in Naples].”
He was found to have hypertrophy of several muscle
groups including especially the deltoids; the right
one being enlarged “approximately three times the
normal volume.” He had lesser enlargement of the
biceps, triceps, brachialis, and other arm muscles,
which were noted “to have a certain hardness about
them.” His abdominal and paraspinal muscles were
also enlarged and seemed “hard and rigid.” In the
legs, the glutei and quadriceps “had grown three
times the normal size. Also the gastrocnemii muscles
were triple in size.” Hypertrophy was also seen in the
tibialis anterior. Interestingly, the tongue was noted
History of Duchenne Dystrophy
to be “somewhat larger than normal . . .[and]
seemed to want to stick out of the mouth as it did not
have enough room.” Nicola had difficulty with
speech, swallowing, and chewing, “augmented by the
enlarged size of the masseters.” His tendons seemed
“thinner and harder” than normal and he had flex-
ion contractures so that,
The forearm was in semiflexion over the arm and
the fingers over the palm so that he could not
bend nor extend the arm to bring it close to his
chest. The thighs were in flexion over the abdo-
men and the legs over the thighs, which formed a
very acute angle so that the heels touched the
glutei. The feet were also distorted so that the
dorsum was on the same line with the external
malleolus and the plantar aspect was in line with
the internal malleolus so that it seemed they were
reversed.
In summarizing the case, Conte and Gioja noted:
“We should remember that the main problem con-
sists in a disease that primarily consists of a patho-
logical increase in size of the neuromuscular system
with a change in. . .the relationship of muscles, of
their tendons, and the bones.”
They felt that the hypertrophy was not due to
changes in nonmuscular components (e.g., blood
vessels), nor was it due simply to contraction or
rigidity of muscles, as this would not be expected to
increase muscle volume. They speculated that it was
caused by a change in the “nutritional process” lo-
cally (i.e., in the muscle itself). They also stressed
that hypertrophy alone was not the only factor in the
disease, as this would not explain the associated
finding of loss of the “natural plasticity” of the in-
volved muscles. Nor was the process simply akin to
continuous muscle contraction as seen in tetany, as
tetanic spasms did not result in increase in muscle
volume. They lamented the unfortunate fact that no
autopsy was available, “as an autopsy would have
helped us in determining if the connective intramus-
cular tissue was increased. . .as we see in people who
have paralysis.” They speculated that if the muscles
contained an “accumulation of extraneous sub-
stances” that this might stretch the fiber beyond its
normal range, making it “lose its irritability and con-
tractile force.”11
These early cases must be considered suggestive
rather than definitive, for the clinical descriptions
are sparse and there is no description of pathology.
Both these objections would be overcome in the
next decade with the reports of the English physi-
cians Partridge and Meryon.
MUSCLE & NERVE October 2003 403
FIRST PATHOLOGICAL EXAMINATIONS OF CASES:
PARTRIDGE AND MERYON
The first pathological examination of a patient with
DMD was probably that of Richard Partridge (1805–
1873), who described a case to the Pathological So-
ciety of London at the meeting on November 15th,
1847.46,47 It would be almost impossible from his
brief description of the clinical features to be sure of
the diagnosis, but the same case and his affected
siblings were described a few years later by both
Edward Meryon38,39 and William Little.37 Partridge’s
patient (corresponding to Case E.H. of Meryon,39
see below), was a 14-year-old boy who, along with his
brother, developed weakness beginning in the prox-
imal muscles of the arms and legs. As Meryon later
noted, “He could not stand when he was two and a
half years old. . ..he was, however, always conspicu-
ously weak, as was also his brother, and in both it was
observed that they never ran, jumped, or played with
other children.”39 The brothers had great difficulty
going up stairs, “laying hold of the balusters with
both hands, then leaning the head on the hands and
fixing themselves in that bent attitude, they dragged
their legs after them.” Meryon later (see below) ob-
tained additional information from the boys’ father,
“Who informed me that just before the loss of power
became apparent, the limbs grew thick and heavy;
from him I also ascertained, that he had two daugh-
ters. . .who were perfectly free of the disease in ques-
tion.” The oldest boy died of pneumonia complicat-
ing measles and was autopsied. The muscles were
not examined microscopically, but grossly:
The deltoid and sternomastoid muscles had under-
gone fatty degeneration. The calves (which were
larger than natural, and had, during the progress
of the paralysis, become permanently contracted)
presented a greater degree of fatty degeneration in
their muscular structure than the upper extremi-
ties, the soleus and gastrocnemius being more af-
fected than the flexor longus pollicis; neither the
nerves nor the tendons had undergone
change.39,46,47
Credit for the first unequivocal clinical and patho-
logical depiction of DMD goes to Edward Meryon
(1807–1880) who submitted a paper entitled, “On
granular and fatty degeneration of the voluntary
muscles” on November 28th, 1851 (read on Decem-
ber 9th) to the Royal Medical and Chirurgical Soci-
ety of London.38,39 Meryon’s paper contains descrip-
tions of three families, “P,” “H,” and “Tyrrel.” The
“P” family included 10 children in which all 4 of the
brothers aged 2 to16 years (and none of 6 girls aged
5 to17 years) were afflicted by progressive muscular
weakness. It was the availability of pathological ma-
404 History of Duchenne Dystrophy
terial from two of the cases that prompted Meryon to
present a detailed report to the Society in 1851,
based on patients he had first seen in November
1848. His first patient, the oldest brother, was the
Honorable George P (Honorable being a title of
respect denoting the patient’s membership in a no-
ble family). As a young child, it was noted that “he
walked heavily” and that when lifted from the
ground by his nurse “he seemed to be a dead weight,
having no power of assisting or jumping from the
ground.” Despite these early symptoms, he was still
able at age 6 or 7 to walk a mile without resting. By
the age of 8, his condition began to deteriorate. At
that time,
He ascended stairs with the greatest difficulty, by
holding the balusters and dragging the leg which
was furthest from them after him: this latter diffi-
culty increased more rapidly than that of walking
on a level surface. He was always disposed to trip,
and could never make the slightest effort to re-
cover himself.39
A local surgeon suspected this his difficulties were
due to “deficient elongation of the spinal cord” and
prescribed a “procrustean plan of treatment” that
included use of a spinal “stretching-board.” By the
age of 11, the child could no longer walk even a step
and could scarcely stand. An operation to divide his
Achilles tendons and those of four other muscles,
and the use of mechanical supports (“irons”) ap-
plied to the feet and legs, resulted in transient im-
provement. In 1850, at the age of 16, the boy died of
a febrile upper respiratory illness. Meryon was noti-
fied by telegraphic dispatch and was able to perform
an autopsy.
He noted that the body was generally emaciated,
“more especially the lower extremities. . .there was
great lateral curvature of the spine. The knees and
hip-joints were rigidly fixed in a bent position.” The
brain, spinal cord, and nerves were all essentially
normal in appearance, but the muscles showed
marked abnormalities (Fig. 1).
The chief structural change existed in the system
of voluntary muscles, which was throughout the
entire body atrophied, soft, and almost bloodless;
and, although the muscular fibres appeared to exist,
yet they were not of that deep red colour as seen in
the natural state. When the muscular tissue was
examined under the microscope, the striped ele-
mentary primitive fibres were found to be com-
pletely destroyed, the sarcous element being dif-
fused, and in many places converted into oil
globules and granular matter, while the sarco-
lemma or tunic of the elementary fibre was broken
down and destroyed.39
At the time Meryon was performing his examina-
tions, microscopy of pathological specimens, such as
MUSCLE & NERVE October 2003
 FIGURE 1. Photographs of the muscle biopsy from Meryon’s cases of DMD.39
muscle tissue, was still in its infancy. Meryon was a
founding member of the Microscopical Society of
London in 1839,21 and was apparently assisted in his
studies by a fellow member, the Honorable and Rev-
erend Lord Sidney Goldolphin Osborne (see
Meryon, 1864, who refers to “my friend” Osborne as,
“an accomplished microscopist, [who] has for many
years taken a lively interest in these cases of granular
degeneration of the voluntary muscles, and has
spent much time in examining the different tissues
obtained at the post-mortem investigation” [of
“W.P.” (Case 86)].40 Gowers would later refer to an
unpublished pamphlet by Reverend Osborne enti-
tled “The construction of voluntary muscle with ref-
erence to muscular degenerative disease, as seen in
certain cases with observations on that disease, by a
member of the Microscopical Society.”27 In this pam-
phlet, Osborne provided additional details about the
History of Duchenne Dystrophy
history of Meryon’s “P” family, and a series of illus-
trations that were almost identical to Gowers’ own
(see below).
Had his initial patient occurred in isolation,
Meryon told his audience,
I should not have presumed to occupy your time
and attention with the details which I have given;
but a second son, the Hon. G. Wr. P--, four years
younger than the former, exhibited precisely the
