A Case of Progressive Muscular Atrophy with 
Sclerosis of the Lateral Columu^ll^ 
By I4r. J. C. SHAW, * 
President New York Neurological Society, Medical" 
Director Kings County Insane Asylum. 
THE following case is of interest in its relation to the path- 
ology of progressive muscular atrophy, and also in view 
of the recent division made by Prof. Charcot of this disease 
into two groups. I have to thank my friend Dr. B. A. Segur 
for the opportunity of seeing this patient. The first part of 
the case was observed by him, the latter part by me. 
Male, aged 44, with apparently no neurotic family history ; at 
20 years of age he had gonorrhoea, followed by stricture, gleet 
and its accompanying pain in back, hips, dec., but otherwise 
he enjoyed good health. In 1870, his first impairment of 
health began ; in February of this year, after an exposure to 
wet and cold, he became quite sick, the exact nature of which 
sickness is not known; it was of such a nature, however, as 
to confine him to his room for two and a half months, and he 
was unable to engage in any occupation for one year after; 
he thinks he never entirely recovered his former vigor; fol- 
lowing this he had some pulmonary hemorrhage and expecto- 
ration, which was slight. In October, 1875, the first symp- 
toms of his present difficulty appeared; he began to notice 
fibrillary twitchings in the small muscles of hands, especially 
those of the thumb, and simultaneously there was a wasting 
of these muscles, their function was also impaired, as shown by 
inability to tear up pieces of paper, &c., which is done by the 
index and thumb; the condition was alike in both hands. 
The atrophy went on so rapidly in the muscles of the hands 
that in January, 1876, he was unable to write; the atrophy 
and fibrillary twitchings then began in the muscles of the 
arm and forearm. He began to have bulbar symptoms about 
May of this year, and by October the glosso-laryngeal paralv- Shaw—Progressive Muscular Atrophy. 
2 
sis was quite marked, and his speech was almost unintelligible ; 
at this time he was also unable to walk with his accustomed 
lirmness, tiring easily. 
I first observed him in May, 1877, when his condition was 
as follows : Unable to utter a word, could make simply a 
grunt, tongue immovable in fioor of buccal cavity, a mass of 
furrows and wrinkles, and the seat of continuous fibrillary 
contractions ; he has the remains of a harelip, a good deal of 
difficulty in swallowing, upper extremities and chest a skele- 
ton, the muscular atrophy has become so great arms hang by 
his side quite flaccid and limp, no contracture present, fibril- 
lary contractions wherever there is any muscular tissue left, 
lower extremities in good condition to inspection, patient can 
stand and walk but is easily fatigued, no anaesthesia, no rectal 
or vesical difficulty, the atrophied muscles are the seat of sore- 
ness, and when the muscles are pressed or stretched it causes 
discomfort and pain; what muscular tissue is left reacts nor- 
mally to faradism ; this condition advanced, and the lower ex- 
tremities began to atrophy rapidly, and in the middle of 
August, 1877, he was unable to stand, and had to keep his 
bed ; he existed in the most deplorable and helpless condition 
until September 27, 1877, when he died, evidently from ex- 
haustion and the bulbar disease. 
Post-mortem twelve hours after death. Unfortunately 1 
had to make the examination in a great hurry. The spinal 
cord and the brain were the only parts examined by me. I 
regret not having been able to examine the peripheral nerves 
and the muscles. The pectoral muscle was the only one ex- 
amined ; to the naked eye it had a pale appearance, what was 
left of it; the cerebrum to the naked eye presented nothing 
abnormal; the spinal cord also showed nothing unusual when 
intact, but when transverse sections were made in it at various 
points previous to hardening, the grey matter was seen to be 
much more vascular than normal; the anterior nerves were 
apparently not diminished in size, but presented an unusual 
translucent appearance. 
Histology. Specimens hardened in solution bichromate 
potassa; the cord was divided into fifteen segments of about 
equal length, and transverse sections made from each of these Shaw—Progressive Muscular Atrophy. 
3 
segments ; stained in carmine and extractum hsematoxyli and 
mounted in Canada balsam after Lockhart Clark’s method. 
The cervical region was the point at which the disease be 
gan, and was examined first; here the morbid changes were 
of a very marked character ; examination of the sections made 
from other regions (of the cord) soon showed that the 
changes which had taken place were identical throughout the 
cord, but differing in degree and in some minor respects, but 
differing in such a manner as to render important aid in the 
interpretation of some of the points in the pathological phys- 
iology of the case, and in the sequence of the pathological 
changes which are seen to. be present. Two very decided 
pathologic changes are seen in the cord : 
1st. Atrophy of the ganglion cells in the anterior horn. 