same physical condition and the same symptoms as
did his brother at the same age.
A third son (Honorable Wm. P.) born in 1845 was
also “much in the same condition as were his broth-
ers at that age.” This child is likely the case Meryon
described in more detail in 1864 as “W.P.” (Case
86).40 He died of pneumonia at the age of 14. Au-
topsy showed that the brain and spinal cord ap-
peared healthy, a point Meryon later reemphasized
MUSCLE & NERVE October 2003 405
in response to Duchenne’s accusations that his pa-
tients were in reality simply cases of progressive mus-
cular atrophy rather than Duchenne’s own disease
(see below). As Meryon noted in response,
I may here state, that in the examination I made of
the spinal cord of G.P... I traced the nerve-fibres of
many of the anterior nerves into the anterior cor-
nua; therefore I should have noticed an atrophied
state of the anterior roots had it existed.40
In distinction to this normal result, Meryon noted
(Fig. 1):
The chief structural change existed in the system
of voluntary muscles, some of which, especially
those of the lower extremities, were ochery in co-
lour, and when examined under a microscope, in
many places the striped elementary primitive fibres
were found to be completely destroyed, the sar-
cous element being diffused about in the form of
granular matter, whilst the sarcolemma or tunic of
the elementary fibre was broken up and de-
stroyed.40
Meryon placed particular emphasis on the “breaking
up of the sarcolemma” which he saw in these cases,
noting that it differed from, “the atrophy of muscles
which supervenes on lesions of the nervous centres
or on simple disuse.”40
The “H” family included two boys. The older
(“E.H.”) “could not stand when he was two and a half
years old” and was always conspicuously weak, as was
also his brother, and in both it was observed that
they never ran, jumped, or played with other chil-
dren.
When between eight and nine years of age they
both manifested the same kind of muscular weak-
ness which I have described in the other cases,
except that the arms were affected before the legs.
In both the diminution of power was most marked
in going up stairs, which was affected by laying
hold of the balusters with both hands, then leaning
the head on the hands, then fixing themselves in
that bent attitude they dragged their legs after
them.39
As Meryon noted, it was this child (E.H.), who died
of measles pneumonia, in whom autopsy showed
that “all the voluntary muscles were wasted, retaining
a fibrous appearance, but were flabby and of a yel-
lowish colour.”39 Meryon then went on to describe
the pathological appearance of the muscles in detail,
quoting from Partridge’s earlier report.46,47
Meryon’s final family (Tyrrel) is of interest for
their later onset of illness, and are likely to have
represented the first description of what would later
be called the Becker variant of DMD. All three broth-
ers in the family were affected, though their sister
remained entirely well.
406 History of Duchenne Dystrophy
[The boys] began to lose the muscular power in
their legs when they were about twelve years of age,
from which epoch they became gradually worse,
and when they were twenty their legs were useless;
their arms then began to fail them, and at the age
of twenty five both legs and arms were totally dis-
abled.39
Meryon felt that “defective nutrition” of the muscles
was important in the pathogenesis of the disease and
directed his treatments to restoring what he felt was
likely an unhealthy condition of the blood, for which
purposes he used iron and a fibrin-rich diet. To
enhance circulation to the muscles, he felt that “ex-
ercise of all the muscles is of paramount importance,
and when the disease is far advanced, artificial exer-
cise should be substituted.” He also utilized electrical
stimulation to try to reproduce the electrical cur-
rents normally produced by “molecular interchanges
in the muscles themselves” and which “exert a
healthy influence on the nervous system by main-
taining its function.”
Meryon initially felt that the weakness in his pa-
tients was due to disease of the spinal cord, and he
was not dissuaded from this viewpoint until he had
an opportunity to perform a careful gross and mi-
croscopic examination of George P.’s spinal cord
and nerves, which revealed “not the slightest trace of
disease.”
I was therefore wrong in my diagnosis, for the
nervous tissues had preserved their integrity; and
the only structural change observed was that which
presented itself in the muscular fibres, which were
broken down, and converted into granular and
fatty matter.
He also noted astutely that this fatty degeneration
did not simply insinuate itself between or displace
muscular fibers but rather filled the sheath of what
was formerly muscular fiber. Meryon went on to
review what was then known about different types of
fatty deposition and their etiologies. He did not feel
that the changes he had seen were similar to those
found in disuse following paralysis or other “defalca-
tion of nervous energy” but rather due to some
intrinsic “deficiency of the elements” in muscle itself
that somehow prevented its necessary consumption
[metabolism] and healthy assimilation.
In 1864,40 1866,41,42 and again in 1870,43 Meryon
described additional cases of progressive muscular
weakness under the title of “granular degeneration
of the voluntary muscles,” clearly grouping them as
examples of the same disorder he had originally
described in 1851.38,39 Unfortunately, several of
these later cases are less straightforward and differ in
many ways from the originals. These later reports
undoubtedly contributed to Duchenne’s subsequent
MUSCLE & NERVE October 2003
claim that Meryon had not described cases of
“pseudohypertrophic muscular paralysis” but rather
of “progressive muscular atrophy,” a point that
Meryon went to great lengths to refute.40 – 43 In sup-
port of his argument, Meryon quoted no less an
authority than Jean Cruveilhier, the great French
pathologist who had first noted atrophy of the ante-
rior roots in cases of atrophic paralysis. Cruveilhier
had told the members of the French Academy of
Medicine (after reviewing the illustrations of the
muscle pathology in Meryon’s papers) that this was a
form of paralysis, “non encore decrite” (not previ-
ously described).41,42
The sparse clinical descriptions and lack of sup-
porting pathological material in many of Meryon’s
later case reports makes it impossible to identify
their exact nature, although several patients had
forms of limb-girdle dystrophy similar to what would
later be described by Leyden and Mobius. For exam-
ple, in 1866, Meryon described a woman aged 24 and
a man aged 22 from a group of nine siblings.41,42
Both patients developed weakness in the legs and a
waddling gait, then difficulty ascending stairs and
flexing their thigh muscles, followed by weakness in
the feet and toes. Ultimately both patients also de-
veloped arm weakness. The woman eventually “lost
all voluntary motions of her arms and hands.” Nei-
ther patient had pain, nor did they experience the
“quivering or starting” (fasciculations) of the dis-
eased muscles, which Cruveilhier had previously de-
scribed in the case of Prosper Lecomte, the first
autopsied case of motor neuron disease. No new
pathological studies were available from either case,
although Meryon accompanied his report with re-
productions of the muscle biopsy from one of his
1851 cases (Wm. P.). In 1870, Meryon described
another family in which two girls (ages 10 and 14)
and their 3-year-old brother developed progressive
weakness beginning in the muscles of the legs and
then progressing “centrifugally.”43 The oldest child
was the most severely affected: “She can no longer
stand, and her arms are beginning to be implicated
in the disease.” Her younger sister had a “waddling
gait” associated with, “gradually increasing weakness
of the muscles of the back and legs.” Weakness oc-
curred in the absence of pain or “any indication of
nervous disturbance” and without, “the quivering or
starting of the diseased muscles which Cruveilhier
has remarked in the cases he has described as “atro-
phie musculaire progressive.”43 As noted, although
exact diagnosis is problematic, these children may
have had limb girdle dystrophy of the type later
described by Leyden and Mobius.
History of Duchenne Dystrophy
LITTLE’S CASES
In 1853, the year after Meryon’s description, William
J. Little (1810 –1894), an English orthopedic sur-
geon who would achieve fame for his early descrip-
tions of cerebral palsy, published a monograph en-
titled, On the Nature and Treatment of Deformities of the
Human Frame, which was based on lectures he had
delivered a decade earlier at the Royal Orthopedic
Hospital.1,37 In a 3-page footnote, he described two
siblings with DMD, noting the characteristic
pseudohypertrophy, and providing the third (after
Partridge and Meryon) gross and microscopic de-
scription of the muscle pathology. His patients were
two brothers, aged 12 and 14, whom he had seen in
consultation in September 1847. Little saw his first
patient 14 months before Meryon saw his original
case, but did not publish his description until a year
after Meryon’s original report. As noted by the
Emerys,21 the family described by Little was almost
certainly the same one described by both Partridge
in November 1847 and Meryon in 1851 (Case E.H.).
Both boys had “abnormal increase of bulk of muscle,
combined with contraction and adipose degenera-
tion.” This was accompanied by “very general paral-
ysis, of the neck, trunk, the upper and lower extrem-
ities.” The older boy (“A.”) had delayed motor
milestones and had “never crawled” and had only
“walked alone weakly from table to chair at age of
nineteen months.” Later acquiring the ability to
walk, he progressively deteriorated and by age 9 was
unable to stand unassisted. He developed progres-
sive contractures of the heel which made him stand
on his toes. At age 11, it was noted that “the muscles
of his calf were as large as those of a well-grown
man.” His arms “showed atrophy generally of both
shoulders and upper arms. . . except the deltoids. . .
are larger in proportion to the remainder of the
shoulder and upper arms; these muscles, however,
do not possess any voluntary power.” He had slight
contractures at the elbows and of the pronators of
the arms.
He possesses very slight power in shoulders or
elbows, more in wrist and fingers. . .The muscles of
the calf are at present larger than those of a
healthy boy of the same age; he possesses power of
volition in them; slight volition also apparent in
anterior tibial, long and short extensor muscles of
the toes, although these muscles are overcome by
contracture of the calf.
His younger brother (“B.”) had a similar but milder
affliction. Neither boy had any intellectual deficits.
Interestingly, the older boy did have some transient
sensory signs and symptoms and “has complained of
sensation of ‘pins and needles’; at one period the
MUSCLE & NERVE October 2003 407
FIGURE 2. Duchenne’s original patient (Case I, Joseph Sarrazin) from a photograph (A) taken by Duchenne,16 and as reproduced in
drawings (B) based on these photographs.15,17–19
legs and feet could be pinched without his being
aware of it.” However, Little noted that “sensation is
now perfect.”
Shortly after Little examined the boys, the older
one died and came to autopsy. “At the autopsy the
gastrocnemii and solei were found to be uncom-
monly large, colour whitish yellow; traces only of
muscular tissue; the mass being composed of adi-
pose matter.” The deltoid, sternomastoid, posterior
tibial, and hand muscles were involved to a milder
degree. “The degenerated muscles exhibited abun-
dance of fat cells, with few traces of muscular fibre;
in some fibrillae the transverse markings were
scarcely distinguishable.” There was no abnormality
in the interior of the brain or “medulla spinalis.”
There can be little doubt that the families de-
scribed by Partridge, Meryon, and Little exhibited all
the cardinal features of DMD, and from a modern
perspective it would be difficult to deny Meryon’s
claim to priority in providing the “first” comprehen-
sive descriptions of DMD.
CLASSIC DESCRIPTIONS BY DUCHENNE
Duchenne (1806 –1875)14,21,35,36 saw his first case of
DMD in his private clinic in 1858, and briefly de-
408 History of Duchenne Dystrophy
scribed the disease in the second edition of his De
L’Electrisation Localisee. . . (1861),15 under the head-
ing of “Paraplegie hypertrophique de l’enfance de
cause cerebrale” (Hypertrophic paraplegia of in-
fancy of cerebral origin). The first case (Joseph Sar-
razin, Observation LXVIII, Case I) appeared under
the heading, “Paraplegia cerebrale, congenitale, hy-
pertrophique” (Cerebral paraplegia, congenital, hy-
pertrophic). Duchenne personally photographed Jo-
seph Sarrazin, and included drawings made from
these photographs in several of his papers (Fig.
2).15–19 It was not until 1865 that he had his first
opportunity to examine “muscular fibres removed
during life from different parts of one of my little
patients” utilizing an instrument he had specially
designed for intra vitam muscle biopsy (his “emporte
piece histologique,” often more colorfully referred
to in England as a “histologic harpoon”). He later
provided expanded and detailed analysis of 13 of his
own cases.17–19,49,54
Duchenne was clearly aware of Meryon’s cases,
and referred repeatedly to Meryon’s original paper39
but insisted that these earlier cases represented ex-
amples of progressive muscular atrophy and not of
his disease.17,18 Essentially all subsequent authorities,
MUSCLE & NERVE October 2003
including Gowers (see below), felt that the disorders
described by Meryon and Duchenne were identical,
a conclusion endorsed by modern experts and hard
to dismiss.21 After Meryon presented one of his cases
to the Royal Medical and Chirurgical Society in Feb-
ruary 186642 and reiterated his claim to priority, one
of those present noted:
In reference to the author’s statement regarding a
recent speaker at the Paris Academy of Medicine
[Duchenne], who had claimed the merit of being
the first to notice the malady now under discus-
sion, it should be remembered that French medi-
cal men rarely read English periodicals and seldom
speak the language; hence no one ought to be
surprised if professional questions occupying at-
tention in England do not always become known
beyond the Channel. In proof of this, he would
mention that at the library of the learned body just
named no English medical journal is accessible for
perusal. . ..Therefore Dr. Meryon need not deem it
strange whenever any French observer thinks him-
self an original discoverer, seeing the circum-
stances above related may furnish a satisfactory
explanation of the assumption narrated.42
This explanation may have been comforting to
Meryon, but by 1868 was clearly incorrect, as Du-
chenne devoted several pages of his monograph to
reviewing the symptomatology of Meryon’s cases and
then another section to arguing that the pathological
features of the cases indicated that they were better
subsumed as examples of progressive muscular atro-
phy.17,18 Duchenne conceded that the clinical features
of Meryon’s cases were in fact typical of pseudohyper-
trophic muscular paralysis, but felt that the “fatty de-
generation of muscle fibres” illustrated were typical of
that seen in a variant of progressive muscular atrophy.
Duchenne then also claimed priority for this observa-
tion, noting that he had first described similar cases in
a communication to the Academy of Sciences under
the name “muscular atrophy with fatty transformation”
in 1849, and hence, “The honor of this discovery be-
longs completely to France.”
In his descriptions in 186817,18 and 1872,19 Du-
chenne replaced his initial suggested name for the
disease (hypertrophic paraplegia of infancy) with a
revised clinical name, “pseudo-hypertrophic muscu-
lar paralysis,” to reflect the fact that further observa-
tion of his early cases made it clear that weakness and
muscular changes were not just limited to the legs,
but spread as the disease advanced to involve the
back and arms, and that pathological studies had not
supported a cerebral etiology. He also suggested an
alternative name, “myo-sclerotic paralysis,” more re-
flective of the disease’s pathology. However, it was
the name pseudo-hypertrophic muscular paralysis,
along with Duchenne’s eponym, that became at-
History of Duchenne Dystrophy
tached to the disorder.27,29 In England, Gowers, the
leading authority on the disease (see below) ac-
knowledged (but was somewhat piqued by) this ten-
dency, noting that Duchenne’s name was also com-
monly applied to glosso-labial paralysis and that,
“The increasing number of diseases and structures
called after men’s names constitutes a serious diffi-
culty for the student, and a frequent cause of confu-
sion in medical writings, especially abroad.”28
As noted, Duchenne saw his first patient (Case I),
Joseph Sarrazin, in early 1858, when the patient was
7 years old (Fig. 2). Joseph had difficulty in learning
to stand and walk, and weakness in his legs was first
noted when he was 8 to10 months old. He began to
walk much later than his siblings. At age 21⁄2 years,
“He could not walk except with legs spread apart for
lateral balance (swinging gait) and somewhat
arched.”17,18 By the age of 3 years,
. . .his mother noted that his lower extremities
grew in volume. Her attention was first drawn to
this by the enlargement of his calves which entered
his stockings with difficulty. . .the excessive devel-
opment of the lower extremities had progressed
during 2 years.17,18
Duchenne noted that the gastrocnemius and lumbar
spinal muscles seemed to bulge through the skin, com-
menting: “I was not a little surprised to learn that these
athletic appearing muscles had been lacking power
since birth and had hardly been exercised.”17,18 All the
movements of the legs were very feeble. Despite this
enfeeblement, all the muscles initially responded per-
fectly to electrical stimulation, although he subse-
quently found that this, too, would disappear in ad-
vanced disease. The patient’s condition deteriorated,
with the weakness ultimately spreading to the upper
extremities. The child was bedridden by age 12 despite
treatment with electrotherapy, hydrotherapy, and mas-
sage. He died of tuberculosis (“phthisis”) at age 14.
Unfortunately, there was no autopsy.
Another notable patient that Duchenne de-
scribed in 186817,18 was Case XII. Duchenne also
photographed this 10-year-old boy, and drawings
made from these photographs appeared in many of
his papers and were widely reproduced (Fig. 3). The
boy had not walked until the age of 26 months, and
even then did so in a “clumsy manner.” Up until age
8, he was quite ambulatory, walking a kilometer each
day to school. However,
. . .little by little walking became more difficult, to
the degree which the limbs, always very volumi-
nous, took on an unwanted development, then
after a time movements became almost impossible,
at this point, every time the child fell he was inca-
pable of getting up.
MUSCLE & NERVE October 2003 409
FIGURE 3. Duchenne’s Case XII is in the center (F. 11), “showing atrophy of the pectorals. Almost all the other muscles have a
hypertrophic appearance.” The surrounding images are muscle specimens “from subjects affected with pseudohypertrophic paralysis of
differing severity; showing the considerable quality of connective and fibrous interstitial tissue.” Muscle biopsy specimens from patients
with DMD at 45⫻ magnification illustrate the “considerable quantity of connective and fibrous interstitial tissue” (F. 12–F. 14). The same
specimens at 200⫻ magnification (F. 15–F. 18). A normal muscle specimen (F. 19). “Different degrees of fatty degeneration of the muscle
fiber” (F. 20 –22). “Necrosis of the muscle fiber” (F. 23a) and “proliferation of elements of fibrous tissue” (F. 23b).17