2d. Sclerosis of the lateral columns. 
The atrophy of the ganglion cells of the anterior horn in 
the cervical enlargement is very nearly complete. In almost 
every section nothing is to be seen but a very small mass of 
yellowish brown pigment, here and there, occupying the place 
of the cell. In only one section from this region did I find 
a cell in fair preservation ; but without any processes, and 
containing a considerable amount of pigment, but having a 
nucleus and a fair amount of protoplasm around it sharply 
stained by the carmine. 
In the dorsal region the cells are almost as much atrophied, 
but as you pass down to the lower dorsal region you find 
more and more cells in a fair degree of preservation ; none, 
however, in a normal condition. In the lumbar region, the 
largest amount of cells are to be seen, and in some places the 
number is almost normal, but there is not one cell which has 
not been affected ; the pigmentation, atrophy and the absence 
of processes are the characteristic changes in these cells ; the 
pigmentation takes place in the body of the cell, usually at 
one edge, and encroaches upon the nucleus ; the pigment is of 
a yellowish brown color; the atrophy of the processes appears 
to come about in an entirely different way, they become more 
and more translucent and attenuated, and at last melt away, 
from the distal end first, without any more positive change, 
and they refuse to take up the carmine; this method of disap- 4 
Shaw—Progressive Muscular Atrophy. 
pearance of the processes gives a peculiar appearance to th6 
stump ; it looks as if the process was cut off somewhat 
abruptly, not sufficiently so, however, but as to leave behind a 
vestige of the process, showing this peculiar translucent ap- 
pearance, which, in some cells, contrasts very decidedly with 
the thick, sharply stained body of the cell ; it would appear 
that all the processes do not undergo this mode of change, for 
occasionally there is to he seen in the grey matter of the ante- 
rior horn a few processes in fair condition, which evidently 
have been cut loose by the section knife ; these, however, are 
very few. 
The sclerosis of the lateral columns is most intense in the 
cervical enlargement, and becomes less so as we go down to 
the end of the cord ; the accompanying wood-cuts show the 
distribution of the sclerosed area; it differs greatly in the dif- 
ferent regions ; the sclerosis is of a very light character 
throughout the cord ; it is a very limited region in which the 
nerve tubes are much altered ; the nerve tubes in the sclerosed 
region have simply become a little smaller, have a cloudy ap- 
pearance and a tendency to run together, and a light granular 
material around them; the septa running between the nerve 
bundles are a trifle thicker, and, therefore, appear more 
numerous in this region, and take up the carmine staining 
very sharply, so that to the naked eye the sclerosed region 
appears more diseased than microscopic examination shows it 
to be in those sections ; from the cervical enlargement quite a 
number of spider cells are to be seen, similar to those described 
by several authors in various pathological conditions of the 
nervous system, also by Dr. E. C. Seguin and myself in 
disseminated cerebro-spinal sclerosis but they are quite 
small; in the other regions there appears to be very little 
change in the neuroglia cells; there is an increase of blood- 
vessels in the diseased regions, grey as well as white matter ; 
everywhere the blood-vessels appear normal. In the cervical 
region the central arteries are surrounded by, and their peri- 
vascular spaces distended with an opaque material which is 
*“ A Contribution to the Pathological Anatomy of Disseminated Cerebro- 
Spinal Sclerosis,” Drs. E. C. Seguin, J. 0. Shaw, and A. Van Derveer, 
Journal of Nervous and Mental Disease, April, 1878. Shaw—Progressive Muscular Atrophy. 
5 
lightly stained by hsematoxylin, and which I take to be ftn 
exndated fluid of some kind, albuminous probably, and which 
has become coagulated ; moreover, there is a cloudy appear- 
ance in the entire diseased area in this region, grey as well as 
white matter, and which is evidently due to an infiltration of the 
same kind of material: the question of its being a defect in the 
method of preparation was soon settled by making many sec- 
tions in different ways, and the additional facts that in the same 
section those parts of the cord remaining normal were not in 
the least cloudy, and that the dorsal and lumbar regions pre- 
pared in the same way, did not present the same appearance. 
Sections made very near together, through the decussation and 
into the medulla, showed that the sclerosis extended into the 
anterior pyramids of the medulla ; but the sclerosis becamb 
more and more light until, in sections made through the 
middle of the olivary bodies, it was a very difficult mat 
ter to tell if there was any sclerosis present; but after 
making a great number of sections through the decussation so 
as to find where the sclerosis ceased, and, after a most careful 
examination of all the specimens in their order, 1 was able to 
satisfy myself that there is a very slight sclerosis here, and 
that it has been growing less and less intense up to this region; 
but I was also able to determine that there is a slight sclerosis 
in this region (sections through middle of olivary bodies) in 
that part of the medulla which Meynert considers as belong- 
ing to the lateral columns of the cord (see Fig. 4, B), and that 
a very light fine strip extended from this down almost to the 
pyramids (see Fig. 4). Almost all the nerve cells in the nuclei 
of origin of nerves have suffered atrophy, the cells in the pneu- 
mogastric nucleus are wasted and indistinct, but the nucleus 
of the hypoglossus is where the disease is greatest, the cells 
have undergone extensive pigmentation and atrophy, not one 
nerve cell is to be seen with a process; the cells in the nucleus 
of the sixth and seventh nerves are in good condition. 