Duchenne noted: “On my first examination, I was
struck, not only by the extraordinary volume of the
muscles, but also by their firmness, even when relaxed.
This child was the patient of Bergeron, a col-
league of Duchenne’s, who compared his muscle
development to that of the famous Farnese Hercules
(Fig. 4), and to the muscles seen in some of Mich-
elangelo’s paintings. However, as Duchenne noted:
The Farnese Hercules is the ideal of physical
strength in antique statuary. . . . It would be a mis-

410 History of Duchenne Dystrophy MUSCLE & NERVE October 2003

FIGURE 4. The Farnese Hercules (A), widely considered in the 19th century to represent the ideal body form. The original marble statue
was widely reproduced, and copies exist in various sizes of plaster and bronze, as well as in a number of engravings including those by
Jacob Bos (c. 1520) (B), and Hendrik Goltzius (c. 1592) (C). The artist was the Roman sculptor Glykon who made the statue for the Baths
of Caracalla in the 3rd century A.D., probably using an earlier statue by the Greek sculptor Lysippus (325 B.C.E.) as a model. The statue
was discovered in 1546, and was displayed in the courtyard of the Farnese Palace, from which it acquired its name. Interestingly, the legs,
which apparently caught the attention of Duchenne and others as an example of extreme muscular development, were originally missing
and were replaced by copies made by a pupil of Michelangelo, until the originals were located.

understanding of its esthetic beauty to compare it
with the monstrous musculature of hypertrophic
paralysis. . . .Current pathological study reveals
that this excessive development of the musculature
is a sign of weakness. Pathological anatomy will
show that these muscle contours, in appearance so
formidable, are formed principally by muscles
stuffed with interstitial connective tissue and inter-
stitial fibrosis.17,18
Summarizing this original case and 12 others, Du-
chenne noted that there were six principal diagnos-
tic features of pseudohypertrophic paralysis:
1. Decrease in strength, at the beginning of the
disease, usually in the muscles of the lower limbs.
2. Lordosis and spreading of the lower limbs on
standing and walking.
3. Excessive development of volume, during a sec-
ond stage, either of some or all of the weakened
muscles.
4. Progressive course of the disease, during a third
stage, with worsening of the paralysis and with its
generalization if it was limited to the inferior
members.
5. Decrease or abolition of electromuscular contrac-
tility in an advanced stage of the disease.
6. Absence of fever, sensory disturbance, and im-
pairment of the functions of the bladder and
intestine during the entire course of the dis-
ease.17,18
Cognizant of criticism that he often failed to
obtain pathological support when he described
“new” diseases, he provided only a limited account in
the second edition (1861)15 of De L’Electrisation locali-
see. . . . As he noted in the 3rd edition (1872):
I have been much blamed abroad for having, in
the different pathological investigations which I
have published, neglected and despised patholog-
ical anatomy, that branch of science inseparable
from all good clinical work. I recognized the re-
proach, and wished to expose myself to it no
longer. I waited in vain for an autopsy to furnish me
with an opportunity of examining the condition of
the muscles whose size has increased so excessively,
and seeking for an explanation of the two contradic-
tory facts co-existing in my little patients, viz., paresis
or paralysis and muscular hypertrophy.19,49
It was to overcome this dependence on autopsy ma-
terial that Duchenne developed his “histological har-
poon” (Fig. 5). “Thanks to this instrument I have

History of Duchenne Dystrophy MUSCLE & NERVE October 2003 411


FIGURE 5. Duchenne’s histologic harpoon (emporte piece his-
tologique), the first instrument designed specifically for perform-
ing muscle biopsy.17 The cavity for collecting the muscle speci-
men is clearly seen in the two right-hand illustrations.
been able to complete my clinical observations by
research into the pathological condition of the mus-
cles of living patients.”19,49 Griesinger, in Germany,
had performed the first biopsy during life from the
deltoid muscle of a 13-year-old boy with DMD in
186432 (Fig. 6), but the procedure was difficult, re-
quired ether anesthesia, and was complicated by an
infection that lasted several weeks. Nonetheless, this
early effort and its associated case report often led to
German authors assigning Griesinger equivalent pri-
ority to Duchenne in the description of DMD.
Duchenne developed his “histological harpoon”
to simplify intra vitam muscle biopsy, and to avoid
the pain, obviate the need for ether anesthesia, and
decrease the risk of infection (which could become
a fatal complication in the pre-antibiotic era). By
1865, Duchenne had used his tissue punch to obtain
fragments of the gemellus and deltoid muscles in an
8-year-old boy with pseudohypertrophic paralysis
(1868, Case VII), noting that “from that moment I
possessed all the necessary elements for a complete
depiction of pseudohypertrophic paralysis.”49 In
1867, he was able to add details based on micro-
scopic analysis of a second biopsied case, which con-
firmed his previous observations, allowing him fi-
nally to provide the long-delayed detailed depiction
412 History of Duchenne Dystrophy
of the disease, free from fear of criticism17,18 (see Fig.
3 for examples of muscle biopsy specimens from
Duchenne’s cases). He found that “hyperplasia of
the interstitial connective tissue, with the production
of more or less fibrous tissue, is the fundamental
anatomical lesion of the muscles in pseudohypertro-
phic paralysis.”17,18,49 It was this increase in non-
muscle tissue that “produces the considerable and
sometimes monstrous increase in muscle volume,
which is in direct proportion to the quantity of hy-
perplastic interstitial connective and fibrous tis-
sue.”17,18 He also observed, “slight or moderate num-
bers of fatty vesicles,” especially in advanced
cases.17,18 The transverse striations of muscle fibers
could become extremely fine, or even disappear in
some affected areas, followed by similar obliteration
of the longitudinal striations until ultimately the
“sarcolemma seems to contain fatty vesicles.”17,18
Obtaining an autopsy in a DMD patient was of
critical importance as, although the muscular
changes seemed unequivocal, it was essential to de-
termine whether there would be changes in the
anterior horns of the spinal cord, analogous to those
seen in cases of infantile atrophic paralysis. Meryon,
whose case was the first autopsied, had not found
such changes, as mentioned earlier.39 In 1865,
Cohnheim added a second autopsy on a patient of
Eulenberg’s,23 clearly showing that the spinal cord
was normal. Duchenne was not able to obtain an
autopsy on a case until 1871, when the second child
he had biopsied (Case XII, see above) died.20 After
fixing some muscle specimens in chromic acid, “Be-
ing desirous of giving additional value to their histo-
logical examination, I requested my friend M. Char-
cot to be good enough to assist me in it” (see
Charcot5). Duchenne gave additional pieces of mus-
cle to Lockhart Clarke, probably the foremost expert
on microscopic neuroanatomy in England (see be-
low).
The microscopic examination of these specimens
showed the muscular changes of pseudo-hypertro-
phic paralysis in an extreme degree, i.e., the mus-
cular fibres smaller than usual, but still preserving
as a rule faint striation, and separated from each
other by a large quantity of fatty tissue, mixed with
fibrous tissue and wavy fibres in small quantity.19,49
As Charcot himself noted (Fig. 7):
With respect to the state of the spinal cord, our
observations were made on transverse sections, co-
loured with carmine. . ..These sections have, be-
sides, been very numerous, and were taken from
different parts of the cervical and dorsal regions of
the cord. I should here notice that the muscles
which receive their nerves from the cervical en-
largement were, for the most part affected to a
MUSCLE & NERVE October 2003

FIGURE 6. (A) Griesinger’s case. A 13-year-old boy with DMD,
the first patient to undergo muscle biopsy during life (July
1864).32 (B) Drawings of the muscle biopsy from this patient.32
high degree, and that the deltoids, among others,
exhibited most markedly the characteristics of hy-
pertrophy by fatty substitution. If, in this case, the
muscular lesions had been connected with spinal
lesions the latter should not have failed to show
themselves well marked in the cervical enlarge-
ment of the spinal cord. Now, the result was abso-
lutely negative. . .the grey substance, which was the
subject of a very special investigation, presented no
trace of alteration. The anterior cornua were nei-
ther atrophied nor deformed. . .and the motor
cells, normal in number, did not present, in the
several parts which go to constitute them, any de-
viation from the normal type. Let us remember
History of Duchenne Dystrophy
that the spinal roots, both anterior and posterior,
appeared also perfectly sound.6,7
There can be no question of the magnitude of Du-
chenne’s contribution. In his books and mono-
graphs, he managed to outline virtually all the car-
dinal clinical features of DMD, save only its heredi-
tary component. He identified the key pathological
findings, and clearly recognized that DMD repre-
sented a primary disease of muscle rather than the
secondary effects of disease within the spinal cord or
brain. Although Duchenne was not the first to rec-
ognize the uniqueness of muscular dystrophy as a
separate clinical species, the clarity and quality of his
observations justify his eponymous recognition. It
would remain for Duchenne’s contemporary, the
great British neurologist, Sir William Richard Gow-
ers, to put the final touches on the clinical picture
based on a large series of both personal and re-
ported cases, and to clearly identify DMD as an
inherited disorder with a striking predilection for
males.
GOWERS AND THE ENGLISH CONTRIBUTION
In England, Sir William Richard Gowers
(1845–1915),12,51 one of the greatest neurological
clinicians of the era, developed an early and abiding
interest in DMD, and even had an opportunity to
examine relatives of Meryon’s original cases.29 Gow-
ers saw his first cases of DMD (Cases 19 –22 from
Gowers 27) “very early in his medical work,” probably
between 1860 –1863 while he was serving as a medi-
cal apprentice, as these patients all lived in the
neighborhood where he worked at that time.12,27 His
first cases were members of a family of 10 children in
which 3 of the 7 boys and none of the 3 girls were
affected. Gowers reported his first case of DMD in
1874, a boy in whom he was able to obtain a
necropsy8(Case 17 in his later monograph27). He
subsequently discussed and presented 21 personal
cases in lectures delivered at the National Hospital
for the Paralysed and Epileptic and to medical stu-
dents at University College (1879).26 These lectures
were published in the The Lancet, and later expanded
into a monograph entitled Pseudo-Hypertrophic Mus-
cular Paralysis (1879),27 which became the definitive
English-language account of the disease. Near the
end of his active career, Gowers returned to the
subject of DMD in lectures he delivered at the Na-
tional Hospital in 1902 30 and 1908.31 The last of
these lectures was unfortunately only published in
Pitman shorthand, in a long defunct and vanishingly
obscure journal known as the Phonographic Record of
Clinical Teaching and Medical Science.53
MUSCLE & NERVE October 2003 413
FIGURE 7. (Right) Transverse section of a muscle from a patient with DMD from Charcot.6 “G” indicates ‘adipose cells,’ “M,”
cross-sections of muscular fascicles, and “I,” islets of connective tissue. (Left) Longitudinal section from a more advanced case showing
isolated muscle fibers, deprived of their fibrillary envelope, and put in immediate contact with cells of the adipose tissue. The muscle
fascicles, even the smallest, have preserved their transverse striations (note variation in size of muscle fibers).6,7