Sections through the middle of pons and crura (left) shows 
nothing abnormal. 
The pectoral muscle shows simple diminution in the size of 
the muscular fibrils, and nothing more. 
The question immediately arises, what is the connection be- 6 
Shaw—Progressive Muscular Atrophy. 
tween the symptoms in this case and the pathologic changes 
found ? Numerous cases have now been reported in support of 
the spinal origin of progressive muscular atrophy, and this case 
is an addition ; this view we can now consider almost definitely 
settled ; the myelitis of the anterior horn and disappearance of 
the ganglion cells explains the muscular atrophy; but as to the 
connection which the lateral sclerosis bears to the myelitis of the 
anterior horns and to the symptomatology we are still in doubt. 
In recent years Prof. Charcot* has announced and taught 
that what has heretofore been called progressive muscular 
atrophy really comprehends two distinct diseases, having a 
special symptomatology and distinct pathological anatomy ; a 
first form he calls progressive muscular atrophy protopathic 
(type Duchenne-Aran), a second form progressive muscular 
atrophy, deuteropathic or lateral amyotrophic sclerosis. 
In the first form muscular atrophy is the first and predominant 
symptom, the disease lasts many years, and bulbar symptoms 
do not occur; myelitis of the anterior horns is the pathologi- 
cal condition ; in the second form, first paralysis or paresis, 
then muscular atrophy and contracture, finally bulbar paralysis; 
the disease lasting about three years, with fatal termination ; 
pathology, lateral sclerosis and secondary myelitis of the ante- 
rior horns. 
Now what is my case, one of lateral amyotrophic sclerosis 
with bulbar paralysis ? 
Clinically, the contracture which (harcot appears to consider 
as constant is wanting, there is not even the least contracture 
in the hands, and the muscular atrophy here was certainly the 
first symptom ; the rapidity of the case and the bulbar paral- 
ysis corresponds to the clinical picture given by Charcot of 
lateral amyotrophic sclerosis. Now, when we come to ex- 
amine the cord there are what appear to be at first sight changes 
which place the case as one of lateral amyotrophic sclerosis, 
but a most careful study of the sections lead me to consder it 
otherwise. 
These are my conclusions : the myelitis of the anterior horns 
(commencing in the cervical enlargement) was the primary 
lesion; the extent and severity of the lesion and the time of 
* Archives de Physiologie, 1875, and Maladies du Systems, Nerveuxi Tome II. Shaw—Progressive Muscular Atrophy. 
7 
appearance of the muscular atrophy lead me to this opinion ; 
the lesion in the lower part of the cord and in the analogues 
of the anterior horns in the medulla was simply a matter of 
extension ; the sclerosis of the lateral columns I look upon as 
entirely secondary, and rather as a form of secondary degener- 
ation than a true sclerosis; I cannot conceive how a sclerosis 
of the lateral columns can exist for such a length of time (if it 
had been the primary lesion) and yet produce so slight an 
effect on the nerve tubes as was found to be the case here. 
I have spoken of this condition of the lateral columns as 
sclerosis, because it has been so called by most observers, but 
to me this appears incorrect, for there certainly is a difference 
between this change and that which takes place in dissemi- 
nated cerebro-spinal sclerosis, and to this latter condition 
would I restrict the word sclerosis as indicating peculiar, 
active, and primary changes in the neuroglia cells ; the con- 
dition spoken of in this case is, as far as the neuroglia cells are 
concerned, comparatively a passive one, and resembles more 
the condition seen in so-called secondary degeneration due to 
primary brain lesion, where the nerve tubes appear to be the 
primary seat of trouble ; the same appearance of the neui-oglia 
cells is seen in the sclerosis of the posterior columns in loco- 
motor ataxia, and is a different process from that in dissemi- 
nated sclerosis. 