Gowers’ poignantly noted: dence of the disease. Harvey S. did not have obvious
muscular wasting or enlargement, but was already
The disease is one of the most interesting, and at
the same time most sad, of all those with which we experiencing difficulty in rising from the floor. Gow-
have to deal: interesting on account of its peculiar
features and mysterious nature; sad on account of
our powerlessness to influence its course, except in
slight degree, and on account of the conditions in
which it occurs. It is a disease of early life and early
growth. Manifesting itself commonly at the transi-
tion from infancy to childhood, it develops with
the child’s development, grows with his
growth—so that every increase in stature means an
increase in weakness, and each year takes him a
step further on the road to hopeless infirmity, and
in most cases to an early and inevitable death.26,27
Gowers publicly presented early cases of this disor-
der to audiences at the National Hospital in 1879.
For several years, he had followed a family with six
afflicted members in two generations. In the second
generation, four of the six brothers were afflicted,
including a 12-year-old (Arthur S., Case 5), a 7-year-
old (William S., Case 4), a 4-year-old (Harvey S., Case
3), and a 3-year-old (name not specified, no case
number) (Fig. 8). Two brothers aged 4 and 10 were
apparently healthy. Gowers was intrigued by the fact
that one of the apparently normal brothers was the
FIGURE 8. Two brothers aged 4 (Harvey S, Case 3) and 7
twin of Harvey S., who was clearly severely afflicted. (William S, Case 4) from Gowers. “The youngest. . .would not
Neither of their parents appeared affected, although suggest to you the idea of disease. There is no obvious muscular
the mother’s only brother and one of her four sisters wasting or enlargement, and yet. . .his movements were greatly
had both died of an apparently similar illness, each impaired. He could only just succeed in rising from the
at the age of 15. This latter case, in a girl, repre- floor. . ..The other boy. . .as his photograph indicates, [has] very
distinct enlargement of the calves. His thighs are small, the back
sented one of only three females afflicted with the thin, hollow in the lumbar region, the angles of the scapulae
disease in his personal series of 21 cases. None of the prominent, the muscles of the upper limbs thin, except the del-
children of the unaffected sisters had shown evi- toids, which are rather large.”27

414 History of Duchenne Dystrophy MUSCLE & NERVE October 2003


FIGURE 9. Gowers’ sign.27 “He helps himself up in a very pecu-
liar way— by putting his hands upon his knees, and grasping his
thighs higher and higher, and so by. . .climbing up his thighs he
pushes his trunk up.”
ers noted that “He could only just succeed in rising
from the floor, getting first his toes upon the
ground, then placing first one hand upon his knee,
then the other, and so working himself up.” William
was more seriously affected. He had distinct enlarge-
ment of his calves (Fig. 8), small, thin thighs and
back, an obvious lumbar lordosis, and prominent
angled scapulae. His arms were also thin, except for
the deltoids, which seemed enlarged. He also had
wasting of his sternocleidomastoid muscles.
In addition to presenting members of the S fam-
ily, Gowers also presented a 9-year-old boy (David W)
(Case 1) to his audience, and described his similarly
affected brother. Noting again:
. . .he helps himself up in a very peculiar way— by
putting his hands upon his knees, and then grasping
History of Duchenne Dystrophy
his thighs higher and higher, and so by. . .climbing
up his thighs he apparently pushes his trunk up. I
wish to call your special attention to this peculiar
action, because it is probably pathognomonic of
the disease. Attention was called to it by Duch-
enne, and I have never seen it absent in a case so
long as the patient possessed the necessary muscu-
lar power. I have never seen it in any other disease,
and every doubtful case in which it was present
ultimately proved to be an example of the affec-
tion. Its diagnostic importance is thus very great.26,27
This peculiar method of arising from the floor (Figs.
9 and 10) would subsequently be referred to as
“Gowers’ sign,”52 although as Gowers himself ac-
knowledged,26,27 Duchenne had described the phe-
nomena previously, as had other earlier observers
(see below).
In addition to describing the changes in muscle
size and power, Gowers noted that several patients
had absent patellar reflexes (an aspect of the clinical
examination that was first described in 1875, and for
which Gowers himself had previously suggested the
term knee-jerk). Gowers also emphasized the aspects
of the clinical examinations that were spared in
DMD. Patients such as David W had a clear and
sharp intellect, no evidence of involvement of either
general or special sensibility, and no involvement of
the sphincters.
In both David W and Arthur S (Cases 1 and 5),
Gowers noted that the Achilles tendon seemed
“tight,” hindering the ability of David W to place his
heels flatly on the ground when standing, and, in the
case of the more severely afflicted Arthur S, the
associated calf contraction was so extreme “that the
heels are drawn up and the feet are in a line with the
legs.” A third patient illustrating this point (Edward
Gloster, E.G., Case 10) was also presented (Fig. 11)
allowing Gowers to comment that he had not seen
this “extreme shortening of enlarged muscles” in any
other disease. In contrast to these changes at the
ankle, which could occur early in the disease, other
contractures tended to be late manifestations.29 For
example, contraction of the knee flexors often led to
fixation of the knee-joint, and contraction of the
biceps in the presence of a weakened triceps could
have the same effect at the elbow. Exaggerated an-
tero-posterior curvature of the spine also often oc-
curred early, followed later by exaggerated lateral
curvature (Fig. 11).
Gowers was not fooled by the apparent enlarge-
ment of some muscles, and clearly noted that these
muscles were always weaker than normal. He noticed
that the disease had a predilection for particular
muscles. Enlargement, which was not invariably
present, was generally greatest in the calf, and one
MUSCLE & NERVE October 2003 415
FIGURE 10. Gowers’ sign as it actually appeared in a child of 12 with muscular dystrophy seen at the Bicetre Hospital in Paris in 1891,
as illustrated by Dejerine.13 “These nine figures represent the different positions taken for passing from the lying to the standing position.”

12-year-old boy in his care had a calf circumference
of 141⁄2 inches!29 After the calf, the next most com-
monly enlarged muscles were the infraspinati and
the deltoids. Other muscles that were often enlarged
included the quadriceps and the glutei, and less
commonly the triceps and biceps. Weakness was gen-
erally most marked in the hip flexors and extensors
and quadriceps,29 a fact that contributed to postural
instability, led most patients to stand with their feet
far apart, and resulted in frequent falls induced by
even slight disturbance of balance. The pattern of
muscle involvement also led to a peculiar “oscillat-
ing” gait26,27,29 in which the body “inclined from side
to side” as the patient walked.
Although few diagnostic tests were available in
Gowers’ era, he did examine the reactions of af-
fected muscles to electrical stimulation. Using both
faradic and galvanic currents, he found that weak-
ened muscles had diminished excitability. As noted,
he was able to examine both the gross and micro-
scopic pathology in one of his patients8 (Case 17 of
ref. 27), and he made several astute pathological
observations. For example, he noted upon section-
ing the muscle in one case that “it was difficult to
believe that the section was that of a muscle,”26 it
appeared rather more like a “fatty tumour” or a
“mass of adipose tissue.”8 Microscopically he found
isolated groups of thin muscular fibers in the midst
of “cells distended with homogenous fat” and “fi-
brous tissue containing many nuclei and elongated
cells” (Fig. 12). Gowers’ colleague, Lockhart-Clarke,
probably the premier nervous system microscopist of

416 History of Duchenne Dystrophy MUSCLE & NERVE October 2003

FIGURE 11. Gowers’ patient, Edward Gloster (E.G., Case 10).27

his era, assisted with the examination of the spinal

cord. Although some pathological changes were
noted, they found that with rare exceptions the “an-
terior cornua [horns] were conspicuously healthy,”
the cells corresponding perfectly in size, sharpness,
length, and distinctness of processes to those found
in healthy spinal cords. Gowers emphasized how
strikingly this finding contrasted with the abnormal
state of the spinal cord in patients with progressive
muscular atrophy, in whom similar, severe muscular
wasting was invariably associated with virtually com-
plete loss of anterior horn cells. Despite some con-
fusing abnormalities present in the spinal cord in
some areas in his DMD cases, Gowers concluded that
“pseudohypertrophic paralysis of early life is not a
disease of the spinal cord.” He also concluded that
there was no real evidence supporting ideas that the
muscle disease resulted indirectly as the conse-
quence of involvement of either sympathetic or tro-
phic nerves.
In 1879,26,27 Gowers reviewed evidence support-
ing the view that that DMD was a primary disease of
the muscular tissue, and approvingly quoted Fried-
reich’s conclusion that it represented “a congenital
nutritive and formative weakness of the striated mus-
cle substance.”24 By 1888, having had an opportunity
to analyze more pathological specimens, he was un-
equivocal: “The significance of the pathological FIGURE 12. Muscle specimen from Gowers (Case 17)27 (Figs. 1
anatomy is that the malady is a primary disease of the and 2 originally appeared as Figs. 7 and 8 in ref. 8). “Under the
microscope the resemblance to a fatty tumour was also strikingly
muscles.” Gowers felt, like his contemporary Du-
close. Cells distended with homogenous fat covered the field.
chenne, that the fibrous changes in muscle, rather Passing among the fat-cells, however, were narrow bands, which
than the muscle atrophy itself, was likely to be the consisted of fibrous tissue and muscular fibres.”
primary pathological process in DMD. He hypothe-
sized that the wasting of the muscular fibers was

History of Duchenne Dystrophy MUSCLE & NERVE October 2003 417

secondary to an overgrowth of the interstitial con-
nective tissue elements.29 Gowers felt that fatty re-
placement was responsible for the enlargement of
the muscles and that the interstitial fibrous tissue
might be responsible for the shortening and contrac-
tion of muscles that he had frequently observed.
Gowers summarized the “special characters of
the disease” based on his experience with 21 cases.
“The first fact which deserves notice is its remarkable
relation to sex. It commonly affects boys, very rarely
girls.” He noted that sex influenced not only the
frequency but the severity of the disease, with the
presentation in girls often seeming to be milder and
of later onset. “The next important fact in the con-
ditions of the origin of the disease is its tendency to
affect several members of the same family.” He
noted that he had seen families with up to six af-
fected members in a single sibship and that Meryon’s
original family, whose collateral relatives he had
later examined, had eight affected brothers (and no
affected daughters). This led him to conclude that
“It might naturally be expected that a disease which
thus evidently depends on conditions which are con-
genital, and not acquired, should be distinctly he-
reditary, and the facts I have just mentioned show
that it is so in some cases.” He noted that “the disease
is never to be heard of on the side of the father;
always when antecedent cases have occurred, they
have been on the side of the mother,” a “very re-
markable fact in the etiological conditions” that he
referred to as unilateral inheritance.26,27 It was this
interesting pattern that later led him to conclude
that “thus the congenital tendency is exclusively due
to the maternal element in the embryo,”29 a fact that
he felt was “also shown by a fact many times observed
that the children of the same women, by different
husbands, suffer in the same way.”29 Later he refined
this idea to conclude that the “developmental ten-
dency which constitutes the malady comes from the
ovum and not from the male element in the germ.”31
This, in turn, led him to the interesting speculation
that, since the disease affected the ovum and appar-
ently only those ova destined to become males, this
made it, “probable that the sex of the future embryo
is also determined in the ovum”!31
Age of onset represented a third important etio-
logical fact of the disease. Gowers recognized that
DMD was a disease of early life, commencing in the
majority of his cases before the age of 6. He noted,
“As a rule (to which there are exceptions), the more
severe the disease the earlier does it commence.”
Gowers recognized the dire prognosis of the dis-
ease, noting, “it is doubtful whether any case in
which the symptoms were well marked has recov-
418 History of Duchenne Dystrophy
ered.” He cautioned that the prognosis “must be
influenced by the period at which the disease com-
mences, and by its observed rate of progress” with
both early onset and rapid progression heralding a
worse prognosis. He also noted that the prognosis
was generally less grave in girls than boys. Death was
not the result of the disease itself, but from intercur-
rent illness, notably pneumonia caused by weakness
and wasting of thoracic muscles and impaired respi-
ratory power, events that led to death in 13 of the 19
personal cases for which he had information.
Treatment, as noted, was of little avail. Gowers
noted:
As a congenital developmental malady, pseudo-
hypertrophic paralysis is one of those diseases in
which medicine is necessarily powerless to cope
with the essential elements of the process. As may
be, therefore, expected, no drug has been found
to exert an influence on the course of the affec-
tion.29
Among the agents he tried were arsenic, phospho-
rus, iron, strychnine, and cod-liver oil. Electrical
stimulation of the muscles had “disappointed the
expectations which had been formed of it,” a con-
clusion also shared by Duchenne. Muscular exercise
did seem to have some effect in retarding the weak-
ness.29 He felt that patients benefited from “carefully
planned gymnastic exercises, so arranged as to call
into action the muscles that most need help.”29 Rub-
bing and passive movements of the limbs partially
counteracted the tendency to contracture and defor-
mity.26,27,29 Section of the Achilles tendon occasion-
ally resulted in improvement in a patient’s ability to
stand or walk,26,27,29 and “mechanical appliances”
enabled patients to use their legs for a longer time
than would otherwise be possible.
The contributions of Duchenne, Gowers, and
others firmly established the basic clinical and patho-
logical features of DMD, and lead to its acceptance
as a unique clinicopathological entity in Europe.
The basic features of DMD were summarized in lead-
ing American medical journals, and lead rapidly to
the first reports of similar cases in the United States.
EARLY AMERICAN CONTRIBUTIONS
In contrast to the seminal contributions made by
French, English, and German physicians, American
contributions to the early history of DMD were quite
modest. In 1868 and again in 1870, Meredith Clymer
provided competent reviews of DMD based on the
literature, but gave no indication he had actually
seen a case.9 The first American patient described in
the literature was a child (J.S.) seen by Ingalls and
MUSCLE & NERVE October 2003
Webber at the Boston Children’s Hospital in Sep-
tember 1870.34 Like Clymer’s paper, this report is
more notable for its review of published literature on
DMD than for its rather sparse case report. At the
age of 3, J.S.
. . .began to move and act as though he had less
strength than usual. . .this condition increased and
the spinal column became very weak, and the “in-
ward crook” of it was noticed. . ..We asked him to
stand upon the floor, and he walked a few steps in
a tottling or shambling manner.
It was noted that Duchenne’s illustrations of his
cases were also a “perfect picture” of J.S. and that,
“the muscles of the calves were largely developed.”
The paper by Ingalls and Webber was followed in
the next year by additional cases from eminent
American physicians, including William Pepper,48 S.
Weir Mitchell,44 (see also Gerhard25 for a later de-
scription of the same patient), and William Ham-
mond.33 In contrast to that of Ingalls and Webber,34
the report by Pepper,48 based on a case he had seen
in the Philadelphia Hospital in April 1871, was re- FIGURE 13. Pepper’s original case (W.E.)48 of DMD (probable
markably detailed and comprehensive. Pepper was Becker variant) at age 20. W.E. was one of the first American
cases illustrated, and one of the first American patient’s to un-
correct when he noted that “it is the first case of this dergo muscle biopsy (1871).
disease that has been carefully studied and described
in this country.” He commented in a footnote: “Un-
fortunately and unavoidably, the report of the case action is perfect.” He noted in particular that “the
[by Ingalls and Webber], which serves as the intro- calves appear as large as those of a vigorous man,
duction to the[ir] paper, is very meagre.” Pepper contrasting very strangely with the wasted thighs.
provided an original illustration of his patient (Fig. They feel quite firm, even when relaxed.” Foreshad-
13), where Ingalls and Webber34 had simply repro- owing Gowers, but not Duchenne who had already
duced one of Duchenne’s. noted a similar phenomena, Pepper noted:
Pepper’s case was unusual, as it likely represented When about to stand up, he throws his body for-
what would today be considered an example of the ward till it almost rests on his thighs, and then,
Becker variant of DMD. His patient (W.E.) was 20 placing his hands on his knees and rising a little
when first seen. At age 14, he had noticed “gradually from his seat, he slowly raises his body by sliding his
increasing loss of strength in the legs, which pro- hands up his thighs; and when he has raised him-
self as far as possible this way, he places one hand
gressed so slowly that for eighteen months he was after the other on a chair-back or edge of a table,
still able to run about, though not so actively as other and leans forward. He then, by jerks of the alter-
boys.” By age 18, he began to use a cane. During the nate sides of the body, draws his legs forward, thus
first 3 years of symptoms, the patient had noted assuming more and more nearly an erect posi-
atrophy beginning in the muscles of the calves, then tion.48
progressing to the thighs, back, and later the shoul- Pepper and his Philadelphia colleague, William
ders and arms. Hammond, were the first American physicians to
perform a muscle biopsy in DMD. As Pepper noted,
About two years ago [age 18], after the atrophy of
the muscles of the calves had become very marked, “I obtained a small scrap of muscular tissue, by
he noticed that they began to increase in size, and means of an ‘emporte piece’ from both gastrocnemii
this growth had continued until they have ac- and the left deltoid muscles. These have been sub-
quired a size much greater than they ever had jected to careful microscopic study.” In the gastroc-
previously. . .during all this time his weakness has nemii, he found:
steadily increased.
A few fibrils presented streaks of minute fatty gran-
Pepper also noted that his intellect was intact, that ules along their centres, and a very small number
he had no sensory or bladder impairment, and that were decidedly fatty. The muscular fibres varies
the “muscles of the face are not involved, and their greatly in size also. . ..There was a large excess of