The presence of contracture in these cases, as a symptom, 
which is always present and due to the sclerosis of the lateral 
columns, and which is one of the distinguishing points of this va- 
riety, as Charcot supposes, is certainly not correct. I have had 
the opportunity of seeing another case similar to this one which 
J describe (but in which I obtained no post-mortem). Here 
there was no contracture, and Prof. Leyden has recently 
recorded several cases* in which post-mortem showed, like my 
case, very light sclerosis of the lateral columns; contracture 
was absent in several of his cases. Leyden’s cases, although 
beginning with bulbar symptoms, are evidently the same dis- 
ease, having its origin in a different point of the cerebro-spinal 
axis. 
*“ Ueber progressive, amyotrophische Bulbarparalyse, etc.” Archtv filer 
Psychiatrie und Nervenkrankheiten, Band 8, heft 3. 8 
Shaw—Progressive Muscular Atrophy. 
The connection between the lesion in the grey matter and 
that in the lateral columns is one which has created much 
interest and some discussion. Charcot is the father of the view 
that in those cases which present the clinical history and symp- 
tomatology, as previously given, and in which microscopic 
examination has shown myelitis of the anterior horns and sym- 
metrical lateral sclerosis, that the sclerosis is primary and the 
lesion of the anterior horn secondary. Upon this he has 
founded the disease, lateral amyotrophic sclerosis. This view 
of Charcot’s has been pretty widely accepted, and recently 
Gombault* has published a monograph on the subject; it has, 
however, met with sharp criticism from many quarters, espe- 
cially German neuropathologists. At this time it appears impos- 
sible to come to any very definite conclusion on the subject. 
Many more observations will have to be recorded before it is 
settled ; this, however, is certain, that there are lesions of the 
grey anterior horns which will produce secondary lesions of 
the lateral columns. The idea that the lesion of the lateral 
columns is due to a bilateral lesion in the cerebrum is not con- 
firmed, and appears, to say the least, rather doubtful. It is 
true, as Flechsig says, that the lesion is most intense in what 
he calls “ Pyramidenbahnen ” (at least it is so in my case), but 
it certainly is not equally intense throughout this bundle, but 
rather occupies the inner part of it; and the idea that the lesion 
shades off from this is to me incomprehensible, as the shading 
off, if it were so, goes almost entirely to the anterior white 
matter. The sclerosis being most intense in the cervical region, 
shows that it is not dependent upon lesion above the cord, 
and the fact that the sclerosis disappears in the medulla, 
supports this, and argues that it is dependent upon the 
myelitis of the anterior horn. I do not deny that there is a 
primary lateral sclerosis with secondary lesion of the anterior 
horns ; but there are certainly cases running the course (about 
three years) having the symptomatology, bulbar paralysis, etc., 
of what Charcot calls lateral amyotrophic sclerosis, in which 
the symmetrical lateral sclerosis is not the primary lesion (my 
own and Leyden’s cases). 
Secondary changes are seen in the lateral white matter in 
* Etude mr le Sclerose laterale amyotrophique. 1877. Fi,J 
nf. 2. 
T,aA- 
rii3: Shaw—Progressive Muscular Atrophy. 
9 
cases of infantile spinal paralysis in which the lesion is an acute 
myelitis of the anterior horns. No special attention appears 
to have been paid to this condition, nor has the question arisen 
why it is there. It must be said that Charcot states that he has 
never seen a case in which the myelitis of the anterior horns 
caused secondary degeneration of the lateral columns, hut he 
does not appear to think that it is impossible. 
One point appears to me of great importance in the micro- 
scopic examination of these cases, and that is a careful obser- 
vation and record of the degree of change in the different 
regions (anterior horns and lateral columns). The conclusion 
from all this is evident, that the symptomatology and the 
interpretation of the pathological changes seen in the so-called 
lateral amyotrophic sclerosis of Charcot will have to undergo 
modifications, and cannot he considered so absolute as Charcot 
has laid it down. 
Explanation op Wood-cuts. 
The shaded regions indicate the sclerosis. 
Fig. 1.—From cervical enlargement, showing distribution of sclerosis in 
lateral white matter. 
Fig. 2.—From dorsal region ; it will be observed that the sclerosis does 
not occupy exactly the same region as in Fig. 1, but keeps very near to the 
posterior horn. In some sections from this region the sclerosis extended 
pretty well forward, and as far as the anterior border of the anterior horn, 
and keeping close to the grey matter. 
Fig. 3.—From lumbar region. Here the sclerosis is very limited in extent 
and is well indicated by wood-cut. 
Fig. 4.—From section through middle of olivary bodies; here the sclerosis 
is of an exceeding slight character. Fig. a.—Sclerosed anterior pyramid. 
Fig. c.—Nucleus of liypoglossus. Fig. b.—Sclerosed region in district which 
Meynert considers as belonging to the lateral regions of the spinal cord; also 
a light band of sclerosis extending from this down almost to the sclerosed 
anterior pyramid.