History of Duchenne Dystrophy MUSCLE & NERVE October 2003 419


FIGURE 14. S. Weir Mitchell’s case,44 Robert Payne, the first
American patient with DMD to be photographed.
interstitial tissue, in places taking the form of long,
narrow, wavy bands of pure white fibrous tis-
sue. . ..There was a considerable amount of inter-
stitial fat, existing as scattered globules, or ar-
ranged in patches of large, closely aggregated fat-
globules. In places isolated muscular fibrils lay
imbedded in this fibrous tissue so as to be scarcely
visible.48
At virtually the same time as Pepper saw his first
patient, his Philadelphia colleague, S. Weir Mitchell,
the dean of American neurologists, also saw his first
cases of DMD.44 In October 1871, Mitchell described
an 8-year-old boy (R.P., Robert Payne) that he saw a
month earlier at his clinic at the Orthopedic Hospi-
tal and Infirmary for Nervous Diseases. He noted
that he had also seen two other cases, suggesting that
he might have also seen the patient described by
Pepper. Unfortunately, he does not provide details
of these patients, but does describe R.P., and pro-
vides the first photographic illustration of an Amer-
ican patient with DMD (Fig. 14). R.P. was one of six
children, the others all apparently healthy. As Mitch-
ell noted:
When stripped, and examined, his posture and
external appearance presented some notable pe-
culiarities. While standing, the shoulders are
thrown back, the blades project, the belly is thrust
forward, the feet four inches apart, and the spine
curved forward in the dorso-lumbar region without
lateral deviation. . .above the waist, there is, with
one exception, nothing remarkable about the mus-
cular developments, which are such as belong to a
person of his age. Both deltoid muscles are unusu-
ally large and hard, and certainly much more con-
spicuous than they should be. They alone, of all
the muscles of the upper extremities, seem to have
shared in all the pathological changes which have
affected the lower limbs. Below the pelvic brim the
muscles are seemingly developed enormously; so
420 History of Duchenne Dystrophy
that the legs are those of an infant athlete sur-
mounted by a body of ordinary dimensions. . . .I
have been tempted, like other describers, into
speaking of the overdeveloped limbs as being like
those of an athlete; but, in fact, both in this and the
two other cases seen by me, the calves are not
symmetrical, and in the present case they are en-
larged too low down, and on the inside of the calf
there is some flattening, so they fail to offer the
appearance of overgrown, but well-formed limbs.
The whole of both legs, including the glutei, are
enlarged and hard. . . .The muscles attacked are
very firm. . . .The father of the lad declined to
permit me to examine the muscular tissue by Du-
chenne’s instrument for removing morsels of tis-
sue for microscopic study, so that I can only infer
as probable the existence of that form of hyperpla-
sia of the muscular connective structures which
gives to these cases the false appearance of muscu-
lar hypertrophy.44
Mitchell, like Pepper, also noted the patient’s pecu-
liar method of rising.44
In the first edition of his textbook, William Ham-
mond was able to describe and illustrate a single
FIGURE 15. Hammond’s original case of DMD.33 This patient,
along with the one shown in Figure 12, were the first American
cases of DMD to be illustrated, and the first American patients to
undergo muscle biopsy.33,48. The patient was a 7-year-old boy
with a “disinclination to learn to walk.” “At three years of age he
could not stand longer than a few seconds, and even for this time
he was obliged to spread the legs apart and to hold on to some
article of furniture.” Hypertrophy was noted at age 5, first in the
right calf, then left calf followed by the glutei. After removing the
muscle with the trocar of Duchenne, Hammond noted disintegra-
tion of muscle fibrillae with disappearance of their transverse
striae, and the presence of large amounts of connective tissue
(inset).
MUSCLE & NERVE October 2003
personal case first seen in March 1871.33 He saw a
second child later that same year (May 1871) (Fig.
15). This second patient may have been the first
American case to undergo muscle biopsy (Fig. 15).
As Hammond noted,
In the case under my care I have made repeated
examinations, removing the muscle with the trocar
of Duchenne.. . .The transverse striae are seen to
have disappeared, the fibrillae are in a state of
disintegration, and the connective tissue is present
in large amount.33
The years that followed would see further enumera-
tion of various subtypes of muscular dystrophy and
refinement of both electrophysiological and his-
topathological diagnostic testing for muscle disease.
The identification of specific gene defects in a vari-
ety of dystrophies would usher in a new molecular
era for understanding and classifying these disor-
ders. All these contributions, in turn, developed
from the astute observations of a small group of
clinicians, in Italy, England, France, Germany, and
the United States, who recognized the uniqueness of
a set of clinical cases and were able to separate out
these inaugural examples of a hereditary primary
dystrophic process affecting muscle from the con-
founding surround of cases of inherited and ac-
quired “spinal” muscular atrophies and other causes
of progressive weakness.
This review was presented in part at the annual meeting of the
American Academy of Neurology, Honolulu, Hawaii, in April
2003. Dr. Tyler is supported by the Ruler-Lewin Family Professor-
ship of Neurology. Assistance with German translations was pro-
vided by Dr. Rolf Malessa, Chefarzt, Klinik fur Neurologie, So-
phien-und Hufeland Klinik, Weimar, Germany, and with Italian
translations by Dr. Piero Antuono, Professor of Neurology, De-
partment of Neurology, Medical College of Wisconsin, Milwau-
kee, Wisconsin. Mr. Ronald Bouchard helped with preparation of
illustrations. The author also gratefully acknowledges the assistant
of the staffs of the Dennison Medical Library at the University of
Colorado School of Medicine, and of the Becker Medical Library
(Tyler collection) of the Washington University School of Medi-
cine in St. Louis.
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